Abstract
Introduction: The outcome of adult acute lymphoblastic leukemia (ALL) patients with chemotherapy only is not promising and overall survival (OS) does not exceed 30%. Allogeneic Hematopoietic Stem Cell transplantation (allo-HSCT) in first or beyond complete remission (≥CR1) has shown a superior OS rate of approximately 50 % over conventional chemotherapy protocols. Total body irradiation plus Cyclophosphamide (TBI/Cy) and oral busulfan plus cyclophosphamide (BU/Cy) are commonly used myeloablative conditioning regimens in ALL. TBI-based conditioning regimen is considered the standard of care.
Aim: To compare the outcomes of allo HSCT using TBI/Cy and BU/Cy conditioning regimens in adult standard and high risk ALL patients in ≥CR1.
Material and methods: We retrospectively analyzed the outcome of TBI/Cy and BU/Cy myeloablative conditioning regimen (MAC). BU/Cy cohort included 33 patients (9 females & 24 males) with a median age of 28 years (19-42). Myeloablative BU oral dose was 16mg/kg/4 days & Cy dose was 120 mg/kg IV over 4 days. TBI/Cy cohort included 45 patients (14 females & 31 males) with a median age of 24 years (19-46). TBI dose was 12 Gy fractionated for 5 days & Cy dose was 120mg/kg IV over 4 days. Both cohorts underwent allo-PBSCT at Nasser Institute Hospital, Cairo, between 1997-2010 (TBI group) and 2010-2017 (BU group) (Table1). All patients received graft-versus-host disease (GVHD) prophylaxis using cyclosporine-A (3mg/kg/day IV) from day -1 and methotrexate (15 mg/m2 IV) on day + 1 then 10 mg/m2 IV on days +3, +6 and +11. Post-transplant neutrophil and platelet engraftment were defined by three successive days with absolute neutrophilic count >=1x 109/L and platelet count >=20 x 109/L (without transfusion).
Results:In the TBI arm, median time to neutrophil and platelet engraftment was 15 days (9-22) and 15 days (7-47), respectively vs. 14 days (10-22) and 12 days (10-21), respectively in the BU arm. 11/45 TBI patients (24.4 %) developed grade ≥2 acute-GVHD vs. 7/33 (21.2%) patients in the BU arm. Extensive cGVHD was reported in 8/45 (17.7 %) TBI arm vs. 6/33 (18%) patients in the BU arm. Limited cGVHD occurred in 5/45 (11.1%) TBI patients vs. 3/33 (9%) in the BU arm. Cumulative survival was 42.2 % and 15 months OS was 36.7% in the TBI arm vs. 63.6 % and 51.3 % in the BU arm (p= 0.02) (Figure 1). The incidence of sepsis and aGVHD as a cause of transplant related mortality (TRM) were significantly higher in the TBI arm vs. BU arm (p<0.001) (Table 2).
Conclusions: Preliminary data demonstrates thatoutcome of BU/Cy is comparable to TBI/Cy as MAC regimen for Allo SCT inadult ALL. With limitation of resources, standard and high risk ALL patients may benefit from allo PBSCT using irradiation-free conditioning regimen associated with lower incidence of sepsis and aGVHD as a cause of transplant related mortality.
No relevant conflicts of interest to declare.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal