Adele Comelli

Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group.

PURPOSE This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission. PATIENTS AND METHODS From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA-matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles. RESULTS Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded. CONCLUSION The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission.

Treatment of acute myelogenous leukemia in children: results of the Italian Cooperative Study AIEOP/LAM 8204.

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.

Malignant mesenchymoma of the liver in children: A clinicopathologic and ultrastructural study

A primary malignant mesenchymoma of the liver in a nine year old boy is reported with the results of ultrastructural investigation. In accordance with previous observations, our study indicates that this type of tumor is remarkable because of its bulky size and possible rapidly fatal outcome. Although the term malignant mesenchymoma can be applied, the tumor is primarily fibrosarcomatous and liposarcomatous. It could be postulated that this tumor and the more frequent benign mesenchymal hamartoma of the liver are two histogenetically related lesions that preferentially affect the liver in children.

Retroperitoneal fibrohistiocytic tumors in children: report of five cases.

Five rare retroperitoneal fibrohistiocytic tumors of children are described mainly in reference to the pathological aspects. A more detailed description is given of a retroperitoneal xanthogranuloma, including an ultrastructural study. This case is particularly interesting for its rapid transformation into a fibroxanthosarcoma. The other cases include two fibroxanthosarcomas, a storiform fibrous xanthoma, and a malignant histiocytoma. The most difficult points in the recognition and in the differential diagnosis of these tumors are discussed, and emphasis is placed on some interesting pathological features. Prognosis of such tumors appears difficult to assess from our series, since two patients died in the immediate postoperative period, one died one and a half years after the discovery of the tumor, and two are alive and well, but with a short follow‐up.

Karyotype evolution in a patient with biphenotypic neonatal leukemia

We present the case of a 4-day-old boy with acute lymphoblastic leukemia showing at onset a karyotype 46,XY,t(4;11)(q21;q23). At relapse an additional change, add(2), was present. Molecular analysis showed the same immunoglobulin rearrangement both at onset and at relapse, but immunohistochemical analysis revealed some cells having myeloid features. A continuous cell line derived from the leukemic blasts of the patient presented typical monoblastic features.

Therapy of Childhood Acute Myelogenous Leukemia: An Update of the AIEOP/LAM 8204 Study

Over the past decade there have been significant advances in the treatment of acute myelogenous leukemia (AML). The introduction of intensive induction and post-remission chemotherapy programs, together with the improvement in supportive care, have resulted in a probability of long-term survival in 30%–50% of children with AML [1–4]. In 1982 the AIEOP (Italian Pediatric Hematology-Oncology Association) cooperative group began a multicenter prospective trial for pediatric AML in order to establish the value of a polychemotherapeutic regimen consisting of intensive induction followed by intensive consolidation and continuation chemotherapy.

Primary cutaneous lymphoma with a nodular pattern in infancy

We present the first reported case of primary lymphoma with a nodular pattern in infancy, accompanied by a detailed histopathological study. The diagnosis is based upon unquestionable histopathological data. Remarkable are the macroscopic findings of the lesion, the very young age of the patient, and the Burkitts lymphoma‐like appearance of the lesion in addition to the nodular pattern. Another case of cutaneous nodular lymphoma in an infant was previously reported by Traggis et al. but without a detailed histopathological description. These two cases, in consideration of the rarity of nodular lymphoma in children, promote speculative considerations, especially in regard to etiology and therapy.

Non-familial hemophagocytic lymphohistiocytosis.

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.

Focusing on late effects in long-term survivors of childhood leukemia and lymphomas

Major advances have occurred in the treatment of children with cancer, leading to a high percentage of cure especially in Acute Lymphoblastic Leukemia (ALL), Hodgkin’s disease (HD) and non-Hodgkin’s Lymphomas (NHL). The remarkable improvement in the prognosis of childhood malignancies has been achieved with the use of combined modalities of treatment [1–4]. Consequently pediatric oncologists are now dealing with an increasing number of long-term survivors of these diseases and with their emerging treatment sequelae [5–9]. Late toxicity attributable to surgery (S) and radiotherapy (RT) is better known than that produced by chemotherpay (CT) or multimodal treatment [10, 11]. The frequency of long-term consequences of antineoplastic drug treatment in the pediatric age group is unknown. In addition there is little information regarding the relationships between their severity and the dose, schedule and duration of therapy [12]. Appropriate investigation of possible late sequelae must include a detailed evaluation of a number of organ systems including the cardiopulmonary, endocrine, hematopoetic, immune, musculoskeletal and central nervous systems [13].

20 SURFACE MARKERS OF CEREBROSPINAL FLUID LYMPHOCYTES FROM ACUTE LYMPHOBLASTIC LEUKEMIA

Studies on CSF lymphocyte markers demonstrated normally a high percentage of E-rosette forming cells ( 90 %). By a microtechnique the relative proportion of T, B and null CSF cells was evaluated in two groups of children with ALL. As CNS prophylaxis patients of the first group received i.t. MTX during induction, cytosine arabinoside during consolidation and MTX every two months for three years as maintenance. Children of the second group received X-ray during induction and consolidation (total dose 2400 rads). Patients were in complete remission from 24 to 32 months for the first group and from 11 to 17 months for the second one. Results showed that the lymphocytes from CSF of the first group had a much lower percentage of T and T gamma cells in comparison to the second group; B cells were virtually absent, null cells were abnormally high in the first group. CSF cells of patients immediately after treatment with TCT demonstrated a high percentage of T cells. The lack of T cells in the group of children treated three years with i.t. MTX seems to cause such an inununological damage to discourage from this type of CNS prophylaxis.