Results of differential treatment of children with juvenile myelomonocytic leukemia with 13-cis retinoic acid and low dose cytosine-arabinoside

Prognosis of patients with juvenile myelomonocytic leukemia not undergoing allogeneic hematopoietic cells transplantation (SCT) is dismal and not affected by any cytotoxic chemotherapy. Differentiating therapy is an attractive approach in JMML, due to ability of JMML cells to differentiate and die under influence of treatment with various agents in vitro. We report results of first-line treatment of 14 patients with JMML with 13-cis retinoic acid (RA) 100 mg/m2 daily peroral intake and low dose Ara-C - 25 mg/m2 daily for 10 days monthly. Complete remission (CR) or hematological improvement (HI) was obtained in 7 patients (50%). Four patients (median age at disease manifestation 5 months, median level of HbF —6,2%) achieved CR after a median of 9 cycles of therapy; in 3 patients the best response was HI (age at disease manifestation - 5; 7 and 46 months, HbF — 4,2; 8,0 and 51,7%) after 2; 3 and 5 cycles. Three out of 4 patients with CR are alive and have been in CR for 10; 17 and 30 months after start of therapy, acute lymphoblastic leukemia developed in one patient after 84 months of CR. Two patients with HI are still receiving treatment and have been in stable condition for 10 months after the initiating therapy, while 1 patient died after 8 months of therapy from catheter-related sepsis. The progression of the disease despite the treatment was registered in 7 patients (median age at disease manifestation 16,3 months, median HbF — 35,4%). We conclude that 13-cis RA in combination with low dose AraC may be useful in the treatment of patients younger than 1 year with low level of HbF, although the general paradigm of treatment of JMML with SCT remains unchanged.

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