Therapy-related Ph+ leukemia after both bone marrow and mesenchymal stem cell transplantation for hypophosphatasia

Pediatr Int. 2013 Jun;55(3):e52-5. doi: 10.1111/ped.12012.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Purging / adverse effects
  • Bone Marrow Transplantation / adverse effects*
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Hypophosphatasia / therapy*
  • Infant
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / etiology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Mesenchymal Stem Cell Transplantation / adverse effects*
  • Myeloablative Agonists / administration & dosage
  • Myeloablative Agonists / adverse effects
  • Retreatment
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives

Substances

  • Myeloablative Agonists
  • Cyclophosphamide
  • Vidarabine
  • fludarabine