53 results on '"Bacigalupo, Andrea"'
Search Results
2. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO
- Author
-
Simona Sica, Laura Cudillo, Marta Stanzani, Antonio M. Risitano, Barbara Montante, Giovanni Pisapia, Maurizio Musso, Clara Pecoraro, Attilio Olivieri, Alessandro Rambaldi, Angelo Michele Carella, Francesca Patriarca, Alessandro Bonini, Anna Paola Iori, Ignazio Majolino, Adriana Vacca, Giuseppe Irrera, Nicola Mordini, Alberto Bosi, Corrado Girmenia, Giuseppe Milone, Domenico Pastore, Alessandro Busca, Donatella Baronciani, Stefano Guidi, Alessandra Algarotti, Alfonso Piciocchi, Giuseppe Bandini, Elio Castagnola, Patrizia Chiusolo, Andrea Bacigalupo, William Arcese, Benedetto Bruno, Elisa Zucchetti, Francesco Onida, Edoardo Lanino, Anna Maria Raiola, Domenico Russo, Daniele Vallisa, Sadia Falcioni, Arcangelo Prete, Anna Locasciulli, Girmenia, Corrado, Raiola, Anna Maria, Piciocchi, Alfonso, Algarotti, Alessandra, Stanzani, Marta, Cudillo, Laura, Pecoraro, Clara, Guidi, Stefano, Iori, Anna Paola, Montante, Barbara, Chiusolo, Patrizia, Lanino, Edoardo, Carella, Angelo Michele, Zucchetti, Elisa, Bruno, Benedetto, Irrera, Giuseppe, Patriarca, Francesca, Baronciani, Donatella, Musso, Maurizio, Prete, Arcangelo, Risitano, ANTONIO MARIA, Russo, Domenico, Mordini, Nicola, Pastore, Domenico, Vacca, Adriana, Onida, Francesco, Falcioni, Sadia, Pisapia, Giovanni, Milone, Giuseppe, Vallisa, Daniele, Olivieri, Attilio, Bonini, Alessandro, Castagnola, Elio, Sica, Simona, Majolino, Ignazio, Bosi, Alberto, Busca, Alessandro, Arcese, William, Bandini, Giuseppe, Bacigalupo, Andrea, Rambaldi, Alessandro, and Locasciulli, Anna
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,Epidemiology ,medicine.medical_treatment ,Mycose ,Hematopoietic stem cell transplantation ,Young Adult ,Internal medicine ,Allogeneic HSCT ,medicine ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,Child ,Transplantation, Homologou ,Aged ,Acute leukemia ,Transplantation ,Hematology ,business.industry ,fungal infection ,Incidence ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Infant ,Middle Aged ,Surgery ,Prospective Studie ,surgical procedures, operative ,Treatment Outcome ,Mycoses ,Italy ,Cord blood ,Child, Preschool ,Invasive fungal disease ,business ,Settore MED/15 - Malattie del Sangue ,Human - Abstract
Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P
- Published
- 2014
3. Haploidentical bone marrow transplants with post transplant cyclophosphamide on day + 3 + 5: The Genova protocol.
- Author
-
Raiola AM, Angelucci E, Sica S, and Bacigalupo A
- Subjects
- Humans, Middle Aged, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation methods, Bone Marrow, Cyclophosphamide therapeutic use, Recurrence, Transplantation Conditioning methods, Leukemia, Myeloid, Acute drug therapy, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation methods
- Abstract
We report 634 patients who underwent unmanipulated haploidentical (HAPLO) bone marrow transplantation (BMT) in two Centers. The diagnosis was acute myeloid leukemia (AML) (n = 251), acute lymphoblastic leukemia (ALL)(n = 107), myelodysplastic syndrome and myelofibrosis (MDS + MF) (n = 125) and chronic lymphoproliferative disorders (n = 151). Median age was 52 years (16-74). Graft versus host disease (GvHD) prophylaxis was intravenous cyclosporin (CSA) starting on day 0, oral mycophenolate on day +1, and post-transplant cyclophosphamide (PTCY) on days +3 + 5. Primary graft failure was seen in 23 patients (3,6%); 17 /23 (74%) were rescued with second HAPLO graft, and were alive at one year. The cumulative incidence of acute GvHD grade II-IV was 29% and 3% for grade III-IV; the cumulative incidence of moderate severe chronic GvHD was 23%: older donor and patients age were significant predictors of both acute and chronic GvHD. The overall non relapse mortality (NRM) at 2 years was 19%: 8%, 21% and 30% in patients aged <40, 41-60 > 60 years. Disease free survival (DFS) at 5 years was 64% for acute leukemia in first remission, 51% for acute leukemia CR2, 25% for acute leukemia advanced disease and 49% for MDS/MPN. We confirm, on a relatively large number of patients, that unmanipulated HAPLO BMT with PTCY on days +3 + 5, mostly after a myeloablative conditioning regimen, is followed by a low incidence of graft failure and grade III-IV GvHD; moderate severe chronic GvHD is 23% and NRM at 2 years 19%; 5 year DFS is influenced by remission status of the underlying disease., Competing Interests: Declaration of Competing Interest No conflicts to disclosure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
4. The next horizon now that everyone has a donor: Precision allogeneic transplantation.
- Author
-
Jones RJ and Bacigalupo A
- Subjects
- Humans, Bone Marrow Transplantation methods, Transplantation, Homologous, Cyclophosphamide, Tissue Donors, Acute Disease, Transplantation Conditioning methods, Antineoplastic Agents, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, B-Cell, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods
- Abstract
Post-transplant cyclophosphamide (PTCy) allows safe and effective partially matched donor allogeneic blood or marrow transplantation (alloBMT), so that almost everyone in need of the procedure now has a donor. Moreover, PTCy and other recent advances have lowered alloBMT mortality rates to less than half of that seen before the turn of the century, at costs that are substantially less than most newly approved anticancer agents. These advances also make tailoring BMT based on patients' unique diseases and characteristics now feasible for further improving outcomes. Personalizing every aspect of alloBMT, including conditioning, donor, graft type, and post-transplant maintenance is now possible. For example, alloBMT's antitumor activity historically was restricted to the allogeneic graft-versus-tumor effect directed against histocompatibility antigens. However, replacing exhausted immune systems with healthy non-exhausted, non-tolerant ones likely can enhance the activity of novel targeted therapies. The impressive results seen with tyrosine kinase inhibitors after alloBMT for patients with both Ph+ acute lymphoblastic leukemia and FLT/ITD+ acute myeloid leukemia herald the potential of precision BMT., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
5. PTCy: The "new" standard for GVHD prophylaxis.
- Author
-
Bacigalupo A and Jones R
- Subjects
- Humans, Cyclophosphamide adverse effects, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
High dose Post transplant cyclophosphamide (PTCy) is now regarded as a very effective way of preventing acute and chronic GvHD, and it's use has rapidly expanded world-wide., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
6. A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia.
- Author
-
Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, Harrison CN, McMullin MF, Vannucchi AM, Ewing J, O'Connell CL, Kiladjian JJ, Mead AJ, Winton EF, Leibowitz DS, De Stefano V, Arcasoy MO, Kessler CM, Catchatourian R, Rondelli D, Silver RT, Bacigalupo A, Nagler A, Kremyanskaya M, Levine MF, Arango Ossa JE, McGovern E, Sandy L, Salama ME, Najfeld V, Tripodi J, Farnoud N, Penson AV, Weinberg RS, Price L, Goldberg JD, Barbui T, Marchioli R, Tognoni G, Rampal RK, Mesa RA, Dueck AC, and Hoffman R
- Subjects
- Disease Progression, Humans, Hydroxyurea adverse effects, Interferon-alpha adverse effects, Polycythemia Vera drug therapy, Polycythemia Vera genetics, Thrombocythemia, Essential drug therapy, Thrombocythemia, Essential genetics, Thrombosis chemically induced, Thrombosis prevention & control
- Abstract
The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856., (© 2022 by The American Society of Hematology.)
- Published
- 2022
- Full Text
- View/download PDF
7. HLA still matters in allogeneic transplants.
- Author
-
Bacigalupo A
- Subjects
- Allografts, Humans, Bone Marrow Transplantation, Tissue Donors
- Published
- 2021
- Full Text
- View/download PDF
8. Coronavirus disease 2019 pandemic and allogeneic hematopoietic stem cell transplantation: a single center reappraisal.
- Author
-
Valentini CG, Chiusolo P, Bianchi M, Metafuni E, Orlando N, Giammarco S, Bacigalupo A, Sica S, and Teofili L
- Subjects
- COVID-19 virology, Cryopreservation, Female, Humans, Male, Middle Aged, SARS-CoV-2 physiology, Tissue Donors, Transplantation, Homologous, Treatment Outcome, COVID-19 epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Pandemics
- Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has deeply modified the complex logistical process underlying allogeneic hematopoietic stem cell transplant practices., Aim: In light of these changes, the authors compared data relative to allogeneic transplants carried out from 2018 at their center before (n = 167) and during the pandemic (n = 45)., Methods: The authors examined patient characteristics, donor and graft types, cell doses and main transplant outcomes. Moreover, the authors evaluated the rise of costs attributable to additional COVID-19-related procedures as well as the risk of adverse events these procedures conveyed to grafts or recipients., Results: Overall, the number of transplants did not decrease during the pandemic, whereas patients at high relapse risk were prioritized. Transplants were mainly from matched unrelated donors, with a significant decrease in haploidentical related donors. Moreover, the use of bone marrow as a graft for haploidentical transplant was almost abandoned. Cryopreservation was introduced for all related and unrelated apheresis products, with a median storage time of 20 days. Notably, transplant outcomes (engraftment, acute graft-versus-host disease and non-relapse mortality) with cryopreserved products were comparable to those with fresh products., Conclusions: Considering that the emergency situation may persist for months, cryopreserving allogeneic grafts can offer a lifesaving opportunity for patients whose allogeneic transplant cannot be postponed until after the end of the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
9. Bone marrow transplantation for acquired aplastic anemia: What's new.
- Author
-
Bacigalupo A and Benintende G
- Subjects
- Adult, Bone Marrow Transplantation, Cyclophosphamide, Humans, Transplantation Conditioning, Anemia, Aplastic therapy, Graft vs Host Disease prevention & control
- Abstract
Bone marrow transplantation is a major therapeutic option for patients with acquired severe aplastic anaemia: improved survival has been achieved in younger patients, thanks to better donor selection, conditioning regimens and graft versus host disease prophylaxis, together with improved supportive care, including diagnosis and treatment of opportunistic infections. This has not been the case for older patients over the age of 40 years. We will discuss transplantation platforms as used for different donor types and we will analyse major breakthroughs of the last years: the combination of Fludarabine and cyclophosphamide as a conditioning regimen, the use of alternative donors including HLA haploidentical related donors and new strategies to prevent acute and chronic graft versus host disease, including post transplantation Cyclophosphamide. These changes extend the option of a bone marrow transplantation for patients who lack an HLA matched donor and appear to improve engraftment and reduce graft versus host disease: whether this will be true for all age groups is currently being investigated., (Copyright © 2021. Published by Elsevier Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
10. Bone marrow haploidentical transplant with post-transplantation cyclophosphamide: does graft cell content have an impact on main clinical outcomes?
- Author
-
Teofili L, Chiusolo P, Valentini CG, Metafuni E, Bellesi S, Orlando N, Bianchi M, Giammarco S, Sica S, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Chimerism, Disease-Free Survival, Female, Graft vs Host Disease etiology, Humans, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local pathology, Neutrophils transplantation, Platelet Transfusion, Proportional Hazards Models, Tissue Donors, Treatment Outcome, Young Adult, Bone Marrow Transplantation adverse effects, Cyclophosphamide pharmacology, Transplantation, Haploidentical adverse effects
- Abstract
We analyzed data relative to cell content in 88 consecutive patients receiving HLA haploidentical bone marrow (BM) transplants with post-transplantation cyclophosphamide (PT-CY). Median age was 54.5 (range, 17-72); diagnoses were acute leukemia (n = 46), lymphoproliferative disorders (n = 24), myelofibrosis (n = 11) and myelodysplastic syndromes (n = 5). Total nucleated cell (TNC) and CD34+, CD3+, CD4+ and CD8+ cell doses were stratified as higher than first, second and third quartile and the dose effect on various clinical outcomes was assessed. Median time to engraftment was 17 days for neutrophils and 24 days for platelets. To receive a dose of TNC ≥3.2 x 10
6 /kg or CD34+ cells ≥2.7 x 106 /kg significantly shortened the time to neutrophil and platelet engraftment and reduced the blood product requirements in the 30-day period after transplantation. Overall, TNC and CD34+ cell doses had no effect on acute graft-versus-host disease (GVHD) incidence, whereas patients receiving higher CD3+ and CD8+ cell doses seemed to have less chronic GVHD. No effect on non-relapse mortality, progression-free survival and overall survival was observed at different cell dose thresholds. These data suggest that in HLA haploidentical BM transplant with PT-CY, appropriate cell doses are relevant to the engraftment. The association between low CD3+/CD8+ cells and chronic GVHD deserves further investigation., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2020 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
11. Transplant outcome for patients with acquired aplastic anemia over the age of 40: has the outcome improved?
- Author
-
Giammarco S, Peffault de Latour R, Sica S, Dufour C, Socie G, Passweg J, Kröger N, Petersen E, Van Lint MT, Oneto R, Signori A, and Bacigalupo A
- Subjects
- Aged, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Retrospective Studies, Survival Rate, Anemia, Aplastic mortality, Anemia, Aplastic therapy, Hematopoietic Stem Cell Transplantation
- Published
- 2018
- Full Text
- View/download PDF
12. How I treat acquired aplastic anemia.
- Author
-
Bacigalupo A
- Subjects
- Anemia, Aplastic drug therapy, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation methods, Humans, Immunosuppression Therapy adverse effects, Immunosuppression Therapy methods, Treatment Outcome, Anemia, Aplastic therapy
- Abstract
Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells plays an important role in pathogenesis, as shown by successful treatment with immunosuppressive agents, leading to transfusion independence or complete recovery of peripheral blood counts in a proportion of patients. Growth factors can be combined with immunosuppressive therapy (IST) and may improve response rates, as recently shown with thrombopoietin analogs. Anabolic steroids may still play a role in combination with IST. The problem with IST is failure to respond and the development of late clonal disorders. Bone marrow transplantation (BMT) is the other therapeutic option: a matched sibling donor remains the best choice. For patients lacking a matched family donor, unrelated donors can be readily found, although mostly for patients of Caucasian origin. Other BMT options include unrelated cord blood or mismatched family donors. Acute and chronic graft-versus-host disease remain important complications of BMT. Patient age is a strong predictor of outcome for both IST and BMT, and must be considered when designing therapeutic strategies. Early diagnosis and treatment, as well as long-term monitoring, remain crucial steps for successful treatment of SAA., (© 2017 by The American Society of Hematology.)
- Published
- 2017
- Full Text
- View/download PDF
13. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia.
- Author
-
Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, Armand P, Antin JH, Chen J, Devine SM, Fowler DH, Luznik L, Nakamura R, O'Donnell PV, Perales MA, Pingali SR, Porter DL, Riches MR, Ringdén OT, Rocha V, Vij R, Weisdorf DJ, Champlin RE, Horowitz MM, Fuchs EJ, and Eapen M
- Subjects
- Adult, Aged, Female, Graft vs Host Disease prevention & control, HLA Antigens genetics, Histocompatibility Testing, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Proportional Hazards Models, Transplantation Conditioning methods, Young Adult, Cyclophosphamide therapeutic use, Hematopoietic Stem Cell Transplantation methods, Immunosuppressive Agents therapeutic use, Leukemia, Myeloid, Acute surgery, Tissue Donors
- Abstract
We studied adults with acute myeloid leukemia (AML) after haploidentical (n = 192) and 8/8 HLA-matched unrelated donor (n = 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P = .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P = .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P = .05) and 34% vs 52% (P = .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P = .38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI, 35-56) and 44% (95% CI, 0.40-47) (P = .71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation.
- Published
- 2015
- Full Text
- View/download PDF
14. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.
- Author
-
Fiz F, Marini C, Campi C, Massone AM, Podestà M, Bottoni G, Piva R, Bongioanni F, Bacigalupo A, Piana M, Sambuceti G, and Frassoni F
- Subjects
- Adolescent, Adult, Aged, Allografts, Female, Fluorodeoxyglucose F18, Humans, Male, Middle Aged, Multimodal Imaging, Positron-Emission Tomography methods, Radiopharmaceuticals, Tomography, X-Ray Computed methods, Young Adult, Adult Stem Cells transplantation, Bone Marrow diagnostic imaging, Bone Marrow Transplantation, Cord Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation
- Abstract
Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites., (© 2015 by The American Society of Hematology.)
- Published
- 2015
- Full Text
- View/download PDF
15. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.
- Author
-
Petersdorf EW, Gooley TA, Malkki M, Bacigalupo AP, Cesbron A, Du Toit E, Ehninger G, Egeland T, Fischer GF, Gervais T, Haagenson MD, Horowitz MM, Hsu K, Jindra P, Madrigal A, Oudshoorn M, Ringdén O, Schroeder ML, Spellman SR, Tiercy JM, Velardi A, Witt CS, O'Huigin C, Apps R, and Carrington M
- Subjects
- Adolescent, Adult, Aged, Alleles, Female, Graft vs Host Disease, Histocompatibility immunology, Humans, Leukemia immunology, Male, Middle Aged, Multivariate Analysis, Myelodysplastic Syndromes immunology, Retrospective Studies, Treatment Outcome, Unrelated Donors, Young Adult, HLA-C Antigens metabolism, Hematopoietic Stem Cell Transplantation, Leukemia therapy, Myelodysplastic Syndromes therapy
- Abstract
Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease., (© 2014 by The American Society of Hematology.)
- Published
- 2014
- Full Text
- View/download PDF
16. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis.
- Author
-
Rondelli D, Goldberg JD, Isola L, Price LS, Shore TB, Boyer M, Bacigalupo A, Rambaldi A, Scarano M, Klisovic RB, Gupta V, Andreasson B, Mascarenhas J, Wetzler M, Vannucchi AM, Prchal JT, Najfeld V, Orazi A, Weinberg RS, Miller C, Barosi G, Silverman LR, Prosperini G, Marchioli R, and Hoffman R
- Subjects
- Adult, Aged, Analysis of Variance, Antilymphocyte Serum therapeutic use, Blood Donors, Female, Follow-Up Studies, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Histocompatibility, Humans, Janus Kinase 2 genetics, Kaplan-Meier Estimate, Male, Melphalan therapeutic use, Middle Aged, Mutation, Primary Myelofibrosis genetics, Prospective Studies, Siblings, Transplantation Conditioning methods, Transplantation, Homologous, Treatment Outcome, Unrelated Donors, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Hematopoietic Stem Cell Transplantation methods, Primary Myelofibrosis therapy
- Abstract
From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2(V617F) status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897., (© 2014 by The American Society of Hematology.)
- Published
- 2014
- Full Text
- View/download PDF
17. Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R.
- Author
-
Della Porta MG, Alessandrino EP, Bacigalupo A, van Lint MT, Malcovati L, Pascutto C, Falda M, Bernardi M, Onida F, Guidi S, Iori AP, Cerretti R, Marenco P, Pioltelli P, Angelucci E, Oneto R, Ripamonti F, Bernasconi P, Bosi A, Cazzola M, and Rambaldi A
- Subjects
- Adolescent, Adult, Aged, Allografts, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes mortality, Prognosis, Proportional Hazards Models, Recurrence, Risk Factors, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation, Myelodysplastic Syndromes surgery
- Abstract
Approximately one-third of patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (HSCT) are cured by this treatment. Treatment failure may be due to transplant complications or relapse. To identify predictive factors for transplantation outcome, we studied 519 patients with MDS or oligoblastic acute myeloid leukemia (AML, <30% marrow blasts) who received an allogeneic HSCT and were reported to the Gruppo Italiano Trapianto di Midollo Osseo registry between 2000 and 2011. Univariate and multivariate survival analyses were performed using Cox proportional hazards regression. High-risk category, as defined by the revised International Prognostic Scoring System (IPSS-R), and monosomal karyotype were independently associated with relapse and lower overall survival after transplantation. On the other hand, older recipient age and high hematopoietic cell transplantation-comorbidity index (HCT-CI) were independent predictors of nonrelapse mortality. Accounting for various combinations of patient's age, IPSS-R category, monosomal karyotype, and HCT-CI, the 5-year probability of survival after allogeneic HSCT ranged from 0% to 94%. This study indicates that IPSS-R risk category and monosomal karyotype are important factors predicting transplantation failure both in MDS and oligoblastic AML. In addition, it reinforces the concept that allogeneic HSCT offers optimal eradication of myelodysplastic hematopoiesis when the procedure is performed before MDS patients progress to advanced disease stages.
- Published
- 2014
- Full Text
- View/download PDF
18. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European Group for Blood and Marrow Transplantation experience.
- Author
-
Peffault de Latour R, Porcher R, Dalle JH, Aljurf M, Korthof ET, Svahn J, Willemze R, Barrenetxea C, Mialou V, Soulier J, Ayas M, Oneto R, Bacigalupo A, Marsh JC, Peters C, Socie G, and Dufour C
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Europe, Female, Follow-Up Studies, Graft vs Host Disease mortality, Hematologic Neoplasms mortality, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Infant, Infant, Newborn, Male, Middle Aged, Proportional Hazards Models, Retrospective Studies, Transplantation, Homologous, Young Adult, Fanconi Anemia mortality, Fanconi Anemia therapy, Hematopoietic Stem Cell Transplantation mortality
- Abstract
Although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with Fanconi anemia (FA), published series mostly refer to single-center experience with limited numbers of patients. We analyzed results in 795 patients with FA who underwent first HSCT between May 1972 and January 2010. With a 6-year median follow-up, overall survival was 49% at 20 years (95% confidence interval, 38-65 years). Better outcome was observed for patients transplanted before the age of 10 years, before clonal evolution (ie, myelodysplastic syndrome or acute myeloid leukemia), from a matched family donor, after a conditioning regimen without irradiation, the latter including fludarabine. Chronic graft-versus-host disease and secondary malignancy were deleterious when considered as time-dependent covariates. Age more than 10 years at time of HSCT, clonal evolution as an indication for transplantation, peripheral blood as source of stem cells, and chronic graft-versus-host disease were found to be independently associated with the risk for secondary malignancy. Changes in transplant protocols have significantly improved the outcome of patients with FA, who should be transplanted at a young age, with bone marrow as the source of stem cells.
- Published
- 2013
- Full Text
- View/download PDF
19. Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD.
- Author
-
Olivieri A, Cimminiello M, Corradini P, Mordini N, Fedele R, Selleri C, Onida F, Patriarca F, Pavone E, Svegliati S, Gabrielli A, Bresciani P, Nuccorini R, Pascale S, Coluzzi S, Pane F, Poloni A, Olivieri J, Leoni P, and Bacigalupo A
- Subjects
- Adult, Aged, Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal adverse effects, Autoantibodies blood, Benzamides adverse effects, Chronic Disease, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease blood, Hematopoietic Stem Cell Transplantation, Humans, Imatinib Mesylate, Lymphoproliferative Disorders, Male, Middle Aged, Monitoring, Physiologic methods, Myeloproliferative Disorders mortality, Myeloproliferative Disorders therapy, Piperazines adverse effects, Prednisolone administration & dosage, Prednisolone adverse effects, Prospective Studies, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Receptors, Platelet-Derived Growth Factor blood, Severity of Illness Index, Survival Rate, Time Factors, Benzamides administration & dosage, Graft vs Host Disease drug therapy, Graft vs Host Disease mortality, Piperazines administration & dosage, Protein Kinase Inhibitors administration & dosage, Pyrimidines administration & dosage
- Abstract
Forty adults aged 28 to 73 years were entered into a prospective trial of imatinib for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD). After 6 months, intention-to-treat (ITT) analysis of 39 patients who received the drug, regardless of the duration of treatment, revealed 14 partial responses (PR), 4 minor responses (MR) with relevant steroid sparing (46%) according to Couriel criteria, and 20 ≥ PR (51.3%), as per the National Institutes of Health (NIH) criteria and NIH severity score changes. The best responses were seen in the lungs, gut, and skin (35%, 50%, and 32%, respectively). After a median follow-up of 40 months, 28 patients were alive, with a 3-year overall survival (OS) and event-free survival of 72% and 46%, respectively. The 3-year OS was 94% for patients responding at 6 months and 58% for nonresponders according to NIH response, suggesting that these criteria represent a reliable tool for predicting OS after second-line treatment. Monitoring of anti-platelet-derived growth factor receptor (PDGF-R) antibodies showed a significant decrease in PDGF-R stimulatory activity in 7 responders, whereas it remained high in 4 nonresponders. This study confirms the efficacy of imatinib against SR-cGVHD and suggests that the response at 6 months significantly predicts long-term survival.
- Published
- 2013
- Full Text
- View/download PDF
20. A closer look at permissive HLA mismatch.
- Author
-
Bacigalupo A
- Subjects
- Female, Humans, Male, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I metabolism
- Abstract
In this issue of Blood, Pidala et al add a missing piece of information on the impact of amino acid substitutions (AASs) at specific peptide positions of class I antigens.
- Published
- 2013
- Full Text
- View/download PDF
21. Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index: a prospective, multicenter GITMO study.
- Author
-
Raimondi R, Tosetto A, Oneto R, Cavazzina R, Rodeghiero F, Bacigalupo A, Fanin R, Rambaldi A, and Bosi A
- Subjects
- Adolescent, Adult, Aged, Comorbidity, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Italy epidemiology, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Lymphoma diagnosis, Lymphoma epidemiology, Lymphoma mortality, Lymphoma therapy, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Prognosis, Prospective Studies, Research Design, Retrospective Studies, Treatment Outcome, Young Adult, Health Status Indicators, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation statistics & numerical data
- Abstract
The development of tools for the prediction of nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (HSCT) would offer a major guidance in the therapeutic decision. Recently, the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) has been associated with increased NRM risk in several retrospective studies, but its clinical utility has never been demonstrated prospectively in an adequately sized cohort. To this aim, we prospectively evaluated a consecutive cohort of 1937 patients receiving HSCT in Italy over 2 years. HCT-CI was strongly correlated with both 2-year NRM (14.7%, 21.3%, and 27.3% in patients having an HCT-CI score of 0, 1-2, and ≥ 3, respectively) and overall survival (56.4%, 54.5%, and 41.3%, respectively). There was an excellent calibration between the predicted and observed 2-year NRM in patients having an HCT-CI score of 0 and 1-2, whereas in the ≥ 3 group the predicted NRM overestimated the observed NRM (41% vs 27.3%). HCT-CI alone was the strongest predictor of NRM in patients with lymphoma, myelodysplastic syndrome, and acute myeloid leukemia in first remission (c-statistics 0.66, 064, and 0.59, respectively). We confirm the clinical utility of the HCT-CI score that could also identify patients at low NRM risk possibly benefiting from an HSCT-based treatment strategy.
- Published
- 2012
- Full Text
- View/download PDF
22. Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party.
- Author
-
Marsh JC, Bacigalupo A, Schrezenmeier H, Tichelli A, Risitano AM, Passweg JR, Killick SB, Warren AJ, Foukaneli T, Aljurf M, Al-Zahrani HA, Höchsmann B, Schafhausen P, Roth A, Franzke A, Brummendorf TH, Dufour C, Oneto R, Sedgwick P, Barrois A, Kordasti S, Elebute MO, Mufti GJ, and Socie G
- Subjects
- Adolescent, Adult, Aged, Animals, Antilymphocyte Serum adverse effects, CD4-Positive T-Lymphocytes drug effects, Cyclosporine adverse effects, Drug Therapy, Combination, Europe, Female, Horses, Humans, Immunosuppressive Agents adverse effects, Male, Middle Aged, Pilot Projects, Prospective Studies, Rabbits, Survival Analysis, Young Adult, Anemia, Aplastic drug therapy, Antilymphocyte Serum therapeutic use, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use
- Abstract
Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age- and disease severity-matched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P = .009). Transplant-free survival was 52% for rATG and 76% for hATG (P = .002). On multivariate analysis, rATG (hazard ratio = 3.9, P = .003) and age more than 37 years (hazard ratio = 4.7, P = .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848.
- Published
- 2012
- Full Text
- View/download PDF
23. Back to the OR?
- Author
-
Bacigalupo A
- Published
- 2011
- Full Text
- View/download PDF
24. A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation.
- Author
-
Tichelli A, Schrezenmeier H, Socié G, Marsh J, Bacigalupo A, Dührsen U, Franzke A, Hallek M, Thiel E, Wilhelm M, Höchsmann B, Barrois A, Champion K, and Passweg JR
- Subjects
- Adolescent, Adult, Anemia, Aplastic diagnosis, Anemia, Aplastic mortality, Child, Child, Preschool, Disease-Free Survival, Drug Therapy, Combination, Female, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Severity of Illness Index, Survival Analysis, Young Adult, Anemia, Aplastic drug therapy, Antilymphocyte Serum administration & dosage, Cyclosporine administration & dosage, Granulocyte Colony-Stimulating Factor administration & dosage, Immunosuppressive Agents administration & dosage
- Abstract
We evaluated the role of granulocyte colony-stimulating factor (G-CSF) in patients with severe aplastic anemia (SAA) treated with antithymocyte globulin (ATG) and cyclosporine (CSA). Between January 2002 and July 2008, 192 patients with newly diagnosed SAA not eligible for transplantation were entered into this multicenter, randomized study to receive ATG/CSA with or without G-CSF. Overall survival (OS) at 6 years was 76% ± 4%, and event-free survival (EFS) was 42% ± 4%. No difference in OS/EFS was seen between patients randomly assigned to receive or not to receive G-CSF, neither for the entire cohort nor in subgroups stratified by age and disease severity. Patients treated with G-CSF had fewer infectious episodes (24%) and hospitalization days (82%) compared with patients without G-CSF (36%; P = .006; 87%; P = .0003). In a post hoc analysis of patients receiving G-CSF, the lack of a neutrophil response by day 30 was associated with significantly lower response rate (56% vs 81%; P = .048) and survival (65% vs 87%; P = .031). G-CSF added to standard ATG and CSA reduces the rate of early infectious episodes and days of hospitalization in very SAA patients and might allow early identification of nonresponders but has no effect on OS, EFS, remission, relapse rates, and mortality. This study was registered at www.clinicaltrials.gov as NCT01163942.
- Published
- 2011
- Full Text
- View/download PDF
25. Acute bronchodilator responsiveness in bronchiolitis obliterans syndrome following hematopoietic stem cell transplantation.
- Author
-
Barisione G, Bacigalupo A, Crimi E, and Brusasco V
- Subjects
- Administration, Inhalation, Adult, Albuterol administration & dosage, Albuterol pharmacology, Albuterol therapeutic use, Bronchodilator Agents administration & dosage, Bronchodilator Agents pharmacology, Female, Forced Expiratory Volume drug effects, Humans, Male, Middle Aged, Muscle, Smooth drug effects, Muscle, Smooth physiopathology, Retrospective Studies, Scopolamine Derivatives administration & dosage, Scopolamine Derivatives pharmacology, Scopolamine Derivatives therapeutic use, Spirometry, Tiotropium Bromide, Vital Capacity drug effects, Bronchiolitis Obliterans drug therapy, Bronchiolitis Obliterans physiopathology, Bronchodilator Agents therapeutic use, Drug Resistance physiology, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Background: The obstructive abnormality of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is deemed to be virtually insensitive to treatment with inhaled bronchodilators. We studied whether nonconventional assessment of bronchodilation may help to detect physiologically meaningful airway responses missed by traditional criteria., Methods: Standard spirometry, partial and maximal expiratory flow-volume curves, and lung volumes were measured before and 90 min after inhalation of albuterol plus tiotropium in 17 patients who developed mild to very severe BOS following HSCT., Results: After treatment with bronchodilators, the standard criteria of reversibility based on FEV1 and FVC were met in seven out of 17 patients. In eight patients, residual volume (RV) decreased beyond its within-session spontaneous variability, and functional residual capacity (FRC) was reduced in four of them. Partial forced expiratory flow (Vpart) increased beyond its within-session spontaneous variability in nine patients. Out of 10 patients in whom neither FEV1 nor FVC met the standard criteria of reversibility, six had a positive increase in Vpart or a decrease of lung hyperinflation (ie, FRC) or RV. In six patients with limited expiratory flow during tidal breathing, the postbronchodilator increase in Vpart was correlated with a decrease in FRC (R2=0.83; P=.011)., Conclusions: This study suggests that airway smooth muscle tone plays a significant role in BOS after HSCT and that the common knowledge of BOS as an irreversible obstructive disease may stem from the limitation of simple spirometry to detect changes in small airways., Trial Registry: ClinicalTrials.gov; No.: NCT01112241 (BOS-01); URL: www.clinicaltrials.gov.
- Published
- 2011
- Full Text
- View/download PDF
26. Association of Human Development Index with rates and outcomes of hematopoietic stem cell transplantation for patients with acute leukemia.
- Author
-
Giebel S, Labopin M, Ehninger G, Beelen D, Blaise D, Ganser A, Bacigalupo A, Czerw T, Holowiecki J, Fagundes EM, Nowara E, Frassoni F, and Rocha V
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Educational Status, Humans, Kaplan-Meier Estimate, Leukemia classification, Longevity, Middle Aged, Outcome Assessment, Health Care methods, Retrospective Studies, Social Class, Socioeconomic Factors, Transplantation, Autologous, Transplantation, Homologous, Transplantation, Isogeneic, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia surgery, Outcome Assessment, Health Care statistics & numerical data
- Abstract
Human Development Index (HDI) is used by the United Nations Organization to measure socioeconomic achievements of countries. We evaluated the association of HDI with rates and outcomes of hematopoietic stem cell transplantation (HSCT) for patients with acute leukemia. For the analysis of HSCT rates, all adults with acute leukemia (n = 16 403) treated in 30 European countries, between 2001 and 2005, were included. Association of HDI with the outcome was analyzed for 2015 patients with acute myeloid leukemia treated with myeloablative allotransplantation. Countries were classified according to HDI quintiles. Highly significant correlation was found for HDI and the total number of HSCT per population (R = 0.78; P < .001), as well as separately for sibling HSCT (R = 0.84; P < .001), unrelated HSCT (R = 0.66; P < .001), and autologous HSCT (R = 0.43; P = .02). The probabilities of leukemia-free survival for 5 consecutive groups of countries with increasing HDI were: 56%, 59%, 63%, 58%, and 68% (P = .01). In a multivariate analysis, transplantations performed in countries belonging to the upper HDI category were associated with higher leukemia-free survival compared with the remaining ones (HR = 1.36, P = .008), which resulted mainly from reduced risk of relapse (HR = 0.72, P = .04). We conclude that, in Europe, the HDI is associated with both rates and results of HSCT for acute leukemia.
- Published
- 2010
- Full Text
- View/download PDF
27. The intra-bone marrow injection of cord blood cells extends the possibility of transplantation to the majority of patients with malignant hematopoietic diseases.
- Author
-
Frassoni F, Varaldo R, Gualandi F, Bacigalupo A, Sambuceti G, Sacchi N, and Podestà M
- Subjects
- Acute Disease, Adult, Disease-Free Survival, Female, Graft Survival, Graft vs Host Disease mortality, HLA Antigens, Hematologic Diseases mortality, Histocompatibility Testing, Humans, Male, Neoplasm Staging, Survival Rate, Transplantation, Homologous, Bone Marrow, Cord Blood Stem Cell Transplantation methods, Hematologic Diseases therapy, Histocompatibility
- Abstract
Cord blood transplant (CBT) in adult patients is scarcely utilized because of the risk of graft failure or very delayed platelet recovery. To improve the capacity and the speed to engraft, we have developed an intra-bone (IB) cord blood transplant technique. 75 patients with hematological malignancies, categorized by disease phase as early (18%), intermediate (20%) and advanced (62%), were transplanted. The median cell dose (TNC) infused was: 2.6 (1.35-5.4)×10(7)/kg; the HLA disparity was: 12 cases=5/6, 62 cases=4/6 and 1 case=3/6 matched antigens. 72/75 patients engrafted (96%); median day of recovery of neutrophils (PMN) >500×10(9)/L and platelets (PLT) >20 000×10(9)/L was: 23 (14-44) and 35 (16-70) days respectively. The outcomes at 2 years according to Kaplan-Meier are: OS=46%±5; RI=18%±2; NRM=39%±5. Acute GVHD incidence/severity was: grade 0-I=64%, II=14%, III-IV=0%. The incidence of Chronic GVHD was globally low but in 3 cases was very severe. Intra-bone CBT is associated with high rate of engraftment, early and robust platelet recovery, low incidence of acute GVHD. A very promising aspect is that the relapse rate is low considering the advanced phase of the disease in two/thirds of patients. A suitable CBU was found for nearly every patient searching for a CBU. Therefore, IB CBT extends the possibility to transplant any patient for whom this approach represents the sole possibility of long-term survival., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
28. Endothelial colony-forming cells from patients with chronic myeloproliferative disorders lack the disease-specific molecular clonality marker.
- Author
-
Piaggio G, Rosti V, Corselli M, Bertolotti F, Bergamaschi G, Pozzi S, Imperiale D, Chiavarina B, Bonetti E, Novara F, Sessarego M, Villani L, Garuti A, Massa M, Ghio R, Campanelli R, Bacigalupo A, Pecci A, Viarengo G, Zuffardi O, Frassoni F, and Barosi G
- Subjects
- Adult, Aged, Cells, Cultured, Chronic Disease, Colony-Forming Units Assay, Female, Fusion Proteins, bcr-abl genetics, Gene Rearrangement, Humans, Janus Kinase 2 genetics, Male, Middle Aged, Mutation genetics, Myeloproliferative Disorders metabolism, Myeloproliferative Disorders pathology, Biomarkers, Tumor genetics, Endothelial Cells pathology, Fusion Proteins, bcr-abl deficiency, Hematopoietic Stem Cells pathology, Janus Kinase 2 deficiency, Myeloproliferative Disorders genetics, Stem Cells pathology
- Abstract
Two putative types of circulating endothelial progenitor cells have been recently identified in vitro: (1) endothelial colony-forming cell (ECFC) and (2) colony-forming unit-endothelial cell (CFU-EC). Only the former is now recognized to belong to endothelial lineage. We have used the ECFC and CFU-EC assays to readdress the issue of the clonal relation between endothelial progenitor cells and hematopoietic stem cells in patients with Philadelphia-positive and Philadelphia-negative chronic myeloproliferative disorders. Both ECFCs and CFU-ECs were cultured from peripheral blood mononuclear cells, and either BCR-ABL rearrangement or JAK2-V617F mutation were assessed in both types of endothelial colonies. We found that ECFCs lack the disease-specific markers, which are otherwise present in CFU-ECs, thus reinforcing the concept that the latter belongs to the hematopoietic lineage, and showing that in chronic myeloproliferative disorders the cell that gives rise to circulating ECFC has a distinct origin from the cell of the hematopoietic malignant clone.
- Published
- 2009
- Full Text
- View/download PDF
29. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation.
- Author
-
Crocchiolo R, Zino E, Vago L, Oneto R, Bruno B, Pollichieni S, Sacchi N, Sormani MP, Marcon J, Lamparelli T, Fanin R, Garbarino L, Miotti V, Bandini G, Bosi A, Ciceri F, Bacigalupo A, and Fleischhauer K
- Subjects
- Adult, Disease-Free Survival, Female, HLA-DRB1 Chains, Humans, Italy, Male, Middle Aged, Recurrence, Registries, Retrospective Studies, Risk Factors, Survival Rate, Transplantation, Homologous, Algorithms, Donor Selection methods, HLA-DR Antigens, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Tissue Donors
- Abstract
The importance of donor-recipient human leukocyte antigen (HLA)-DPB1 matching for the clinical outcome of unrelated hematopoietic stem cell transplantation (HSCT) is controversial. We have previously described an algorithm for nonpermissive HLA-DPB1 disparities involving HLA-DPB1*0901,*1001,*1701,*0301,*1401,*4501, based on T-cell alloreactivity patterns. By revisiting the immunogenicity of HLA-DPB1*02, a modified algorithm was developed and retrospectively tested in 621 unrelated HSCTs facilitated through the Italian Registry for oncohematologic adult patients. The modified algorithm proved to be markedly more predictive of outcome than the original one, with significantly higher Kaplan-Meier probabilities of 2-year survival in permissive compared with nonpermissive transplantations (55% vs 39%, P = .005). This was the result of increased adjusted hazards of nonrelapse mortality (hazard ratio [HR] = 1.74; confidence interval [CI], 1.19-2.53; P = .004) but not of relapse (HR = 1.02; CI, 0.73-1.42; P = .92). The increase in the hazards of overall mortality by nonpermissive HLA-DPB1 disparity was similar in 10 of 10 (HR = 2.12; CI, 1.23-3.64; P = .006) and 9 of 10 allele-matched transplantations (HR = 2.21; CI, 1.28-3.80; P = .004), both in early-stage and in advanced-stage disease. These data call for revisiting current HLA matching strategies for unrelated HSCT, suggesting that searches should be directed up-front toward identification of HLA-DPB1 permissive, 10 of 10 or 9 of 10 matched donors.
- Published
- 2009
- Full Text
- View/download PDF
30. Imatinib for refractory chronic graft-versus-host disease with fibrotic features.
- Author
-
Olivieri A, Locatelli F, Zecca M, Sanna A, Cimminiello M, Raimondi R, Gini G, Mordini N, Balduzzi A, Leoni P, Gabrielli A, and Bacigalupo A
- Subjects
- Adolescent, Adult, Benzamides, Child, Female, Graft vs Host Disease complications, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Humans, Imatinib Mesylate, Intestinal Diseases, Lung Diseases, Male, Middle Aged, Pilot Projects, Piperazines toxicity, Pyrimidines toxicity, Remission Induction, Skin Diseases, Survival Analysis, Treatment Outcome, Fibrosis pathology, Graft vs Host Disease drug therapy, Piperazines administration & dosage, Pyrimidines administration & dosage, Salvage Therapy methods
- Abstract
We previously reported that patients with fibrotic, chronic graft-versus-host disease (cGVHD) have antibodies activating the platelet-derived growth factor receptor pathway. Because this pathway can be inhibited by imatinib, we performed a pilot study including 19 patients with refractory cGVHD, given imatinib at a starting dose of 100 mg per day. All patients had active cGVHD with measurable involvement of skin or other districts and had previously failed at least 2 treatment lines. Patient median age was 29 years (range, 10-62 years), and median duration of cGvHD was 37 months (range, 4-107 months). The organs involved were skin (n = 17), lung (n = 11), and bowel (n = 5); 15 patients had sicca syndrome. Imatinib-related, grade 3 to 4 toxicity included fluid retention, infections, and anemia. Imatinib was discontinued in 8 patients: in 3 because of toxicity and in 5 because of lack of response (n = 3) or relapse of malignancy (n = 2). Overall response rate at 6 months was 79%, with 7 complete remissions (CRs) and 8 partial remissions (PRs). With a median follow-up of 17 months, 16 patients are alive, 14 still in CR or PR. The 18-month probability of overall survival is 84%. This study suggests that imatinib is a promising treatment for patients with refractory fibrotic cGVHD.
- Published
- 2009
- Full Text
- View/download PDF
31. A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease.
- Author
-
Flowers ME, Apperley JF, van Besien K, Elmaagacli A, Grigg A, Reddy V, Bacigalupo A, Kolb HJ, Bouzas L, Michallet M, Prince HM, Knobler R, Parenti D, Gallo J, and Greinix HT
- Subjects
- Adolescent, Adult, Aged, Chronic Disease, Demography, Female, Galvanic Skin Response, Graft vs Host Disease mortality, Graft vs Host Disease physiopathology, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Mortality, Photopheresis adverse effects, Prospective Studies, Quality of Life, Steroids therapeutic use, Time Factors, United States epidemiology, Graft vs Host Disease therapy, Photopheresis methods
- Abstract
Chronic graft-versus-host disease (cGVHD) is a major limitation of successful hematopoietic cell transplantation. The safety and efficacy of extracorporeal photopheresis (ECP) for 12 to 24 weeks together with standard therapy was compared with standard therapy alone in patients with cutaneous manifestations of cGVHD that could not be adequately controlled by corticosteroid treatment. The primary efficacy end point was a blinded quantitative comparison of percent change from baseline in Total Skin Score (TSS) of 10 body regions at week 12. Ninety-five patients were randomized to either ECP and standard therapy (n = 48) or standard therapy alone (n = 47). The median percentage improvement in TSS at week 12 was 14.5% for the ECP arm and 8.5% for the control arm (P = .48). The proportion of patients who had at least a 50% reduction in steroid dose and at least a 25% decrease from baseline in TSS was 8.3% in the ECP arm at week 12 and 0% in the control arm (P = .04). The nonblinded investigator assessment of skin complete or partial responses revealed a significant improvement in favor of ECP (P < .001). ECP was generally well tolerated. These results suggest that ECP may have a steroid-sparing effect in the treatment of cGVHD. Clinical trials registered at www.ClinicalTrials.gov as NCT00054613.
- Published
- 2008
- Full Text
- View/download PDF
32. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).
- Author
-
Alessandrino EP, Della Porta MG, Bacigalupo A, Van Lint MT, Falda M, Onida F, Bernardi M, Iori AP, Rambaldi A, Cerretti R, Marenco P, Pioltelli P, Malcovati L, Pascutto C, Oneto R, Fanin R, and Bosi A
- Subjects
- Adolescent, Adult, Aged, Blood Transfusion, Classification, Female, Humans, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Prognosis, Recurrence, Survival Rate, World Health Organization, Hematopoietic Stem Cell Transplantation mortality, Myelodysplastic Syndromes classification, Myelodysplastic Syndromes therapy
- Abstract
We evaluated the impact of World Health Organization (WHO) classification and WHO classification-based Prognostic Scoring System (WPSS) on the outcome of patients with myelodysplastic syndrome (MDS) who underwent allogeneic stem cell transplantation (allo-SCT) between 1990 and 2006. Five-year overall survival (OS) was 80% in refractory anemias, 57% in refractory cytopenias, 51% in refractory anemia with excess blasts 1 (RAEB-1), 28% in RAEB-2, and 25% in acute leukemia from MDS (P = .001). Five-year probability of relapse was 9%, 22%, 24%, 56%, and 53%, respectively (P < .001). Five-year transplant-related mortality (TRM) was 14%, 39%, 38%, 34%, and 44%, respectively (P = .24). In multivariate analysis, WHO classification showed a significant effect on OS (P = .017) and probability of relapse (P = .01); transfusion dependency was associated with a reduced OS (P = .01) and increased TRM (P = .037), whereas WPSS showed a prognostic significance on both OS (P = .001) and probability of relapse (P < .001). In patients without excess blasts, multilineage dysplasia and transfusion dependency affected OS (P = .001 and P = .009, respectively), and were associated with an increased TRM (P = .013 and P = .031, respectively). In these patients, WPSS identified 2 groups with different OS and TRM. These data suggest that WHO classification and WPSS have a relevant prognostic value in posttransplantation outcome of MDS patients.
- Published
- 2008
- Full Text
- View/download PDF
33. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.
- Author
-
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, and Ringdén O
- Subjects
- Adult, Child, Female, Follow-Up Studies, Graft vs Host Disease classification, Graft vs Host Disease mortality, Histocompatibility Testing, Humans, Immunotherapy, Male, Middle Aged, Neoplasms therapy, Severity of Illness Index, Survival Rate, Transplantation Conditioning methods, Transplantation, Homologous, Treatment Outcome, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation adverse effects, Mesenchymal Stem Cell Transplantation
- Abstract
Background: Severe graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells. Mesenchymal stem cells modulate immune responses in vitro and in vivo. We aimed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation., Methods: Patients with steroid-resistant, severe, acute GVHD were treated with mesenchymal stem cells, derived with the European Group for Blood and Marrow Transplantation ex-vivo expansion procedure, in a multicentre, phase II experimental study. We recorded response, transplantation-related deaths, and other adverse events for up to 60 months' follow-up from infusion of the cells., Findings: Between October, 2001, and January, 2007, 55 patients were treated. The median dose of bone-marrow derived mesenchymal stem cells was 1.4x10(6) (min-max range 0.4-9x10(6)) cells per kg bodyweight. 27 patients received one dose, 22 received two doses, and six three to five doses of cells obtained from HLA-identical sibling donors (n=5), haploidentical donors (n=18), and third-party HLA-mismatched donors (n=69). 30 patients had a complete response and nine showed improvement. No patients had side-effects during or immediately after infusions of mesenchymal stem cells. Response rate was not related to donor HLA-match. Three patients had recurrent malignant disease and one developed de-novo acute myeloid leukaemia of recipient origin. Complete responders had lower transplantation-related mortality 1 year after infusion than did patients with partial or no response (11 [37%] of 30 vs 18 [72%] of 25; p=0.002) and higher overall survival 2 years after haemopoietic-stem-cell transplantation (16 [53%] of 30 vs four [16%] of 25; p=0.018)., Interpretation: Infusion of mesenchymal stem cells expanded in vitro, irrespective of the donor, might be an effective therapy for patients with steroid-resistant, acute GVHD.
- Published
- 2008
- Full Text
- View/download PDF
34. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia.
- Author
-
Schrezenmeier H, Passweg JR, Marsh JC, Bacigalupo A, Bredeson CN, Bullorsky E, Camitta BM, Champlin RE, Gale RP, Fuhrer M, Klein JP, Locasciulli A, Oneto R, Schattenberg AV, Socie G, and Eapen M
- Subjects
- Adult, Female, HLA Antigens, Humans, Male, Siblings, Survival Rate, Tissue Donors, Transplantation, Homologous, Treatment Outcome, Anemia, Aplastic therapy, Bone Marrow Transplantation, Graft vs Host Disease etiology, Peripheral Blood Stem Cell Transplantation
- Abstract
We analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic graft-versus-host disease (GVHD) were similar after PBPC and BM transplantations regardless of age at transplantation. In patients older than 20 years, chronic GVHD and overall mortality rates were similar after PBPC and BM transplantations. In patients younger than 20 years, rates of chronic GVHD (relative risk [RR] 2.82; P = .002) and overall mortality (RR 2.04; P = .024) were higher after transplantation of PBPCs than after transplantation of BM. In younger patients, the 5-year probabilities of overall survival were 73% and 85% after PBPC and BM transplantations, respectively. Corresponding probabilities for older patients were 52% and 64%. These data indicate that BM grafts are preferred to PBPC grafts in young patients undergoing HLA-matched sibling donor transplantation for SAA.
- Published
- 2007
- Full Text
- View/download PDF
35. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease.
- Author
-
Svegliati S, Olivieri A, Campelli N, Luchetti M, Poloni A, Trappolini S, Moroncini G, Bacigalupo A, Leoni P, Avvedimento EV, and Gabrielli A
- Subjects
- Adolescent, Adult, Aged, Case-Control Studies, Chronic Disease, Female, Fibrosis etiology, Fibrosis immunology, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Signal Transduction, Transplantation, Homologous, Autoantibodies immunology, Graft vs Host Disease immunology, Receptors, Platelet-Derived Growth Factor immunology
- Abstract
Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (PDGF) receptor (PDGFR) have been found in patients with scleroderma and are responsible for the activation of skin fibroblasts, we tested the hypothesis that these autoantibodies are also present in patients affected by ecGVHD. Serum from 39 patients subjected to allogeneic stem cell transplantation for hematologic malignancies (22 with ecGVHD and 17 without cGVHD) and 20 healthy controls was assayed for the presence of stimulatory autoantibodies to the PDGFR by incubating purified IgG with mouse-embryo fibroblasts lacking PDGFR alpha or beta chains or with the same cells expressing PDGFR alpha. Stimulatory antibodies to the PDGFR were found selectively in all patients with ecGVHD but in none of the patients without cGVHD. Higher levels were detected in patients with generalized skin involvement and/or lung fibrosis. Antibodies recognized native PDGFR, induced tyrosine phosphorylation, accumulation of reactive oxygen species (ROS), and stimulated type 1 collagen gene expression through the Ha-Ras-ERK1/2-ROS signaling pathway. The biologic activity of these autoantibodies suggests a role in the development of fibrosis and argues for a common pathogenetic trait in ecGVDH and scleroderma phenotypes.
- Published
- 2007
- Full Text
- View/download PDF
36. Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia.
- Author
-
Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F, Grasso R, Zupo S, Raiola AM, Gobbi M, Frassoni F, and Bacigalupo A
- Subjects
- Acute Disease, Graft vs Host Disease metabolism, Humans, Immunotherapy, Adoptive, Neoplasm, Residual, Predictive Value of Tests, Recurrence, Remission Induction, Risk, Time Factors, Transplantation, Homologous, Leukemia therapy, Lymphocyte Transfusion methods, Stem Cell Transplantation methods
- Published
- 2007
- Full Text
- View/download PDF
37. Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT).
- Author
-
Socie G, Mary JY, Schrezenmeier H, Marsh J, Bacigalupo A, Locasciulli A, Fuehrer M, Bekassy A, Tichelli A, and Passweg J
- Subjects
- Adolescent, Adult, Anemia, Aplastic complications, Antilymphocyte Serum administration & dosage, Cyclosporine administration & dosage, Data Collection, Europe, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Immunosuppressive Agents administration & dosage, Male, Middle Aged, Recombinant Proteins, Risk Factors, Anemia, Aplastic drug therapy, Granulocyte Colony-Stimulating Factor adverse effects, Myelodysplastic Syndromes etiology
- Abstract
Previous studies suggested a link between the use of G-CSF and increased incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST) for severe aplastic anemia (SAA). This European survey included 840 patients who received a first-line IST with (43%) or without (57%) G-CSF. The incidences of MDS/AML in patients who did or did not receive G-CSF were 10.9% and 5.8%, respectively. A significantly higher hazard (1.9) of MDS/AML was associated with use of G-CSF. Relapse of aplastic anemia was not associated with a worse outcome in patients who did not receive G-CSF as first therapy, whereas relapse was associated with a significantly worse outcome in those patients who received G-CSF. These results emphasize the necessity of the current European randomized trial comparing IST with or without G-CSF and to alert physicians that adding G-CSF to IST is currently not standard treatment for SAA.
- Published
- 2007
- Full Text
- View/download PDF
38. Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma.
- Author
-
Vacca A, Scavelli C, Serini G, Di Pietro G, Cirulli T, Merchionne F, Ribatti D, Bussolino F, Guidolin D, Piaggio G, Bacigalupo A, and Dammacco F
- Subjects
- Cell Division, Cells, Cultured, Chemotaxis, DNA Primers, Endothelial Cells pathology, Humans, Multiple Myeloma genetics, Neovascularization, Physiologic, Reverse Transcriptase Polymerase Chain Reaction, Bone Marrow Cells pathology, Multiple Myeloma pathology, Receptors, Vascular Endothelial Growth Factor genetics, Semaphorin-3A deficiency, Semaphorin-3A genetics, Vascular Endothelial Growth Factor A genetics
- Abstract
Vascular endothelial growth factor165 (VEGF165) and semaphorin3A (SEMA3A) elicit pro- and antiangiogenic signals respectively in endothelial cells (ECs) by binding to their receptors VEGFR-2, neuropilin-1 (NRP1), and plexin-A1. Here we show that the VEGF165-driven angiogenic potential of multiple myeloma (MM) ECs is significantly higher than that of monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs) and human umbilical vein (HUV) ECs. This is probably due to a constitutive imbalance of endogenous VEGF165/SEMA3A ratio, which leans on VEGF165 in MMECs but on SEMA3A in MGECs and HUVECs. Exogenous VEGF165 induces SEMA3A expression in MGECs and HUVECs, but not in MMECs. Moreover, by counteracting VEGF165 activity as efficiently as an anti-VEGFR-2 antibody, exogenous SEMA3A restrains the over-angiogenic potential of MMECs. Our data indicate that loss of endothelial SEMA3A in favor of VEGF165 could be responsible for the angiogenic switch from MGUS to MM.
- Published
- 2006
- Full Text
- View/download PDF
39. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes.
- Author
-
Martino R, Iacobelli S, Brand R, Jansen T, van Biezen A, Finke J, Bacigalupo A, Beelen D, Reiffers J, Devergie A, Alessandrino E, Mufti GJ, Barge R, Sierra J, Ruutu T, Boogaerts M, Falda M, Jouet JP, Niederwieser D, and de Witte T
- Subjects
- Adolescent, Adult, Aged, Dose-Response Relationship, Drug, Female, HLA Antigens, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Myelodysplastic Syndromes mortality, Recurrence, Retrospective Studies, Siblings, Survival Analysis, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes therapy, Transplantation Conditioning methods
- Abstract
In this multicenter retrospective study, the outcomes of 836 patients with myelodysplastic syndrome (MDS) who underwent transplantation with a human leukocyte antigen (HLA)-identical sibling donor were analyzed according to 2 types of conditioning: reduced-intensity conditioning (RIC) in 215 patients, and standard myeloablative (or high-dose) conditioning (SMC) in 621 patients. In multivariate analysis, the 3-year relapse rate was significantly increased after RIC (hazard ratio [HR], 1.64; 95% confidence interval [95% CI], 1.2-2.2; P = .001), but the 3-year nonrelapse mortality (NRM) rate was decreased in the RIC group (HR, 0.61; 95% CI, 0.41-0.91; P = .015). The 3-year probabilities of progression-free and overall survivals were similar in both groups (39% after SMC vs 33% in RIC; multivariate P = .9; and 45% vs 41%, respectively; P = .8). In conclusion, the lower 3-year NRM after RIC is encouraging, since these patients were older (age > 50 years in 73% RIC vs 28% in SMC, P < .001) and had more adverse pretransplantation variables. However, based on the higher risk of relapse, patients with no contraindications for SMC should not receive RIC outside of prospective randomized trials, which are needed to establish the position of RIC-based transplantation in the treatment of patients with MDS.
- Published
- 2006
- Full Text
- View/download PDF
40. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin.
- Author
-
Van Lint MT, Milone G, Leotta S, Uderzo C, Scimè R, Dallorso S, Locasciulli A, Guidi S, Mordini N, Sica S, Cudillo L, Fagioli F, Selleri C, Bruno B, Arcese W, and Bacigalupo A
- Subjects
- Adolescent, Adult, Anti-Inflammatory Agents therapeutic use, Child, Child, Preschool, Female, Graft vs Host Disease mortality, Humans, Immunosuppressive Agents therapeutic use, Incidence, Male, Middle Aged, Risk Assessment, Survival Analysis, Antilymphocyte Serum therapeutic use, Graft vs Host Disease drug therapy, Methylprednisolone therapeutic use
- Abstract
Newly diagnosed patients with acute graft-versus-host disease (GvHD, grades I-IV; n = 211) were given 6-methylprednisolone (6MPred) 2 mg/kg per day for 5 consecutive days; 150 patients (71%) tapered 6MPred on day +5 and were considered responders; 61 patients (29%) could not taper their steroid dose and were considered nonresponders. The cumulative incidence of transplant-related mortality (TRM) for responders and nonresponders is, respectively, 27% and 49% (P = .009), and the 5-year survival is 53% and 35% (P = .007). Nonresponders on day +5 (n = 61) were randomized to receive 6MPred 5 mg/kg per day for 10 days alone (n = 34) or in combination with rabbit anti-thymocyte globulin (ATG, 6.25 mg/kg in 10 days; n = 27). The 2 groups were balanced for clinical and GvHD characteristics. One month after randomization, 26% had a complete response; 23%, a partial response; 33%, stable GvHD; 10%, worsened; and 8%, died. There was no significant difference in response, TRM, and survival between the non-ATG and ATG group. In conclusion, 5 days of prednisolone as first-line therapy of acute GvHD identifies patients with different risk of TRM, and second-line therapy with a combination of 6MPred + ATG does not improve patient outcome, compared with 6MPred alone.
- Published
- 2006
- Full Text
- View/download PDF
41. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT.
- Author
-
Crawley C, Szydlo R, Lalancette M, Bacigalupo A, Lange A, Brune M, Juliusson G, Nagler A, Gratwohl A, Passweg J, Komarnicki M, Vitek A, Mayer J, Zander A, Sierra J, Rambaldi A, Ringden O, Niederwieser D, and Apperley JF
- Subjects
- Adolescent, Adult, Aged, Benzamides, Disease Progression, Europe, Female, Graft vs Host Disease, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive immunology, Male, Middle Aged, Piperazines therapeutic use, Prognosis, Pyrimidines therapeutic use, Risk Factors, Societies, Scientific, Survival Rate, Transplantation Conditioning, Treatment Outcome, Bone Marrow Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive surgery
- Abstract
This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7) and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are feasible in CML in first or second CP. Since no other RIC regimen demonstrated superiority, Fd/Bu/ATG should be considered as baseline in future prospective trials.
- Published
- 2005
- Full Text
- View/download PDF
42. Allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning in intermediate- or high-risk patients with myelofibrosis with myeloid metaplasia.
- Author
-
Rondelli D, Barosi G, Bacigalupo A, Prchal JT, Popat U, Alessandrino EP, Spivak JL, Smith BD, Klingemann HG, Fruchtman S, and Hoffman R
- Subjects
- Adult, Aged, Female, Graft vs Host Disease immunology, Humans, Male, Middle Aged, Primary Myelofibrosis immunology, Primary Myelofibrosis surgery, Retrospective Studies, Risk Factors, Survival Rate, Time Factors, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Primary Myelofibrosis complications, Primary Myelofibrosis therapy, Transplantation Conditioning
- Abstract
A total of 21 patients with myelofibrosis with myeloid metaplasia (MMM), with a median age of 54 years (range, 27-68 years), were prepared with a reduced-intensity conditioning (RIC) regimen. The patients received an allogeneic marrow (n = 3) or peripheral blood stem-cell (n = 18) transplant from HLA-matched related (n = 18) or unrelated (n = 2), or 1 Ag-mismatched related (n = 1), donors. RIC regimens included fludarabine/total body irradiation 200 cGy (n = 5) or 450 cGy (n = 1), fludarabine/melphalan (n = 7), thiotepa/cyclophosphamide (n = 7), and thiotepa/fludarabine (n = 1). At the time of transplantation, all of the patients were at intermediate (n = 13) or high (n = 8) risk, according to the Dupriez classification. Of the patients, 19 had grade III or IV marrow fibrosis. All of the patients achieved full engraftment but one. Posttransplantation chimerism analysis showed more than 95% donor cells in 18 patients, while 2 patients achieved complete donor chimerism after donor leukocyte infusion (DLI). Acute graft-versus-host disease (GVHD) grades II to IV was observed in 7 patients, grades III to IV in 2, and extensive chronic GVHD in 8 of 18 evaluable patients. There were 3 patients who died from acute GVHD, infection, and relapse. There are 18 patients alive 12 to 122 months (median, 31 months) after transplantation, and 17 are in remission (1 after a second transplantation). The use of RIC regimens in allogeneic stem cell transplantation results in prolonged survival in intermediate/high-risk MMM patients.
- Published
- 2005
- Full Text
- View/download PDF
43. Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112).
- Author
-
Pende D, Spaggiari GM, Marcenaro S, Martini S, Rivera P, Capobianco A, Falco M, Lanino E, Pierri I, Zambello R, Bacigalupo A, Mingari MC, Moretta A, and Moretta L
- Subjects
- Cells, Cultured, Gene Expression Regulation, Neoplastic, Histocompatibility Antigens Class I metabolism, Humans, Interleukin-2 Receptor beta Subunit, Killer Cells, Natural metabolism, Ligands, Membrane Proteins metabolism, Receptors, Immunologic metabolism, Receptors, Interleukin metabolism, Receptors, KIR, Receptors, Virus metabolism, Cell Communication, Cytotoxicity, Immunologic, Killer Cells, Natural physiology, Leukemia, Lymphoid pathology, Leukemia, Myeloid pathology
- Abstract
On the basis of recent clinical and experimental data, natural killer (NK) cells appear to play a crucial role in eradication of acute myeloid leukemias. In the present study, by exploiting our current knowledge on NK receptors and their ligands on target cells, we investigated the interactions between NK and leukemic cells. We show that the size of the NK cell subset expressing the killer immunoglobulin-like receptor (KIR) not engaged by the HLA-class I alleles of the patient parallels the degree of NK cytotoxicity against leukemic cells. A sharp down-regulation of HLA-class I molecules has been detected in various leukemias and it was more frequent in myeloid than in lymphoblastic leukemias. Analysis of the ligands for triggering NK receptors revealed the consistent expression of Poliovirus receptor (PVR) and Nectin-2 in myeloid leukemias. In contrast, major histocompatibility complex class I-related chain molecules A/B (MICA/B) and UL1b-binding protein (ULBPs) were either absent or weakly expressed. Accordingly, NK-mediated lysis of these leukemias was dependent on DNAM-1 but not NKG2D. The major role of NKp46 and NKp30 was also confirmed. The expression of PVR and/or Nectin-2 was less frequent in lymphoblastic leukemias. In most leukemias, both CD48 and NTBA were down-regulated. The correlation found between marker expression and susceptibility to lysis may reveal useful information for NK-based immunotherapy.
- Published
- 2005
- Full Text
- View/download PDF
44. Mesenchymal stem cells and haematopoietic stem cell transplantation.
- Author
-
Bacigalupo A
- Subjects
- Animals, Bone Marrow Cells cytology, Bone Marrow Cells immunology, Bone Marrow Transplantation, Humans, Treatment Outcome, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Mesenchymal Stem Cell Transplantation adverse effects, Mesenchymal Stem Cell Transplantation methods
- Abstract
The bone marrow serves as a reservoir for different classes of stem cells. In addition to haemopoietic stem cells, the bone marrow comprises a population of marrow stromal cells or mesenchymal stem cells (MSCs). These cells exhibit multilineage differentiation capacity, and are able to generate progenitors with restricted developmental potential, including fibroblasts, osteoblasts, adipocytes and chondrocyte progenitors. In addition, MSCs have been shown to possess immunosuppressive activity in vitro and in vivo. Clinical trials are underway to test whether MSCs are beneficial in patients undergoing allogeneic bone marrow transplantation. With the expanding role of stem cell transplants in different areas of medicine, including cardiology and orthopaedics, MSCs may become very important in the next few years.
- Published
- 2004
- Full Text
- View/download PDF
45. A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation.
- Author
-
Zino E, Frumento G, Marktel S, Sormani MP, Ficara F, Di Terlizzi S, Parodi AM, Sergeant R, Martinetti M, Bontadini A, Bonifazi F, Lisini D, Mazzi B, Rossini S, Servida P, Ciceri F, Bonini C, Lanino E, Bandini G, Locatelli F, Apperley J, Bacigalupo A, Ferrara GB, Bordignon C, and Fleischhauer K
- Subjects
- Algorithms, Alleles, Amino Acid Sequence, Cross Reactions, Epitopes, T-Lymphocyte genetics, Graft vs Host Disease immunology, HLA-DP Antigens genetics, HLA-DP beta-Chains, Humans, Isoantigens genetics, Isoantigens immunology, Molecular Sequence Data, Retrospective Studies, T-Lymphocytes immunology, Epitopes, T-Lymphocyte immunology, HLA-DP Antigens immunology, Hematopoietic Stem Cell Transplantation
- Abstract
The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P =.046) and transplantation-related mortality (HR = 2.69, P =.027) but not relapse (HR = 0.98, P =.939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P =.1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation.
- Published
- 2004
- Full Text
- View/download PDF
46. Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma.
- Author
-
Corradini P, Cavo M, Lokhorst H, Martinelli G, Terragna C, Majolino I, Valagussa P, Boccadoro M, Samson D, Bacigalupo A, Russell N, Montefusco V, Voena C, and Gahrton G
- Subjects
- Adult, Disease-Free Survival, Female, Genetic Markers, Humans, Longitudinal Studies, Male, Middle Aged, Multiple Myeloma epidemiology, Predictive Value of Tests, Prognosis, Recurrence, Remission Induction, Risk Factors, Gene Rearrangement, B-Lymphocyte genetics, Hematopoietic Stem Cell Transplantation, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Abstract
Patients in complete clinical remission after myeloablative allogeneic stem cell transplantation (allo-SCT) were enrolled in a longitudinal study to assess the predictive value of molecular monitoring. Using polymerase chain reaction (PCR) for immunoglobulin gene rearrangements it was possible to generate a clone-specific molecular marker in 48 of 70 patients. Of these 48 patients, 16 (33%) attained durable PCR-negativity after transplantation, whereas 13 (27%) remained persistently PCR-positive and 19 (40%) showed a mixed pattern. The cumulative risk of relapse at 5 years was 0% for PCR-negative patients, 33% for PCR-mixed patients, and 100% for PCR-positive patients. Within the group studied it was not possible to identify any clinical feature predictive of durable PCR-negativity. We believe that these findings could prompt the design of prospective studies to evaluate if the treatment of molecular disease can extend remission duration and survival.
- Published
- 2003
- Full Text
- View/download PDF
47. Haemopoietic stem cell transplants: the impact of haemorrhagic complications.
- Author
-
Bacigalupo A
- Subjects
- Factor VII therapeutic use, Factor VIIa, Graft vs Host Disease complications, Hematopoietic Stem Cell Transplantation mortality, Hemorrhage drug therapy, Humans, Recombinant Proteins therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hemorrhage etiology
- Abstract
Acute graft-versus-host disease (GVHD) is the most important complication of allogeneic haemopoietic stem cell transplantation (HSCT), increasing susceptibility to haemorrhage and risk of early mortality. We evaluated 807 allogeneic HSCT patients to assess both the association between bleeding and GVHD, and the influence of haemorrhagic complications on clinical outcome. Up to 55% of patients with grade III-IV GVHD experienced bleeding, compared with 23% of patients with grades 0-l. Furthermore, 45% of patients receiving non-HLA-identical transplants suffered haemorrhage, whereas only 23% of patients receiving transplants from HLA-identical donors experienced bleeding. This can be explained by the higher incidence of severe GVHD among recipients of non-HLA-identical transplants. Our findings also demonstrated that haemorrhagic complications--particularly bleeding from the GI tract--markedly increase patient mortality. An ongoing, multi-centre, randomised, double-blind trial is currently investigating the efficacy and safety of recombinant factor VIIa (rFVIIa; NovoSeven) in the treatment of HSCT-associated bleeding. The trial will examine the ability of three dose levels of rFVIIa to reduce--or even eliminate entirely--the incidence and severity of haemorrhage following such procedures. A total enrollment of 100 patients is anticipated, and preliminary data are expected at the end of 2003.
- Published
- 2003
- Full Text
- View/download PDF
48. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors.
- Author
-
Giebel S, Locatelli F, Lamparelli T, Velardi A, Davies S, Frumento G, Maccario R, Bonetti F, Wojnar J, Martinetti M, Frassoni F, Giorgiani G, Bacigalupo A, and Holowiecki J
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Graft vs Host Disease drug therapy, Graft vs Host Disease prevention & control, Haplotypes, Hematologic Neoplasms complications, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation mortality, Histocompatibility, Histocompatibility Testing, Humans, Infant, Ligands, Male, Prospective Studies, Receptors, KIR, Recurrence, Survival Analysis, Tissue Donors, Transplantation, Homologous immunology, Hematopoietic Stem Cell Transplantation methods, Killer Cells, Natural immunology, Receptors, Immunologic immunology, Transplantation Immunology
- Abstract
Killer immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction was demonstrated to be associated with improved outcome in patients given haploidentical, T-cell-depleted hematopoietic stem cell transplants (HSCTs). The goal of this study was to evaluate whether that observation could be generalized for patients receiving unmanipulated HSCTs from unrelated donors (URD). One hundred thirty patients with hematologic malignancies entered the study. Graft-versus-host disease (GVHD) prophylaxis was uniform and consisted of cyclosporin, short-term methotrexate, and pretransplantation antithymocyte globulin (ATG). Patients were divided into those with (n = 20) and those without (n = 110) KIR ligand incompatibility with respect to their donors. At 4.5 years patients with KIR ligand incompatibility had higher probability of overall survival (87% versus 48%, P =.006) and disease-free survival (87% versus 39%, P =.0007) compared with those without KIR ligand incompatibility. Transplant-related mortality for the 2 groups equaled 6% and 40% (P =.01), respectively. Relapse rates for patients receiving transplants from a donor with or without KIR ligand incompatibility were 6% and 21%, respectively (P =.07). All patients with myeloid malignancies receiving transplants from KIR ligand-disparate donors (n = 13) are alive and disease free. These data indicate that natural killer (NK) cell alloreactivity is associated with better outcome after URD-HSC transplantation when ATG is used as part of GVHD prophylaxis.
- Published
- 2003
- Full Text
- View/download PDF
49. Cord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation.
- Author
-
Frassoni F, Podesta M, Maccario R, Giorgiani G, Rossi G, Zecca M, Bacigalupo A, Piaggio G, and Locatelli F
- Subjects
- Adolescent, Cell Differentiation physiology, Child, Child, Preschool, Female, Hematologic Diseases therapy, Hematopoietic Stem Cells cytology, Humans, Infant, Male, Bone Marrow Transplantation standards, Cord Blood Stem Cell Transplantation standards, Graft Survival, Hematopoiesis
- Abstract
Delayed hematopoietic recovery is the main factor precluding a wider use of cord blood (CB) transplants. We hypothesized that this delayed engraftment might not be related to an insufficient number of stem cells in the graft, but to an intrinsic difficulty of these cells to undergo differentiation. To test our hypothesis, 2 groups of children were compared; 12 received a CB transplant and 12 an adult bone marrow (BM) transplant. We studied neutrophil and platelet recovery and, at a median time of approximately 1 year after transplantation, the frequency of colony-forming cells (CFCs) and long-term culture initiating cells (LTC-ICs) in the BM of the 2 groups. Recipients of BM transplants received 1-log more cells and had significantly faster neutrophil and platelet recovery. Conversely, the frequency of committed and early progenitors was significantly higher in the BM of children given CB cells compared with BM transplant recipients (median count of CFC/2 x 10(4) BM mononuclear cells, 20 versus 11, P =.007; median count of LTC-IC/10(6) BM mononuclear cells, 8.2 versus 0.2 P =.001). CB, but not adult BM stem cells, can better restore the host hematopoietic progenitor cell reservoir; the delayed engraftment after CB transplantation may reflect the difficulty of CB progenitors to reprogram themselves toward differentiation.
- Published
- 2003
- Full Text
- View/download PDF
50. Transplant-related mortality and long-term graft function are significantly influenced by cell dose in patients undergoing allogeneic marrow transplantation.
- Author
-
Dominietto A, Lamparelli T, Raiola AM, Van Lint MT, Gualandi F, Berisso G, Bregante S, Di Grazia C, Soracco M, Pitto A, Frassoni F, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Bone Marrow Transplantation adverse effects, Cause of Death, Cell Count, Child, Child, Preschool, Female, Hemoglobins metabolism, Humans, Infant, Leukocyte Count, Male, Middle Aged, Multivariate Analysis, Platelet Count, Recurrence, Survival Analysis, Transplantation, Homologous adverse effects, Transplantation, Homologous methods, Transplantation, Homologous mortality, Bone Marrow Transplantation methods, Bone Marrow Transplantation mortality, Graft Survival physiology
- Abstract
We have studied the impact of cell dose on short- and long-term graft function and outcome in 905 patients undergoing an unmanipulated allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling (n = 735), a one-antigen mismatched related donor (n = 35), or a matched unrelated donor (n = 135). Median number of nucleated cells infused was 3.4 x 10(8)/kg (25th percentile 2.4 x 10(8)/kg, 75th percentile 5 x 10(8)/kg). Patients were stratified according to cells infused in 3 groups: < or = 2.4 x 10(8)/kg (n = 247; low dose); >2.4 x 10(8)/kg and < or = 5 x 10(8)/kg (n = 452; intermediate dose); and >5 x 10(8)/kg (n = 206; high dose). Patients receiving high cell dose had significantly higher platelet counts on days +20, +50, +100, +180, and +365 after BMT (P <.01) and higher white blood cell counts on days +50, +100, and +180 after BMT (P <.01) as compared with other patients. The actuarial 5-year transplant-related mortality (TRM) was 41% versus 36% versus 28% (P =.01); overall survival was 45% versus 51% versus 56% (P =.0008); and disease-free survival was 41% versus 42% versus 48%, respectively, (P =.04) in patients receiving low, intermediate, or high cell dose. The cell dose effect was more pronounced in patients older than 30 years of age, with advanced disease, with chronic myeloid leukemia, and with alternative donors. In multivariate Cox analysis on TRM, cell dose was a significant predictor (P =.002; relative risk 0.6) together with donor type (P =.0001), year of transplantation (P =.0001), conditioning regimen (P =.02), and recipient age (P =.02). In conclusion, transplantation of high marrow cell dose is associated with reduced transplant mortality and improved survival and results in improved graft function both short and long term.
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.