title: Phase I study of azacitidine following donor lymphocyte infusion for relapsed acute myeloid leukemia post allogeneic stem cell transplantation.
abstract: Donor lymphocyte infusion (DLI) without prophylactic immunosuppression has been used for relapsed AML after allogeneic stem cell transplant (allo-SCT). However DLI is associated with an increased incidence of acute Graft vs. Host Disease (aGVHD). In mice, administration of azacitidine (AzaC) on days 4, 6, 8, and 10 post DLI increases regulatory T cell (Treg) numbers and prevents GVHD without hindering Graft vs. Leukemia (GVL). Based on these findings, we conducted a phase 1 study of AzaC post DLI for AML relapse post allo-SCT. AzaC was administered on days 4, 6, 8 and 10 post-DLI. Dose escalation was done using a 3+3 design with three AzaC dose levels: 30mg/m(2) (level -1), 45mg/m(2) (level 1) and 75mg/m(2) (level 2). Three patients were treated in the 45mg/m(2) dose level and 5 patients were treated in the 75mg/m(2) dose level; no DLTs or grade 3-5 treatment related toxicities were observed. After a median follow-up of 5.2 months, no patients developed grade III-IV aGVHD and no patients died of aGVHD. Six out of 8 patients in the treatment group responded to treatment including two cytogenetic complete remissions, one hematologic complete remission, and three complete remissions with incomplete count recovery. In conclusion, administration of AzaC early post DLI is well tolerated and can potentially prevent GVHD after DLI. Further studies are required to evaluate the effect of azacitidine early post DLI on GVHD and GVL.
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States. Electronic address: aghobadi@wustl.edu.
authors: Armin
authors: A
authors: Ghobadi
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Jaebok
authors: J
authors: Choi
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Mark A
authors: MA
authors: Fiala
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Theresa
authors: T
authors: Fletcher
authors: Division of Biostatistics, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Jingxia
authors: J
authors: Liu
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Linda G
authors: LG
authors: Eissenberg
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Camille
authors: C
authors: Abboud
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Amanda
authors: A
authors: Cashen
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Ravi
authors: R
authors: Vij
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Mark A
authors: MA
authors: Schroeder
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Iskra
authors: I
authors: Pusic
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Keith
authors: K
authors: Stockerl-Goldstein
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Meagan
authors: M
authors: Jacoby
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Geoffrey
authors: G
authors: Uy
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: John
authors: J
authors: DiPersio
authors: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis MO, United States.
authors: Peter
authors: P
authors: Westervelt
mesh_terms: D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D020544:Graft vs Leukemia Effect; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D033581:Stem Cell Transplantation / Q000009:adverse effects; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D001374:Azacitidine
keywords: Acute myeloid leukemia; Allogeneic stem cell transplantation; Azacitidine; Donor lymphocyte infusion; Graft versus host disease