Approximately one-third of patients with TP53-mutated acute leukemias or myelodysplastic syndromes (MDS) who underwent hematopoietic stem cell transplantation (HSCT) developed limited or extensive chronic graft-versus-host disease (GVHD).
Amrita Desai, MD, of the City of Hope National Medical Center, and colleagues conducted the research and presented the results at the 64th American Society of Hematology Annual Meeting and Exposition.
They retrospectively studied 99 patients with TP53-mutated acute myeloid leukemia (48.5%), acute lymphoblastic leukemia (23.2%), or MDS who underwent HSCT between January 2015 and December 2021 with mobilized peripheral blood stem cells as the graft source. The median patient age was 61 years and 62.6% of patients were male.
Most patients (63.6%) had a high or very high disease risk index score. The patients had matched unrelated donors (40.4%) or matched sibling donors (38.4%). Most patients (64.6%) received reduced intensity conditioning with fludarabine and melphalan, whereas the remaining 35.4% received radiation-based myeloablative conditioning. Most patients (72.7%) received GVHD prophylaxis with tacrolimus/sirolimus, whereas 27.3% received post-transplant cyclophosphamide-based prophylaxis.
The 1-year overall survival rate was 48.4%, with a disease-free survival rate of 36.9%. The cumulative incidence of relapse was 36.2%, and the nonrelapse mortality rate was 27%. The cumulative incidence of grade II-IV acute GVHD at day 100 was 37.4%, and the cumulative incidence of grade III-IV acute GVHD at that time was 17.6%. The cumulative 1-year incidence of limited chronic GVHD was 33.8%, and the cumulative 1-year incidence was 31.2% for extensive chronic GVHD.
“Outcomes of TP53-mutated patients undergoing [reduced intensity conditioning with fludarabine and melphalan] was comparable to patients with [a radiation]-based [myeloablative conditioning] regimen, regardless of GVHD prophylaxis intensity,” Dr. Desai and colleagues concluded. “Our data provide insight on possible strategies for patient selection and optimization of pre-/post-[HSCT] management and indicate that improving transplant outcomes in patients with TP53-mutated acute leukemias or MDS remains an unmet need.”
Desai A, Sandhu KS, Koller PB, et al. Outcome of patients undergoing hematopoietic cell transplantation for TP53-mutated acute leukemias and MDS: effect of conditioning and GvHD prophylaxis regimens intensity. Abstract #4766. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.