Irradiation free conditioning regimen is associated with high relapse rate in Egyptian patients with acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation

Abstract

Background Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment for adult patients with acute lymphoblastic leukemia (ALL). Cyclophosphamide plus total body irradiation (TBI/Cy) or plus busulfan (Bu/Cy) is a widely used pre-transplant conditioning regimen for ALL. We retrospectively compared the overall survival (OS), disease-free survival (DFS), and other transplant outcomes of allo-HSCT in 119 adult patients with ALL who received an HLA-matched sibling allo-HSCT using TBI-based versus non-TBI-based conditioning regimens. Patients were divided into two groups by their conditioning regimen: TBI/Cy or Bu/Cy. Results Median OS was 11 months in the TBI/Cy group and 6.2 months in the Bu/Cy group. Median DFS was 11.1 months in the TBI group versus 6.8 months in the Bu group, without a statistically significant difference. A higher risk of relapse was observed with the Bu/Cy regimen (HR 2.709, CI 95% 1.106 to 6.638, p = 0.029). Patients who received a transplant in ≥ CR2 were associated with poor DFS. Conclusion Despite the high relapse rate in the non-TBI regimen (Bu/Cy), both regimens had no statistically significant differences in OS, DFS, and NRM. Additional prospective studies are indeed warranted to evaluate the long-term outcomes of radiation-free regimens, including oral and intravenous busulfan, and compare these regimens with TBI-based ones.

Busulfan‐containing conditioning regimens in allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia: A Taiwan observational study

“…The TRM of our patients seemed to be acceptable, yet the incidence of relapse (33.7%–47.8%) remained alarming. While the studies by Kebriaei et al and Abdelaty et al revealed a markedly increased relapse incidence in the busulfan group, 33,38 the relapse rates among three groups in our study were not that different. Interestingly, in a recent study, Speziali and colleagues analyzed outcomes of 146 ALL patients receiving TBI/Cy (1200 cGy) or fludarabine, busulfan, and low‐dose TBI (400 cGy) as conditioning regimens.…”

“…A higher proportion of patients (63.4%) in our study received Bu-based conditioning compared with patients in Western cohorts (4.2%-52.6%, Table 4). [30][31][32][33][34][35][36][37][38] Long-term TBI toxicities, including delayed growth and secondary malignancy, might be the main reason preventing our patients from receiving irradiation therapy.…”

Total Body Irradiation–Based Conditioning Regimen Improved the Survival of Adult Patients With T-Cell Lymphoblastic Lymphoma After Allogeneic Peripheral Blood Stem Cell Transplantation

“…For pediatric patients, TBI-based regimen was superior to chemotherapy-based regimen with a lower CIR and a better OS 40 . While for adult patients, the benefit of lowering the relapse frequencies from TBI-based conditioning regimen was offset by its higher NRM as compared with BU-based regimen, resulting in a similar RFS and OS 41 – 43 . Kalaycio et al 44 comparatively analyzed the data of adult ALL patients with BU- and TBI-based regimens, which showed the incidence of initial relapse in extramedullary sites following BU was 50%, but only 9% following TBI ( P = 0.005), but no survival advantage in either event-free survival (EFS) ( P = 0.11) or OS ( P = 0.20) for TBI-based regimen.…”

How I Treat Adult Acute Lymphoblastic Leukemia in India

“…43 When the decision has been made to proceed with an alloSCT, conditioning using myeloablative regimens using total body irradiation (TBI) are preferred in patients with ALL. 44,45 At our center, for Ph−ve ALL, we reserve alloSCT in CR1 (myeloablative conditioning with fludarabine-busulfan) for young (<50 years) and fit patients with one or more conventional high-risk features (high-risk cytogenetics, early thymic precursor [ETP] ALL) only when a matched sibling donor is available. In the absence of a matched sibling donor, these patients are usually treated in the high-risk arm of the BFM-95 protocol.…”