L. Nespoli

Natural cytotoxicity impairment in familial haemophagocytic lymphohistiocytosis.

Ten children with the characteristic clinical and haematological features of haemophagocytic lymphohistiocytosis are reported. Four patients treated with a combination of drugs comprising etoposide, methotrexate, and steroids were in complete remission after 10 to 30 months. Natural cytotoxic mechanisms including natural killer cell activity, antibody dependent cell mediated cytotoxicity, lymphokine activated killer cell activity, and natural killer cell like activity were persistently absent or severely impaired in these four patients despite their clinical remission. Their parents and one healthy sibling also had impaired natural cytotoxic mechanisms. Constitutional impairment of natural cytotoxic mechanisms could be important in the pathogenesis of haemophagocytic lymphohistiocytosis.

Selective IgA deficiency: Clinical and immunological evaluation of 50 pediatric patients

Fifty children with IgA deficiency were followed for 1 to 4 years from 1975 to 1978. Thirty-five had complete deficiency of serum IgA (<2.5 IU/ml) and 15 partial deficiency (serum IgA below the 10th centile for age). Patients with another associated immunodeficiency, such as ataxia-telangiectasia, were not included. Most children with complete deficiency of IgA had recurrent respiratory and/or gastrointestinal infections, about half with onset in the first year of life, while partial deficiency of IgA has probably little if any importance for anti-infectious immunity but is important in the pathogenesis of atopy. Atopic diseases were frequent in both groups. Chromosomal abnormalities were found in 2 patients: trisomy 21 in one and in the other a ring chromosome 18. No important defects in cellular immunity were detected but some isolated, borderline abnormalities were often present.

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.

Cell-mediated cytotoxicity in down syndrome: impairment of allogeneic mixed lymphocyte reaction, NK and NK-like activities

Peripheral blood mononuclear cells (PBMC) from 16 non-institutionalized patients with Down syndrome (DS) were studied with various monoclonal antibodies and analysed for natural killer (NK), and NK-like activity. Lymphocyte proliferation and cytotoxic T-lymphocyte (CTL) cytotoxicity generated in mixed lymphocyte culture (MLC) were also evaluated in 11 DS patients. Phenotypic characterization of PBMC from DS subjects confirms our previous findings of high numbers of CD8+ lymphocytes and HNK-1+, and CD16+ cells. Lymphocyte proliferation and CTL cytotoxicity generated in MLC were low or absent in most patients. NK activity was low in almost all DS patients, while NK-like cytotoxicity generated in MLC was normal in the majority and did not correlate with NK activity from unstimulated PBMC.

Lymphocyte subpopulations in the neonate: a subset of HNK-1−, OKT3−, OKT8+ lymphocytes displays natural killer activity

It has been recently reported that cord blood lymphocytes (CBL) contain a subpopulation of OKT8+, sheep erythrocyte-rosetting negative (E-) cells not detectable in adult peripheral blood lymphocytes (a-PBL). The present studies were undertaken to characterize this subset of lymphocytes functionally and phenotypically. OKT8+ cells were purified from E-depleted CBL by negative selection on nylon-wool columns as well as by positive selection on plates coated with rabbit antibody to murine IgG (panning). The purified CBL displayed natural killer (NK) activity against K562 erythroleukemic cells. Although most of these CBL were large granular lymphocytes, they lacked typical NK markers such as HNK-1 and OKM1 surface antigens. Most OKT8+, OKT3- cells were also OKT10+, Ia+ and had the receptor for peanut agglutinin. These CBL may represent a stage along the differentiation pathway leading to mature NK or T cells.

Peripheral blood 'Rosette forming lymphocytes' in Down's syndrome

La reattività alla fitoemoagglutinina e la capacità di formare «rosette» con eritrociti di montone dei linfociti di sangue periferico è risultata significativamente depressa in soggetti adulti affetti da sindrome di Down. Si può ritenere che la funzione timo-dipendente vada incontro in questi pazienti ad un deterioramento assai più rapido che nella popolazione generale.

Kaposi's Sarcoma in a child after autologous bone marrow transplantation for non-Hodgkin's lymphoma

A case of Kaposis sarcoma in a child with no serologic evidence of human immunodeficiency virus (HIV) infection is reported. A 7‐year‐old boy with Stage IV non‐Hodgkins lymphoma, after conventional chemotherapy, underwent autologous bone marrow transplantation (ABMT). Five months later he presented with supraclavicular mass and mediastinal enlargement. A bone marrow biopsy showed hypoplasia with no signs of the underlying disease, whereas the excised mass revealed a typical histologic pattern of Kaposis sarcoma. The child is currently being treated with recombinant α‐interferon (α‐IFN) and regression of the disease has been achieved.

Randomized Multicentric Italian Study on two Treatment Regimens for Marrow Relapse in Childhood Acute Lymphoblastic Leukemia

This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.

Long term survival after heart transplantation for doxorubicin induced cardiomyopathy.

A 10 year old child developed severe cardiomyopathy after combined, multicycle chemotherapy for Ewings sarcoma and was treated by heart transplantation with good results. Long term azathioprine and cyclosporin caused only mild impairment of immune function and there were no recurrent infections, local recurrences of the tumour, or distant metastases.

Plaque Assay with Protein A‐coated Erythrocytes for the Evaluation of Human Immunoglobulin‐secreting Cells Induced by Pokeweed Mitogen

Cells secreting IgM, IgG and IgA were evaluated in cultures of human peripheral blood lymphocytes stimulated in vitro with pokeweed mitogen by a haemolytic plaque assay using protein A‐coated erythrocytes in the presence of class‐specifie antisera. Kinetic study revealed that immunoglobulin‐secreting cells appeared after 3 days of culture and peaked between days 5 and 7. IgM‐secreting cells predominated throughout the culture period. This plaque assay is a useful and sensitive in vitro test for the evaluation of polyclonal B‐cell activation in humans and may provide a good approach to the study of disturbances in the synthesis of the various classes of immunoglobulins.