Long-Term Survival and Late Deaths in 2-Year Survivors of Myeloablative Allogeneic Hematopoietic-Cell Transplantation for Hematologic Disorders.

Allogeneic hematopoietic-cell transplantation (HCT) is potentially curative therapy for a variety of hematologic disorders. Most deaths after HCT occur within the first 2-years, due to relapse, acute or chronic graft-versus-host disease (GVHD) or regimen-related toxicities. Among allogeneic HCT recipients who had survived in complete remission (CR) for at least 2-years following transplantation, we (1) investigated their long-term survival, (2) evaluated risk factors for late mortality, and (3) compared their long-term survival to that of the general population. Our study cohort consisted of 10,632 patients who received a myeloablative allogeneic HCT through 2003, surviving in CR for 2-years after transplant reported to the CIBMTR. The median followup of our cohort was 9 (range, 2-31) years; 37% of survivors were followed for ≥10-years and 12% for ≥15-years. Diagnoses included acute myeloid leukemia (AML, N=4,017), acute lymphoblastic leukemia (ALL, N=2,895), myelodysplastic syndrome (MDS, N=930), lymphoma (N=619) and severe aplastic anemia (SAA, N=2,171). Donors were HLA-identical siblings (72%), unrelated donors (22%) or other related donors (6%). Patients <20 years of age comprised 45% of our cohort and 17% were >40 years at HCT. Total body irradiation (TBI) based conditioning regimens were given to 60% of patients. Most frequent conditioning regimens were cyclophosphamide + TBI for AML, ALL and lymphoma, busulfan + cyclophosphamide for MDS and cyclophosphamide alone for SAA. Acute grade 2-4 GVHD had occurred in 39% and 43% patients experienced chronic GVHD by 2-years after HCT. Probability of overall survival at 10-years after HCT was 84% (95% CI, 82-85%) for AML, 84% (82-85%) for ALL, 80% (77-83%) for MDS, 84% (81-87%) for lymphoma and 92% (91-93%) for SAA. Disease relapse was the most common cause of death for AML, ALL, MDS, and lymphoma while GVHD was the most common cause of death for SAA. The cumulative incidence of relapse at 10-years post-HCT was 10% (9-11%) for AML, 9% (8-10%) for ALL, 10% (8-12%) for MDS and 6% (4-8%) for lymphoma. Older age at HCT and chronic GVHD were both associated with greater late mortality for all diseases in Cox-regression analyses that accounted for important patient, disease and transplant related factors (Table). Furthermore, some risk factors were associated with increased mortality for specific diseases only, including: more advanced disease (AML, ALL), peripheral blood as graft source (ALL), acute GVHD (MDS and SAA), unrelated donor (lymphoma) and longer time from diagnosis (SAA). Overall survival rates at 10-years post-HCT for patients with and without chronic GVHD were 79% and 89% for AML, 80% and 87% for ALL, 75% and 87% for MDS, 80% and 90% for lymphoma and 87% and 95% for SAA. At 15-years after HCT, the relative mortality of patients who had received HCT for AML, ALL, MDS and SAA remained significantly higher than in age-, race- and gender-matched normal populations. Mortality rates for lymphoma patients were not significantly different than those of the matched general population after 8-years post-HCT. Recipients of myeloablative allogeneic HCT for AML, ALL, MDS, lymphoma and SAA who remain in remission for at least 2-years have favorable subsequent long-term survival. Older age at HCT and chronic GVHD are important risk factors for late deaths in all diseases evaluated.

No relevant conflicts of interest to declare.