Improved outcome for acute lymphoblastic leukemia in children of a developing country: results of the Chilean National Trial PINDA 87.

BACKGROUND: The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. PROCEDURE: From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12-18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 instead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. RESULTS: Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% +/- 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5-9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. CONCLUSIONS: We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series.

C-reactive protein: a valuable aid for the management of febrile children with cancer and neutropenia.

The usefulness of determining serum levels of C-reactive protein (CRP) for the identification of bacterial infections in febrile neutropenic patients with cancer was evaluated. Two hundred children with cancer were monitored prospectively for the occurrence of neutropenia and fever; serum was collected from these children for determining baseline levels of CRP. Of these 200 children, 75 had 85 febrile neutropenic episodes; serum was collected daily from these 75 children for CRP analysis by nephelometry. Children were included into one of the three following groups by physicians blinded to results of CRP analysis: group I, demonstrated bacterial infection (24 episodes); group II, probable bacterial infection (31 episodes); and group III, viral infection or no infection (30 episodes). Baseline CRP values were low (mean, 9 mg/L; range, 0-35 mg/L) irrespective of tumor type or stage of therapy. Mean CRP values on day 1 for children in groups I and II (194 and 143 mg/L, respectively) were higher than those for children in group III (29 mg/L) (P < .001). A CRP value of > 40 mg/L discriminated children with a demonstrated bacterial infection (sensitivity, 100%; specificity, 76.6%). Children with an unfavorable outcome had persistently high levels of serum CRP. For children with cancer, neutropenia, and fever, determination of the serum CRP level is useful for early diagnosis of bacterial infections and for monitoring the course of infection.

Intra-arterial cisplatin given prior to surgery in osteosarcoma: grade of necrosis and size of tumor as major prognostic factors.

From January 1983 to August 1987, 29 evaluable patients with high-grade osteosarcoma were treated in our institution with preoperative intra-atrial cisplatin, 100 mg/m2 every 14 days for three courses. Surgery was done on day 42. Surgery consisted of limb salvage in six, amputations in 15, and disarticulations in eight. Postoperative chemotherapy included Adriamycin (ADR), 45 mg/m2 for 2 days every 6 weeks, alternated with cisplatin 120 mg/m2 every 6 weeks. The nephrotoxicity (18 out 29) was reversible in all cases. Cardiotoxicity was prominent; it was observed in 31% of patients. In six, there was congestive heart failure, but there were no fatal cases. The hematological toxicity was severe. There were three patients with fatal infections who had no evidence of disease after they had finished treatment. Seventeen of 29 patients (58.6%) were good responders and showed 60-100% tumoral necrosis after intra-atrial cisplatin. The 6-year, relapse-free survival rate was 58.6%--70.5% for the good responders and 41.6% for the poor responders (p less than 0.05). The size of the tumor was the other important prognostic factor. The rate of 6-year, relapse-free survival was 73.6% for small tumors (those measuring less than 100 cm2) and 33.3% for large tumors (p less than 0.05).

[Second cancer in pediatric patients]. / Segundo cáncer en pacientes pediátricos.

Studies were made on the appearance of second malignant tumors (SMT) in children followed in a pediatric hospital at metropolitan Santiago, Chile, between years 1968 and 1987. A retrospective analysis identified SMT in 7 of 430 patients who survived a childhood cancer (incidence 1.62%). An 8th patient was added, whose first neoplasm was treated in another hospital. The initial diagnosis in the affected children were medulloblastoma, neuroblastoma, Wilm's tumor retinoblastoma, Ewing's sarcoma, Hodgkin's disease and, in two cases, acute lymphocytic leukemias. The age range was 6 months to 11 years. Treatment was done by surgery in 5/8, chemotherapy in 7/8 and radiotherapy in all patients. The latent period between the diagnosis of the first cancer and the diagnosis of the SMT was 3.5 to 12 years (median 8.5 years). Osteosarcomas were the most frequent SMT (5/8). The other SMT were a rhabdomyosarcoma, a non Hodgkin lymphoma and an astrocytoma. The majority of SMT were located in the area of prior radiotherapy (6/8). In the other two cases, one had an osteosarcoma, after a bilateral retinoblastoma, which grew outside the previously treated area, and the last one consisted of a lymphoma which was identified 9 years after an acute lymphocytic leukemia. Only 3/8 SMT patients are alive after 14.21 and 34 months follow up. The other children died between 11 and 20 months after diagnosis of SMT. Notwithstanding these kinds of outcome, benefits of therapy for patients with primary tumors greatly outweight the later risk of cancer induction in a small proportion of them.

Infantile embryonal carcinoma of testis.

Between 1968 and 1979 we treated 19 patients with infantile embryonal carcinoma of the testis. All 10 patients treated with orchiectomy plus chemotherapy (methotrexate, actinomycin D and cyclophosphamide) are well with no evidence of disease, whereas 2 of 4 who underwent orchiectomy alone and 2 of 5 treated with orchiectomy plus lymphadenectomy are dead. Infantile tumors with yolk sac elements have an apparent increase in hematogenous spread and, despite negative lymph nodes in the majority, a significant number have subsequent disseminated metastases. This suggests that infantile embryonal carcinoma is different from the adult type and implies that in clinical stage A disease retroperitoneal lymphadenectomy is unnecessary. The alpha-fetoprotein correlates with the presence of yolk sac tissue in biopsy and the radioimmunoassay level assists in monitoring the treatment.