title: Therapy-related Ph+ leukemia after both bone marrow and mesenchymal stem cell transplantation for hypophosphatasia.
abstract: Bone marrow (BM) transplantation (BMT) is one of the treatment strategies for congenital metabolic disease, but leukemia secondary to intensive cytoreductive treatment is a major concern. Besides BM cells, mesenchymal stem cells (MSC) are also used for transplantation. An 8-month-old girl with hypophosphatasia underwent transplantation of haploidentical BM cells followed by two transplants of MSC obtained from her father to facilitate osteogenesis. Fludarabine(Flu)/cyclophosphamide (CPA)/anti-thymocyte globulin were used for myeloablative conditioning, but the patient developed therapy-related leukemia harboring t(9;22)(q34;q11.2); minor BCR-ABL (t-leukemia with Ph) at the age of 32 months. At the age of 40 months she underwent a second BM and third MSC transplant from the same donor. Thereafter, she achieved complete histological and molecular remission. The present case suggests that the combination of cytotoxic agents (Flu/CPA) and MSC led to t-leukemia with Ph as a consequence of chromosome instability and suppression of host anti-tumor immunity.
authors.affiliation: Division of Blood Transfusion, Shimane University Hospital, Shimane, Japan. ttaketani@med.shimane-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.forename: Rie
authors.initials: R
authors.lastname: Kanai
authors.forename: Mariko
authors.initials: M
authors.lastname: Abe
authors.forename: Seiji
authors.initials: S
authors.lastname: Mishima
authors.forename: Mika
authors.initials: M
authors.lastname: Tadokoro
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Katsube
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yuba
authors.forename: Hajime
authors.initials: H
authors.lastname: Ogushi
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
mesh_terms: D016465:Bone Marrow Purging / Q000009:adverse effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007014:Hypophosphatasia / Q000628:therapy*; D007223:Infant; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects*; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects; D019233:Retreatment; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine