Outcome of 46 children with refractory leukemia treated with unrelated donor hematopoietic stem cell transplantation / 中华儿科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy of matched unrelated donor hematopoietic stem cell transplantation (UDT) and influencing factors in children with refractory leukemia.</p><p><b>METHOD</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>