19 results on '"Beelen, Dietrich"'
Search Results
2. Explaining survival differences between two consecutive studies with allogeneic stem cell transplantation in patients with chronic myeloid leukemia
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Pfirrmann, Markus, Saussele, Susanne, Hochhaus, Andreas, Reiter, Andreas, Berger, Ute, Hossfeld, Dieter K., Nerl, Christoph, Scheid, Christof, Spiekermann, Karsten, Mayer, Jiri, Hellmann, Andrzej, Lechner, Klaus, Falge, Christiane, Sayer, Herbert G., Bunjes, Donald, Ganser, Arnold, Beelen, Dietrich W., Baldomero, Helen, Schanz, Urs, Heimpel, Hermann, Kolb, Hans-Jochem, Hasford, Joerg, Gratwohl, Alois, Hehlmann, Rüdiger, and for the Schweizerische Arbeitsgemeinschaft für Klinische Forschung (SAKK) and the German CML Study Group
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- 2014
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3. Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)
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Schetelig, Johannes, de Wreede, Liesbeth C., Andersen, Niels S., Moreno, Carol, van Gelder, Michel, Vitek, Antonin, Karas, Michal, Michallet, Mauricette, Machaczka, Maciej, Gramatzki, Martin, Beelen, Dietrich, Finke, Jürgen, Delgado, Julio, Volin, Liisa, Passweg, Jakob, Dreger, Peter, Schaap, Nicolaas, Wagner, Eva, Henseler, Anja, van Biezen, Anja, Bornhäuser, Martin, Iacobelli, Simona, Putter, Hein, Schönland, Stefan O., Kröger, Nicolaus, Esteve, Jordi, Ljungman, Per, de Witte, Theo, Stelljes, Matthias, Sierra, Jorge, Socié, Gerard, Ganser, Arnold, Wulf, Gerhard G., Deconinck, Eric, Faber, Edgar, Feguex, Nathalie, Gedde-Dahl, Tobias, Kolbe, Karin, Chalandon, Yves, Krüger, William, Huynh, Anne, Bourhis, Jean Henri, Schouten, Harry, Ribera Santasusana, Josep M., Interne Geneeskunde, MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Chalandon, Yves
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Oncology ,Male ,Transplantation Conditioning ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Chronic lymphocytic leukemia ,Medizin ,QUALITY MANAGEMENT-SYSTEM ,Kaplan-Meier Estimate ,risk factor analysis ,GUIDELINES ,Biochemistry ,allogeneic stem cell transplantation ,centre effects ,chronic lymphocytic leukaemia ,frailties ,Transplantation Conditioning / methods ,0302 clinical medicine ,Recurrence ,Risk Factors ,Leukemia, Lymphocytic, Chronic, B-Cell / mortality ,Registries ,Delivery of Health Care / statistics & numerical data ,IBRUTINIB ,ddc:616 ,0303 health sciences ,ALEMTUZUMAB ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Professional Practice ,Hematology ,Middle Aged ,3. Good health ,Europe ,030220 oncology & carcinogenesis ,ABT-199 ,Cohort ,SURVIVAL ,Alemtuzumab ,Female ,Europe / epidemiology ,medicine.drug ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Immunology ,Lower risk ,DIAGNOSIS ,Settore MED/01 - Statistica Medica ,03 medical and health sciences ,Leukemia, Lymphocytic, Chronic, B-Cell / therapy ,Hematopoietic Stem Cell Transplantation / methods ,Internal medicine ,medicine ,Humans ,Karnofsky Performance Status ,030304 developmental biology ,Aged ,Retrospective Studies ,business.industry ,Proportional hazards model ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,Retrospective cohort study ,STEM-CELL TRANSPLANTATION ,Cell Biology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Confidence interval ,Surgery ,Professional Practice / statistics & numerical data ,Transplantation ,business ,Delivery of Health Care ,030215 immunology ,RESPONSES - Abstract
Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Outcomes of interest were Event-Free Survival (EFS) up to 5 years after transplantation and mortality in the first 100 days after alloHCT. Outcomes were analyzed by means of the Kaplan-Meier method and Cox proportional hazards models with a frailty (random effects) component to take into account unexplained center heterogeneity. The following factors describing center characteristics or the transplant procedure were analyzed: experience in alloHCT in general and, for CLL specifically, accreditation by the Joint Accreditation Committee-ISCT & EBMT (JACIE), Gross National Income (GNI)/capita based on purchasing power parity (PPP) (GNI/cap), donor type, donor-patient sex-match, type of conditioning, stem cell source and T-cell depletion (TCD). Results:Five-year EFS of the whole cohort was 37% (95% Confidence Interval, 33%-42%), Day-100 survival was 90% (88%-92%). Experience of the transplant center was measured by the number of all alloHCTs, and alloHCTs for patients with CLL respectively. The median total number of alloHCTs per center per year was 45 (range 0-169) and the median number of CLL alloHCTs was only 2 per center per year (range 0-19). Greater experience with transplantation of patients with CLL (Hazard Ratio (HR) 0.96 per additional transplant, p=0.002), JACIE accreditation (HR 0.7, p=0.045) and a higher GNI/cap (HR 0.4, 95% CI 0.2-0.96, p=0.04) showed a protective impact on 5-year EFS in the Cox model. In vivo TCD with alemtuzumab (HR 1.5 compared to no TCD, p=0.03) and a female donor for a male patient (HR 1.4 compared to a male donor for a male patient, p=0.02) were the only procedure-related factors significantly associated with EFS. Event-Free Survival after in vivo TCD with Anti-Thymocyte-Globulin or after ex vivo TCD was comparable to EFS without TCD (HR 0.9, 0.7-1.3, p=0.6; HR 0.9, 0.5-1.6, p=0.8). Non-myeloablative conditioning did not have a negative impact on 5-year EFS, and exposed patients to a lower risk of non-relapse mortality. Measured and unmeasured center characteristics did not have a significant impact on 100-day mortality. Even when correcting for patient-, procedure- and center-related characteristics, there was still significant variation in center outcome, expressed by center-specific HRs derived from the frailty models, ranging from 0.6 to 1.2. Their impact is illustrated in a model-based plot for EFS (see Figure) which shows outcomes for three reference patients with the same characteristics who would be transplanted in three centers with the same measured characteristics but with the highest, average and lowest HRs in the dataset. These unexplained center effects likely represent a mixture of differences which could apply to the location of the transplant center, unmeasured characteristics of the patient population transplanted at this center, selection criteria which were not reported and factors determining the success of the transplant procedure which might differ between centers. Conclusion: We have confirmed that both center- and procedure-related factors have a significant impact on the EFS of patients with CLL undergoing alloHCT. Our results may help to interpret outcomes of single or multicenter studies better. Since non-myeloablative conditioning did not have a negative impact on EFS and exposed patients to a lower risk of non-relapse mortality, this approach should be favored for future alloHCT for CLL. Probability of Event-Free Survival up to Five Years Post-HCT for three Reference Patients Contribution: J.S. designed the research and wrote the paper. L.C.d.W conducted the statistical analysis and produced the figure. Figure Figure. Disclosures Schetelig: Sanofi: Honoraria. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Dreger:Gilead: Consultancy; Gilead: Speakers Bureau; Janssen: Consultancy; Novartis: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy.
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- 2017
4. Treosulfan conditioning for allogeneic transplantation in multiple myeloma – improved overall survival in first line haematopoietic stem cell transplantation – a large retrospective study by the Chronic Malignancies Working Party of the EBMT.
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Gran, Charlotte, Wang, Junfeng, Nahi, Hareth, Koster, Linda, Gahrton, Gösta, Einsele, Herman, Niittyvoupio, Riitta, Edinger, Matthias, Beelen, Dietrich, Ciceri, Fabio, Bornhäuser, Martin, Finke, Jürgen, Wreede, Liesbeth C., Ljungman, Per, Mielke, Stephan, Tischer, Johanna, Garderet, Laurent, Schönland, Stefan, Yakoub‐Agha, Ibrahim, and Kröger, Nicolaus
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TOTAL body irradiation ,STEM cell transplantation ,MULTIPLE myeloma - Abstract
Treosulfan conditioning for allogeneic transplantation in multiple myeloma - improved overall survival in first line haematopoietic stem cell transplantation - a large retrospective study by the Chronic Malignancies Working Party of the EBMT Keywords: multiple myeloma; allogeneic stem cell transplantation; treosulfan; reduced intensity conditioning; myeloablative conditioning EN multiple myeloma allogeneic stem cell transplantation treosulfan reduced intensity conditioning myeloablative conditioning e213 e217 5 06/08/20 20200601 NES 200601 Allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of multiple myeloma (MM) is controversial mainly due to the high non-relapse mortality (NRM) with myeloablative conditioning (MAC). Our study shows that Treo-conditioning in upfront-treated patients is superior to other RIC- or MAC-conditioning regimens for reducing NRM without hampering long-term survival, despite a slightly increased relapse rate. Treosulfan, treosulfan included in a conditioning regime; RIC, non-treosulfan-reduced intensity conditioning; MAC, non-treosulfan myeloablative conditioning. [Extracted from the article]
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- 2020
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5. A prospective non-interventional study on the impact of transfusion burden and related iron toxicity on outcome in myelodysplastic syndromes undergoing allogeneic hematopoietic cell transplantation.
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Cremers, Eline M.P., de Witte, Theo, de Wreede, Liesbeth, Eikema, Diderik-Jan, Koster, Linda, van Biezen, Anja, Finke, Jürgen, Socié, Gerard, Beelen, Dietrich, Maertens, Johan, Nagler, Arnon, Kobbe, Guido, Ziagkos, Dimitris, Itälä-Remes, Maija, Gedde-Dahl, Tobias, Sierra, Jorge, Niederwieser, Dietger, Ljungman, Per, Beguin, Yves, and Ozkurt, Zubeyde Nur
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CELL transplantation ,MYELODYSPLASTIC syndromes ,RED blood cell transfusion ,CHELATION ,BLOOD transfusion reaction ,CHELATION therapy ,LONGITUDINAL method ,FETOFETAL transfusion - Abstract
Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p =.02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p =.04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation. [ABSTRACT FROM AUTHOR]
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- 2019
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6. Impact of primary disease on outcome after allogeneic stem cell transplantation for transformed secondary acute leukaemia.
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Kröger, Nicolaus, Eikema, Diderik‐Jan, Köster, Linda, Beelen, Dietrich, de Wreede, Liesbeth C., Finke, Jürgen, Koenecke, Christian, Niederwieser, Dietger, Bornhäuser, Martin, Schoenland, Stefan, Potter, Victoria, Wolschke, Christine, Maertens, Johan, Theobald, Matthias, Kobbe, Guido, Itälä‐Remes, Maija, Wulf, Gerald, Kahls, Peter, Forcade, Edouard, and Greinix, Hildegard
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STEM cell transplantation ,KARNOFSKY Performance Status ,MYELODYSPLASTIC syndromes ,DISEASES ,STEM cells - Abstract
Summary: Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukaemia (CMML) can progress to secondary acute myeloid leukaemia (sAML). We compared the outcome of 4214 sAML patients who received allogeneic haematopoietic stem cell transplantation (allo‐HSCT) from an unrelated (62%) or human leucocyte antigen (HLA)‐identical sibling donor (38%) according the underlying disease: MDS (n = 3541), CMML (n = 251) or MPN (n = 422). After a median follow up of 46·5 months, the estimated 3‐year progression‐free (PFS) and overall survival (OS) for the entire group was 36% (34–37%) and 41% (40–43%), respectively. The cumulative incidence of relapse and non‐relapse mortality (NRM) was 37% (35–39%) and 27% (26–29%), respectively. In a multivariable analysis for OS, besides age (P < 0·001), unrelated donor (P = 0·011), cytomegalovirus ± constellation (P = 0·007), Karnofsky index ≤ 80 (P < 0·001), remission status (P < 0·001), peripheral blood as stem cell source (P = 0·009), sAML from MPN (P = 0·003) remained a significant factor in comparison to sAML from MDS, while worse outcome of sAML from CMML did not reach statistical significance (P = 0·06). This large registry study demonstrates a major impact of the underlying disease on outcome of sAML after allo‐HSCT. [ABSTRACT FROM AUTHOR]
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- 2019
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7. Relapse and survival after transplantation for complex karyotype acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and the University of Texas MD Anderson Cancer Center.
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Ciurea, Stefan O., Labopin, Myriam, Socie, Gerard, Volin, Liisa, Passweg, Jakob, Chevallier, Patrice, Beelen, Dietrich, Milpied, Noel, Blaise, Didier, Cornelissen, Jan J., Fegueux, Nathalie, Polge, Emmanuelle, Kongtim, Piyanuch, Rondon, Gabriela, Esteve, Jordi, Mohty, Mohamad, Savani, Bipin N., Champlin, Richard E., and Nagler, Arnon
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ACUTE myeloid leukemia treatment ,KARYOTYPES ,CANCER relapse ,CANCER patients ,HEMATOPOIETIC stem cell transplantation - Abstract
Background: Despite recent advances in allogeneic hematopoietic stem cell transplantation (AHSCT), the outcome of patients who have acute myeloid leukemia (AML) with a complex karyotype (CK) remains poor. The objective of this study was to identify prognostic factors associated with post-transplantation survival in a large cohort of patients with CK AML.Methods: In total, data on 1342 consecutively patients who underwent transplantation for CK (≥3 chromosomal abnormalities) AML were provided by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and from the University of Texas MD Anderson Cancer Center database were included in the analysis. The median patient age was 52 years. The donors were human leukocyte antigen-matched related donors (N = 749), matched unrelated donors (N = 513), and mismatched unrelated donors (N = 80).Results: Relapse was the main cause of treatment failure. Overall, 51% of patients relapsed, 17.6% died of treatment-related mortality, and 31.3% survived leukemia-free. In multivariate analysis, the factors associated with an increased risk of relapse were age (>40 years; hazard ratio [HR], 1.1 per 10 years; P = .02), secondary AML (HR, 1.35; P = .01), active disease at transplantation (HR, 1.98; P < .001), and deletion/monosomy 5 (HR, 1.5; P < .001); whereas age (HR, 1.15 per 10 years; P < .001), secondary AML (HR, 1.36; P = .001), active disease at transplantation (HR, 1.99; P < .001), deletion/monosomy 5 (HR, 1.24; P = .008), and deletion/monosomy 7 (HR, 1.44; P < .001) predicted for leukemia-free survival.Conclusions: Disease relapse remains the most common cause of treatment failure for patients with CK AML after transplantation. Novel approaches to decrease the relapse rate and improve survival are needed in these patients. Cancer 2018;124:2134-41. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2018
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8. Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Nagler, Arnon, Labopin, Myriam, Beelen, Dietrich, Ciceri, Fabio, Volin, Liisa, Shimoni, Avichai, Foá, Roberto, Milpied, Noel, Peccatori, Jacopo, Polge, Emmanuelle, Mailhol, Audrey, Mohty, Mohamad, Savani, Bipin N., and Foá, Roberto
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HEMATOPOIETIC stem cell transplantation ,ACUTE myeloid leukemia treatment ,ACUTE myeloid leukemia ,TOXICOLOGY ,IMMUNOSUPPRESSIVE agents ,PATIENTS ,ALKYLATING agents ,ANTINEOPLASTIC agents ,THERAPEUTIC use of antimetabolites ,ANTIMETABOLITES ,ANTIVIRAL agents ,CAUSES of death ,GRAFT versus host disease ,IMMUNOSUPPRESSION ,PROGNOSIS ,SURVIVAL ,TREATMENT effectiveness ,ACQUISITION of data ,DISEASE remission ,RETROSPECTIVE studies ,BUSULFAN ,THERAPEUTICS - Abstract
Background: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile.Methods: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20-73 years). Donors were human leukocyte antigen-identical siblings (n = 187), unrelated donors (n = 235), or mismatched related donors (n = 98). Conditioning regimens included treosulfan (42 g/m2 [n = 396], 36 g/m2 [n = 109], or 30 g/ m2 [n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468).Results: At a median follow-up of 61 months, the 5-year overall survival, leukemia-free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II-IV acute and chronic graft-versus-host disease was 24% (grade III-V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno-occlusive disease, with two deaths (0.4%) from veno-occlusive disease.Conclusions: Treosulfan-based conditioning regimens provide an acceptable long-term survival with favorable nonrelapse mortality and a very low risk of veno-occlusive disease. Further studies are needed to optimize the treosulfan-based conditioning regimen for patients with AML. Cancer 2017;123:2671-79. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2017
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9. The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease.
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Kordelas, Lambros, Steckel, Nina-Kristin, Horn, Peter A., Beelen, Dietrich W., and Rebmann, Vera
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KILLER cell receptors ,STEM cell transplantation ,GRAFT versus host disease ,CD94 antigen ,DENDRITIC cells ,NATURAL immunity ,HLA histocompatibility antigens ,THERAPEUTICS - Abstract
Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT.
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Rubio, Marie T., Savani, Bipin N., Labopin, Myriam, Piemontese, Simona, Polge, Emmanuelle, Ciceri, Fabio, Bacigalupo, Andrea, Arcese, William, Koc, Yener, Beelen, Dietrich, Gülbas, Zafer, Depei Wu, Santarone, Stella, Tischer, Johanna, Afanasyev, Boris, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, and Nagler, Arnon
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STEM cell treatment ,ACUTE leukemia ,STEM cell transplantation ,GRAFT versus host disease ,CALCINEURIN ,MYCOPHENOLIC acid ,LEUKEMIA treatment ,THERAPEUTICS - Abstract
Background: Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. Methods: We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria. Results: A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25 %) patients in RIC and 125 (32 %) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92 %; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29 %, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p=0.02) without impact on relapse incidence (HR 0.99, p = 0.94). Conclusions: These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL. [ABSTRACT FROM AUTHOR]
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- 2016
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11. Achievement of complete remission predicts outcome of allogeneic haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
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Symeonidis, Argiris, Biezen, Anja, Wreede, Liesbeth, Piciocchi, Alfonso, Finke, Juergen, Beelen, Dietrich, Bornhäuser, Martin, Cornelissen, Jan, Volin, Liisa, Mufti, Ghulam, Chalandon, Yves, Ganser, Arnold, Bruno, Benedetto, Niederwieser, Dietger, Kobbe, Guido, Schwerdtfeger, Rainer, Witte, Theo, Robin, Marie, and Kröger, Nicolaus
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GRAFT versus host disease ,STEM cell transplantation research ,LEUKEMIA ,PROGNOSIS ,MYELODYSPLASTIC syndromes - Abstract
The results of allogeneic stem cell transplantation (allo- SCT) in chronic myelomonocytic leukaemia ( CMML) are usually reported together with other categories of myelodysplastic syndrome. We analysed transplantation outcome in 513 patients with CMML, with a median age of 53 years reported to the European Group for Blood and Marrow Transplantation. Conditioning was standard ( n = 249) or reduced-intensity ( n = 226). Donors were human leucocyte antigen-related ( n = 285) or unrelated ( n = 228). Disease status at transplantation was complete remission ( CR) in 122 patients, no CR in 344, and unknown in 47. Engraftment was successful in 95%. Grades 2-4 acute graft- versus-host disease (Gv HD) occurred in 33% of the patients and chronic Gv HD was reported in 24%. The 4-year cumulative incidence of non-relapse mortality was 41% and 32% for relapse, resulting in a 4-year estimated relapse-free and overall survival (OS) of 27% and 33%, respectively. Patients transplanted in CR had lower probability for non-relapse death ( P = 0·002) and longer relapse-free and OS ( P = 0·001 and P = 0·005, respectively). In multivariate analysis the only significant prognostic factor for survival was the presence of CR at transplantation ( P = 0·005). Allo- SCT remains a curative treatment option for patients with CMML and should preferably be performed early after diagnosis or after establishing the best possible remission status. [ABSTRACT FROM AUTHOR]
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- 2015
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12. Pre-Transplant Serum Leptin Levels and Relapse of Acute Myeloid Leukemia after Allogeneic Transplantation.
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Schwarzbich, Mark-Alexander, Dai, Hao, Kordelas, Lambros, Beelen, Dietrich W., Radujkovic, Aleksandar, Müller-Tidow, Carsten, Dreger, Peter, and Luft, Thomas
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ACUTE myeloid leukemia ,LEPTIN ,PEPTIDE hormones ,STEM cell transplantation ,ACUTE leukemia - Abstract
Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT). This study evaluates pre-conditioning Leptin, a peptide hormone involved in metabolism and immune homeostasis, as a prognostic factor for survival, relapse and non-relapse mortality (NRM) following alloSCT. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies (n = 524) and correlated retrospectively with clinical outcome. Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. Low pre-conditioning serum Leptin was an independent prognostic marker for increased risk of relapse (but not of NRM and overall mortality) following alloSCT for AL of intermediate and advanced stage (beyond first complete remission). Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59–0.96, p = 0.020). This effect was similar in an independent validation cohort. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation.
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Radujkovic, Aleksandar, Kordelas, Lambros, Bogdanov, Rashit, Müller-Tidow, Carsten, Beelen, Dietrich W., Dreger, Peter, and Luft, Thomas
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HEMATOPOIETIC stem cell transplantation ,INTERLEUKINS ,POSTOPERATIVE care - Abstract
Simple Summary: We have previously shown that high pre-conditioning levels of Interleukin-18 were associated with worse survival after allogeneic stem cell transplantation due to increased non-relapse mortality. While no correlations with acute graft-versus-host disease were observed, interleukin-18-related excess mortality was mainly driven by fatal infectious complications. In multiple studies, delayed hematopoietic recovery and poor graft function following allogeneic stem cell transplantation has been demonstrated as a powerful predictor of non-relapse mortality. The present study links high interleukin-18 to delayed platelet recovery in allografted patients. Given the functions of interleukin-18 in regulating the quiescence of hematopoietic stem/progenitor cells, our findings may be explained by Interferon gamma-independent inhibitory effects of interleukin-18 on stem cell proliferation and hematopoietic reconstitution in allografted patients. Importantly, considering recent successful interleukin-18-neutralizing approaches in autoimmune disorders, our results provide a rationale to explore modulation of interleukin-18 for improving hematopoietic recovery and outcomes in allogeneic stem cell transplantation recipients. Interleukin-18 (IL-18) is an immunoregulatory cytokine and a context-dependent regulator of hematopoietic stem/progenitor cell (HSPC) quiescence in murine models. In a previous study, high pre-conditioning levels of IL-18 were associated with increased non-relapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). To investigate the clinical impact of IL-18 status on hematopoietic function, the associations of pre-conditioning and day 0–3 cytokine levels with platelet and neutrophil recovery were analyzed in a training cohort of 714 allografted patients. In adjusted logistic regression analyses, both increasing pre-conditioning and day 0–3 IL-18 levels had a significantly higher adjusted odds ratio (aOR) of delayed platelet and neutrophil recovery on day +28 post-transplant (aOR per two-fold increase: 1.6–2.0). The adverse impact of high pre-conditioning IL-18 on day +28 platelet recovery was verified in an independent cohort of 673 allografted patients (aOR per two-fold increase: 1.8 and 1.7 for total and free IL-18, respectively). In both cohorts, a platelet count ≤20/nL on day +28 was associated with a significantly increased hazard of NRM (hazard ratio 2.13 and 2.94, respectively). Our findings support the hypothesis that elevated peritransplant IL-18 levels affect post-transplant HSPC function and may provide a rationale to explore modulation of IL-18 for improving alloSCT outcomes. [ABSTRACT FROM AUTHOR]
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- 2020
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14. Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia Older Than 50 Years: A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Shimoni, Avichai, Labopin, Myriam, Savani, Bipin, Byrne, Michael, Volin, Liisa, Finke, Jürgen, Niederwieser, Dietger, Ehninger, Gerhard, Blaise, Didier, Beelen, Dietrich, Tabrizi, Reza, Sengeloev, Henrik, Ganser, Arnold, Cornelissen, Jan J., Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation , *ACUTE myeloid leukemia , *ACUTE leukemia , *SIBLINGS , *BONE marrow , *ALEMTUZUMAB - Abstract
• Marked improvement has been achieved in recent years in stem cell transplantation (SCT) from unrelated donors. • Long-term outcome is equivalent after SCT from unrelated and sibling donors. • Patients who are leukemia-free 2 years after SCT can expect a favorable outcome. Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P =.005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P <.001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P =.78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P =.30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P =.0001) or CR2 (HR, 1.51; P =.02) compared with CR1, female recipients (HR, 0.71; P =.006), adverse cytogenetics (HR, 2.52; P =.01), and prior graft-versus-host disease (HR, 1.31; P =.04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P =.97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P =.15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome Patients with a 5q Deletion.
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Garderet, Laurent, Ziagkos, Dimitris, van Biezen, Anja, Iacobelli, Simona, Finke, Jürgen, Maertens, Johan, Volin, Liisa, Ljungman, Per, Chevallier, Patrice, Passweg, Jakob, Schaap, Nicolaas, Beelen, Dietrich, Nagler, Arnon, Blaise, Didier, Poiré, Xavier, Yakoub-Agha, Ibrahim, Lenhoff, Stig, Craddock, Charles, Schots, Rik, and Rambaldi, Alessandro
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HEMATOPOIETIC stem cell transplantation , *MYELODYSPLASTIC syndromes treatment , *HOMOGRAFTS , *DELETION mutation , *DISEASE incidence , *SURVIVAL analysis (Biometry) - Abstract
The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities (del [5q]+) are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+ . A total of 162 patients, of median age 54 years (range, 9 to 73), having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46% (95% CI, 38 to 54), whereas the estimated 4 year survival, relapse-free and overall, was 25% (95% CI, 18 to 33) and 30% (95% CI, 23 to 38), respectively. In a multivariate analysis patients with del (5q) and a blast excess displayed poorer survival (hazard ratio, 2.38; 95% CI, 1.44 to 3.93; P < .001), whereas female recipient sex resulted in improved survival (hazard ratio, .61; 95% CI, .41 to .90; P = .01). We conclude that allogeneic HCT can cure a subset of patients with MDS and a del (5q) abnormality. [ABSTRACT FROM AUTHOR]
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- 2018
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16. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study
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Katie S. Gatwood, Jordi Esteve, Patrice Chevallier, Peter Dreger, Matthias Stelljes, Myriam Labopin, Bipin N. Savani, Norbert Claude Gorin, Arnold Ganser, Audrey Mailhol, Juergen Finke, Dietrich W. Beelen, Sebastian Giebel, Ghulam J. Mufti, Gerhard Ehninger, Arnon Nagler, Christoph Schmid, Frédéric Baron, Didier Blaise, Ariane Boumendil, Dietger Niederwieser, Mohamad Mohty, Fabio Ciceri, Salyka Sengsayadeth, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Hannover Medical School [Hannover] (MHH), Westfälische Wilhelms-Universität Münster (WWU), University of Münster, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Dept. of Bone Marrow Transplantation, University Hospital, Essen, University Hospital Essen, Division Hematology, Oncology and Hemostasiology [Leipzig, Germany], University Hospital in Leipzig [Germany], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Department of Medicine V, Universität Heidelberg [Heidelberg], King's College Hospital (KCH), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (DRPH/SRBE/LTCRA), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), IRCCS Ospedale San Raffaele [Milan, Italy], Université de Liège, Ludwig Maximilian University [Munich] (LMU), Cancer Center Gliwice, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Sengsayadeth, Salyka, Labopin, Myriam, Boumendil, Ariane, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gatwood, Katie S., Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N., Nagler, Arnon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (IRSN/DRPH/SRBE/LTCRA), Service de RadioBiologie et d'Epidémiologie (IRSN/DRPH/SRBE), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
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Adult ,Male ,medicine.medical_specialty ,Secondary ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Medizin ,Hematopoietic stem cell transplantation ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Secondary Acute Myeloid Leukemia ,Cumulative incidence ,ddc:610 ,Aged ,Bone Marrow Transplantation ,Aged, 80 and over ,Acute leukemia ,Univariate analysis ,Transplantation ,Acute myeloid leukemia ,Toxicity ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Confidence interval ,3. Good health ,Allogeneic stem cell transplantation ,Europe ,Antileukemic effect ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology ,Conditioning - Abstract
International audience; Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [Cl], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% Cl, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (
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- 2018
17. Allogeneic Stem Cell Transplantation for Myelofibrosis with Leukemic Transformation: A Study from the Myeloproliferative Neoplasm Subcommittee of the CMWP of the European Group for Blood and Marrow Transplantation.
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Alchalby, Haefaa, Zabelina, Tatjana, Stübig, Thomas, van Biezen, Anja, Bornhäuser, Martin, Di Bartolomeo, Paolo, Beelen, Dietrich, Cahn, Jean Yves, Dreger, Peter, Schroyens, William, de Witte, Theo, Olavarria, Eduardo, and Kröger, Nicolaus
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STEM cell transplantation , *MYELOFIBROSIS , *ACUTE myeloid leukemia , *MORTALITY , *MYELOPROLIFERATIVE neoplasms , *BONE marrow transplantation , *CONFIDENCE intervals , *THERAPEUTICS - Abstract
Abstract: Transformed acute myeloid leukemia in myelofibrosis results in a median survival of less than 5 months. We identified 46 of 1048 myelofibrosis patients in the European Group for Blood and Marrow Transplantation registry who received allogeneic stem cell transplantation for acute leukemia evolving from myelofibrosis. The cumulative incidence of treatment-related mortality at 1 year was 28% (95% confidence interval, 14 to 42) and of relapse at 3 years was 47% (95% confidence interval, 31 to 63). The 3-year progression-free (PFS) and overall survival (OS) rates were 26% and 33%, respectively. The only significant factor for survival was complete remission versus no complete remission before transplantation (69% versus 22%, P = .008); however, complete remission was achieved only in 8 patients. Allogeneic stem cell transplantation can cure myelofibrosis patients transformed to leukemia. [Copyright &y& Elsevier]
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- 2014
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18. Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Arnon, Nagler, Myriam, Labopin, Dietrich, Beelen, Fabio, Ciceri, Liisa, Volin, Avichai, Shimoni, Roberto, Foá, Noel, Milpied, Jacopo, Peccatori, Emmanuelle, Polge, Audrey, Mailhol, Mohamad, Mohty, Bipin N, Savani, Nagler, Arnon, Labopin, Myriam, Beelen, Dietrich, Ciceri, Fabio, Volin, Liisa, Shimoni, Avichai, Foã¡, Roberto, Milpied, Noel, Peccatori, Jacopo, Polge, Emmanuelle, Mailhol, Audrey, Mohty, Mohamad, and Savani, Bipin N.
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Adult ,Male ,Registrie ,Alkylating Agents ,Cancer Research ,Transplantation Conditioning ,Treosulfan ,Medizin ,Graft vs Host Disease ,acute myeloid leukemia ,Myeloablative Agonist ,conditioning regimen ,Disease-Free Survival ,Young Adult ,Conditioning regimen ,allogeneic stem cell transplantation ,Retrospective Studie ,Cause of Death ,Humans ,Acute myeloid leukemia ,Allogeneic stem cell transplantation ,Graft-versus leukemia effect ,Toxicity ,Oncology ,Registries ,Antineoplastic Agents, Alkylating ,Busulfan ,Retrospective Studies ,Aged ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,toxicity ,Myeloablative Agonists ,Middle Aged ,Alkylating Agent ,Survival Rate ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Female ,graft-versus leukemia effect ,treosulfan ,Vidarabine ,Human - Abstract
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20-73 years). Donors were human leukocyte antigen-identical siblings (n = 187), unrelated donors (n = 235), or mismatched related donors (n = 98). Conditioning regimens included treosulfan (42 g/m2 [n = 396], 36 g/m2 [n = 109], or 30 g/ m2 [n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468). RESULTS: At a median follow-up of 61 months, the 5-year overall survival, leukemia-free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II-IV acute and chronic graft-versus-host disease was 24% (grade III-V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno-occlusive disease, with two deaths (0.4%) from veno-occlusive disease. CONCLUSIONS: Treosulfan-based conditioning regimens provide an acceptable long-term survival with favorable nonrelapse mortality and a very low risk of veno-occlusive disease. Further studies are needed to optimize the treosulfan-based conditioning regimen for patients with AML. Cancer 2017;123:2671-79. © 2017 American Cancer Society.
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- 2017
19. Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT
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Zafer Gulbas, Bipin N. Savani, Marie T Rubio, Sebastian Giebel, Depei Wu, Yener Koc, Stella Santarone, Andrea Bacigalupo, William Arcese, Mohamad Mohty, Simona Piemontese, Christoph Schmid, Emmanuelle Polge, Fabio Ciceri, Arnon Nagler, Boris V. Afanasyev, Myriam Labopin, Johanna Tischer, Dietrich W. Beelen, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Acute Leukemia Working Party of EBMT, European Society for Blood and Marrow Transplantation (EBMT), Vanderbilt University [Nashville], Ospedale San Raffaele, Ospedale San Martino, University of Rome 'Tor Vergeta', Università degli Studi di Roma Tor Vergata [Roma], Medical Park Hospitals, Antalya, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Anadolu Medical Center Hospital, Department of Hematology - First Affiliated Hospital of Soochow University, Soochow University, Ospedale Civile BMT Center, Ludwig-Maximilians-Universität München (LMU), SPb State I. Pavlov, Medical University, Klinikum Augsburg, University of Munich, Cancer Center Gliwice, Tel Aviv University (TAU), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Pierre et Marie Curie - Paris 6 (UPMC), Vanderbilt University Medical Center [Nashville], Vanderbilt University Medical Center, Centre International des greffes (EBMT), CHU Saint-Antoine [APHP], Department of Haematology II, Haematology Stem Cell Transplant Unit, Tor Vergata University, Dept. of Bone Marrow Transplantation, University Hospital, Essen, Bone Marrow Transplantation, Department of Internal Medicine III, Department of Bone Marrow Transplantation and Hemato-Oncology, Cancer center, Hematology Division, The Chaim Sheba Medical Center at Tel hashomer, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Tel Aviv University [Tel Aviv], Rubio, Marie T., Savani, Bipin N., Labopin, Myriam, Piemontese, Simona, Polge, Emmanuelle, Ciceri, Fabio, Bacigalupo, Andrea, Arcese, William, Koc, Yener, Beelen, Dietrich, Gülbas, Zafer, Wu, Depei, Santarone, Stella, Tischer, Johanna, Afanasyev, Bori, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Nagler, Arnon, and HAL UPMC, Gestionnaire
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Oncology ,Myeloid ,Male ,Cancer Research ,Transplantation Conditioning ,medicine.medical_treatment ,Medizin ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,0302 clinical medicine ,Retrospective Studie ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Acute Leukemia ,Allogeneic stem cell transplantation ,Anti-leukemic effect ,Conditioning regimen ,Haplo-identical donor ,Toxicity ,Melphalan ,Multivariate Analysi ,ComputingMilieux_MISCELLANEOUS ,Acute leukemia ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Leukemia ,Hazard ratio ,Cytarabine ,Hematopoietic Stem Cell Transplantation ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Treatment Outcome ,Local ,Leukemia, Myeloid ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,medicine.drug ,Human ,Adult ,medicine.medical_specialty ,Cyclophosphamide ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,lcsh:RC254-282 ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,Humans ,Multivariate Analysis ,Mycophenolic Acid ,Neoplasm Recurrence, Local ,Retrospective Studies ,Molecular Biology ,ddc:610 ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,lcsh:RC633-647.5 ,Research ,Transplantation ,Regimen ,Settore MED/15 - MALATTIE DEL SANGUE ,Neoplasm Recurrence ,Immunology ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030215 immunology - Abstract
Background Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. Methods We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria. Results A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25 %) patients in RIC and 125 (32 %) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92 %; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29 %, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94). Conclusions These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0248-3) contains supplementary material, which is available to authorized users.
- Published
- 2016
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