High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study.

We investigated the feasibility and efficacy of high-dose vincristine (4 mg/m2 over 4 d) combined with fractionated total body irradiation (F-TBI) (200 cGy x 2 over 3 d) and cyclophosphamide (60 mg/kg for 2 d) as a preparative regimen in allogeneic (AlloBMT) and autologous (ABMT) bone marrow transplantation for 75 consecutive children (median age at transplant 8.5 years) with acute lymphoblastic leukaemia in second complete remission (CR). Median duration of first CR was 26 and 25 months in the AlloBMT and ABMT group, respectively. Of the 46 patients who underwent AlloBMT, 33 had isolated or combined marrow relapse and 13 isolated extramedullary relapse. Of the 29 patients given ABMT, 23 had preBMT isolated or combined marrow relapse and six isolated extramedullary relapse. 44/75 patients are alive and in CR at a median follow-up of 35 months (range 10-90 months). Seven children given AlloBMT (15.8%) and two given ABMT (7%) died from transplant-related causes. No major early organ toxicity, including vincristine-related toxicity, was recorded. The overall 3-year EFS estimate (95% CL) was 53.8% (42-66%): in particular, 58.2% (40-76%) for AlloBMT and 27.6% (9-46%) for ABMT patients who experienced a marrow relapse before transplant. The overall 3-year relapse rate estimate (95% CL) was 39.2% (27-51%): in particular, 30.1% (12-49%) in the AlloBMT group and 72% (54-91%) in the ABMT group (P < 0.01) who presented a preBMT isolated or combined marrow relapse. We conclude that the conditioning regimen with high-dose vincristine combined with cyclophosphamide and F-TBI is feasible and promising, although its therapeutic advantage should be tested in larger series of patients enrolled in randomized studies.

The use of antibiotics in the treatment and prevention of infection in HIV-infected children.

Children with HIV infection have an unusual susceptibility to bacterial infection, related to several immune abnormalities. Selection of initial antibiotic therapy must be individualized in these children. Patients with community-acquired disease are most likely to have infection by polysaccharide-encapsulated bacterial organism, most commonly Streptococcus pneumoniae and less frequently by Haemophilus influenzae type b. If it is possible to treat the patients at home, the use of amoxicillin-clavulanic acid might be appropriate. Other authors propose management with parenteral ceftriaxone because of the better compliance and the malabsorption. In hospitalized patients, concern for Gram-negative enteric pathogens other than polysaccharide-encapsulated organisms requires initial therapy with a third-generation cephalosporine in combination with an aminoglycoside. Trimethoprim-sulfamethizole is the most common drug used in HIV-infected children because it is recommended for the initial therapy and for prophylaxis of pneumocystis carinii pneumonia, which occurs in as many as 42% of these children.

Paediatric AIDS: a new child abuse.

In relation to youth rights, a new view has been created in recent decades that is included in the fundamental law of the child: the recognition of the right to education and the chance to develop a mature personality capable of creativity and liberty. Because of HIV infection it is very important to pay particular attention to the rights of the seropositive child and children born to seropositive mothers, which may be hampered not only in developing countries but also in the industrial world. HIV-affected children and their families are becoming abused and at high risk of becoming abused and this encroaches upon youth rights. As a consequence, in 1991 the Italian Society of Paediatrics issued a "Charter for the rights of seropositive children", which became an important document for all health care and social workers who deal with HIV-affected children. In this paper, we also consider the impact of HIV infection on the three main rights of children: the right to live, the rights of security and the rights of socialization.

[Acute inflammatory polyradiculoneuritis during bone marrow transplantation. A report of 2 cases]. / Poliradicoloneurite infiammatoria acuta in corso di trapianto di midollo osseo. Descrizione di due casi.

Acute polyradiculoneuritis (AP) is a self-immunity based disease of the peripheral nerve caused by macrophages, usually activated by T-lymphocytes. Recent clinical and experimental evidence show that early high dose treatment with Ig slows disease progression. In this study, two cases of AP with different onset in two patients showing definitely compromised cellular and/or humoral immunity, are reported. The hypothesis that the different temporal profiles may be related to a distinct involvement of the immunity system and the effectiveness of high dose Ig treatment in blocking the disease's evolution are discussed.

Low incidence of GvHD and rejection after pharmacological ex vivo modulation of bone marrow in 2-3 antigens mismatched BMT.

2-3 antigens mismatched BMT were performed on 32 children without a matched sibling donor. In the light of previous in vitro studies, which suggested a role of Vincristine and Methilprednisolone ex vivo treatment in modulating alloreactivity of T cells, bone marrow was treated with such a pharmacological cocktail before being infused. Acute GVHD 2 degrees to 4 degrees degree occurred in 46% of cases, chronic GVHD in 28%, graft failure in 13%. There was no significant difference between 2- and 3-antigens mismatched BMT as far as GVHD and graft failure are concerned.

Early deaths in children after BMT. Bone Marrow Transplantation Group of the Italian Association for Pediatric Hematology and Oncology (AIEOP) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

In order to determine the incidence and causes of death during the first 100 days after BMT (early deaths) in a pediatric population we have examined data reported in the AIEOP BMT Registry. Up to July 1990, data on 486 children who underwent allogeneic (180) or autologous (306) BMT were evaluable. The children had acute lymphoblastic leukemia (148 cases), acute non-lymphoblastic leukemia (127 cases), neuroblastoma (82 cases), chronic myelogenous leukemia (15 cases), aplastic anemia (nine cases), solid tumors, lymphoma, immunodeficiency or storage diseases. The overall survival is 55% for allogeneic HLA matched and 38% for autologous transplants at 5 years, 24% for HLA mismatched graft at 2 years. Out of the 486 children, 70 (14%) died during the first 100 days after BMT: 33/306 (11%) after autologous BMT, 24/150 (16%) after allogeneic matched BMT and 13/30 (43%) after mismatched BMT. Causes of early death were as follows: disease progression: 12 children (10/306 after autologous and 2/180 after allogeneic BMT); infection: 12 children (five after autologous and seven after allogeneic BMT); interstitial pneumonitis: 21 children (seven after autologous and 14 after allogeneic BMT); cardiac failure: five children (four after autologous BMT); veno-occlusive disease: eight children (three after autologous, five after allogeneic BMT); acute renal failure: three children (one after autologous and two after allogeneic BMT); multiple organ failure: two cases (one after autologous BMT); cerebral hemorrhage: three children (one after autologous BMT); hypertension: one child; acute GVHD: three children (12% of early deaths after allogeneic BMT).

Functional depletion of T cells by vincristine and methylprednisolone as an in vitro model for the prevention of graft versus host disease.

BACKGROUND AND METHODS. The outcome of mismatched bone marrow transplantation is still severely hampered by graft versus host disease (GVHD) and graft rejection. Procedures for the recognition and selective elimination of T cells are still unsatisfactory due to the increased incidence of graft failure and late rejection. Lymphocyte proliferation and generation of cytotoxic T cells (CTL) in response to allogeneic cells are considered good in vitro correlates of GVHD and have been used in the present study to asses the capacity of two drugs (vincristine, VCR, and methylprednisolone, MP) to affect the T cells involved in these reactions. RESULTS AND CONCLUSION. Treatment in vitro with VCR and MP has been shown to inhibit the functional capacity of peripheral blood lymphocytes to proliferate (mean reduction 95.8%) and to generate CTL in response to haploidentical stimulator cells. Responsiveness to antigens and mitogens was affected to a minor extent (mean reduction 40% and 65.5%, respectively), and the method allowed recovery of hemopoietic precursors. The results suggest that treatment of donor bone marrow with VCR and MP is worth studying as a new approach to the prevention of GVHD in haploidentical bone marrow transplantation.

[Bone marrow transplantation in pediatrics: its current status, the problems and prospects]. / Il trapianto di midollo osseo in pediatria: stato attuale, problemi e prospettive.

Notwithstanding the high proportion that achieve a cure after chemotherapy, there are still a case in which only a BMT can offer a chance of cure. This minority of patients can undergo an allogeneic BMT if a HLA matched donor is available or an autologous BMT if a good remission is achieved before the BMT. Not all the patients comply with these criteria. Therefore we need to widen the availability of the donors searching for unrelated matched donors or facing the problems of an aplohidendical BMT. The efforts to treat even children with advanced disease are based on the possibility of overcoming the blasts resistance or of stimulating the non-HLA restricted cytotoxicity with IL2.

[Neutropenia caused by low-dose trimethoprim-sulfamethoxazole in children with chronic pathology of the urinary tract]. / Neutropenia da trimetoprim-sulfametossazolo a basso dosaggio nei bambini con patologia cronica delle vie urinarie.

Neutropenia is the most common hematologic abnormality detected as consequence of Trimethoprim Sulfamethoxazole (TMP-SMX) therapy. Its incidence is evaluated in 27 children affected by urinary tract anomalies and treated with low doses of TMP SMX (2 + 10 mg/kg/die) for more than one month. A slight neutropenia was detected in 8 children (6 of these were in their first two years of life). In all the 27 cases a supplementation of folinic acid was started: a significant increase of PMN count was noted in all cases. Neutropenia can also appear after low (prophylactic) dosage of TMP-SMX, and can be prevented by concomitant administration of folinic acid.

Immunological patterns in monoarticular juvenile rheumatoid arthritis.

Seven pediatric patients with monoarticular arthritis, three of whom had a recent onset form and the remaining four a disease of longer duration, were examined for possible modifications of their immunological parameters. The diagnosis of JRA was made on all these patients according to the ARA criteria after a follow-up of at least two years. Humoral and cellular abnormalities of the immune system were searched for in peripheral blood, synovial fluid and synovial membrane. No evidence for complement consumption and for increased levels of immune-complexes was found in the sera and in the synovial fluids of these patients, who were all seronegative. Some patients had antinuclear antibodies in their sera and synovial fluids. With regard to the lymphocyte distribution, whereas only some patients had an increased number of circulating B cells, the majority had a decreased CD4+/CD8+ ratio in the synovial fluid compared to the ratio found in the peripheral blood. A massive infiltration of CD4+ cells and macrophages and the presence of a substantial number of OKT9+ cells was found in the synovial membranes.

[Long-term remission induced by measles infection and followed by immunosuppressive therapy in a case of refractory juvenile rheumatoid arthritis]. / Remissione a lungo termine in caso di artrite reumatoide giovanile intrattabile indotta da infezione morbillosa seguita da terapia immunosoppressiva.

A case of severe juvenile rheumatoid arthritis, polyarticular type, refractory to FANS and long acting therapy which showed a quick remission after measles is described. An immunosuppressive therapy to strengthen the immunosuppression induced by virus infection was performed for six months. The remission has been maintained for 4 years and appears up to now to be stable with no therapy. On the basis of this observation, the possibility of a vaccination therapy with measles virus, which equally gives immunosuppression, is discussed.