Humanized anti-CD25 monoclonal antibody for prophylaxis of graft-vs-host disease (GVHD) in haploidentical bone marrow transplantation without ex vivo T-cell depletion.
OBJECTIVE
To investigate the effects of a novel anti-IL-2 receptor (CD25) monoclonal antibody, basiliximab, on graft-vs-host disease (GVHD) and engraftment in haploidentical bone marrow transplantation (BMT).


METHODS
Thirteen consecutive high-risk leukemia patients (age 9-41) underwent haploidentical BMT with G-CSF-primed marrow as stem cells without ex vivo T-cell depletion. Basiliximab, along with a combination of cyclosporine (CSA), methotrexate (MTX), and mycophenolate mofetil (MMF), was used for GVHD prophylaxis. Immunophenotyping, limited-dilution assay, and colony-forming assays were used to measure the effect of basiliximab on the subsets of lymphocytes, cytotoxic T-lymphocyte precursors (CTLp), and hematopoietic cells.


RESULTS
All patients established successful trilineage engraftment with full donor chimerism. No patients developed grade II-IV acute GVHD. Patients who survived more than 12 months and were free of relapse showed limited chronic skin GVHD. Ten of 13 patients are currently alive with a Karnofsky performance score of 100% at median follow-up of 17 months (range 12-24 months). Basiliximab significantly decreased alloreactive CTLp by 10-fold to 100-fold in limiting-dilution assays. It had no effect on hematopoietic stem and progenitor cells as determined by in vitro colony-forming assays.


CONCLUSIONS
The addition of basiliximab to CSA, MMF, and MTX as GVHD prophylaxis effectively reduced severe lethal GVHD in haploidentical BMT. It is possible to selectively eliminate or reduce the number of alloreactive T cells with anti-CD25 antibody, which results in prevention of or a reduction in the severity of GVHD.
Research Institution Of Air Force Hematology PLA, Beijing, China.
Hui-Ren
HR
Chen
Shu-Quan
SQ
Ji
Heng-Xiang
HX
Wang
Hong-Ming
HM
Yan
Ling
L
Zhu
Jing
J
Liu
Mei
M
Xue
Chang-Qing
CQ
Xun
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000077552:Basiliximab; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007938:Leukemia / Q000628:therapy; D008212:Lymphocyte Depletion; D008297:Male; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab