(035) Clofarabine, melphalan and thiotepa reduced-intensity conditioning chemotherapy with post-transplant cyclophosphamide-based graft versus host disease prophylaxis for allogeneic stem cell transplant

Poster Abstract: Background/

Objectives:
Recent fludarabine shortages led to investigation of clofarabine as alternative therapy in conditioning chemotherapy regimens for patients receiving allogeneic stem cell transplant (allo-HSCT). Combination of thiotepa, melphalan, and clofarabine (TMC) has been described previously, with clofarabine doses ranging between 50 mg/m2 x 4 days and 20 mg/m2 x 5 days. We present our experience of utilizing clofarabine in combination with melphalan and thiotepa.

Methods:
This IRB approved retrospective analysis included patients over age 18 years undergoing allo-HSCT using TMC as conditioning chemotherapy. Patients were excluded if they received an allo-HSCT from umbilical cord donor source or received methotrexate-based graft vs. host disease (GVHD) prophylaxis.

Results:
Fifteen patients underwent allo-HSCT since 2022 using TMC chemotherapy conditioning. Median age was 60 years. 10 patients were male and 5 female. Ten patients had a diagnosis of acute leukemia, 4 had MDS, and 1 had CML. Median HCT-CI was 3. Modified Disease Risk Index was Low/Intermediate in 8 and High in 7 patients. Donor sources were MUD in 8 patients, MMUD in 2 patients, haploidentical in 3 patients and MRD/MMRD in 2 patients. Patients received reduced intensity conditioning (RIC) with clofarabine 30 mg/m2, melphalan (50-140 mg/m2) +/- Thiotepa (1-5 mg/kg). All patients received GVHD prophylaxis with post-transplant cyclophosphamide 50 mg/kg on days +3 and day + 4 post-HSCT. Additional GVHD prophylaxis starting day +5 included tacrolimus/sirolimus in 7 patients, and tacrolimus/sirolimus/rabbit ATG in 7 patients.

All patients engrafted neutrophils and platelets with a median time to engraftment of 19 days, and 17 days respectively. Thirteen patients are alive at a median follow-up of 159 days. Non-relapse mortality occurred in 2 patients (GI toxicity; CVA). All patients have 97% or higher reported donor chimerisms 30 days after allo-HSCT. Grade 2-4 GVHD was reported in 4 patients. Out of the 10 patients who were followed for more than 100 days, 4 developed limited stage chronic GVHD. Four patients experienced grade 3 or higher diarrhea suspected to be due to conditioning chemotherapy. Six patients reported nausea/vomiting, with 2 instances being grade 3 or higher. Four patients developed mucositis, 3 were grade 3 or higher. No instances of either sinusoidal obstructive syndrome (SOS) or capillary leak syndrome (CLS) occurred.

Conclusion:
Allo-HSCT with TMC RIC results in successful neutrophil and platelet engraftment comparable to historical cohort that received thiotepa, melphalan and fludarabine. Mortality, severe GVHD, and toxicity were also observed to be relatively low.

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