CT-505 Fractionated Total Body Irradiation and Fludarabine Based Conditioning Regimen With Post-Transplant Cyclophosphamide (PTCy) for Mismatched Related and Unrelated Donors HCT for Acute Leukemia and MDS

Abstract

Allogeneic hematopoietic cell transplantation (HCT) remains the only curable treatment option for malignant hematological disorders. Conditioning regimen and GVL are both important in preventing graft rejection, relapses and GVHD. Choice of regimen depends on the diagnosis, patient characteristic, donor type, disease status and graft source. We present the outcome of patients undergoing FTBI/Fludarabine myeloablative conditioning for mismatched (related or unrelated) donor HCT and PTCy as GVHD prophylaxis. We plan to assess toxicity, outcomes and feasibility of this regimen. To evaluate HCT outcomes in patients undergoing mismatched (related and unrelated) donor transplantation with FTBI/ fludarabine based regimen with posttransplant cyclophosphamide (PTCy). Retrospective design. Single academic center. 155 patients underwent conditioning with FTBI/fludarabine with PTCy-based GVHD prophylaxis for hematologic malignancy at City of Hope from January 2015 to December 2021. All patients received radiation dose ≥ 1200 cGy with fludarabine and GVHD prophylaxis with PTCy 50 mg/kg on days +3 and +4, mycophenolate mofetil (MMF) on days +5 to +35, and tacrolimus or sirolimus started on day +5. Using EMRs, detailed information was obtained on baseline demographics, disease and transplantation characteristics like donor type, CMV status, ABO compatibility, acute & chronic GVHD and relapse data. The primary study outcome is overall survival. Secondary outcomes are GRFS, NRM, relapse, aGVHD, cGVHD and DFS. One hundred and fifty-five patients with median age of 38 (range 9-60) received FTBI/fludarabine based conditioning with PTCy. 56.8% of patients were male and 97.5% had a Karnofsky performance status ≥ 80 with a HCT comorbidity index ≥ 3 in 36.1% cases. The main reason for transplantation was ALL (46.5% cases) and AML (36.1%cases). The median donor age was 31 with 67.1% haplo donors & 32.9% mismatched unrelated. With a median follow-up of 24 months (range: 3 to 81), 100-day NRM was 1.9%, 2-year relapse rate was 11.8%, 2-year OS was 80.1%, and DFS 76.9%. FTBI/ fludarabine is well tolerated MAC regimen in mismatched donors with leukemia and MDS with low transplant related mortality and good outcomes. The study shows FTBI/fludarabine based conditioning regimen as a promising regimen which needs to be studied in future prospective randomized trials.