Comparison of Myeloablative versus Reduced-intensity Conditioning Regimens in Allogeneic Stem Cell Transplantation Recipients with Acute Myelogenous Leukemia with Measurable Residual Disease-Negative Disease at the Time of Transplantation: A Retrospective

Collaborative Research Study Published in Transplantation and Cellular Therapy
Sarfraz Ahmad
Rushang D. Patel
Juan Carlos Varela
Shahram Mori

Blood and Marrow Transplant Program
AdventHealth Cancer Institute

James Yu¹, Yuan Du², Sarfraz Ahmad³, Rushang D. Patel⁴, Juan Carlos Varela⁴, Chung-Che Chang⁵, Shahram Mori⁴

¹Department of Internal Medicine, ²Research Institute, 3Gynecologic Oncology Program, 4Blood and Marrow Transplant Center, 5Department of Pathology and Laboratory Medicine, AdventHealth Hospital, AdventHealth Cancer Institute, Orlando, FL 32804

Summary
The ideal conditioning intensity in allogeneic hematopoietic stem cell transplantation (HSCT) is evolving. Previous prospective studies comparing myeloablative conditioning (MAC) versus reduced-intensity conditioning (RIC) regimens in adults with acute myelogenous leukemia (AML) have shown mixed results. In many of these studies, patients were not stratified based on measurable residual disease (MRD).

We evaluated the effect of conditioning intensity on the outcomes of AML patients in complete remission (CR) with flow cytometry evidence of MRD negativity. A total of 135 patients age 20 to 75 years with AML in CR1 or CR2 and flow cytometry evidence of MRD negativity who underwent allogeneic HSCT at our center between 2011 and 2019 were evaluated. We compared overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), relapse, and acute and chronic graft-versus-host disease (GVHD) in recipients of MAC (n=89) and RIC (n=46).

Although the patients receiving RIC were older (62 versus 51 years; p<0.0001), there were no statistically significant differences between the groups in terms of Eastern Cooperative Oncology Group and European Leukemia Network risk criteria and disease status (CR1 or CR2) at the time of transplantation. At a median follow-up of 24.6 months, no statistically significant differences in OS (hazard ratio [HR], 0.78; 95% confidence interval [CI] 0.42 to 1.42, p=0.411) or RFS (HR, 1.004; 95% CI, 0.48 to 2.09, p=0.99) were identified. The cumulative incidence of NRM (HR, 0.595; 95% CI, 0.24 to 1.48; p=0.2644) and relapse (HR, 1.007; 95% CI, 0.45 to 2.23; p=0.9872) was not different between the 2 groups. Grade II-IV and grade III-IV acute GVHD were more frequent in the MAC group (39.3% versus 19.9% [p=0.018] and 19.3% versus 2.3% [p<0.001], respectively), as was moderate/severe chronic GVHD (23.6% versus 15.8%; p=0.038).

Our data indicate that conditioning intensity did not appear to affect OS, RFS, NRM, and relapse risk in patients with MRD-negative AML as measured by flow cytometry. RIC resulted in less severe acute and chronic GVHD.

Highlights

• The ideal conditioning intensity in allogeneic HSCT in patients with MRD negativity is evolving.
• At a median follow-up of 24 months, no significant differences in OS and RFS were noted between patients receiving MAC and those receiving RIC with flow cytometry evidence of MRD negativity.
• The rates of grade III-IV acute GVHD and moderate/severe chronic GVHD were higher in the MAC group compared with the RIC group.
• RIC may be an option in younger patients without evidence of MRD, although further prospective randomized trials with longer follow-up will be needed to confirm our findings.

For more information or to refer a patient, call one of our Bone Marrow Transplant Nurse Navigators: Austin Carroll, BSN, RN; Anna Cullivan, BSN, RN; Vielka Hernandez, RN; or Heather Brown, RN, at Call407-303-2825.

Link to Article: https://www.astctjournal.org/article/S2666-6367(21)00864-2/pdf