title: Cord blood transplantation from unrelated donors for children with acute lymphoblastic leukemia in Japan: the impact of methotrexate on clinical outcomes.
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.
authors.affiliation: Division of Hematology Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nakamura-ku, Nagoya, Japan. kokato@nagoya-1st.jrc.or.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.forename: Ayami
authors.initials: A
authors.lastname: Yoshimi
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oki
authors.forename: Juinichi
authors.initials: J
authors.lastname: Hara
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nagatoshi
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Tokiko
authors.initials: T
authors.lastname: Nagamura-Inoue
authors.forename: Shunro
authors.initials: S
authors.lastname: Kai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azuma
authors.forename: Minoko
authors.initials: M
authors.lastname: Takanashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Isoyama
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kato
mesh_terms: D001792:Blood Platelets / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D009504:Neutrophils / Q000166:cytology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D061349:Unrelated Donors; D014916:Whole-Body Irradiation
chemical_list: D008727:Methotrexate