Prospective phase II study of prophylactic low-dose azacitidine and donor lymphocyte infusions following allogeneic hematopoietic stem cell transplantation for high-risk acute myeloid leukemia and myelodysplastic syndrome

• Published in: Bone marrow transplantation (Basingstoke) Vol. 54; no. 11; pp. 1815 - 1826
• Main Authors: Guillaume, Thierry, Malard, Florent, Magro, Leonardo, Labopin, Myriam, Tabrizi, Reza, Borel, Cécile, Chevallier, Patrice, Vigouroux, Stéphane, Peterlin, Pierre, Garnier, Alice, Rubio, Marie-Thérèse, Huynh, Anne, Milpied, Noël, Moreau, Philippe, Gaugler, Béatrice, Yakoub-Agha, Ibrahim, Mohty, Mohamad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2019; Nature Publishing Group
• Subjects: 692/308/2779; 692/308/2779/109/1941; Acute myeloid leukemia; Adolescent; Adult; Aged; Allografts; Analysis; Antimitotic agents; Antineoplastic agents; Azacitidine - administration & dosage; Cancer; Cell Biology; Clinical trials; Disease-Free Survival; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Human health and pathology; Humans; Incidence; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Life Sciences; Lymphocyte Transfusion; Lymphocytes; Maintenance; Male; Medicine; Medicine & Public Health; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - therapy; Myeloid leukemia; Prospective Studies; Public Health; Risk; Risk Factors; Stem cell transplantation; Stem Cells; Survival Rate; Transplantation; Transplants & implants; Unrelated Donors; France; relapse prevention; azacitidine; donor lymphocyte infusion
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/s41409-019-0536-y

Thirty patients, with high-risk acute myeloid leukemia (AML, n  = 20) or myelodysplastic syndrome (MDS, n  = 10), were enrolled in a phase II trial entailing prophylactic post-transplant azacitidine (AZA) plus escalated doses of donor lymphocyte infusion (DLI). The median number of AZA cycles was 5 (1–12) with 10 patients (33%) completing the 12 projected cycles. DLI were performed in 17 patients: 5 received one DLI, 2 received 2 DLI and 8 received 3 infusions. AZA was well tolerated, but discontinued in 20 patients primarily due to graft-versus-host disease (GvHD) and relapse. The cumulative incidence (CI) of grade 1–3 acute GvHD was 31.5% and the chronic GvHD CI was 53% at 2 years. At a median follow-up of 49 months (27–63), 18 patients are alive. The overall and disease-free survivals are 65.5% (CI 95% = 48.2–82.8) at 2 years. Cause of death was mainly relapse for 9 patients. The median time to relapse was 7 months (2.5–58) and the cumulative incidence of relapse at 2 years was 27.6% (CI 95% = 12.8–44.6). These results confirm that AZA is well tolerated as a prophylactic treatment to reduce the risk of post-transplantation relapse and compared favorably to those of patients who receive no post-transplant maintenance.