A third hematopoietic cell transplant (HCT) may be a viable treatment option for select patients who experience multiple relapses following their initial transplants, although high mortality rates are common, according to research presented at the 2021 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.
The use of a second HCT has increased among patients with hematologic malignancies who relapse after their initial HCT. The safety and efficacy of third HCTs has not been studied widely.
Researchers from the Fred Hutchinson Cancer Research Center (Seattle, WA) identified all patients with acute hematologic malignancies who received a third HCT at their institution between 2008 and 2018. Data on outcomes, complications and survival were collected to assess relapse and overall survival (OS) in this patient population.
In total, nine patients underwent a third HCT during the study period (median age at first HCT, 12 years; range, 5-6). The most common diagnosis was acute myeloid leukemia (n = 5); other diagnoses included acute lymphocytic leukemia (n = 2), myelodysplastic syndrome (n = 1) and undifferentiated acute leukemia (n = 1).
The median interval between first and second HCT was 1.6 years (range, 0.6-3.7), and the median interval between second and third HCT was 1.9 years (range, 0.1-12.6).
Eight patients required a third HCT due to relapse, at a median interval of 0.97 years (range, 0.4-11.8) after their second HCT. One patient underwent a third HCT due to graft failure. At the time of third HCT, Karnofsky/Lansky Performance Scale scores ranged from 60 to 100.
Six patients received nonmyeloablative, total body irradiation (TBI) conditioning prior to third HCT, with three patients receiving myeloablative conditioning (TBI, n = 2). Sources used included peripheral blood stem cells (n = 3), cord blood (n = 3) and marrow (n = 3).
In total, six patients entered the third HCT in complete remission (CR) by flow cytometry. In addition to the patient with graft failure, one patient with acute myeloid leukemia has 0.7% residual disease, and one patient with acute myeloid leukemia had aplasia following chemotherapy.
Prophylactic natural killer cells were administered post-transplant to all patients who underwent haploidentical HCT.
The researchers observed a median time to neutrophil engraftment of 16 days (range, 13-48). Seven patients developed acute graft-versus-host disease (GVHD), peaking at grade 2 (n = 6) or grade 3 (n = 1), and two developed chronic GVHD.
Seven patients died of relapse (n = 4) and non-relapse (n = 3) causes. Causes of death included chronic GVHD, veno-occlusive disease and multisystem organ failure. The median time from third HCT to death was 0.6 years (range, 0.1-2.6).
Two patients remained alive at the time of reporting. One patient (age at third HCT, 65 years) had acute myeloid leukemia, relapsed 7.6 years after second HCT, and achieved CR3 after nonmyeloablative unrelated donor transplant (follow-up, 13.1 years). The other patient (age at third HCT, 13 years) had acute lymphocytic leukemia, relapsed 1.6 years after second HCT, and achieved CR3 after nonmyeloablatve haploidentical transplant (follow-up, 10.9 years).
The relapse estimates after third HCT were 63% at 6 months, 63% at 1 year and 63% at 5 years. The OS estimates were 88% at 6 months, 63% at 1 year and 22% at 5 years.
“Given the poor outcomes, research trials investigating novel prophylactic post–HCT therapies and maintenance strategies may prolong disease remission and extend OS,” the researchers concluded.