[CD25 monoclonal antibody for GVHD prophylaxis in non-T-cell depleted haploidentical bone marrow transplantation for treatment of childhood leukemia].
OBJECTIVE
Allogeneic bone marrow transplantation (Allo-BMT) has improved long-term survival in children patients with refractory leukemia. For patients who do not have an HLA-identical sibling, the treatment option is limited. Using related mismatch donors or parental donors for Allo-BMT was at high risk for acute severe GVHD. The purpose of this study was to explore the effects of CD25 monoclonal antibody on reducing the incidence of severe acute GVHD in haploidentical bone marrow transplantation for the treatment of childhood leukemia.


METHODS
Ten children with leukemia received haplotype Allo-BMT from HLA two or three loci mismatched related donors. Most patients were classified as in high risk category. The donors of patients were given G-CSF (Lenograstim Chugai) 250 microg/day for seven doses prior to marrow harvest. The non-T-cell depleted haploidentical bone marrow was infused. In addition to combination of CSA, MTX, ATG (Fresenius Hemocare, Germany) and mycophenolate mofetil (MMF) for GVHD prophylaxis, CD(25) monoclonal antibody (Simulect, Novartis Pharma Switzerland) was administered to prevent acute severe GVHD.A total of 40 mg Simulect was given in two doses of 20 mg each by 30 min intravenous infusion 2 h before transplantation and day 4 after transplantation. The outcomes were compared with those of 8 children patients with leukemia who received haploidentical bone marrow transplantation without CD(25) antibody for GVHD prophylaxis.


RESULTS
All patients were engrafted and sustained full donor-type engraftment. 100% donors hematopoietic cells after transplantation was determined by cytogenetic evidence analysis. The median days of granulocyte exceeding 0.5 x 10(9)/L and pallets exceeding 20 x 10(9)/L were 19 and 22 days, respectively. Patients were monitored till up to days 100 for the sign of aGVHD. None developed the grade II-IV acute GVHD. However, the incidence of the grade II-IV acute GVHD in control group was 50% (P = 0.0147). Eight patients could be evaluated for chronic GVHD. All experienced chronic GVHD confined to the skin. The median follow-up duration was 12 months (range 9 - 24 months). Two patients died from transplant related mortality, one had patient relapsed disease and died. The remaining seven patients were alive in disease-free situation.


CONCLUSIONS
The use of Simulect in haploidentical bone marrow transplantation for the treatment of children patients with leukemia is effective for preventing acute severe GVHD and may reduce transplant-related mortality.
Chen
Hui-ren
HR
Department of Hematology, The General Hospital of PLA Air Force, Beijing 100036, China.
Ji
Shu-quan
SQ
Yan
Hong-min
HM
Wang
Heng-xiang
HX
Liu
Jing
J
Xue
Mei
M
Zhu
Ling
L
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods; D002648:Child; D005190:Family; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2