No abstract

Five patients with Fanconi anaemia have been treated by bone marrow transplantation from HLA identical donors. Only one patient survived for more than 3 years. She is now perfectly healthy with complete haematological reconstitution with chimaerism and disparition of chromosomal abnormalities. In contrast, four patients died of acute severe GVHD soon after grafting. In addition, all had signs of severe cyclophosphamide toxicity. This evolution could be explained by a special sensitivity of FA cells to alkylating agents and may indicate the need to modify the conditioning regimen in FA patients.

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as 'primary' (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the fur girls studied exhibited a polyclonal pattern of X-inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues. This study suggests that some MDS in childhood can exhibit particular features such as congenital anomalies associated with MDS, bone marrow hypoplasia, polyclonality, and spontaneous remission. It emphasizes that the FAB classification is not adequate for children and addresses the question of whether these MDS are always malignant diseases.

In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account.

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.