1.
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.
2.
Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for High-Risk Acute Lymphoblastic Leukemia
Srour, S. A., Milton, D. R., Bashey, A., Karduss-Urueta, A., Al Malki, M. M., Romee, R., Solomon, S., Nademanee, A., Brown, S., Slade, M., et al
Biology of Blood & Marrow Transplantation. 2017;23(2):318-324
Abstract
Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months. Thirty-two patients were in first complete remission (CR1), while the rest were beyond CR1. Neutrophil engraftment occurred in 95% of the patients. The cumulative incidences of grades II to IV and III and IV acute GVHD at day 100 after transplantation were 32% and 11%, respectively, whereas chronic GVHD, nonrelapse mortality, relapse rate, and disease-free survival (DFS) at 1 year after transplantation were 32%, 21%, 27%, and 51%, respectively. Patients in CR1 had 52% DFS at 3 years. These results suggest that haploidentical transplants performed with PTCy-based GVHD prophylaxis provide a very suitable alternative to HLA-matched transplantations for patients with ALL.