Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study

Abstract

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990–2010) during first or second complete remission (CR) to identify factors associated with longer post-relapse survival. Median time of post HCT relapse was 7 months (mo; range, 1–177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy (CT) alone (n=660), donor lymphocyte infusion (DLI)±CT (n=202; %), or 2nd alloHCT±CT ±DLI (n=369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 mo (range, <1–193). Survival for all patients was 23% at 1 year post-relapse; however, 3-yr overall survival correlated with time from HCT to relapse (4% for relapse during 1–6 mo period, 12% during 6 mo-2 yr, 26% during 2–3 yr, and 38% for ≥3 yr). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (RR 0.55 for 6 mo-2 yr, RR 0.39 for 2–3 yr, and RR 0.28 for ≥3 yr; p<0.0001) and a 1st HCT using reduced-intensity conditioning (RR=0.77; 95% CI 0.66–0.88, p=0.0002). In contrast, inferior survival was associated with age >40 yr (RR=1.42, 95% CI 1.24–1.64; p<0.0001), active GVHD at relapse (RR=1.25, 95% CI 1.13–1.39; p<0.0001), adverse cytogenetics (RR=1.37, 95% CI 1.09–1.71; p=0.0062), mismatched URD (RR=1.61, 95% CI 1.22–2.13; p=0.0008), and use of cord blood for 1st HCT (RR=1.23, 95% CI 1.06–1.42; p=0.0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 mo after their initial alloHCT had better survival and may benefit from intensive therapy such as 2nd alloHCT±DLI.

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

“…233 Outcome for patients relapsing after allogeneic HCT during first or second CR is particularly poor. 234,235 The Center for International Blood and Marrow Transplant Research (CIBMTR) recently found 234 3-year OS was 4%, 12%, 26%, and 38% for relapses within 1 to 6 months, 6 months to 2 years, 2 to 3 years, and $3 years after allogeneic HCT, respectively. Lower mortality was independently associated with longer time from HCT to relapse and a first HCT using RIC; and inferior outcome associated with age .40 years, active GVHD, adverse cytogenetics, mismatched unrelated donor, and use of cord blood for first HCT.…”

Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research

“…Although small numbers meant the poor and very poor groups had to be combined for analysis, we demonstrate a significant adverse effect of adverse cytoge-netics on relapse and RFS, underlying the importance of considering the pretransplantation karyotype on prognosis. The relapse incidence of 61% at 3 years in these patients, along with currently re ported poor outcomes in those who relapse after transplantation [15,16], indicates the urgent need for strategies directed at prevention of post-HSCT relapse.…”

Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation

“…In a recent CIBMTR (Center for International Blood and Marrow Transplantation Research) analysis, patients with relapsed acute myelogeneous leukemia after mismatchedunrelated or double cord transplantation had a worse PRS than recipients of a matched sibling or matched-unrelated HCT. 8 The available treatment options for relapsed patients include intensive chemotherapy, donor lymphocyte infusion (DLI), withdrawal of immunosuppression, second allogeneic HCT and supportive care. [9][10][11] Theoretical concerns regarding severe uncontrolled GVHD resulting from the use of unmanipulated DLI in HIDT patients may lead to a reluctance to use DLI following relapse of malignancy in HIDT than following conventional matched donor transplants.…”

“…In a recent CIBMTR (Center for International Blood and Marrow Transplantation Research) analysis, patients with relapsed acute myelogeneous leukemia after mismatchedunrelated or double cord transplantation had a worse PRS than recipients of a matched sibling or matched-unrelated HCT. 8 The available treatment options for relapsed patients include intensive chemotherapy, donor lymphocyte infusion (DLI), withdrawal of immunosuppression, second allogeneic HCT and supportive …”