lndiao J Pcdiatr 1992; 59 : 443-448

Childhood Myelodysplastic Syndromes : Clinical Features, Cytogenetics and Prognosis R. Nair, U.A. Athale, R.S. Iyer, C.N. Nair, S.K. Pal, P.A. Kurkure, P.R. Kadam and S.It. Advani

Department of Medical Oncolog% Tata MemorialHospital, Pard, Bombay Sixteen children with myelodysplastic syndrome as defined by the FrenchAmerican-British co-operative group are presented. The mean age was 10.5 (2.5 to 16) years, with a male predominence. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Seven patients presented with refractory anaemia with excess blasts, six had refractory anemia with excess blasts in transformation, and three had chronic myelomonocyti c leukemia. Cytogenetic analysis done in 7 of the 16 patients, revealed karyotype abnormalities involving chromosomes 7, 8 and 17. One patient with Down's syndrome had karyotype of 47, XY, +21 (major clone) and 46, XY (minor clone). Five of these patients evolved to acute leukemia. The mean duration of survival was 5.5 months. Aggressive chemotherapy as a primary line of treatment induced remission in five out of six patients. Predominence of aggressive types of myelodysplastic syndromes in children and their good but short-lived response to aggressive chemotherapy suggests the need for early bone marrow transplantation following chemotherapy. Key words : Bone marrow transplantation; Chemotherapy; Katyotype; Leukemic transformation

Myelodysplastic syndrome (MDS) is a disease of the elderly and only a few series describing this disorder in childhood have been published in literature. I'~ The overall survival in childhood MDS is short and because of its infrequency, no single report comprising a large number of patients, has been able to define the prognostic significance of the initial clinical and hematological findings. We present the clinical, hematological features and

Reprint requests : Dr. S.H. Advani, Department of Medical Oncology,Tata Memorial Hospilal, Parel, Bombay-400 012.

progression of 16 cases of childhood MDS. MATERIAL AND METHODS Sixteen children in the age group of 2.5 to 16 years, fulfilling the criteria of MDS by the French-American-British co-operative group (FAB) 3 were diagnosed from January 1985 to December 1988 in our department of medical oncology, at Tata Memorial Hospital, Bombay. The clinical history, peripheral blood, bone marrow' aspirate and biopsy examinations using standard hematological methods and cytochemical stains were performcd in all cases. Cytogenetic

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analysis was performed on 7 cases at initial presentation and repeated in 3 cases during remission and 2 cases after progression to acute leukemia. The bone marrow was processed by direct method as well as 24 hours cultures, and Giemsa-trypsin-G banding was done in all the cases according to Seabright method. 4 Phytohemagglulinin (PHA) stimulated peripheral blood lymphocytes were used for cytogenetics when necessary. Two different modalities of therapy were used. Six patients received aggressive acute myeloid leukaemia (AML) induction therapy consisting of daunomycin 60 rag/M2 IV on day 1 and cytosine arabinoside (Ara-C) in the dose of 200 mg/M2/day as a 24 hours infusion for I to 7 days. On achieving remission, two additional courses were given as consolidation. Six patients received monotherapy. One patient received oral hydroxyurea in the dose of 25 mg/kg/day for one month and 5 patients received low dose Ara-C in a dose of 10 mg/M2/12 hourly subcutaneously for 21 days to be repeated after a gap of three weeks for a total of 3 cycles. Four patients were treated with supportive care only as per the parents wish. All patients received blood component therapy and antibiotics when necessary.. Complete remission was defined as the presence of less than 5% blasts in the bone marrow, disappearance of features of dysmyelopoiesis and normalisation of the peripheral blood, while partial remission was defined as the presence of less than 5% blasts along with persistence of features of dysmyclopoiesis. No response was defined as persistence of the pretreatment marrow features or a progression to acute leukemia. RESULTS

Sixteen patients, 10 males and 6 females

Vol. 59, No. 4 aged 2.5 to 16 (mean 10.5) years were studied. The main symptoms were fever and weakness for an average duration of 16 weeks before diagnosis. None had any prior exposure to cytotoxic drugs or chcmicals. Organomegaly was seen in 5 patients. One patient had clinical features of Down's syndrome and was proven to be mosaic for trisomy 21 by karyotype analysis. The patient characteristics, periphcral blood, bone marrow findings, therapy and outcome are summarised in Table 1. The presenting fcatues were weakness '(100%), fcver (70%), and cutaneous hemorrhagcs (30%) in our study. Pallor was seen in 75% and organomegaly in 30% of patients. All patients presented with anemia of less than 12 gms/dl and thrombocytopenia of less than 100X 109/L. Five patients had icukopcnia. Five patients had more'than 5% circulating blasts, 6 patients had immature cells and 5 had nucleated erythrocytes in lhc peripheral blood. Foetal hemoglobin was elevated in 5 patients. Bone marrow smears were hypercellular in 13 and normocellular in 3 patients. Dysmyelopoeitic features such as abnormalities of maturation, hypogranularity and nuclear abnormalities (including Pelger-Huet anomalies) wcre seen in all. Bone marrow blast percentage ranged from 2 to 26 (mean 14.6)% and auer rods were seen in 5 patients. Dyserythropoeitic features in the form of macroblasts or megaloblasts and nuclear abnormalities were seen in 11 patients Sideroblasts were not seen in any of the six patients on whom special iron staining was performed. Megakaryocytic series was suppressed in 13 and absent in 3 patients. Dysmcgakaryopocitic features such as micromegakaryocytes and nuclear abnormalities were observed in 4 patients. Chromosomal aberrations were detected

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Childhood myelodysplastic syndromes: clinical features, cytogenetics and prognosis.

Sixteen children with myelodysplastic syndrome as defined by the French-American-British co-operative group are presented. The mean age was 10.5 (2.5 ...
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