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Cord Blood Transplantation from Unrelated Donors for Children with Acute Lymphoblastic Leukemia in Japan: The Impact of Methotrexate on Clinical Outcomes
- Source :
- Biology of Blood and Marrow Transplantation. (12):1814-1821
- Publisher :
- American Society for Blood and Marrow Transplantation. Published by Elsevier Inc.
-
Abstract
- Cord blood transplantation (CBT) from an unrelated donor is recognized as one of the major treatment modalities in allogeneic stem cell transplantation (SCT) for children with hematologic malignancies. We analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified the risk factors for the transplant outcomes. From 1997 to 2006, 332 children with ALL underwent CBT from unrelated donors, 270 of which had no prior transplant. Their disease statuses at transplant were first complete remission (CR) (n = 120), second CR (n = 71), and more advanced stages (n = 75). As preconditioning for SCT, total body irradiation (TBI) was given to 194 patients and, for the prophylaxis of graft-versus-host disease (GVHD), methotrexate (MTX) was given to 159 patients. The cumulative incidents of neutrophil and platelet recovery (>20 K) were 88.5% and 78.4%, respectively. The incidents of grade II-IV, III-IV acute GVHD (aGVHD), and chronic GVHD (cGVHD) were 45.6%, 20.4%, and 19.2%, respectively, and treatment-related mortality was 22.6%. The 5-year event-free survival (EFS) and overall survival (OS) at CR1, CR2, and advanced status were 47.4%, 45.5%, 15.0%, and 63.7%, 59.7%, and 20.7%, respectively. Multivariate analysis revealed that MTX with calcineurin inhibitor (CNI) was associated with decreased incidence of grade II-IV GVHD (CNI alone: hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.06-2.83, P = .027; CNI + prednisolone (PSL), HR = 1.61, 95% CI = 1.03-2.50, P = .036), III-IV aGVHD (CNI alone: HR = 3.02, 95% CI = 1.55-5.91, P = 0.001; CNI + PSL, HR = 1.89, 95% CI = 0.93-3.83, P = .078), or cGVHD (CNI alone: HR = 1.78, 95% CI = 0.83-3.82, P = .143; CNI + PSL, HR = 2.44, 95% CI = 1.24-4.82, P = .01), compared with CNI alone or CNI + PSL. At an advanced stage of disease, GVHD prophylaxis with MTX + CNI is associated with improved OS compared with CNI alone (CNI alone: HR = 3.20, 95% CI = 1.43-7.15, P = .005; CNI + PSL, HR = 1.47, CI = 0.67-3.20, P = .332). Our retrospective study showed that CBT for children with ALL is feasible and GVHD prophylaxis with MTX + CNI is associated with significant favorable outcomes in prevention of aGVHD and cGVHD as well as survival advantage in advanced cases.
- Subjects :
- Blood Platelets
Male
medicine.medical_specialty
Transplantation Conditioning
Cord blood transplantation
Neutrophils
Graft vs Host Disease
Acute lymphoblastic leukemia
Gastroenterology
Japan
Risk Factors
Internal medicine
medicine
Humans
Child
Survival rate
Retrospective Studies
Transplantation
business.industry
Incidence (epidemiology)
Hazard ratio
Infant, Newborn
Hematology
Total body irradiation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Surgery
Calcineurin
Survival Rate
HLA
Treatment Outcome
Methotrexate
Child, Preschool
Prednisolone
Female
Cord Blood Stem Cell Transplantation
business
Unrelated Donors
Whole-Body Irradiation
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 10838791
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Biology of Blood and Marrow Transplantation
- Accession number :
- edsair.doi.dedup.....d599dce266056488c38e84309f7f7501
- Full Text :
- https://doi.org/10.1016/j.bbmt.2011.05.013