Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes—Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial

• Published in: Transplantation and cellular therapy Vol. 27; no. 6; pp. 483.e1 - 483.e6
• Main Authors: Scott, Bart L., Pasquini, Marcelo C., Fei, Mingwei, Fraser, Raphael, Wu, Juan, Devine, Steve M., Porter, David L., Maziarz, Richard T., Warlick, Erica, Fernandez, Hugo F., Soiffer, Robert J., Alyea, Edwin, Hamadani, Mehdi, Bashey, Asad, Giralt, Sergio, Geller, Nancy L., Leifer, Eric, Hourigan, Christopher S., Gui, Gege, Mendizabal, Adam, Horowitz, Mary M., Deeg, H. Joachim, Horwitz, Mitchell E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2021
• Subjects: Acute myelogenous leukemia; Adolescent; Adult; Aged; Conditioning intensity; Diterpenes; Follow-Up Studies; Hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute - therapy; Middle Aged; Myelodysplastic syndrome; Myelodysplastic Syndromes - therapy; Prospective Studies; Transplantation Conditioning; Transplantation, Homologous; Young Adult; Acute myelogenous leukemia; Hematopoietic cell transplantation; Myelodysplastic syndrome; Conditioning intensity
• ISSN: 2666-6367; 2666-6375; 2666-6367
• DOI: 10.1016/j.jtct.2021.02.031

•There was a higher rate of treatment-related mortality with myeloablative conditioning, but this was offset by a much higher rate of relapse with reduced-intensity conditioning.•There was no difference in survival following relapse based on conditioning intensity.•Myeloablative conditioning led to improved overall survival in patients with myelodysplastic syndrome or acute myelogenous leukemia who underwent allogeneic transplantation. Several prospective randomized trials comparing conditioning intensity before allogeneic hematopoietic cell transplantation (HCT) have been performed, with conflicting results. Although reduced-intensity conditioning (RIC) leads to lower treatment-related mortality (TRM), this is offset by higher rates of relapse. Long-term follow-up of randomized comparative trials are limited. Here we present long-term follow-up of a randomized comparison of myeloablative conditioning (MAC) compared with RIC before HCT for acute myelogenous leukemia (AML) or myelodysplasia (MDS). Long-term comparative analyses of overall survival, relapse, and relapse-free survival were performed. Patients age 18 to 65 years with <5% marrow myeloblasts were randomized to receive MAC (n = 135) or RIC (n = 137), followed by HCT from an HLA-matched donor. The primary endpoint of the trial was an 18-month pointwise comparison of overall survival. The analyses were performed using a proportional hazards model. The median follow-up of the entire cohort was 51 months. At 4 years, the transplant-related mortality (TRM) was 25.1% for MAC, compared with 9.9% for RIC (P < .001). Patients who received RIC had a significantly higher risk of relapse compared to those who received MAC (hazard ratio [HR], 4.06; 95% CI, 2.59 to 6.35; P < 0.001). Among the patients who relapsed after HCT, postrelapse survival was similar at 3 years (24% for MAC and 26% for RIC). Overall survival was superior for patients who received MAC compared to those who received RIC (HR, 1.54; 95% CI, 1.07 to 2.2; P = .03). Our data show that patients who received MAC were at higher risk of late TRM compared with those who received RIC; however, because of the exceedingly high rates of relapse in the RIC arm, overall survival remained significantly better for patients who received MAC. Among patients with MDS or AML eligible for either MAC or RIC regimens, long-term follow up demonstrates a survival advantage for patients who received MAC.