Clin Pediatr Hematol Oncol.  2012 Oct;19(2):86-91.

Cytarabine Monotherapy as Bridging Treatment for Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia

• Suh WS
• Cho MS
• Lee JW
• Jang PS
• Chung NG
• Jeong DC
• Cho B
• Kim HK

Abstract

BACKGROUND
Mutations leading to hyperactivation of the RAS pathway play a critical role in the pathogenesis of juvenile myelomonocytic leukemia (JMML). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy, and the role of anti-leukemic treatment prior to HSCT is still controversial. In this study, we analyzed the response of cytarabine monotherapy as a bridging therapy for HSCT in children recently diagnosed with JMML.
METHODS
We retrospectively reviewed the medical records of patients with JMML at Seoul St. Mary's Hospital from December 2009 to April 2012.
RESULTS
A total 7 patients with JMML were diagnosed and treated with chemotherapy and HSCT. At presentation, all patients showed hepatosplenomegaly and the median leukocyte count was 41.9x109/L (range, 34.3-85.0), median monocyte count was 5.6x109/L (range, 2.7-26.3) and median fetal hemoglobin (HbF) was 13.5% (range, 2.8-42.7). Karyotypic abnormalities in bone marrow cells were noted in 2 cases. Three patients had mutation of NRAS and 2 patients had mutation of NF1. One of the patients with NF1 mutations had characteristic clinical features and familial history of neurofibromatosis. All patients were treated with non-intensive sequential cytarabine chemotherapy (70 mg/m2/day, I.V., 4-12 days) before HSCT and achieved complete hematologic response. All patients underwent unrelated (N=2) or familial mismatched (N=5) HSCT, and all patients successfully engrafted. All patients, except one who relapsed, are alive with leukemia free, although the duration of follow-up is short.
CONCLUSION
In our cohort of NRAS prevalent patients, non-intensive cytarabine monotherapy was effective as pre-transplant bridging treatment for JMML.

Keyword

Juvenile myelomonocytic leukemia; Cytarabine; RAS pathway; Mutation; Hematopoietic stem cell transplantation

MeSH Terms

Bone Marrow Cells
Child
Cohort Studies
Cytarabine
Fetal Hemoglobin
Follow-Up Studies
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
Leukemia
Leukemia, Myelomonocytic, Juvenile
Leukocyte Count
Medical Records
Monocytes
Neurofibromatoses
Retrospective Studies
Cytarabine
Fetal Hemoglobin