title: Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.
abstract: Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options.
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri; Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Ibraheem H
authors.initials: IH
authors.lastname: Motabi
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Armin
authors.initials: A
authors.lastname: Ghobadi
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Mark
authors.initials: M
authors.lastname: Schroeder
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Camille N
authors.initials: CN
authors.lastname: Abboud
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Amanda F
authors.initials: AF
authors.lastname: Cashen
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Keith E
authors.initials: KE
authors.lastname: Stockler-Goldstein
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Uy
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Peter
authors.initials: P
authors.lastname: Westervelt
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: jdipersi@dom.wustl.edu.
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000628:therapy*; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000628:therapy*; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents
keywords: AML; Allogeneic stem cell transplant; Chemotherapy; DLI; Hypomethylating agents; MDS