Myelodysplastic syndromes in childhood: is the FAB classification relevant? Report of 81 children from a French multicentre study. French Group of Cellular Hematology.

We reviewed the peripheral blood and bone marrow smears of 81 children with myelodysplastic syndrome (MDS). The morphological FAB classification was applicable in 59 children (72.8%): RAEB and RAEBt were the most frequent, 32 cases (39.5%). CMML was observed in 15 cases (18.5%) and in 25% of them, serological evidence for a recent EBV infection was demonstrated. In 22 cases (27.2%), the FAB classification was not convenient. In some of these children, dysmyelopoiesis was associated with constitutional disorders. Among these various inherited conditions, Down syndrome in which myelodysplasia is the expression of an abnormal clonal hematopoiesis, and mitochondrial cytopathies in which MDS is the hematological expression of a polyclonal multi-organ disease. The FAB classification does not appear to be satisfactory for all the disorders included in the group of childhood MDS and should be modified for specific use in children.

Heterogeneity of t(1;19)(q23;p13) acute leukaemias. French Haematological Cytology Group.

The t(1;19)(q23;p13) translocation occurs commonly in B-lineage ALL. Previous reports have demonstrated a predominance of cases with expression of cytoplasmic Ig mu (C mu+), and FAB L1/L2 phenotype, a poor prognosis and expression of a fusion transcript involving the E2A and PBX1 genes in C mu+ but not in C mu- cases. Of 38 patients with karyotypically proven t(1;19) (q23;p13) leukaemias, we extensively analysed 18 patients with acute leukaemia including 16 B-lineage ALLs, one T-ALL and one AML M4. The AML was associated with a classic E2A-PBX1 fusion transcript and may represent the human counterpart of the AMLs induced by E2A-PBX1 retroviral infection of murine marrow progenitors. The T-ALL was E2A-PBX1 negative and neither the E2A nor the LYL-1 genes, both situated at chromosome 19 p13, were rearranged. Of the 16 B-lineage ALLs, four had cytological features resembling an 'L3-like' phenotype classically associated with Burkitt's lymphoma, two at diagnosis and relapse and two exclusively at relapse. E2A-PBX1 fusion transcripts were detected by RT-PCR in all 13 C mu+ patients and in 2/3 C mu- cases. The 'L3-like' phenotype did not correlate with a particular stage of maturation arrest (one sIg+, one C mu+, one C mu-) or type of E2A-PBX1 transcript, but was associated in all cases with a trisomy 8. Translocation, rearrangement, amplification or over-expression of the c-myc gene was not observed in these cases, demonstrating that the apparent association with trisomy 8 is not due to deregulation of this gene. We therefore show that the E2A-PBX1 transcript, although occurring predominantly in C mu+ pre-B ALL, also occurs in C mu- early pre-B ALL, sIg+ B-ALL and even in AML. These results suggest that the stage of maturation arrest, and indirectly the prognosis, are not solely due to the type of fusion transcript associated with the t(1;19).

Hypereosinophilic syndrome in childhood: trisomy 8 and transformation to mixed acute leukaemia.

We report a pediatric case of hypereosinophilic syndrome (HES) with trisomy 8 and terminal blastic transformation to mixed acute leukaemia. Literature cases are reviewed, with emphasis on prognostic factors to differentiating "benign" from malignant HES.

Interdigitating cells sarcoma: occurrence during incomplete remission of a lymphoblastic lymphoma.

The authors report the successive occurrence of an interdigitating-cell sarcoma and a lymphoblastic lymphoma in an 8-year old child. The observation is documented by immunophenotype and genotype. The link between the two malignancies is discussed.

Myelofibrosis in a child suffering from a hypereosinophilic syndrome with trisomy 8: response to corticotherapy.

The idiopathic hypereosinophilic syndrome (IHS) is extremely rare in childhood and relationships of this syndrome with myeloproliferative diseases are controversial. We reported the observation of a 7-year-old girl suffering from an IHS with myelofibrosis. A clonal cytogenetic abnormality, trisomy 8, was detected in the bone marrow cells of this child. This is the decisive proof of a myeloproliferative disorder. IHS with myelofibrosis is usually considered as unresponsive to corticotherapy. In our case, corticotherapy resulted in a rapid, complete, and lasting disappearance of myelofibrosis. Complete remission of the disease, however, was not achieved and the trisomy 8 persisted after treatment.

[Acute lymphoblastic leukemia in children. Results of a protocol including bone marrow transplantation during the first remission in high-risk forms for relapse]. / Leucémie aiguë lymphoblastique de l'enfant. Résultats d'un protocole incluant la transplantation médullaire en première rémission pour les forms à très haut risque de rechute.

Ninety-two previously untreated children with ALL were admitted to the same institution between November 1984 and November 1988. According to early prognostic factors, patients were divided into 3 groups: group 1 at "low risk" for relapse (n = 18), group 2 at "intermediate risk" (n = 62) and group 3 at "high risk" (n = 12). Every patient received an 8 week-long induction chemotherapy; after CNS prophylaxis, groups 1 and 2 children received a consolidation chemotherapy and then a classical maintenance treatment. Group 3 patients were selected to receive a bone-marrow transplantation during their first remission because of the presence, at diagnosis, of at least one of the following criteria: hyperleukocytosis greater than 100,000 (7 cases), translocation t(1;19) and t(4;11) (2 cases), adolescents (2 cases), no remission at day 30 (2 cases). Ninety-one of 92 children achieved a complete remission and none died during induction therapy. Probability of leukemia-free survival at 4 years is 73 +/- 7% for the whole patient population and 95%, 71% and 60% for patients of groups 1, 2, and 3 respectively. Persistence or disappearance of leukaemic cells in bone marrow after the initial 15 days of chemotherapy appears to influence the probability of a leukemia-free survival.

[Multicentric bone chloroma disclosed by pleural cytology]. / Un chlorome multicentrique osseux révélé par la cytologie pleurale.

We report a case of granulocytic sarcoma of the bone with pleural involvement diagnosed upon cytologic analysis of the pleural fluid (centrifugation spots stained by May-Grunwald-Giemsa) and confirmed by more complex investigations, i.e., demonstration of granulomonocytic membrane antigens by immunohistochemical monoclonal antibody techniques on frozen sections of the tumor. This case draws attention to the value of cytologic studies in granulocytic sarcomas whose histologic features are suggestive of lymphoma.

[Richter's syndrome. A morphological study apropos of 3 cases]. / Le syndrome de Richter. Etude morphologique à propos de trois cas.

The occurrence of a large cell lymphoma in the course of chronic lymphocytic leukemia is rare and its evolution is fatal at short term. This is the definition of Richter's syndrome. The authors report three cases documented by cytology, histology. The immunological study was performed for one of these by typing on a suspension of fresh bone marrow and lymph node cells. It showed the immunological identity of the chronic phase and the transformation phase (Richter's syndrome). These findings are in line with recent studies showing the immunocellular filiation of the two hemopathies despite the morphological differences, the transformation phase showing the differentiation of the B clone of the chronic phase.

[Automated hemogram and myeloperoxidase deficiency. Analysis of 33 cases]. / Hémogramme automatisé et déficit en myélopéroxydase. Analyse de trente-trois observations.

The daily use of the D Hemalog machine allowed us to recognize thirty-three cases of myeloperoxydase deficiency, on the basis of different "alarms", the most important of which is called LPX (Low Peroxydase). Some patients had a blood disease which was lacking among the other subjects. In no case the enzymatic defect has led to a clinical infection.