Subacute and chronic myelomonocytic leukemia in children (juvenile CML). Clinical and hematologic observations, and identification of prognostic factors

Abstract

The clinical and hematologic characteristics of 38 children with subacute and chronic myelomonocytic leukemia (S & CMMOL) are described, and the prognostic significance of these characteristics as recorded at diagnosis is reported. The common and distinctive feature of these children was the excessive proliferation of cells of neutrophilic and monocytic series. The disease predominated in younger children, 95% were younger than 4 years, and boys were more affected than girls (22/16). The onset of the disease was heralded most often by acute or subacute symptoms. Splenomegaly was the most common physical finding at diagnosis. Leukocytosis was usually under 100 × 109/I. Monocytosis and granulocytosis were often associated with normoblastosis, and, in some cases, with moderate blastosis (≦30%). Severe anemia and marked thrombocytopenia were found in about one third of patients, increased fetal hemoglobin levels in 53%, and increased γ‐globulin levels in 50% of cases. The Philadelphia chromosome was absent in all blood and marrow cell karyotypes. Thirty‐three of 38 patients were treated with moderate or intensive chemotherapy, and in all cases treatment never resulted in a complete remission. Terminal acute leukemia occurred in 11 cases. Of the 38 patients, 29 have died (median survival time, 16 months). Initial characteristics predicting a short survival (log‐rank test) included: older age (≦2 years) (P < 0.001), hepatomegaly (P < 0.05), bleeding (P < 0.001), thrombocytopenia (P < 0.01), high counts of blasts and normoblasts in peripheral blood (P < 0.01, P < 0.01). Sex, infections, cutaneous manifestations, lymphadenopathy, degree of splenomegaly, hemoglobin levels, fetal hemoglobin, leukocyte counts, percent of blasts in bone marrow, and serum γ‐globulin levels were of no prognostic value. When survival was plotted on a semilogarithmic scale, a change in death rate was evident at the second year of survival suggesting that there may be two subgroups of patients with myelomonocytic picture, one with very rapid, and another with a much slower rate of mortality. A stepwise discriminant‐function analysis was performed in an attempt to distinguish between those children who lived ≦2 years and those who lived longer. A linear combination of variables which best discriminated between these two subgroups was found. Nearly all patients could be classified as a short‐survivor or long‐survivor on the basis of age and platelet, blast, and normoblast counts in peripheral blood. This discriminant function may be used for the estimation of prognosis and, accordingly, for the selection of the appropriate therapy of new cases.

Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia

“…In other laboratory parameters, hypergammaglobulinemia can also be noted. 11 Karyotype analysis in JMML, by definition, must be negative for the Philadelphia chromosome t(9;22). There are no consistently recurring chromosomal translocations noted in JMML.…”

“…11,27 Owing to infiltration by relatively normal-appearing monocytes and macrophages into nonhematopoietic organs, JMML patients can also present with secretory diarrhea or bloody diarrhea, as well as pulmonary abnormalities or pulmonary failure, from frequent infiltration into the lungs and gastrointestinal tract. 28 Central nervous system involvement is quite rare.…”

“…In the 1980s, it was most commonly known as juvenile chronic myelogenous leukemia, but other names ascribed to this disease in the past included juvenile chronic granulocytic leukemia, chronic and subacute myelomonocytic leukemia, CMML of childhood, infantile monosomy 7 and monosomy 7 syndrome. [10][11][12][13][14][15] Some argued that it should be classified as a childhood form of MDS. 16 But, similar to 'adult-type' CMML, this disease clearly had some characteristics of an MPD.…”

Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7

“…These children have most often been referred to as juvenile chronic myeloid leukemia (JCML) in the British and American literature, 7,8 whereas others have favored the FAB term CMML. 4,[9][10][11] An International Working Group concluded that the different terminology did not reflect the existence of different disorders and proposed the term juvenile myelomonocytic leukemia (JMML). The term has attained international acceptance 6,[12][13][14] and will be used throughout this paper.…”

Transient monosomy 7

“…All 3 de novo cases occurred in children age Ͻ than 2 years. The prognosis of MDS is somewhat better in very young children, 20 and Bader-Meunier et al recently reported spontaneous hematologic disease remissions in three children with Noonan syndrome-associated chronic myelomonocytic leukemia. 21 None of their patients had monosomy 7.…”