Therapy of childhood acute myelogenous leukemia: an update of the AIEOP/LAM 8204 study. Italian Pediatric Hematology-Oncology Association.
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Biomedical subjects
Publications and source records attributed to A Comelli.
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Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.
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A case of non-familial hemophagocytic lymphohistiocytosis (HLH) is described. The patient had a chronic course being alive and doing relatively well 3 years since onset. The specific pathological features of this disorder are discussed with emphasis on the fact that a remarkable loss of lymph node structure is sustained by a mature lymphohistiocytic infiltrate. Erythrophagocytosis is assessed as an important but not specific finding. Lymphocyte depletion is an important feature of the lesion. The presence of overlapping features in HLH, infection-associated hemophagocytic syndrome (IAHS) and X-linked recessive lymphoproliferative syndrome (XLS) is emphasized.
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The clinical features and the treatment of undifferentiated (embryonal) sarcoma of the liver in 8 patients younger than 19 years old were analyzed. All these cases were registered in the retrospective multicentric study on childhood malignant tumors of the liver, conducted between 1983 and 1985 by the Italian Association of Pediatric Hematology Oncology. The age of the patients ranged from 94 to 190 months (median = 113.5 months); all children were males. An abdominal mass was the common presenting features. Abnormalities in hemogram and common liver tests were rarely reported. Angiography revealed various degrees of vascularization in these tumors. Two patients achieved a surgical complete remission (CR) at diagnosis; one patient achieved surgical CR after primary chemotherapy with vincristine, adriamycin, cyclophosphamide and 5-fluorouracil, which reduced the tumor volume and permitted surgical resection. Two of these patients are still in CR at 14 and 60 months after diagnosis; the third patient died of liver failure without evidence of recurrence 6 months after diagnosis. All of the other patients, who never achieved CR, died of disease. One was lost to follow-up, and one surgical death occurred. Reports of childhood undifferentiated sarcoma are reviewed.
One hundred thirty-three children with acute myelogenous leukemia (AML) entered the multicenter Pediatric Branch of the Italian Association Against Leukemia trial AIEOP/LAM 8204 between July 1982 and May 1986. Induction therapy consisted of two courses of daunomycin (DNM) plus cytosine arabinoside (Ara-C). Those patients who achieved remission were given four courses of consolidation with DNM, 6-thioguanine (6-TG) and escalated doses of Ara-C followed by six courses of sequential continuation therapy using monthly pairs: etoposide (VP-16)/Ara-C, Ara-C/6-TG, and DNM/Ara-C. Periodic intrathecal Ara-C was used for CNS prophylaxis. One hundred seven (80%) children achieved complete remission (CR). Kaplan-Meier estimates of 3-year disease-free survival (DFS) and event-free survival (EFS) are 41% and 33%, respectively. Relapses occurred in 34 patients after 5 to 97 weeks (32 marrow; 2 marrow plus CNS). Overall, 14 patients died of complications during treatment (nine during induction; five during the postremission phase), mostly from infection. Risk factor analysis showed that induction failures occurred predominantly in children with French-American-British (FAB) M5 and in those with elevated leukocyte counts; by step-up Cox analysis, only FAB subtype was predictive of remission success. None of the variables examined was significant for predicting the duration of remission. Hyperleukocytosis was predictive of a significantly worse EFS rate. These results are encouraging and further support the use of intensive chemotherapy programs for childhood AML.
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A total of 17 pediatric patients with pretreated acute lymphoblastic leukemia were included in a phase II study of idarubicin. Four of 16 complete remissions were obtained, confirming the activity of the drug in this indication. Toxicity was acceptable, though caution is needed in patients who have already received high cumulative doses of anthracyclines.
Thirty-six children with acute lymphoblastic leukaemia (ALL) in second remission were treated with conventional chemotherapy or with cyclophosphamide and fractionated total-body irradiation followed by an allogeneic bone marrow transplant; the choice of treatment was dictated by the availability of an HLA-identical sibling. The age, sex, clinical data at presentation of the disease and duration of first remission were comparable for the two groups of patients. In the bone marrow transplantation group two patients died of graft-versus-host disease and five of leukaemia. Ten patients survive, nine disease free, 13-53 months from second remission (6-51 months post-bone marrow transplantation). In the chemotherapy group 14 patients died of leukaemia (2-29 months from second remission) and five survive (22-34 months from second remission). The actuarial survival for patients with bone marrow transplantation is 48% at 4 years as compared with 22% for those of the chemotherapy group (P = 0.04); the actuarial probabilities of being in remission are 58 and 18% in the two groups respectively (P = 0.01). This study confirms that allogeneic bone marrow transplantation is superior to chemotherapy in patients in second remission with ALL and should be considered in the presence of an HLA-identical sibling.
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We report two examples of an unusual expression of fatal granulomatosis with primary lymph node location, characterized histologically by numerous giant cells of the Langhans' type, effacement of the nodal structure, mixed lymphohistiocytic infiltrate, and marked histiocyte cell maturity, all features which initially did not exclude the possibility of a granulomatous process of infectious origin. The clinical features of these cases include cellular or combined immunodeficiency, a possible family history and a rapidly fatal course. The present article emphasizes the great similarity which can exist between histiocytic and granulomatous disorders, the great variability of histiocytic diseases from the pathological view-point, the presence of borderline examples, and the several overlapping features of different entities. Specifically, the most remarkable finding of these two cases is the existence of numerous mature giant cells of the Langerhans' type within a massive obliteration of the nodal structure. Furthermore, these giant cells characterized by a strikingly orderly disposition of peripheral nuclei in a wreath-like pattern, frequently suggesting the structure of Touton's giant cells.
119 children with acute lymphoblastic leukemia at onset underwent radiography of the whole body in order to determine whether initial radiological bone lesions were correlated with subsequent clinical course. Radiological findings were divided into three groups: 101 children (84.8%) had no bone involvement (group 0); 10 had bone changes compatible with acute lymphoblastic leukemia, such as slight metaphyseal transverse lucent bands with or without diffuse demineralization (group 1); 8 had bone changes, such as periosteal reaction with or without intramedullary osteolytic mottling. Bone involvement was not correlated with prognostic factors. Furthermore there was no significant correlation between bone changes and complete remission or survival.