8 research outputs found
Reduced-intensity Transplantation For Lymphomas Using Haploidentical Related Donors Versus Hla-matched Sibling Donors: A Center For International Blood And Marrow Transplant Research Analysis
Purpose: Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods: We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Results: Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion: Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD
Autologous Transplantation Versus Allogeneic Transplantation in Patients with Follicular Lymphoma Experiencing Early Treatment Failure
BACKGROUND: Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. METHODS: This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age \u3e/= 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). RESULTS: Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P \u3c .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P \u3c .0001). CONCLUSIONS: Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. (c) 2018 American Cancer Society
Importance of immunoglobulin heavy chain variable region mutational status in del(13q) chronic lymphocytic leukemia
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Bridging the Gap in Access to Transplant for Underserved Minority Patients Using Mismatched Unrelated Donors and Post-Transplant Cyclophosphamide: A National Marrow Donor Program/be the Match (NMDP/BTM) Initiative
Background Despite international unrelated donor (URD) registries listing >36 million volunteer donors, 25-80% of U.S. patients lack an HLA-matched (8/8 alleles) URD, with greater disparities in access for ethnic minorities. We hypothesized that hematopoietic cell transplantation (HCT) with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCY), a strategy successful in overcoming genetic disparity in related haplo-identical donor HCT (haplo HCT) would be associated with similar outcomes to haplo HCT and expand access to HCT. Selecting a MMUD may have benefits over a haplo donor, such as removing risk associated with donor specific antibodies, and allowing for preferential selection of other favorable donor factors, such as younger age. Methods The NMDP/BTM performed a prospective phase II study of MMUD bone marrow (BM) HCT with PTCY for patients with hematologic malignancies, with the primary hypothesis that 1-year overall survival (OS) would be 65% or greater. Patients with a suitable HLA matched sibling or URD were excluded. Matching for 4-7/8 at HLA-A, -B, -C, and -DRB1 was permitted. 80 patients enrolled (40 myeloablative conditioning (MAC) - using cyclophosphamide/TBI (n=6), busulfan/cyclophosphamide (n=3) or fludarabine/ busulfan (n=31); 40 reduced intensity conditioning (RIC) - using fludarabine/cyclophosphamide/TBI) at 11 U.S. transplant centers between Dec 2016 and March 2019. Patients received a fresh BM graft, PTCY on days +3, +4, with sirolimus/mycophenolate mofetil starting on day +5. Regimen intensity was at the center's discretion. We compared outcomes to three groups of contemporaneous controls, all receiving PTCY, whose data was collected by CIBMTR: MMUD using peripheral blood stem cells (PBSC) (n=143), and haplo using BM (n=398) or PBSC (n=1191). All analyses used standard stepwise Cox regression modeling, performed separately for MAC and RIC cohorts. The main variable of interest was the donor/graft type (all groups compared to the trial cohort of MMUD BM). Statistical significance is p=0.05. Results The study achieved its primary endpoint with 1-year OS of 76% (90% CI: 67.3-83.3) in the entire cohort; survival and GVHD-/relapse-free survival (GRFS, defined in table 1) were 72% and 37% in the MAC cohort and 79% and 53% in the RIC cohort, respectively. Additional study outcomes are shown in Table 1. Median patient age was 49 years old (yo) (range: 18-66, MAC) and 60 yo (range: 23-70, RIC). HCT were performed for acute leukemia (n=58), MDS (n=2), lymphoma (n=17) and CLL (n=3). Disease risk index was low (n=11), intermediate (n=63), high (n=13) or very high (n=4). KPS was <90 and HCT-CI was ≥3 in 43% and 54% of patients, respectively. Notably, 48% of patients were ethnic minorities and 39% were <7/8 HLA matched with their donor. 59% of donors were <30 yo and 55% ABO matched with the recipient. Multivariate analysis comparing the study population to the comparator groups found no significant differences in OS (figure 1), GRFS, PFS, NRM or II-IV grade aGVHD in either the MAC or RIC setting, and no differences in III-IV aGVHD or relapse in the RIC setting. In the MAC setting, there was significantly lower grade III-IV aGVHD in haplo BM (HR 0.12, p=0.001), haplo PBSC (HR 0.45, p=0.026), with a trend in MMUD PBSC (HR 0.37, p=0.078), compared to the study subjects. Relapse risk was lower in haplo BM (HR 0.44, p=0.023) and haplo PBSC (HR 0.42, p=0.005), but not significantly different to MMUD PBSC (HR 0.52, p=0.119) when compared to study subjects. Additionally, younger donor age was associated with lower NRM and less aGVHD in the MAC setting and better GRFS, DFS, lower grade III-IV aGVHD, cGVHD and NRM in the RIC setting. Conclusion Our prospective study demonstrated that outcomes using MMUD in the setting of PTCY are similar to those obtained using a haplo donor. Approximately half of the study participants were ethnic minorities, a figure consistent with expectations based on donor availability within registries, but exceeding expectations in accrual to a prospective study. These results support the feasibility of using volunteer MMUDs to expand access to HCT, especially for ethnically diverse patients. Next steps include expanding the MMUD PTCY approach to incorporate PBSC as a graft source and prospectively studying questions related to selection based on donor characteristics and additional GVHD prophylaxis agents. Disclosures Shaw: Orca Bio: Consultancy. Khimani:Bristol Myers Squibb-Moffitt-Alliance: Research Funding. Shah:Cell Vault: Research Funding; Celgene: Consultancy, Honoraria; Verastim: Consultancy; Lily: Consultancy, Honoraria; TG Therapeutics: Consultancy; Incyte: Consultancy; Miltenyi Biotec: Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria. Farhadfar:CSL Behring: Research Funding; Incyte pharmaceutical: Other: Member of GVHD advisory forum. Hardy:Kite/Gilead: Other: Advisory Board Member; Incyte Corporation: Other: Advisory Board Member; American Gene Technologies: Other: DSMB Member. Perales:Medigene: Membership on an entity's Board of Directors or advisory committees, Other; NexImmune: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Other; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Kite/Gilead: Honoraria, Research Funding; Miltenyi Biotec: Research Funding; Incyte Corporation: Honoraria, Research Funding; MolMed: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cidara Therapeutics: Other; Celgene: Honoraria. Komanduri:Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Takeda: Consultancy; Kiadis: Consultancy. Luznik:Merck: Research Funding, Speakers Bureau; AbbVie: Consultancy; WindMil Therapeutics: Patents & Royalties: Patent holder; Genentech: Research Funding. Pidala:Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Johnson and Johnson: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding; BMS: Research Funding. Devine:Magenta Therapeutics: Consultancy. Bolanos-Meade:Incyte: Other: DSMB Fees
High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease
Because of its potent immunosuppressive yet stem cell–sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)–matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell–replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017)