Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for High-Risk Acute Lymphoblastic Leukemia

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 incidence (CI) of grades II–IV and III–IV acute GVHD at day 100 post-transplant was 32% and 11%, while chronic GVHD, non-relapse mortality, relapse rate and disease-free survival (DFS) at 1 year post-transplant 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 an excellent alternative to HLA matched transplants for patients with ALL.

Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

“…According to a recent analysis by the EBMT, including 91 patients with ALL in CR1, the probability of LFS at 3 years after unmanipulated MMRD-HSCT was 47% [35]. Similar results (52% LFS rate) were reported by Srour et al [36].…”

Busulfan‐based myeloablative conditioning regimens for haploidentical transplantation in high‐risk acute leukemias and myelodysplastic syndromes

“…Finally, our results are almost identical to those of previous series on myeloablative conditioning in AL, 14,15,[30][31][32] and to those of other alternative donor approaches such as cord blood transplants. 25,33 Our findings confirm the feasibility and safety of PT-Cy HAPLO-MAC in advanced AL and MDS in a real-world, multicenter setting where patients were managed under conditions of daily clinical practice.…”

Advances in adult acute lymphoblastic leukemia therapy

“…As similarly found in other hematological malignancies, haploidentical HCT was feasible in ALL and produced encouraging results [73,74]. In a multicenter retrospective analysis of 109 patients with high-risk ALL, 1-year non-relapse mortality (NRM), relapse rate (RR), and disease-free survival (DFS) for all patients were 21%, 27%, and 51%, respectively, and 3-year DFS for those in first CR was 52% [73]. As relapse remains the leading cause of treatment failure after haploidentical HCT, novel modalities are being developed to overcome this hurdle, including escalating the dose of targeted radiation-based condition regimens (NCT#02446964) and post-transplant preemptive chimeric-antigen receptor (CAR) T cell therapy [75].…”

“…The recent innovation in T cell replete HLA-haploidentical HCT using post-transplant cyclophosphamide allowed more patients to have a donor choice to proceed with transplantation when needed. As similarly found in other hematological malignancies, haploidentical HCT was feasible in ALL and produced encouraging results [73,74]. In a multicenter retrospective analysis of 109 patients with high-risk ALL, 1-year non-relapse mortality (NRM), relapse rate (RR), and disease-free survival (DFS) for all patients were 21%, 27%, and 51%, respectively, and 3-year DFS for those in first CR was 52% [73].…”