Vico Vecchi

Discontinuing therapy in childhood acute lymphocytic leukemia. A multicentric survey in Italy.

The results of discontinuing therapy in children with acute lymphocytic leukemia observed at four associated institutions are presented. Of the 247 patients who achieved complete remission, 122 (49.3%) reached the point of discontinuing therapy after 2–4 years of continuous remission. The median period off therapy was 13 months with a range of 1–69 months. Of the 122 children removed from therapy, 27 (22.1%) relapsed, mainly in the bone marrow; relapses occurred 1–32 months after cessation of therapy (median ten months) with only two relapses occurring later than two years. By actuarial analysis, 57% of the patients are projected in continuous remission after five years from cessation of therapy. Neither selected features at diagnosis nor single modalities of treatment were found to predict whether relapse would occur after discontinuing therapy. Long‐term remission and possibly cure can be expected in over one‐third of newly diagnosed children with ALL after 2–4 years of antileukemic treatment.

PROGNOSTIC SIGNIFICANCE OF LYMPHOBLAST MORPHOLOGY IN ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL) IN CHILDHOOD

In our original report we suggested that the incidence of the normal Hb A, forms of p thalassaemia ‘may be’ as high as lo%, based on normal Hb A2 levels in parents o f p thalassaemia homozygotes (Kattamis et al, 1972) but acknowledged that this may be an overestimate ‘since non paternity and coexisting a thalassaemia or iron deficiency . . . were not rigorously excluded in these studies’. The finding of four double heterozygotes for normal and high Hb A2 p thalassaemia among 40 consecutive patients was used to confirm a high incidence, and not to derive the figure of 10%. It is extremely difficult to get more accurate estimates of the incidence since there is no straightforward screening method for either type I or type I1 normal Hb A2 f l thalassaemia. Thus we will continue to screen the parents of all new p thalassaemia patients presenting to the Paediatric Clinic until we have more reliable figures. However, we doubt if the incidence of either form is as low as Dr Kaltsoya-Tassiopoulou et a1 suggest. From the genetic counselling point of view, it is the detection of the more severe type II form of normal Hb A2 p thalassaemia which is important. It is not possible with any practical screening procedure to detect the type I form, but fortunately its interaction with a high Hb A2 p thalassaemia gene appears to produce a mild disease. However, although the type I1 form should be detected by screening for abnormal red cell indices, it must be differentiated from a thalassaemia (also prevalent in Greece) and this can only be achieved by measuring globin chain synthesis. Compound heterozygotes for a and D thalassaemia are not severely affected, whereas double heterozygotes for the high Hb A2 and normal Hb A2 (type 11) forms of 8 thalassaemia result in a clinical picture of transfusion dependent thalassaemia major and would be suitable candidates for antenatal diagnosis. Department of Paediatrics, Aghia Sophia Children’s Hospital, Athens Nufield Department of Clinical Medicine, John Radclife Hospital, Oxjord C. KATTAMIS A. METAXOTOU-MAVROMATI

Efficacy of Propranolol Treatment in Thyroid Dysfunction Associated with Severe Infantile Hepatic Hemangioma

Infantile hepatic hemangioma can be associated to consumptive hypothyroidism due to overexpression of type 3 deiodinase in the endothelium of vascular tumor, which catalyzes the conversion of T4 to reverse T3 (rT3) and of T3 to T2, both of which are biologically inactive. Here, we report an infant with a massive biopsy-proven infantile hepatic hemangioma who developed thyroid dysfunction without a typical biochemical profile consistent with severe consumptive hypothyroidism, despite the large tumor burden. Our patient was treated with propranolol that rapidly resolved both hepatic hemangioma and thyroid dysfunction. We propose propranolol as a first-line therapy of thyroid dysfunction associated with infantile hepatic hemangioma, in order to avoid interference with neurological development caused by hypothyroidism in the first months of life.

CORRELATION BETWEEN CRANIAL COMPUTED TOMOGRAPHIC SCANS AT DIAGNOSIS IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKAEMIA AND CENTRAL NERVOUS SYSTEM RELAPSE

145 children with acute lymphoblastic leukaemia (ALL) were evaluated over a period of 3 years in a multicentre study in which serial cranial computed tomographic (CT) scans of the brain were done. All patients were symptom-free. CT scans were graded as normal, borderline (slight or moderate cerebral atrophy), or pathological (severe cerebral atrophy). 62% (90/145) of children had CT scan abnormalities at diagnosis. After a median follow-up of 24 months (range 6-36) 12 of 108 evaluable patients had central nervous system (CNS) relapses (6 isolated relapses and 6 combined with relapse at another site). All patients with CNS relapse had an abnormal CT scan at diagnosis (8 pathological and 4 borderline). No relapses were observed among the 42 patients with a normal cranial CT scan at diagnosis. A significantly higher proportion of severe cerebral atrophy, both following CNS prophylaxis and after the discontinuation of treatment, was found among patients with a borderline CT scan at diagnosis than among patients with a normal CT scan at diagnosis. Thus an abnormal cranial CT scan at diagnosis in children with ALL seems to have prognostic significance.

Childhood Non-Hodgkin's Lymphoma and “Leukemia-Lymphoma Syndrome”: Long-Term Results with the Modified LSA2-L2 Protocol

From June 1976 to December 1984, 48 previously untreated children with non-Hodgkins lymphoma (NHL) were treated according to the LSA2-L2 protocol, modified by inclusion of cranial irradiation for patients in stage III and stage IV disease. According to the staging system proposed by Wollner, 4 patients were in stage I, 8 in stage II, 11 in stage III, 8 in stage IVA (less than or equal to 25% blasts in the bone marrow), 15 in stage IVB (greater than 25% blasts in the bone marrow), and 2 in stage IV central nervous system disease. The complete remission rate was 95.8%. The relapse-free survival (RFS) rate of 46 complete responders was 76% after a median observation time of 47+ months. Only 1 of 35 high-risk responder patients developed CNS relapse after prophylactic treatment. Clinical stages were related to the RFS: 100% in stage I-II vs. 69% in stage III-IV. All 8 patients in stage IV were alive without evidence of disease with a median observation time of 59+ months. Fifteen patients in stage IVB who had leukemia-lymphoma syndrome attained 59% RFS with a median observation time of 39+ months. After a median observation time of 38+ months, 29 of 37 patients are off therapy. The results emphasize the value of both the histologic and immunologic features and the stage of disease in predicting the outcome of NHL in children. The LSA2-L2 regimen appears to be a very effective protocol for children with lymphoblastic lymphoma, although it may be less efficacious for patients with large bone marrow involvement.

Mixed Epithelial and Stromal Tumor of Kidney: An Exceptional Renal Neoplasm in an 8-Year-Old Prepubertal Girl with Isolated Clitoral Hypertrophy

1Department of Pediatrics, Pediatric Oncology Unit, “Infermi” Hospital, Rimini, Italy; 2Department of Oncology, “Infermi” Hospital, Rimini, Italy; 3Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 4Department of Pathology, “Infermi” Hospital, Rimini, Italy; 5Department of Pediatrics, Pediatric Oncology Unit, “Infermi” Hospital, Rimini, Italy; 6Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 7Department of Pediatrics, Pediatric Surgery Unit, “Infermi” Hospital, Rimini, Italy; 8Department of Pediatrics, Pediatric Oncology Unit, “Infermi” Hospital, Rimini, Italy

Primary Epstein-Barr virus infection in children with malignant disorders: effect of therapy on EBV-antibodies.

Summary Serum samples were examined from 125 children (1–12 years) entering a paediatric unit for haematological disorders (74: acute lymphoblastic leukaemia; 11: Hodgkins disease; 17: solid tumors; 23: non neoplastic disorders). Fifty healthy children were also studied. The sera were tested for class specific IgG and IgM antibodies to EB viral capsid antigen (VCA) and early antigen (EA), and for heterophil antibody. Serological findings consistent with a recent EBV primary infection, not related to the onset of the diseases, were found in six per cent of the patients. Antibodies against EBV-VCA were found in a significantly ( P

Long-term results of the AIEOP MH’96 childhood Hodgkin’s lymphoma trial and focus on significance of response to chemotherapy and its implication in low risk patients to avoid radiotherapy

Abstract Identify a subset of early-stage HL children (GR1) curable with limited chemotherapy+/-radiotherapy; improve outcome of intermediate (GR2) and high-risk (GR3) patients; establish impact of response to chemotherapy evaluated with conventional imaging (CI). One hundred and sixty GR1-patients received 3ABVD + involved-field (IF) low-dose (LD) (20 Gy) irradiation if mediastinal mass or partial response (PR) after chemotherapy. Eighty-five GR2- and 315 GR3-patients received 4 and 6 COPP/ABV + IFRT, respectively. The 63 GR1 patients spared from radiotherapy had 15-year survival and EFS of 100 and 84.5%, respectively. The GR2 and GR3 15-year FFP were 84.7 and 78.6%, respectively. No different prognosis for patients in CR or PR evaluated during and after chemotherapy was observed. In conclusion, low-risk patients in CR may be successfully treated with radiation-free, low-intensity chemotherapy. Good, but less satisfactory, results were registered in GR2 and GR3. Response evaluated with CI is not a prognostic factor, but permits identification of low-risk patients who can avoid radiotherapy.

Original articlePrimary Epstein-Barr virus infection in children with malignant disorders: Effect of therapy on EBV-antibodies

Summary Serum samples were examined from 125 children (1–12 years) entering a paediatric unit for haematological disorders (74: acute lymphoblastic leukaemia; 11: Hodgkins disease; 17: solid tumors; 23: non neoplastic disorders). Fifty healthy children were also studied. The sera were tested for class specific IgG and IgM antibodies to EB viral capsid antigen (VCA) and early antigen (EA), and for heterophil antibody. Serological findings consistent with a recent EBV primary infection, not related to the onset of the diseases, were found in six per cent of the patients. Antibodies against EBV-VCA were found in a significantly ( P