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Ninety patients with biopsy-proven Langerhans cell histiocytosis (LCH) were enrolled from June, 1983, to December, 1988, in the multicenter AIEOP-CNR-H.X. '83 study. They were divided into two groups: poor prognosis (PP), comprising 11 children with organ dysfunction (OD), and good prognosis (GP), made up of 79 patients without OD. Eighty-four patients were evaluable for treatment results. Among GP patients, 16 with a single lesion received only local treatment, while 59 entered a clinical trial of immunotherapy and/or monochemotherapy with vinblastine (VBL). Nonresponders, sequentially received doxorubicin (ADM) and then etoposide (VP16). PP patients were treated with 4 week cycles of vincristine, ADM, cyclophosphamide, and prednisone for nine courses. The overall survival was 92.8% (100% for GP patients and 45.5% for PP patients) at 48 months. The complete response (CR) rates for immunotherapy, VBL, ADM, and VP16 were 10%, 62.9%, 42.8%, and 88.2%, respectively. Two of the 11 PP patients had a CR (18.2%), while six died and three are still alive with recurrent disease. The overall incidence of disease-related disabilities was 47.7%, while that of diabetes insipidus was 20%. Monochemotherapy is probably adequate in GP patients, while more effective treatments are needed for PP patients.

Background. Infants (age 0–11 months) with disseminated neuroblastoma are known to have a better prognosis than older children with the disease, but there is little information regarding factors that influence the outcome of the disease in these patients. Methods. The authors report a series of 110 infants with disseminated neuroblastoma with disease diagnosed between March 1976 and February 1991 in 21 institutions participating in the Italian Cooperative Group on Neuroblastoma (ICGNB). Of the 110 infants, 34 had Stage IV disease, and 76 had Stage IV-S disease. Results. The 5-year survival probability was 77% for all patients, 71% for those with Stage IV disease, and 81% for those with Stage IV-S disease. Of the 34 infants with Stage IV disease, the 9 who were 5 months or younger at the time of disease diagnosis are all alive (1 with active disease) at 7–143 months after diagnosis, whereas of the 25 infants who were 6–11 months of age at the time of disease diagnosis, 10 have died. Of the 76 infants with Stage IV-S disease, 12/64 who were 5 months of age or younger at the time of disease diagnosis died (mostly of massive hepatomegaly); 9 of these deaths occurred in infants with disease diagnosed before they were 2 months old, whereas 1 death occurred in the 12 infants with disease diagnosed when they were 6–11 months old. Four infants with Stage IV-S disease achieved complete disease remission and subsequently had relapse of disease. High levels of serum LDH and low urinary excretion of vanillylmandelic acid were associated with worse prognosis. Conclusions. The authors suggest that infants older than 6 months of age who have Stage IV disease require aggressive therapy. For infants with disease diagnosed before they are 2 months old, Stage IV-S disease may have a worse prognosis than Stage IV disease.

Between March 1983 and June 1986 127 patients with localized osteosarcoma of the extremity were treated with neoadjuvant chemotherapy. Preoperative chemotherapy consisted of two cycles of methotrexate (MTX) (high or moderate doses) followed by 6 days by cisplatin (CDP). Surgery was an amputation or a rotation plasty, or a limb salvage. Necrosis was good in 52% of cases, fair in 36%, and poor in 12%. Postoperative chemotherapy consisted of Adriamycin (doxorubicin [ADM]) and bleomycin (BCD) for poor responders; and ADM, MTX, and CDP for fair responders. Good responders were treated as fair responders or with only MTX and CDP. At a 47-month follow-up, 66 patients remained continuously disease free and 61 patients developed metastases. Six of these patients had also a local recurrence. According to the grade of necrosis, the cumulative disease-free probability at 5 years was 67% for good responders, 42% for fair responders, and for poor responders 10% at 45 months. According to the doses of MTX, survival at 5 years was 58% for patients who received high doses and 42% for patients treated with moderate doses. No differences in the rate of survivors were observed between amputated patients and patients treated with limb salvage. The authors conclude that (1) a limb salvage procedure is possible in about 70% of cases and as safe as demolitive surgery, if adequate surgical margins are achieved; (2) good responders have a better prognosis than fair and poor responders if postoperative chemotherapy is sufficiently prolonged and also includes ADM; (3) a different postoperative chemotherapy for poor responders did not improve their prognosis; and (4) a multidrug regimen using high doses of MTX is probably more effective than moderate doses.

Eighteen evaluable children with recurrent Langerhans' cell histiocytosis (LCH) which was resistant to standard therapy, were treated with etoposide (VP 16-213), 200 mg/m2/day for 3 days every 3 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses were demonstrated in 15 patients (83.3%). Only one of the 12 children achieving a complete remission has relapsed. No dose-limiting major toxicities were registered. Although etoposide might be an effective treatment in recurrent LCH which needs a chemotherapeutic approach, it is emphasized that this drug must be used carefully.

Smooth-muscle antibodies (SMA) were detected in 16 of 18 (89%) children with neuroblastoma and in 43 of 172 (25%) pediatric hospital patients without malignancies. The SMA were mainly of the IgG class. The most common immunofluorescence pattern was SMA-V (vessel) and titers did not exceed 1:160. Absorption and immunodiffusion tests with action (from rabbit skeletal muscle) showed that the SMA associated with neuroblastoma are mainly directed against actin, although different antigen specificities (myosin, meromyosin) are probably involved in some cases. In both chronic active hepatitis and neuroblastoma, SMA would represent a specific response to intracellular contractile proteins (mainly actin) induced by tissue damage. A feedback role in controlling cellular proliferation has been postulated for experimentally raised SMA. This would be relevant in cases of malignancy.