“Flipped” Pretransplant Conditioning Regimens and GVHD Incidence

By Cecilia Brown - October 5, 2022

Patients receiving a pretransplant conditioning regimen of fractionated total body irradiation followed by fludarabine had a greater incidence of graft-versus-host disease (GVHD) than patients treated with fractionated total body irradiation followed by cyclophosphamide, according to a recent study.

Vincent Mendiola, MD, MPH, of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, and colleagues conducted the research and presented their findings at the Tenth Annual Meeting of the Society of Hematologic Oncology.

Dr. Mendiola and colleagues said they conducted the study because conditioning regimens of fludarabine followed by fractionated total body irradiation are “well-studied” in allogeneic hematopoietic stem-cell transplantation (HSCT), but there has been little research on use of fludarabine after fractionated total body irradiation.

The researchers conducted the retrospective chart review of 26 patients with hematologic malignancies who underwent allogeneic HSCT at a single center. Transplants from matched unrelated donors were the most common (38.5%), followed by haploidentical stem cells (34.6%) and matched sibling donor transplants (26.9%).

The median patient age was 47.5 years (range, 18-99 years), 65% of patients were male, and 65% were Hispanic. Most patients had acute lymphocytic leukemia (50%) or acute myeloid leukemia (42.3%). Most patients (73.1%) had an intermediate disease risk index, while 23.1% had a high disease risk index. All patients were diagnosed between January 2015 and February 2021. Most patients (65.4%) were in their first complete remission (CR) before transplant, while 23.1% were in their second or third CR.

Fractionated total body irradiation followed by fludarabine was administered to 84.6% of patients, and fractionated total body irradiation followed by cyclophosphamide was administered to 15.4% of patients. Cytoxan/tacrolimus/mycophenolate was the most common GVHD prophylaxis (80.8%), followed by tacrolimus/methotrexate (19.2%).

Acute GVHD of any grade and any type occurred in 77.3% of patients receiving the fludarabine regimen, while it occurred in 50% of patients receiving the cyclophosphamide regimen (P=.29). Grade III acute gut GVHD occurred in 15.4% of patients who received the fludarabine regimen and in none of the patients who received the cyclophosphamide regimen. Chronic gut GVHD occurred in 50% of patients receiving the fludarabine regimen and in none of the patients receiving the cyclophosphamide conditioning regimen. Chronic GVHD of any grade and any type occurred in 27.3% of patients who underwent conditioning with the fludarabine regimen and in 50% of patients receiving the cyclophosphamide regimen (P=.56).

The 3-year overall survival (OS) rate since transplant in all patients was 81%, with nonrelapse mortality occurring in 15.4% of patients. The 3-year event-free survival (EFS) rate in all patients was 72.5%, with relapse occurring in 7.7% of patients.

When divided by conditioning regimen type, the 2-year OS rate was 77.5% in patients receiving the fludarabine regimen and 100% in patients receiving the cyclophosphamide regimen (P=.38). The EFS rate was 77.5% in patients receiving the fludarabine regimen and 50% in patients receiving the cyclophosphamide regimen (P=.24).

“Given most of our patients had intermediate/high [disease risk index], the OS and EFS using both flipped conditioning regimens were generally similar and appreciable,” Dr. Mendiola and colleagues concluded. “However, more any type/grade, acute GVHD and [grade] III acute/chronic gut GVHD cases were identified in the [fractionated total body irradiation followed by fludarabine] population, although not significant.”

Mendiola V, Chen D, Rodman J, Yaghmour G. Outcomes using “flipped” conditioning regimens (fractionated total body irradiation then fludarabine or cyclophosphamide) for allo-HSCT at the University of Southern California, a retrospective study. Poster ALL-331. Presented at the Tenth Annual Meeting of the Society of Hematologic Oncology; September 28-October 1, 2022; Houston, TX.

Post Tags:SOHO 2022: Focus on GVHD
Advertisement
Advertisement