Publication Date:
2012-11-16
Description:
Abstract 955 Hematopoietic stem cell transplantation (HSCT) has improved survival of children with JMML considerably. Since it became apparent that JMML is a heterogeneous disease it has been questioned whether HSCT is the therapy of choice for all subtypes of JMML. Here we report the outcome of children with JMML registered to the retrospective or prospective studies of the European Working Group of MDS and JMML in Childhood (EWOG-MDS) with respect to clinical and mutational subtypes and presence or absence of HSCT. Among the 488 children with JMML studied by EWOG-MDS 43 patients (8.8%) were known to have Noonan syndrome, while 48 (9.7%) carried the clinical diagnosis of neurofibromatosis type 1 (NF1). Mutational analysis was carried out in 254 of the remaining 397 children. Somatic mutations in PTPN11, KRAS and NRAS were seen in 116, 46 and 47 children, respectively; 8 patients were noted to have germline CBL mutations in the absence of Noonan phenotype and 37 children with complete typing (N=203) had none of these abnormalities (all negative group). For the 51 patients with Noonan syndrome and/or germline CBL mutations overall survival at 5 years was 0.72 (0.58-0.86) irrespective whether HSCT was performed or not. A normal karyotype was observed in all but 3 of these 51 children. Normal chromosomal studies were also observed in 74%, 66% and 60% of the NF1, PTPN11 mutated and the all negative group, respectively. Interestingly, monosomy 7, and other aberrations were noted in 52% and 10% of KRAS mutated patients, respectively, but only in 7% and 5% of the NRAS mutated group (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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