[Outcome of 46 children with refractory leukemia treated with unrelated donor hematopoietic stem cell transplantation].
OBJECTIVE
To evaluate the efficacy of matched unrelated donor hematopoietic stem cell transplantation (UDT) and influencing factors in children with refractory leukemia.


METHODS
Retrospective analysis was performed on clinical data of 46 consecutive children received UDT between Nov. 2002 and Dec. 2008. A 12-14 GY fractioned total body irradiation (TBI) was given to children with acute lymphoblastic leukemia (ALL). Busulphan based myeloablative regimen was applied to all the other patients. ATG (Fresenius) 15 - 20 mg/kg + low dose cyclosporine A oral [CSA, 8 - 12 mg/(kg * d) with serum trough levels 150 - 200 ng/ml] +/- methotrexate (without methotrexate for cord blood transplant) were administered as graft versus host disease (GVHD) prophylaxis. Mycophenolate mofetil [MMF, 20 - 30 mg/(kg * d)] was added for 13 CML after Jan 1, 2006 because of more severe GVHD was observed in this group.


RESULTS
The median age was 8.0 (2 - 17) years with the median follow up period of 23.5 (0.7 - 85) months. The estimated 3 years overall survival (OS) was 63.0%; 23.9% patients died of transplant related mortality, 13.0% patients died of leukemia relapse. Cytomegalovirus (CMV) infection recurred in 50% patients and hemorrhagic cystitis in 15.2% patients; 33.3% patients developed grade III-IV acute GVHD and 55.6% developed chronic GVHD (13.9% with extensive chronic GVHD). The OS was significantly different between the patients older (n = 20) and younger (n = 26) than 10 years (45.0% vs. 76.9%, P = 0.015) and among the patients with ALL (n = 13), CML (n = 18) and AML (n = 15) (38.4%, 66.7% vs.80.0%, P = 0.034). The OS in patient with high risk leukemia (n = 24) was lower than that in the patient with low risk leukemia (n = 22) (45.8% vs. 81.8%, P = 0.012). Except 8 cord blood transplant the OS of patients with HLA 6/6 high resolution completely matched (n = 16) and 1/6 mismatched (n = 16) bone marrow and peripheral blood stem cell transplants was significantly higher than patients with 2/6 mismatched (n = 6) UDT (75.0%, 75.0% vs. 16.7%, P = 0.007). But the OS was not significantly different between patients with grade 0-II acute GVHD and III-IV acute GVHD (60.0% vs. 66.7%, P = 0.494).


CONCLUSIONS
The outcome of UDT for Chinese children with refractory leukemia is encouraging. Patients younger than 10 years with 0-1/6 high resolution mismatched UDT had the best OS. The outcome of patients with myeloid and low risk leukemia is superior to those with other types of leukemia.
Chen
Jing
J
Shanghai Jiao Tong University School of Medicine Shanghai Children's Medical Center Hematology/Oncology Department, Shanghai 200127, China.
Luo
Cheng-juan
CJ
Jiang
Hua
H
Luo
Chang-ying
CY
Xue
Hui-liang
HL
Tang
Jing-yan
JY
Pan
Ci
C
Dong
Lu
L
Zhou
Min
M
Ye
Qi-dong
QD
Wang
Yao-ping
YP
Gu
Long-jun
LJ
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000601:surgery*; D008297:Male; D012189:Retrospective Studies; D014019:Tissue Donors; D016896:Treatment Outcome