Clinical characteristics of 15 children with juvenile myelomonocytic leukaemia who developed blast crisis: MDS Committee of Japanese Society of Paediatric Haematology/Oncology

Abstract

Summary Juvenile myelomonocytic leukaemia (JMML) is a rare haematopoietic stem cell disease of early childhood, which can progress to blast crisis in some children. A total of 153 children diagnosed with JMML were reported to the Myelodysplastic Syndrome Committee in Japan between 1989 and 2007; 15 of them (9·8%) had 20% or more blasts in the bone marrow (blast crisis) during the disease course. Blast crisis occurred during observation without therapy (n = 3) or with oral 6‐mercaptopurine treatment (n = 9) and in relapse after haematopoietic stem cell transplantation (HSCT; n = 3). Six patients had a complex karyotype (5 including monosomy 7) and an additional three patients had isolated monosomy 7 at blast crisis. Seven patients received HSCT after blast crisis and four of them achieved remission. Eleven out of the 15 patients died; the cause of death was disease progression in 10 patients and transplant‐related complication in one patient. In summary, patients with blast crisis have poor prognosis and can be cured only by HSCT. The emergence of monosomy 7 and complex karyotype may be characteristic of blast crisis in a substantial subset of children.

Blastic transformation of juvenile myelomonocytic leukemia caused by the copy number gain of oncogenic KRAS

“…In the present case, blastic transformation occurred 1.5 years after diagnosis while the patient was still under oral 6‐MP therapy. Although our patient was successfully treated with systemic chemotherapy followed by HSCT, JMML in the blastic phase is known to be associated with high mortality . Therefore, it is expected that the mechanism and risk factors of blastic transformation will be clarified in the near future.…”

“…The clinical course of JMML is heterogeneous, ranging from spontaneous regression to a highly aggressive phenotype that requires timely hematopoietic stem cell transplantation (HSCT). Previous studies have reported several cases of JMML developing blastic transformation during an indolent clinical course, but the underlying mechanism of transformation has not been well understood . Here we report a case of JMML with blastic transformation caused by additional copy number gains (CNGs) of the KRAS mutant allele.…”

Sustained remission with azacitidine monotherapy and an aberrant precursor B‐lymphoblast population in juvenile myelomonocytic leukemia

“…The finding of an aberrant B‐lymphoblast population was another unique feature for our patient. The blast phase of JMML is typically myeloid, similar to chronic myeloid leukemia (CML), though B‐ and T‐cell transformations have been reported . In CML, a minority of patients will have a small abnormal B‐lymphoblast population that does not necessarily signify impending progression to a B‐lymphoblastic phase .…”

Diagnosis and treatment of juvenile myelomonocytic leukemia

“…It is known that JMML can progress to blast crisis (≥20% blasts in BM). In a Japanese study, Honda et al . reported that 15 (9.8%) of 153 patients with JMML had progressed to blast crisis, and Luna‐Fineman et al .…”

“…found that an abnormal clone already existed in approximately 5% of BM cells at diagnosis in all the patients who initially possessed a normal karyotype but acquired chromosomal abnormalities 1–14 months after treatment with 6‐mercaptopurine (6MP). Moreover, Honda et al . reported that 12 of 15 patients with developing blast crisis had a normal karyotype at diagnosis, but that karyotypic abnormalities were detected in 10 of 15 children at the time of blast crisis.…”