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The Role of Allogeneic Transplant for Adult Ph+ ALL in CR1 with Complete Molecular Remission: A Retrospective Analysis
Ghobadi, A., Slade, M., Kantarjian, H. M., Alvarenga, J., Aldoss, I., Mohammed, K., Jabbour, E. J., Faramand, R. G., Shah, B. D., Locke, F. L., et al
Blood. 2022
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Abstract
Historically, Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has been associated with poor outcomes and allogeneic hematopoietic cell transplantation (allo-HCT) is recommended in first complete remission (CR1). However, in the tyrosine kinase inhibitor (TKI) era, rapid attainment of a complete molecular remission (CMR) is associated with excellent outcomes without allo-HCT, suggesting transplant may not be required for these patients. To test this hypothesis, we retrospectively identified adult patients with Ph+ ALL treated with induction therapy including TKIs and attained CMR within 90 days of diagnosis at 5 transplant centers in the United States. We compared outcomes of those who did and did not receive allo-HCT in first remission. We identified 230 patients (Allo-HCT: 98, non-HCT: 132). The allo-HCT cohort was younger with better performance status. On multivariable analysis (MVA), allo-HCT was not associated with improved overall survival (aHR 1.05, 95% C.I. 0.63 - 1.73) or relapse-free survival (aHR: 0.86, 95% C.I. 0.54 - 1.37) compared to non-HCT treatment. Allo-HCT was associated with a lower cumulative incidence of relapse (aHR 0.32, 95% C.I. 0.17 - 0.62) but higher non-relapse mortality (aHR: 2.59, 95% C.I. 1.37 - 4.89). Propensity score matching analysis confirmed results of MVA. Comparison of reduced-intensity HCT to non-HCT showed no statistically significant difference in any of the above endpoints. In conclusion, adult patients with Ph+ ALL who achieved CMR within 90 days of starting treatment did not derive a survival benefit from allo-HCT in CR1 in this retrospective study.
PICO Summary
Population
Adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL) from five centres in the USA (n=230)
Intervention
Allogeneic transplant in first remission (Allo-HCT, n=98)
Comparison
No allogeneic transplant in first remission (non-HCT, n=132)
Outcome
The allo-HCT cohort was younger with better performance status. On multivariable analysis (MVA), allo-HCT was not associated with improved overall survival (aHR 1.05, 95% C.I. 0.63 - 1.73) or relapse-free survival (aHR: 0.86, 95% C.I. 0.54 - 1.37) compared to non-HCT treatment. Allo-HCT was associated with a lower cumulative incidence of relapse (aHR 0.32, 95% C.I. 0.17 - 0.62) but higher non-relapse mortality (aHR: 2.59, 95% C.I. 1.37 - 4.89). Propensity score matching analysis confirmed results of MVA. Comparison of reduced-intensity HCT to non-HCT showed no statistically significant difference in any of the above endpoints.
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The Effect of Donor Type on Outcomes in Adults with Acute Myeloid Leukemia after Reduced Intensity Hematopoietic Peripheral Blood Cell Transplant
Rashid, N., Slade, M., Abboud, R., Gao, F., DiPersio, J. F., Westervelt, P., Uy, G., Stockerl-Goldstein, K., Romee, R., Schroeder, M. A.
Transplant international : official journal of the European Society for Organ Transplantation. 2020
Abstract
We retrospectively analyzed outcomes in patients with acute myeloid leukemia (AML) receiving reduced intensity conditioning (RIC) hematopoietic stem cell transplants (HCT) from a peripheral blood (PB) source. We identified 46 haploidentical HCT (haplo), 59 matched unrelated donor HCT (MUD), and 40 matched related donor HCT (SIB) patients at a single institution. Haplo had improved overall survival (OS) when compared to MUD, HR 2.03 (p=0.01) but not SIB, HR 1.17, (p=0.61). There were no differences in relapse rates or treatment related mortality (TRM). Haplo had higher rates of acute graft versus host disease (GVHD) grade II-IV at day 180 than MUD (44% vs 25%, p=0.03) and SIB (44% vs 13% p<0.01). Rates of acute GVHD III-IV and chronic GVHD were similar among the groups. Haplo had slower engraftment rates compared to MUD with neutrophil engraftment at 87% vs 93%, (p<0.01) and platelet engraftment at 59% vs 86%, (p<0.01) at 28 days. Although patients receiving haplo had higher acute GVHD II-IV and slower engraftment, they did not have increased TRM. These data may suggest that patients receiving haplo have improved OS compared to MUD for AML patients receiving RIC transplants. This should be confirmed using a larger cohort.
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Post-transplant high-dose cyclophosphamide after HLA-matched vs haploidentical hematopoietic cell transplantation for AML
Rashidi, A., Slade, M., DiPersio, J. F., Westervelt, P., Vij, R., Romee, R.
Bone Marrow Transplantation. 2016;51(12):1561-1564
Abstract
Post-transplant cyclophosphamide (PT-Cy) is the backbone of GvHD prophylaxis following haploidentical hematopoietic cell transplantation (haplo-HCT). PT-Cy has also been used in matched related (MRD) and unrelated (MUD) settings. It is not known whether outcomes are similar between haplo-HCT and MRD/MUD HCT when PT-Cy is used. We performed a retrospective analysis of 83 patients with AML who underwent HCT (using PT-Cy-based GvHD prophylaxis) from MRD, MUD or haploidentical donors. The groups were similar in baseline characteristics with the exception of older age in the MRD/MUD group (P=0.012). In multivariate analysis, the effect of donor type (MRD/MUD vs haploidentical) on transplant outcomes was not significant in any of the models except for faster neutrophil recovery after MRD/MUD transplants (hazard ratio: 2.21; 95% confidence interval: 1.31-3.72, P=0.002). In conclusion, we showed similar outcomes in MRD/MUD vs haploidentical HCT (except slower count recovery following haplo-HCT) when PT-Cy is used for GvHD prophylaxis. Although slower count recovery following haplo-HCT (compared with MRD/MUD transplants without PT-Cy) has been attributed to using PT-Cy, our results suggest that HLA disparity is the primary cause of this difference. Furthermore, our analysis supports PT-Cy as a viable option for GvHD prophylaxis after MRD/MUD transplants.
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Remobilization of hematopoietic stem cells in healthy donors for allogeneic transplantation
Fiala, M. A., Park, S., Slade, M., DiPersio, J. F., Stockerl-Goldstein, K. E.
Transfusion. 2016;56(9):2331-5
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Abstract
BACKGROUND The need to repeat peripheral blood (PB) stem cell mobilization and collection in healthy donors arises infrequently but may be required due to insufficient initial collection, graft failure, or relapse of the recipient's disease. Little data exist on the efficacy of remobilization. Therefore, we retrospectively reviewed 18 years of remobilization records from healthy stem cell donors at our institution. STUDY DESIGN AND METHODS We identified 62 healthy donors who underwent remobilization, a cohort of 30 mobilized and remobilized with cytokines and a cohort of 32 mobilized with a CXCR4 antagonist and remobilized with cytokines. For each cohort we compared the PB CD34+/L level, the number of CD34+ cells collected/kg (recipient weight), and the number of CD34+ cells/L collected on the first day of leukapheresis during initial mobilization and remobilization. RESULTS Initial mobilization with cytokines was associated with reduced remobilization. The mean PB CD34/L level at initial mobilization was 69 x 10(6) compared to 37 x 10(6) at remobilization (p=0.029). In contrast, initial mobilization with a CXCR4 antagonist was not associated with reduced remobilization. The mean PB CD34/L level at initial mobilization was 15 x 10(6) compared to 68 x 10(6) at remobilization (p<0.001). In both cohorts, initial mobilization results were positively correlated with remobilization results but the interval between was not. CONCLUSIONS This study suggests that poor remobilization yields may be due to decreased efficacy of cytokines after repeat exposure. The underlying mechanism of these findings remains unclear and further studies are needed. Copyright © 2016 AABB.