Abstract
Patients with high-risk hematolymphoid malignancies who relapse or who do not achieve a complete remission to induction chemotherapy generally do not achieve long-term survival when treated with the best available non-transplant therapies. The benefit of allogeneic hematopoietic cell transplantation has been well described for patients in first complete remission, but less so for patients with advanced disease. We report the long-term follow-up of 131 patients with leukemia or lymphoma who received an HLA-matched related donor transplant following myeloablative conditioning with fractionated total body irradiation (1320cGy), etoposide (60mg/kg), and cyclophosphamide (60mg/kg). Eligibility for transplantation under this protocol included induction failure or high-risk disease that was beyond first remission. All patients were treated at a single institution. Diagnosis at the time of transplantation included ALL (n=57), AML (n=38), NHL (n=20), CML (n=10), MDS (4), JMML (n=2). Of the 95 patients with acute leukemia, 62 (65%) were not in remission at the commencement of the conditioning regimen. The median age at transplantation was 29 years (range 2–55). Seventy-four (56%) patients received unmanipulated bone marrow and the remainder received filgrastim-mobilized peripheral blood. Median follow-up of surviving patients was 8 years (range 0.3–17). The estimated five-year overall survival and event-free survival were 34% (95% confidence interval: 22–42%) and 32% (95% confidence interval: 24–39%), respectively. Leading causes of death included relapse (n=43), infection (n=11), acute graft-versus-host disease (n=8), respiratory failure (n=5) and hepatic veno-occlusive disease (n=4). Grade II–IV acute graft-versus-host disease occurred in 26% of patients. The cumulative incidence of extensive chronic graft-versus-host disease among those patients who survived beyond day 100 was 32%. These results indicate that patients with high-risk or advanced disease can experience long-term disease-free survival following an aggressive conditioning regimen that combines radiotherapy, etoposide, and cyclophosphamide. Relapse remains the most significant cause of mortality, and future efforts should focus on augmenting the graft-versus-malignancy effect.
Effects of Low-Dose Glucocorticoid Prophylaxis on Chronic Graft-versus-Host Disease and Graft-versus-Host Disease–Free, Relapse-Free Survival after Haploidentical Transplantation: Long-Term Follow-Up of a Controlled, Randomized Open-Label Trial