Juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia is an aggressive neoplasia of early childhood. Only allogeneic stem cell transplantation (SCT) offers long-term cure. In the absence of an HLA-matched family donor, early SCT from an unrelated donor is the treatment of choice for most children. With clear evidence of a graft-versus-leukemia effect and a high post-transplant relapse rate, the outcome of SCT depends, in part, on the management of immunosuppression during the procedure. The impact of pretransplant cytoreductive treatment, such as intensive chemotherapy, splenectomy, or 13-cis retinoic acid, is unclear. Hypersensitivity for granulocyte-macrophage colony-stimulating factor and pathologic activation of the Ras/MAPK pathway play an important role in the pathophysiology of juvenile myelomonocytic leukemia and provide the opportunity for several novel therapeutic approaches.