title: Low-dose methotrexate may preserve a stronger antileukemic effect than that of cyclosporine after modified donor lymphocyte infusion in unmanipulated haploidentical HSCT.
abstract: To compare the impacts of low-dose methotrexate (MTX) with cyclosporine (CSA) on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after haploidentical modified donor lymphocyte infusion (DLI). Fifty-five consecutive patients who had relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation (HSCT) and received modified DLI were retrospectively studied. Forty-one patients received CSA and 14 received low-dose MTX after DLI to prevent DLI-associated GVHD. The incidence of acute GVHD and grade 2-4 acute GVHD in MTX group showed a trend toward being higher than in CSA group (61.0% vs. 37.3%, p = 0.198 and 61.0% vs. 35.5%, p = 0.155). However, no significant difference in the incidence of grade 3-4 acute GVHD between two groups (p = 0.982) was observed. Moreover, compared with CSA, patients treated with MTX had lower re-relapse rate (38.1% vs. 80.8%, p = 0.029), better disease-free survival (DFS) (51.9% vs. 15.6%, p = 0.06), and higher absolute lymphocyte counts at 30, 45, 60, and 90 d after modified DLI (p < 0.05). This study suggested that after haploidentical modified DLI, low-dose MTX is at least as effective as CSA in the prevention of DLI-associated GVHD and probably allowed stronger GVL effect than CSA. This phenomenon was probably due to a direct antitumor effect and a better reconstitution of lymphocytes after modified DLI induced by low-dose MTX.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Yan
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Dai-hong
authors.initials: DH
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Jing-zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Feng-rong
authors.initials: FR
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D020544:Graft vs Leukemia Effect / Q000187:drug effects*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017710:Lymphocyte Transfusion / Q000009:adverse effects*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate
keywords: cyclosporine; graft-versus-host disease; graft-versus-leukemia effect; haploidentical hematopoietic stem cell transplantation; methotrexate; modified donor lymphocyte infusion