Juvenile myelomonocytic leukemia

Overview

A rare form of malignant bone marrow cancer that occurs in children and involves the proliferation of immature precursors of certain blood cells - myelocytes and monocytes. The proliferation is slower than in acute forms of the disease.

Symptoms

  • Failure to thrive
  • Lethargy
  • Fever
  • Persistent infections
  • Easy brusing
  • Bleeding
  • Bleeding gums
  • Enlarged liver
  • Enlarged spleen
  • Enlarged lymph nodes
  • Skin rash
  • Small yellowish skin tumors
  • Brown skin spots

Causes

Research on predisposing factors isn't conclusive but points to some combination of viruses (viral remnants have been found in leukemic cells), genetic and immunologic factors, and exposure to radiation and certain chemicals. Pathogenesis isn't clearly understood, but immature, nonfunctioning WBCs appear to accumulate first in the tissue where they originate (lymphocytes in lymph tissue, granulocytes in bone marrow). These immature WBCs then spill into the bloodstream and from there infiltrate other tissues, eventually causing organ malfunction because of encroachment or hemorrhage. Acute leukemia is more common in males than in females, in whites (especially people of Jewish descent), in children (between ages 2 and 5; 80% of all leukemias in this age-group are ALL), and in people who live in urban and industrialized areas. Acute leukemia accounts for 20% of all adult leukemias. Among children, however, it's the most common form of cancer. Incidence is 6 out of every 100,000 people.

Diagnosis

The following criteria are required in order to diagnose JMML: All 3 of the following: - No Philadelphia chromosome or BCR/ABL fusion gene. - Peripheral blood monocytosis >1 x 109/L. - Less than 20% blasts (including promonocytes) in the blood and bone marrow (blast count is less than 2% on average) Two or more of the following criteria: - Hemoglobin F increased for age. - Immature granulocytes and nucleated red cells in the peripheral blood. - White blood cell count>1 x 109/L. - Clonal chromosomal abnormality (e.g., monosomy 7). - Granulocyte-macrophage colony-stimulating factor (GM-CSF) hypersensitivity of myeloid progenitors in vitro. These criteria are identified through blood tests and bone marrow tests. Blood tests: A Combined Blood Count (CBC) will be performed on a child suspected of having JMML and throughout the treatment and recovery of a child diagnosed with JMML.

Prognosis

Without treatment, the survival of children with JMML is approximately 5%. Only Hematopoietic Stem Cell Transplantation (HSCT), commonly referred to as a bone marrow or (umbilical) cord blood transplant, has been shown to be successful in curing a child of JMML. With HSCT, recent research studies have found the survival rate to be approximately 50%. Relapse is a significant risk after HSCT for children with JMML. It is the greatest cause of death in JMML children who have had stem cell transplants. Relapse rate has been recorded as high as 50%. Many children have been brought into remission after a second stem cell transplant.

Treatment

Systemic chemotherapy includes alkylating agents — usually chlorambucil, cyclophosphamide, vincristine, or fludarabine (singly or in combination) — and steroids (prednisone) when autoimmune hemolytic anemia or thrombocytopenia occurs. An advance in the treatment of CLL has been the emergence of the humanized monoclonal antibodies rituximab and alemtuzumab. Alemtuzumab acts as an antibody against the surface of CLL cells and is used when fludarabine fails. Rituximab, a monoclonal antibody, acts similiarly to alemtuzumab; studies are ongoing. When chronic lymphocytic leukemia causes obstruction or organ impairment or enlargement, local radiation treatment can be used to reduce organ size. Allopurinol can be given to prevent hyperuricemia, a relatively uncommon finding. Prognosis is poor if anemia, thrombocytopenia, neutropenia, bulky lymphadenopathy, and severe lymphocytosis are present.