CT-374: Outcomes of Allogeneic SC Transplant in Hematological Malignancy Patients Using a Busulfan 3 (9.6 mg/kg)-Based Conditioning Regimen

Abstract

Introduction Busulfan is often used in a myeloablative conditioning regimen at an IV dose of 12.8 mg/kg (BU4). A reduced intensity regimen using 6.4 mg/kg (BU2) is commonly used in older patients or those with comorbid diseases. Data on use of BU3 (9.6 mg/kg) based regimen are limited. At KFSHRC, the busulfan-based MAC regimen’s IV-BU dose is 12.8 mg/kg (BU4), but for those who do not tolerate the full MAC, BU can be reduced to 9.6 mg/kg (BU3). Objective To study the outcomes of hematological malignancy patients who received allo-HCT using BU3-based conditioning from matched related or unrelated donors. Methods A retrospective analysis of the KFSHRC-BMT Database for patients who received allo-HCT between October 2005 and December 2019. Results A total of 65 patients were identified: 47 AML (72.3%), 8 MDS (12.3%), 8 myelofibrosis (12.3%), and 2 CML (3.1%) patients. Median age was 52 years (16–66), and 35 (54%) were males. Pre-transplant status showed 57% were in CR1, 17% in CR2, and 3% not in CR. Fifty-seven (88%) patients received PBSC, 6 (9%) received BM source, and 2 (3%) received both PBSC and BM from HLA-matched related [N= 61 (93%)] or unrelated [N=4 (7%)] donors. Forty (61.5%) patients received Bu/Flu as a conditioning regimen, 14 (21.5%) received Bu/Cy, 7 (10.8%) received Bu/Flu/ATG, and 4 (6.2%) received Bu/Cy/ATG. GVHD prophylaxis consisted of cyclosporine and methotrexate for all patients. Fifty-two (80%) patients had comorbidities with comorbidity index between 1–2 in 29 (44.6%) patients and more than 2 in 23 (35.4%). Sixty-two (95%) patients engrafted; median ANC and platelet engraftment were 18 days. Acute GvHD grade II–IV and III–IV occurred in 29% and 14%, respectively. Chronic GvHD occurred in 55% and was extensive in 24% of patients. With median follow-up of 60.5 months, the 2 year- and 5 year-OS were 58.5% and 44.1% respectively. The 2 year- and 5 year-DFS were 52.9% and 44.5%, respectively. Cumulative incidence of relapse and NRM at 2 years were 29.5% and 17.4%, respectively. Day +100 TRM was 10.7%. Conclusions Allogeneic SCT using BU3-based regimen appears feasible to use in patients who are not suitable for a fully myeloablative (BU4) regimen. TRM, DFS, and OS rate were comparable to reports from studies using a BU4-based regimen, warranting prospective studies in these patients.