Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myeloproliferative neoplasm characterized by RAS pathway activation. Hematopoietic stem cell transplantation (HSCT) cures approximately 50% of children with JMML, but less than 10% of children who relapse survive beyond 2 years. Stieglitz and colleagues conducted the first-ever prospective clinical trial in relapsed or refractory JMML: an open-label phase II trial of the MEK inhibitor trametinib. Two patients had a clinical complete response, three had a clinical partial response, and two had stable disease. Three patients in remission continue to receive trametinib off-protocol, and four underwent successful HSCT; all are alive with a median follow-up of 24 months. These results raise the possibility that trametinib may be a new standard of care for JMML.

See article, p. 1590.

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