22 results on '"Westervelt, Peter"'
Search Results
2. The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) Score for HLA Class I Graft-versus-Host Disparity Is Associated with Increased Acute Graft-versus-Host Disease in Haploidentical Transplantation with Post-Transplantation Cyclophosphamide.
- Author
-
Rimando J, Slade M, DiPersio JF, Westervelt P, Gao F, Liu C, and Romee R
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Female, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Cyclophosphamide administration & dosage, Epitopes blood, Graft vs Host Disease blood, Graft vs Host Disease drug therapy, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, HLA Antigens blood, Peptides blood, Registries
- Abstract
The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score quantifies the number of PIRCHEs in patient-donor pairs and represents an in silico measure of indirect alloreactivity. This biologic process is defined as T cell recognition of epitopes derived from mismatched, allogeneic HLA peptides that are subsequently presented by shared HLA molecules. Its association with clinical outcome has not been examined in haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy). We hypothesized that the PIRCHE score (PS) would correlate with indirect alloreactivity and predict graft-versus-host disease (GVHD) risk and the incidence of relapse after haplo-HCT with PTCy. We retrospectively analyzed 148 patients who underwent peripheral blood stem cell T cell-replete haplo-HCT with PTCy at a single center between 2009 and 2016. For each patient-donor pair, the PS was calculated using the PIRCHE online matching tool. PSs were categorized by class and vector. The median class I graft-versus-host (GVH) PS was 11 (range, 0 to 56), and the median class I host-versus-graft (HVG) PS was 10 (range, 0 to 51). Class I GVH PS was associated with increased risk of grade II-IV acute GVHD (adjusted hazard ratio, 1.03 per PS unit increase; 95% confidence interval, 1.01 to 1.05; P= .008) but not of chronic GVHD or relapse. Our data show that use of the PS is a novel strategy for predicting clinical outcome in haplo-HCT; further studies using registry data and prospective cohorts are warranted to validate these findings., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
3. Effect of Antihuman T Lymphocyte Globulin on Immune Recovery after Myeloablative Allogeneic Stem Cell Transplantation with Matched Unrelated Donors: Analysis of Immune Reconstitution in a Double-Blind Randomized Controlled Trial.
- Author
-
Gooptu M, Kim HT, Chen YB, Rybka W, Artz A, Boyer M, Johnston L, McGuirk J, Shea TC, Jagasia M, Shaughnessy PJ, Reynolds CG, Fields M, Alyea EP, Ho VT, Glavin F, Dipersio JF, Westervelt P, Ritz J, and Soiffer RJ
- Subjects
- Adolescent, Adult, Aged, Antilymphocyte Serum pharmacology, Double-Blind Method, Female, Graft vs Host Disease immunology, Humans, Male, Middle Aged, Unrelated Donors, Young Adult, Antilymphocyte Serum therapeutic use, Graft vs Host Disease drug therapy, Hematopoietic Stem Cell Transplantation methods, Immune Reconstitution immunology, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe chronic graft-versus-host disease (cGVHD) but not cGVHD-free survival was reduced in patients receiving anti-T lymphocyte globulin (ATLG) versus placebo. In a companion study we performed immunophenotypic analysis to determine the impact of ATLG on immune reconstitution (IR) and to correlate IR with clinical outcomes. The randomized study (n = 254) included patients (aged 18 to 65 years) who underwent myeloablative transplants for acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia from HLA-matched unrelated donors. Ninety-one patients consented for the companion IR study (ATLG = 44, placebo = 47). Blood samples were collected on days 30, 100, 180, and 360 after hematopoietic cell transplantation (HCT), and multiparameter flow cytometry was performed in a blinded fashion. Reconstitution of CD3
+ and CD4+ T cells was delayed up to 6 months post-HCT in the ATLG arm, whereas absolute regulatory T cell (Treg) (CD4+ 25+ 127-) numbers were lower only in the first 100 days. Analysis of the CD4+ Treg and conventional T cells (Tconv) (CD4+ 25- 127+ ) compartments showed a profound absence of naive Tregs and Tconv in the first 100 days post-HCT, with very slow recovery for 1 year. B cell and natural killer cell recovery were similar in each arm. Higher absolute counts of CD3+ , CD4+ , CD8+ T, Tregs, and Tconv were associated with improved overall survival, progression-free survival, and nonrelapse mortality but not moderate/severe cGVHD. Although ATLG delays CD3+ and CD4+ T cell recovery post-transplant, it has a relative Treg sparing effect after the early post-HCT period, with possible implications for protection from cGVHD. ATLG severely compromises the generation of naive CD4+ cells (Treg and Tconv), potentially affecting the diversity of the TCR repertoire and T cell responses against malignancy and infection., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
4. Propensity Score Analysis of Conditioning Intensity in Peripheral Blood Haploidentical Hematopoietic Cell Transplantation.
- Author
-
Huselton E, Slade M, Trinkaus KM, DiPersio JF, Westervelt P, and Romee R
- Subjects
- Adolescent, Adult, Aged, Allografts, Cyclophosphamide administration & dosage, Disease-Free Survival, Female, Graft vs Host Disease prevention & control, Humans, Male, Middle Aged, Propensity Score, Retrospective Studies, Survival Rate, Transplantation, Haploidentical, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning
- Abstract
T cell replete HLA-haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide was originally described using a reduced-intensity conditioning (RIC) regimen. Given that myeloablative conditioning (MAC) is more effective at preventing disease relapse, we compared outcomes of patients receiving MAC and RIC regimens. We evaluated overall survival (OS), disease-free survival (DFS), relapse, nonrelapse mortality (NRM), and graft-versus-host disease (GVHD) of 148 patients that underwent haplo-HCT with either MAC (n = 61) or RIC (n = 87). Propensity score adjustment (PSA) was used to balance baseline characteristics between groups and more effectively compare outcomes based on conditioning intensity. After the PSA analysis, relapse was significantly decreased with MAC (hazard ratio [HR], .47; 95% confidence interval [CI], .31 to .70), but was associated with higher NRM (HR, 1.74; 95% CI, 1.13 to 2.67). OS and DFS were not significantly different between groups (HRs for MAC versus RIC were .87 [95% CI, .64 to 1.18] and .90 [95% CI, .68 to 1.18] for OS and DFS, respectively). Rates of acute and chronic GVHD were not significantly different between groups. This analysis suggests that both MAC and RIC regimens are effective in haplo-HCT and that MAC regimens may result in less relapse in selected patients. These results need to be verified in a larger registry study., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
5. A Phase 1 Trial of CNDO-109-Activated Natural Killer Cells in Patients with High-Risk Acute Myeloid Leukemia.
- Author
-
Fehniger TA, Miller JS, Stuart RK, Cooley S, Salhotra A, Curtsinger J, Westervelt P, DiPersio JF, Hillman TM, Silver N, Szarek M, Gorelik L, Lowdell MW, and Rowinsky E
- Subjects
- Adult, Aged, Cell Count, Cell Line, Tumor, Disease-Free Survival, Female, Humans, Killer Cells, Natural transplantation, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Secondary Prevention, Tissue Donors, Transplantation, Haploidentical, Treatment Outcome, Immunotherapy, Adoptive methods, Killer Cells, Natural immunology, Leukemia, Myeloid, Acute therapy
- Abstract
Natural killer (NK) cells are an emerging immunotherapy approach to acute myeloid leukemia (AML); however, the optimal approach to activate NK cells before adoptive transfer remains unclear. Human NK cells that are primed with the CTV-1 leukemia cell line lysate CNDO-109 exhibit enhanced cytotoxicity against NK cell-resistant cell lines. To translate this finding to the clinic, CNDO-109-activated NK cells (CNDO-109-NK cells) isolated from related HLA-haploidentical donors were evaluated in a phase 1 dose-escalation trial at doses of 3 × 10
5 (n = 3), 1 × 106 (n = 3), and 3 × 106 (n = 6) cells/kg in patients with AML in first complete remission (CR1) at high risk for recurrence. Before CNDO-109-NK cell administration, patients were treated with lymphodepleting fludarabine/cyclophosphamide. CNDO-109-NK cells were well tolerated, and no dose-limiting toxicities were observed at the highest tested dose. The median relapse-free survival (RFS) by dose level was 105 (3 × 105 ), 156 (1 × 106 ), and 337 (3 × 106 ) days. Two patients remained relapse-free in post-trial follow-up, with RFS durations exceeding 42.5 months. Donor NK cell microchimerism was detected on day 7 in 10 of 12 patients, with 3 patients having evidence of donor cells on day 14 or later. This trial establishes that CNDO-109-NK cells generated from related HLA haploidentical donors, cryopreserved, and then safely administered to AML patients with transient persistence without exogenous cytokine support. Three durable complete remissions of 32.6 to 47.6+ months were observed, suggesting additional clinical investigation of CNDO-109-NK cells for patients with myeloid malignancies, alone or in combination with additional immunotherapy strategies, is warranted., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
6. Lack of a Prognostic Impact of the MyD88 L265P Mutation for Diffuse Large B Cell Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.
- Author
-
Lee YS, Liu J, Fricano KA, Webb EM, Toolsie DR, Jones S, Rhoads JA, Vij R, Cashen AF, Abboud CN, Westervelt P, Bartlett NL, Dipersio JF, Kreisel FH, and Lim KH
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Humans, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse mortality, Lymphoma, Large B-Cell, Diffuse therapy, Male, Middle Aged, Mutation, Prognosis, Salvage Therapy, Survival Analysis, Transplantation, Autologous, Young Adult, Lymphoma, Large B-Cell, Diffuse genetics, Myeloid Differentiation Factor 88 genetics, Stem Cell Transplantation methods
- Abstract
Cell-of-origin determination has emerged as an important prognostic factor for patients initially diagnosed with diffuse large B cell lymphoma (DLBCL). Specifically, the nongerminal center B cell-like (non-GCB) subtype, composed predominantly of the activated B cell-like (ABC) molecular subtype, has been shown to portend poor prognosis because of its more aggressive nature and resistance to standard cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (CHOP)-like chemotherapy compared with the GCB subtype. The recurrent MyD88 L265P mutation, present in 29% of ABC DLBCL, was reported as an independent poor prognostic factor for patients with newly diagnosed DLBCL. For patients whose disease relapses or is refractory to first-line chemotherapy, high-dose chemotherapy with autologous stem cell transplantation (ASCT) is frequently offered as salvage therapy. However, the impact of MyD88 mutation status on post-ASCT outcome has not been reported. Here, we retrospectively analyzed, with up to 20 years of follow-up, 165 patients who underwent ASCT for relapsed/refractory DLBCL at our institution. We found that MyD88 mutation status did not correlate with overall survival (OS), post-ASCT OS, or progression-free survival (PFS). Patients with non-GCB subtype had significantly worse OS from initial diagnosis and after ASCT. Notably, high International Prognostic Index score was predictive of poor pre- and post-transplant PFS and post-transplant OS., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
7. Results of a Prospective Randomized, Open-Label, Noninferiority Study of Tbo-Filgrastim (Granix) versus Filgrastim (Neupogen) in Combination with Plerixafor for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma and Non-Hodgkin Lymphoma.
- Author
-
Bhamidipati PK, Fiala MA, Grossman BJ, DiPersio JF, Stockerl-Goldstein K, Gao F, Uy GL, Westervelt P, Schroeder MA, Cashen AF, Abboud CN, and Vij R
- Subjects
- Aged, Antigens, CD34 analysis, Benzylamines, Cyclams, Drug Therapy, Combination, Female, Filgrastim therapeutic use, Hematopoietic Stem Cell Transplantation methods, Heterocyclic Compounds therapeutic use, Humans, Male, Middle Aged, Transplantation, Autologous, Treatment Outcome, Filgrastim administration & dosage, Hematopoietic Stem Cell Mobilization methods, Heterocyclic Compounds administration & dosage, Lymphoma, Non-Hodgkin therapy, Multiple Myeloma therapy
- Abstract
Autologous hematopoietic stem cell transplantation (auto-HSCT) improves survival in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen; recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, a biosimilar recombinant G-CSF (Tevagrastim) has been approved for various indications similar to those of reference filgrastim, including stem cell mobilization for auto-HSCT; however, in the United States, tbo-filgrastim (Granix) is registered under the original biological application and is not approved for stem cell mobilization. In retrospective studies, stem cell mobilization with tbo-filgrastim has shown similar efficacy and toxicity as filgrastim, but no prospective studies have been published to date. We have conducted the first prospective randomized trial comparing the safety and efficacy of tbo-filgrastim in combination with plerixafor with that of filgrastim in combination with plerixafor for stem cell mobilization in patients with MM and NHL. This is a phase 2 prospective randomized (1:1) open-label single-institution noninferiority study of tbo-filgrastim and filgrastim with plerixafor in patients with MM or NHL undergoing auto-HSCT. Here 10 µg/kg/day of tbo-filgrastim/filgrastim was administered s.c. for 5 days (days 1 to 5). On day 4 at approximately 1800 hours, 0.24 mg/kg of plerixafor was administered s.c. Apheresis was performed on day 5 with a target cumulative collection goal of at least 5.0 × 10
6 CD34+ cells/kg. The primary objective was to compare day 5 CD34+ cells/kg collected. Secondary objectives included other mobilization endpoints, safety, engraftment outcomes, and hospital readmission rate. A total of 97 evaluable patients were enrolled (tbo-filgrastim, n = 46; filgrastim, n = 51). Tbo-filgrastim was not inferior to filgrastim in terms of day 5 CD34+ cell collection (mean, 11.6 ± 6.7 CD34+ cells/kg versus 10.0 ± 6.8 CD34+ cells/kg. Multivariate analysis revealed a trend toward increased mobilization in the tbo-filgrastim arm, but this was not statistically significant. The tbo-filgrastim and filgrastim arms were similar in all secondary endpoints. Tbo-filgrastim is not inferior in efficacy and has similar safety compared to reference filgrastim when used for stem cell mobilization in patients with MM and NHL. Granix can be safely used instead of Neupogen for stem cell collection in patients undergoing auto-HSCT for MM or NHL. The study is registered at https://clinicaltrials.gov/ct2/show/NCT02098109., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
8. Haploidentical Hematopoietic Cell Transplant with Post-Transplant Cyclophosphamide and Peripheral Blood Stem Cell Grafts in Older Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome.
- Author
-
Slade M, DiPersio JF, Westervelt P, Vij R, Schroeder MA, and Romee R
- Subjects
- Adult, Age Factors, Aged, Cyclophosphamide therapeutic use, Female, Haplotypes, Humans, Male, Middle Aged, Recurrence, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Peripheral Blood Stem Cell Transplantation methods, Transplantation, Haploidentical
- Abstract
Many hematologic malignancies are diseases of aging, and the use of hematopoietic cell transplant (HCT) is growing rapidly among older adults. Modern post-transplant cyclophosphamide (PTCy) protocols with haploidentical (haplo) donors have dramatically expanded the donor pool for patients requiring HCT. Initial studies were performed with bone marrow grafts, which require the donor to undergo anesthesia during harvest. However, the use of mobilized peripheral blood stem cells (PBSCs) may be desirable, especially with older donors. However, data on PBSC haplo-HCT in older adults are lacking. To characterize the impact of age on outcomes in haplo-HCT, we identified all adult patients undergoing haplo-HCT with PTCy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) at our institution from January 2009 to June 2016. Patients were grouped into 3 cohorts: Age 1 (≤55), Age 2 (55 to 65), and Age 3 (≥65). To characterize the impact of donor type on outcomes in older patients, we identified age- and disease risk index (DRI)-matched patient age ≥ 65 undergoing HLA-matched unrelated donor (MUD) HCT for AML or MDS during the same time frame. Patients were scored for disease risk and underlying comorbidities using the DRI and HCT-specific comorbidity index. Overall survival (OS) was analyzed using 3 different Cox proportional hazards models. We identified 112 haplo-HCT patients, 95 with AML and 17 with MDS. There were 61 patients in Age 1, 29 patients in Age 2, and 22 in Age 3. Median OS was 448, 397, and 147 days in Age 1, Age 2, and Age 3 patients (log-rank, P = .04). After adjusting for other risk factors, age ≥ 65 was associated with significantly worse OS after haplo-HCT (aHR, 2.16; 95% CI, 1.15 to 4.07). There was a trend toward increased relapse among older patients at 2 years (56%; 95% CI, 32% to 79%) versus Age 1 (41%; 95% CI, 28% to 54%) and Age 2 (31%; 95% CI, 12% to 50%) (P = .08). Among patients age ≥ 65, donor type (MUD versus haplo) did not impact OS (aHR, 1.03; 95% CI, .56 to 1.88) after adjusting for other risk factors. Prior allo-HCT (aHR, 4.95; 95% CI, 1.82 to 13.49) and myeloablative conditioning (aHR, 1.97; 95% CI, 1.04 to 3.73) were associated with inferior survival. Although age ≥ 65 was associated with inferior OS in our haplo-HCT cohort, no difference was seen in survival between MUD and haplo-HCT. Therefore, the use of haploidentical donors in older patients is a reasonable treatment option, especially if there is concern for clinical deterioration. A careful pretransplant evaluation and analysis of risks and benefits is warranted when offering this transplant modality to older adults, especially in patients with previous transplant or poor performance status. Strategies to reduce the risk of relapse and decrease nonrelapse mortality in older adults are areas of ongoing research, and prospective studies are needed., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
9. Phase I/II Study of Intravenous Plerixafor Added to a Mobilization Regimen of Granulocyte Colony-Stimulating Factor in Lymphoma Patients Undergoing Autologous Stem Cell Collection.
- Author
-
Cashen AF, Rettig M, Gao F, Smith A, Abboud C, Stockerl-Goldstein K, Vij R, Uy G, Westervelt P, and DiPersio J
- Subjects
- Adolescent, Adult, Aged, Autografts, Benzylamines, Cyclams, Female, Granulocyte Colony-Stimulating Factor adverse effects, Heterocyclic Compounds adverse effects, Humans, Male, Middle Aged, Granulocyte Colony-Stimulating Factor administration & dosage, Hematopoietic Stem Cell Mobilization methods, Hematopoietic Stem Cell Transplantation, Heterocyclic Compounds administration & dosage, Lymphoma therapy, Multiple Myeloma therapy
- Abstract
Plerixafor, given subcutaneously with granulocyte colony-stimulating factor (G-CSF), improves autologous stem cell collection in patients with lymphoma and multiple myeloma. Intravenous (i.v.) administration of plerixafor allows administration of plerixafor on the same day as pheresis and it may improve stem cell collection. The primary objectives of this phase I/II study were to determine the maximum tolerated dose of i.v. plerixafor and the efficacy of i.v. plerixafor + G-CSF to mobilize ≥ 2 × 10
6 CD34+ cells/kg from patients with lymphoma. In phase I, 25 patients were treated with G-CSF + i.v. plerixafor at escalating doses; in phase II, 36 patients were treated with G-CSF + plerixafor .40 mg/kg. The treatment was well tolerated. Fifty-nine of 61 patients (98%) met the collection goal and 47 of 61 patients (77%) collected ≥ 5.0 × 106 CD34+ cells/kg in a median of 2 pheresis days. Analysis of CD34+ hematopoietic stem and progenitor cells (HSPCs) revealed that G-CSF-mobilized grafts were enriched with CD34+ CD45RA- CD123+/- primitive HSPCs whereas plerixafor preferentially mobilized CD34+ CD45RA+ CD123++ plasmacytoid dendritic cell precursors. In conclusion, i.v. plerixafor is well tolerated and effective when added to G-CSF for the mobilization of stem cells from patients with lymphoma, with mobilization kinetics and stem cell collections that compare favorably with subcutaneous dosing., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
10. Fresh or Cryopreserved CD34 + -Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation.
- Author
-
Ghobadi A, Fiala MA, Ramsingh G, Gao F, Abboud CN, Stockerl-Goldstein K, Uy GL, Grossman BJ, Westervelt P, and DiPersio JF
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Pilot Projects, Antigens, CD34 metabolism, Hematopoietic Stem Cell Transplantation methods, Stem Cells metabolism, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
CD34
+ -selected stem cell boost (SCB) without conditioning has recently been utilized for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this study utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34+ -selected boost infusions for the treatment of PGF. Additionally, to explore relationship of CD34+ dose and response, we included a cohort of donors mobilized with plerixafor in addition to the standard granulocyte colony-stimulating factor (G-CSF). Twenty-six patients with PGF were included in this study. Seventeen donor-recipient pairs were enrolled onto the prospective study; an additional 9 patients treated off protocol were reviewed retrospectively. Three different donor products were used for CD34+ selection: (1) fresh mobilized product using G-CSF only, (2) fresh mobilized products using G-CSF and plerixafor, and (3) cryopreserved cells mobilized with G-CSF. CD34+ cell selection was performed using a CliniMACS. The infusion was not preceded by administration of any chemotherapy or conditioning regimen. The primary objective was hematologic response rate and secondary objectives included CD34+ yields, incidence and severity of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), and relapse-free survival (RFS). The median post-selection CD34+ counts per kilogram of recipient weight were 3.1 × 106 , 10.9 × 106 , and 1 × 106 for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. The median CD34+ yields (defined as the number of CD34+ cells after selection/CD34+ cells before CD34+ selection) were 69%, 66%, and 28% for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. After SCB, 16 of the 26 recipients (62%) had a complete response, including 5 of 8 (63%) who received cryopreserved products. Five had a partial response (19%), resulting in an overall response rate of 81%. One-year RFS and OS were 50% and 65%, respectively. There was no treatment-related toxicity reported other than GVHD: 6 (23%) developed acute GVHD (2 grade I and 4 grade II) and 8 (31%) developed chronic GVHD (2 limited and 6 extensive). Cryopreserved products are viable alternatives to create SCB for the treatment of PGF. When collecting fresh products is an option, the addition of plerixafor increases CD34+ yield over G-CSF alone; however, it is currently unclear if the CD34+ cell dose impacts the efficacy of the SCB., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
11. T Cell-Replete Peripheral Blood Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide Results in Outcomes Similar to Transplantation from Traditionally Matched Donors in Active Disease Acute Myeloid Leukemia.
- Author
-
How J, Slade M, Vu K, DiPersio JF, Westervelt P, Uy GL, Abboud CN, Vij R, Schroeder MA, Fehniger TA, and Romee R
- Subjects
- Adult, Age Factors, Aged, Cyclophosphamide therapeutic use, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation standards, Histocompatibility, Humans, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Analysis, Transplantation, Haploidentical methods, Transplantation, Haploidentical standards, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation mortality, Leukemia, Myeloid, Acute mortality, T-Lymphocytes cytology, Tissue Donors supply & distribution, Transplantation, Haploidentical mortality
- Abstract
Outcomes for patients with acute myeloid leukemia (AML) who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there are little data comparing outcomes for AML patients with active disease who receive haploidentical versus traditionally matched HCT. We retrospectively analyzed data from 99 AML patients with active disease undergoing allogeneic HCT at a single institution. Forty-three patients received unrelated donor HCT, 32 patients received matched related donor HCT, and 24 patients received peripheral blood haploidentical HCT with post-transplantation cyclophosphamide. We found no significant differences between treatment groups in terms of overall survival (OS), event-free survival, transplantation-related mortality, cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GVHD). We performed univariate regression analysis of variables that modified OS in all patients and found only younger age at transplantation and development of chronic GVHD significantly improved outcome. Although limited by our relatively small sample size, these results indicate that haploidentical HCT in active AML patients have comparable outcomes to HCT with traditionally matched donors. Haploidentical HCT can be considered in this population of high-risk patients when matched donors are unavailable or when wait times for transplantation are unacceptably long., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
12. Severe Cytokine-Release Syndrome after T Cell-Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated with Poor Survival and Anti-IL-6 Therapy Is Safe and Well Tolerated.
- Author
-
Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, Meier S, Fehniger TA, Abboud CN, Uy GL, Vij R, Trinkaus KM, Schroeder MA, and Romee R
- Subjects
- Adult, Aged, Antibodies, Monoclonal, Humanized therapeutic use, Female, Humans, Interleukin-6 antagonists & inhibitors, Interleukin-6 blood, Interleukin-6 immunology, Male, Middle Aged, Peripheral Blood Stem Cell Transplantation mortality, Survival Analysis, Syndrome, T-Lymphocytes, Transplantation, Haploidentical mortality, Young Adult, Cytokines metabolism, Lymphocyte Depletion methods, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cell Transplantation methods, Transplantation, Haploidentical adverse effects, Transplantation, Haploidentical methods
- Abstract
Use of high-dose post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis has expanded the use of unmanipulated haploidentical hematopoietic cell transplantation. The immediate post-transplantation course in T cell-replete peripheral blood haploidentical hematopoietic cell transplantation (haplo-HCT) is often complicated by symptoms resembling cytokine-release syndrome (CRS), previously described in recipients of targeted cellular therapeutics. However, we know little about the incidence and impact of CRS on outcomes in these patients. To understand this syndrome in haplo-HCT patients, we reviewed data from 75 consecutive patients who received granulocyte colony-stimulating factor-mobilized T cell-replete peripheral blood haplo-HCT at a single center. Using CRS criteria described in recipients of chimeric antigen receptor T cell therapies, we found 65 of 75 (87%) met criteria for CRS, although most cases were only mild (grades 1 or 2). However, 9 patients (12%) experienced severe (grades 3 or 4) CRS. Median survival was 2.6 months (95% confidence interval [CI], .43 to 5.8) in patients with severe CRS, compared with 13.1 months (95% CI, 8.1 to not reached) in patients with mild CRS. Transplantation-related mortality was worse in the severe CRS cohort with a hazard ratio of 4.59 (95% CI, 1.43 to 14.67) compared with that in the mild CRS cohort. Severe CRS patients had a significant delay in median time for neutrophil engraftment. Serum IL-6 levels were measured in 10 haplo-HCT patients and were elevated in the early post-transplantation setting. Seven patients with CRS were treated with tocilizumab, resulting in a complete resolution of their CRS symptoms. Severe CRS represents a potential complication of peripheral blood haplo-HCT and is associated with worse outcomes. Anti-IL-6 receptor therapy is associated with rapid resolution of the CRS symptoms., Competing Interests: Disclosures, (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
13. Comparison of Outcomes after Peripheral Blood Haploidentical versus Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia: A Retrospective Single-Center Review.
- Author
-
Rashidi A, DiPersio JF, Westervelt P, Vij R, Schroeder MA, Cashen AF, Fehniger TA, and Romee R
- Subjects
- Adolescent, Adult, Aged, Cyclophosphamide therapeutic use, Female, Hematopoietic Stem Cell Transplantation standards, Humans, Male, Middle Aged, Peripheral Blood Stem Cell Transplantation methods, Peripheral Blood Stem Cell Transplantation standards, Retrospective Studies, Transplantation Conditioning, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Transplantation, Haploidentical methods, Unrelated Donors
- Abstract
Recent studies comparing allogeneic hematopoietic cell transplantation (HCT) using HLA-matched unrelated donors (MUD) versus HLA-haploidentical donors in patients with acute myeloid leukemia (AML) have suggested equivalent outcomes. The graft source used in most studies of haploidentical transplants has been bone marrow. Similar comparisons between MUD and haplo-HCT using peripheral blood as a graft source have not been adequately performed. We reviewed the records of all 52 AML patients who underwent haplo-HCT (using peripheral blood and post-transplantation high-dose cyclophosphamide) between January 2010 and August 2015 at our institution and compared their outcomes with 88 patients who had a MUD transplant in the same time frame and were frequency matched (preanalysis) to the haploidentical group for conditioning intensity. Multivariate analysis found no difference in outcomes between the 2 groups with the exception of slower count recovery after haploidentical allografts (HR, .48; 95% CI, .32 to .74 for platelets, and HR, .47; 95% CI, .32 to .71 for neutrophils; P < .001 for both comparisons). Our retrospective analysis, although limited by the small sample size, suggests largely similar outcomes with peripheral blood haploidentical versus MUD transplants for AML., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
14. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.
- Author
-
Motabi IH, Ghobadi A, Liu J, Schroeder M, Abboud CN, Cashen AF, Stockler-Goldstein KE, Uy GL, Vij R, Westervelt P, and DiPersio JF
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Agents therapeutic use, Female, Humans, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Myelodysplastic Syndromes drug therapy, Recurrence, Transplantation, Homologous, Treatment Outcome, Young Adult, Antimetabolites, Antineoplastic therapeutic use, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Lymphocyte Transfusion methods, Myelodysplastic Syndromes therapy, Salvage Therapy methods
- Abstract
Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
15. Peritransplant Serum Albumin Decline Predicts Subsequent Severe Acute Graft-versus-Host Disease after Mucotoxic Myeloablative Conditioning.
- Author
-
Rashidi A, DiPersio JF, Westervelt P, Abboud CN, Schroeder MA, Cashen AF, Pusic I, and Romee R
- Subjects
- Acute Disease, Adult, Aged, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Humans, Leukemia, Myeloid, Acute complications, Middle Aged, Mucositis chemically induced, Myeloablative Agonists therapeutic use, Myeloablative Agonists toxicity, Myelodysplastic Syndromes complications, Predictive Value of Tests, Reproducibility of Results, Sensitivity and Specificity, Transplantation Conditioning methods, Transplantation, Homologous, Young Adult, Graft vs Host Disease diagnosis, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Serum Albumin analysis, Transplantation Conditioning adverse effects
- Abstract
Conditioning-related gut toxicity can result in a protein-losing enteropathy manifesting as a decline in serum albumin in the peritransplant period. Inspired by the pathogenesis of acute graft-versus-host disease (aGVHD), we hypothesized that the magnitude of decline in serum albumin from the day of conditioning initiation until its nadir in the first 2 weeks after hematopoietic cell transplantation HCT (DeltaAlb) predicts the risk for subsequent severe aGVHD. We reviewed the medical records of all 88 patients with acute myeloid leukemia or myelodysplastic syndrome who underwent highly mucotoxic myeloablative (busulfan/cyclophosphamide or cyclophosphamide/total body irradiation) allogeneic HCT from a matched related donor (MRD) or matched unrelated donor (MUD) at our institution between January 1, 2012 and January 1, 2015. Severe aGVHD was associated with MUD (47% versus 14% with MRD; P = .001) and DeltaAlb, which was significantly greater among patients who developed versus did not develop severe aGVHD (1.2 ± .5 versus .8 ± .4 g/dL, respectively; P < .001). In multivariate analysis DeltaAlb remained a significant predictor of severe aGVHD (odds ratio, 5.68; 95% CI, 1.65 to 19.64; P = .006; area under the ROC curve, .74; 95% CI, .63 to .86; P < .001). The best cutoff for DeltaAlb to predict severe aGVHD was .9, with a sensitivity, specificity, and overall classification accuracy of 77%, 66%, and 69%, respectively. The model was validated using the bootstrap technique, with no significant change in its performance. These results were not generalizable to a cohort of 30 patients who received less mucotoxic myeloablative or reduced-intensity conditioning. In conclusion, with mucotoxic myeloablative HCT, each .1-g/dL increase in DeltaAlb was associated with an approximately 23% increase in the odds of developing severe aGVHD. As an early biomarker of gut damage, DeltaAlb can be incorporated in composite risk models for aGVHD prediction, with hopes for ultimately allowing for individualized GVHD prophylaxis and potential intervention according to the predicted risk., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
16. Maintenance Therapy with Decitabine after Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndrome.
- Author
-
Pusic I, Choi J, Fiala MA, Gao F, Holt M, Cashen AF, Vij R, Abboud CN, Stockerl-Goldstein KE, Jacoby MA, Uy GL, Westervelt P, and DiPersio JF
- Subjects
- Adult, Aged, Allografts, Antimetabolites, Antineoplastic adverse effects, Azacitidine adverse effects, Azacitidine therapeutic use, Combined Modality Therapy, Decitabine, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Gastrointestinal Diseases chemically induced, Graft vs Host Disease etiology, Hematologic Diseases chemically induced, Humans, Infusions, Intravenous, Leukemia, Myeloid, Acute therapy, Male, Maximum Tolerated Dose, Middle Aged, Myelodysplastic Syndromes therapy, Prospective Studies, Young Adult, Antimetabolites, Antineoplastic therapeutic use, Azacitidine analogs & derivatives, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute drug therapy, Maintenance Chemotherapy methods, Myelodysplastic Syndromes drug therapy
- Abstract
Decitabine is a hypomethylating agent that irreversibly inhibits DNA methyltransferase I, inducing leukemic differentiation and re-expression of epigenetically silenced putative tumor antigens. We assessed safety and efficacy of decitabine maintenance after allogeneic transplantation for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Decitabine maintenance may help eradicate minimal residual disease, decrease the incidence of graft-versus-host disease (GVHD), and facilitate a graft-versus-leukemia effect by enhancing the effect of T regulatory lymphocytes. Patients with AML/MDS in complete remission (CR) after allotransplantation started decitabine between day +50 and +100. We investigated 4 decitabine doses in cohorts of 4 patients: 5, 7.5, 10, and 15 mg/m(2)/day × 5 days every 6 weeks, for a maximum 8 cycles. The maximum tolerated dose (MTD) was defined as the maximum dose at which ≤ 25% of people experience dose-limiting toxicities during the first cycle of treatment. Twenty-four patients were enrolled and 22 were evaluable. All 4 dose levels were completed and no MTD was reached. Overall, decitabine maintenance was well tolerated. Grade 3 and 4 hematological toxicities were experienced by 75% of patients, including all patients treated at the highest dose level. Nine patients completed all 8 cycles and 8 of them remain in CR. Nine patients died from relapse (n = 4), infectious complications (n = 3), and GVHD (n = 2). Most occurrences of acute GVHD were mild and resolved without interruption of treatment; 1 patient died of acute gut GVHD. Decitabine maintenance did not clearly impact the rate of chronic GVHD. Although there was a trend of increased FOXP3 expression, results were not statistically significant. In conclusion, decitabine maintenance is associated with acceptable toxicities when given in the post-allotransplantation setting. Although the MTD was not reached, the dose of 10 mg/m(2) for 5 days every 6 weeks appeared to be the optimal dose rather than 15 mg/m(2), where most hematological toxicities occurred., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
17. Hematologic Recovery after Pretransplant Chemotherapy Does Not Influence Survival after Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients.
- Author
-
Vu K, Manjappa S, DiPersio JF, Gao F, Westervelt P, Vij R, Stockerl-Goldstein KE, Uy GL, Abboud CN, Schroeder MA, Fehniger TA, Cashen AF, and Romee R
- Subjects
- Adolescent, Adult, Aged, Cohort Studies, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Transplantation Conditioning mortality, Transplantation, Homologous mortality, Treatment Outcome, Young Adult, Hematologic Diseases etiology, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Pretransplant remission status in patients with acute myeloid leukemia (AML) is 1 of the most important factors determining their outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Most patients are in complete remission with full hematologic recovery (CR) before undergoing allo-HCT. However, some patients achieve CR without recovery of platelet count (CRp) or a morphologic leukemia-free state (MLFS), defined as meeting all CR criteria without recovery of both neutrophil and platelet counts. Currently, there is a paucity of data regarding transplant outcomes in AML patients achieving MLFS after chemotherapy. To address this question, we evaluated transplant outcomes in 270 AML patients who received 6/6 HLA-matched sibling or 10/10 HLA-matched unrelated donor transplantation at a single institution between 2006 and 2013. Of our 270 patients, 206 were in CR, 45 were in CRp, and 19 were in MLFS before allo-HCT. Patients in CR, CRp, or MLFS had similar 3-year overall survival rates (49%, 46%, and 47%, respectively; P = .88) and 3-year event-free survival rates (45%, 36%, and 40%, respectively; P = .53). However, the cumulative incidence of nonrelapse mortality was significantly higher in patients in MLFS compared with those in CR (58% versus 22%, P = .0004), whereas the cumulative incidence of relapse in patients in MLFS was significantly lower compared with those in CR (11% versus 36%, P = .03). Our results suggest that survival outcomes in AML patients are not influenced by degree of hematologic recovery before allo-HCT., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
18. Protective effect of cytomegalovirus reactivation on relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia patients is influenced by conditioning regimen.
- Author
-
Manjappa S, Bhamidipati PK, Stokerl-Goldstein KE, DiPersio JF, Uy GL, Westervelt P, Liu J, Schroeder MA, Vij R, Abboud CN, Fehniger TA, Cashen AF, Pusic I, Jacoby M, Meera SJ, and Romee R
- Subjects
- Adolescent, Adult, Aged, Female, Graft vs Leukemia Effect, HLA Antigens immunology, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute virology, Lymphocyte Depletion, Male, Middle Aged, Multivariate Analysis, Risk, Secondary Prevention, Siblings, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes pathology, Transplantation, Homologous, Unrelated Donors, Cytomegalovirus physiology, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Myeloablative Agonists therapeutic use, Transplantation Conditioning methods, Virus Activation drug effects
- Abstract
Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplant (allo-HCT) has been associated with a reduced risk of relapse in patients with acute myeloid leukemia (AML). However, the influence of the conditioning regimen on this protective effect of CMV reactivation after allo-HCT is relatively unexplored. To address this, we evaluated the risk of relapse in 264 AML patients who received T cell-replete, 6/6 HLA matched sibling or 10/10 HLA matched unrelated donor transplantation at a single institution between 2006 and 2011. Of these 264 patients, 206 received myeloablative (MA) and 58 received reduced-intensity conditioning (RIC) regimens. CMV reactivation was observed in 88 patients with MA conditioning and 37 patients with RIC. At a median follow-up of 299 days, CMV reactivation was associated with significantly lower risk of relapse in patients who received MA conditioning both in univariate (P = .01) and multivariate analyses (hazard ratio, .5246; P = .006); however, CMV reactivation did not significantly affect the risk of relapse in our RIC cohort. These results confirm the protective effect of CMV reactivation on relapse in AML patients after allo-HCT reported by previous studies but suggest this protective effect of CMV reactivation on relapse is influenced by the conditioning regimen used with the transplant., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
19. Prognostic significance of FDG-PET in relapsed or refractory classical Hodgkin lymphoma treated with standard salvage chemotherapy and autologous stem cell transplantation.
- Author
-
Smeltzer JP, Cashen AF, Zhang Q, Homb A, Dehdashti F, Abboud CN, Dipersio JF, Stockerl-Goldstein KE, Uy GL, Vij R, Westervelt P, Bartlett NL, and Fehniger TA
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Disease-Free Survival, Female, Follow-Up Studies, Hodgkin Disease drug therapy, Hodgkin Disease surgery, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Recurrence, Transplantation, Autologous methods, Young Adult, Fluorodeoxyglucose F18, Hematopoietic Stem Cell Transplantation methods, Hodgkin Disease diagnostic imaging, Hodgkin Disease therapy, Positron-Emission Tomography methods, Salvage Therapy methods
- Abstract
Positron emission tomography using [(18)F]fluorodeoxyglucose (FDG-PET) has emerged as the standard response assessment tool in frontline therapy for classical Hodgkin lymphoma (cHL). The ability of FDG-PET to predict outcomes in patients with relapsed cHL treated with modern standard salvage chemotherapy and autologous stem cell transplantation (ASCT) remains uncertain. Forty-six patients with relapsed/refractory cHL treated from 2001 to 2007 with standard salvage/ASCT therapy had FDG-PET available for blinded review. The results of pre-ASCT FDG-PET interpreted by the international harmonization project (IHP) criteria were compared with published prognostic models for prediction of event-free survival (EFS) and overall survival (OS). Overall, 3-year EFS was 62% and OS was 78%, with a median follow-up of 38 months. Pre-ASCT FDG-PET response significantly predicted 3-year EFS in FDG-PET-negative (82%) versus FDG-PET-positive (41%) patients (P = .02). A trend was observed for 3-year OS comparing FDG-PET-negative (91%) versus -positive (64%) patients (P = .08). Multivariate analysis demonstrated the independent prognostic significance of pre-ASCT FDG-PET for EFS with a hazard ratio (HR) of 3.2 (confidence interval [CI] 1.1-9.0, P = .03). Pre-ASCT FDG-PET scans predict EFS in patients with relapsed cHL patients treated with modern salvage/ASCT therapy and warrant prospective evaluation., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
20. Reduced-intensity allogeneic transplantation provides high event-free and overall survival in patients with advanced indolent B cell malignancies: CALGB 109901.
- Author
-
Shea T, Johnson J, Westervelt P, Farag S, McCarty J, Bashey A, Isola L, Baxter-Lowe LA, Kelly M, Owzar K, and Linker C
- Subjects
- Adult, Aged, Antineoplastic Agents therapeutic use, Cyclophosphamide therapeutic use, Dose-Response Relationship, Drug, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia, B-Cell mortality, Lymphoma, B-Cell mortality, Male, Middle Aged, Survival Rate, Transplantation, Homologous, Treatment Outcome, Vidarabine Phosphate analogs & derivatives, Vidarabine Phosphate therapeutic use, Antineoplastic Agents administration & dosage, Hematopoietic Stem Cell Transplantation methods, Leukemia, B-Cell therapy, Lymphoma, B-Cell therapy, Transplantation Conditioning methods
- Abstract
Cancer and Leukemia Group B conducted a phase II study to evaluate the safety and efficacy of a reduced-intensity conditioning regimen with allogeneic transplantation to treat patients with recurrent low-grade B cell malignancies. Patients over age 18 with a diagnosis of relapsed, chemotherapy-sensitive disease underwent transplantation with a matched sibling donor, and conditioning with cyclophosphamide (1 g/m(2)/day × 3) and fludarabine phosphate (25 mg/m(2)/day × 5). Graft-versus-host prophylaxis included cyclosporine or tacrolimus plus low-dose methotrexate. Forty-four evaluable patients with a median age of 53 and median of 2 prior regimens were accrued. Sixteen patients had follicular non-Hodgkin lymphoma and 28 had histologies including 7 indolent B cell lymphomas, 4 mantle cell, 15 chronic lymphocytic leukemia (CLL), and 2 prolymphocytic leukemia (PLL) patients. The 6-month treatment-related mortality (TRM) was 2.4% and 3-year TRM was 9%. Three-year event-free and overall survival were 0.75 and 0.81 for the follicular patients, 0.59 and 0.71 for the CLL/PLL patients, and 0.55 and 0.64 for the other histologies. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 29%, and extensive chronic GVHD was 18%. This report demonstrates that allogeneic sibling transplantation with a reduced-intensity conditioning regimen is safe and efficacious for patients with advanced indolent B cell malignancies enrolled on a Cooperative Group study., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
21. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.
- Author
-
Pusic I, Jiang SY, Landua S, Uy GL, Rettig MP, Cashen AF, Westervelt P, Vij R, Abboud CN, Stockerl-Goldstein KE, Sempek DS, Smith AL, and DiPersio JF
- Subjects
- Antigens, CD34, Benzylamines, Cyclams, Female, Hematologic Neoplasms therapy, Humans, Leukocyte Count, Male, Middle Aged, Recombinant Proteins, Retrospective Studies, Transplantation, Autologous, Anti-HIV Agents administration & dosage, Blood Component Removal methods, Granulocyte Colony-Stimulating Factor administration & dosage, Hematopoietic Stem Cell Mobilization methods, Hematopoietic Stem Cells, Heterocyclic Compounds administration & dosage, Stem Cell Transplantation
- Abstract
The purpose of this article was to examine historic institutional autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for autologous transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of > or =2 x 10(6) CD34(+) cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34(+) cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected > or =2 x 10(6) CD34(+) cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34(+) cell yield and required less aphereses to collect > or =2 x 10(6) CD34(+) cells/kg. Mobilized, preapheresis, peripheral blood CD34(+) count correlated with first day apheresis yield (r = .877, P < .001) and 20 cells/microL was the minimum threshold needed for a successful day 1 collection. For the remobilization analysis we included patients from the whole database. A total of 269 of 1834 patients underwent remobilization using G/C, G-CSF, and/or GM-CSF, and G-CSF plus plerixafor. Only 23% of remobilized patients achieved > or =2 x 10(6) CD34(+) cells/kg and 29.7% failed to pool sufficient number of stem cells from both collections. Patients receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients remobilized with G-CSF who waited > or =25 days before remobilization had lower CD34(+) cell yield than those who waited < or =16 days, P = .023. Current mobilization regimens are associated with a substantial failure rate irrespective of underlying disease. Patients who fail initial mobilization are more likely to fail remobilization. These findings suggest that there is a need for more effective first-line mobilization agents.
- Published
- 2008
- Full Text
- View/download PDF
22. A phase II multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid-refractory acute graft-versus-host disease.
- Author
-
Carpenter PA, Lowder J, Johnston L, Frangoul H, Khoury H, Parker P, Jerome KR, McCune JS, Storer B, Martin P, Appelbaum F, Abonour R, Westervelt P, and Anasetti C
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Antibodies, Monoclonal, Humanized, Child, Child, Preschool, Female, Graft vs Host Disease mortality, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Humans, Male, Middle Aged, Steroids administration & dosage, Survival Analysis, Antibodies, Monoclonal administration & dosage, Graft vs Host Disease drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
- Published
- 2005
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.