Biomedical subjects
Publications and source records attributed to G Paolucci.
A total of 17 pediatric patients with pretreated acute lymphoblastic leukemia were included in a phase II study of idarubicin. Four of 16 complete remissions were obtained, confirming the activity of the drug in this indication. Toxicity was acceptable, though caution is needed in patients who have already received high cumulative doses of anthracyclines.
A phase II multicenter evaluation of cisplatin (90 mg/m2, Day 1) and etoposide (150 mg/m2, Days 2, 3, and 4) in 4-week cycles was carried out in 21 relapsed children with rhabdomyosarcoma (RMS) and six with non-RMS soft tissue sarcomas (NRSTS). Clinical responses were evaluated after four cycles. There were three complete responses (CRs) and four partial responses (PRs) among the 21 patients with RMS and no responses among the patients with NRSTS. The durations of the three CRs and the four PRs were 11, 9, and 8 months, and 5, 2, 2, and 1 month, respectively. Bone marrow and renal toxicity was cumulative and predictable, but not life threatening. The response rate (CR + PR = 33.3%) to cisplatin and etoposide warrants testing as front-line therapy for RMS.
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This retrospective study was undertaken to evaluate the clinical characteristics, course and treatment of children (0-14 years of age) diagnosed with a primary CNS tumor during the period 1976-1982 in Italy. Four hundred and sixty-two patients (263 males and 199 females) were followed by 18 various neurosurgical and pediatric oncology centers. The histologic types most frequently reported were: medulloblastoma (23%), astrocytoma (16%), ependymoma (11%) and spongioblastoma (11%). Of the 388 patients who underwent surgery, radical excision was reported in 42%, partial excision in 32%, biopsy only in 6%, and unqualified surgery in 4%; 19% had no surgery. Radiotherapy and chemotherapy combined were administered in 61% of the 143 patients followed at pediatric oncology centers; 19% received radiotherapy alone, 3% chemotherapy alone, and 17% neither treatment. Forty-six percent of the patients were reported alive, 40% dead, and 14% lost to follow-up. Performance status was identified for 62 patients. The investigation revealed marked differences in the therapeutic treatment administered, thus precluding valid data analysis. This emphasizes the need to coordinate efforts among the institutions and the disciplines involved in the treatment of this form of childhood cancer.
Nine cases of adrenocortical tumor are presented, six were males. Four were less than three years and five were between 5 and 10 years of age. Clinical virilization was found in 8 children, one had only signs of hypercortisolism and another showed signs of virilization and hypercortisolism simultaneously. Urinary 17-KS and 17-OHCS were high in all patients. Plasma levels of testosterone and of the other adrenal androgens were high in all the cases tested. Plasma level of cortisol was elevated only in few cases. In two out of five cases steroids were only partially suppressed by dexamethasone. Computed tomography and abdominal sonography have been useful tools for the localization of the tumour. The resection of the tumour, independent of histopathological diagnosis, led to a complete normalization of the clinical and hormonal picture in eight cases evaluated at a distance of 2 months 10 years after surgery. In one case a hepatic metastasis was observed and removed three years after surgery.
From June 1976 to December 1984, 48 previously untreated children with non-Hodgkin's lymphoma (NHL) were treated according to the LSA2-L2 protocol, modified by inclusion of cranial irradiation for patients in stage III and stage IV disease. According to the staging system proposed by Wollner, 4 patients were in stage I, 8 in stage II, 11 in stage III, 8 in stage IVA (less than or equal to 25% blasts in the bone marrow), 15 in stage IVB (greater than 25% blasts in the bone marrow), and 2 in stage IV central nervous system disease. The complete remission rate was 95.8%. The relapse-free survival (RFS) rate of 46 complete responders was 76% after a median observation time of 47+ months. Only 1 of 35 high-risk responder patients developed CNS relapse after prophylactic treatment. Clinical stages were related to the RFS: 100% in stage I-II vs. 69% in stage III-IV. All 8 patients in stage IV were alive without evidence of disease with a median observation time of 59+ months. Fifteen patients in stage IVB who had leukemia-lymphoma syndrome attained 59% RFS with a median observation time of 39+ months. After a median observation time of 38+ months, 29 of 37 patients are off therapy. The results emphasize the value of both the histologic and immunologic features and the stage of disease in predicting the outcome of NHL in children. The LSA2-L2 regimen appears to be a very effective protocol for children with lymphoblastic lymphoma, although it may be less efficacious for patients with large bone marrow involvement.
This paper reviews a series of 70 consecutive children with rhabdomyosarcoma (RMS) diagnosed during 1971-1978 and treated in five Italian institutions. Thirteen were classified as group I, 12 as group II, 37 as group III, and 8 as group IV according to the Intergroup RMS Study staging system. Survival was influenced by tumor extension at diagnosis, primary site, and response to therapy. The 5-year-survival rate was 92% for group I patients, 67% for group II, 44% for group III, and 0% for group IV. Thirty-four children had all therapy stopped after 12-32 months of complete remission, 7 had late recurrences, and 3 died from disease. Musculoskeletal sequelae were diagnosed in 11 children, short stature in 3, corneal opacity in 2, and cardiac failure in 1.
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The clinical features of 30 children with IV-S neuroblastoma have been reviewed. They were treated at 11 Italian pediatric institutions in the period 1970-1981. Patients with IV-S neuroblastoma comprise 6.1% of all the neuroblastoma cases observed during that period. The age at diagnosis ranged from birth to 11 months (mean, 3 months). The distribution of "primary" lesions was of interest. The adrenal gland was affected most often (57% of patients), but tumors of the chest and neck were also encountered. No specific "primary" lesion was identified in ten children. The most frequent site of widespread disease was the liver (87%). Neither the size of the "primary" tumor, nor the number or size of subcutaneous nodules was of prognostic significance. Unfavorable features were age less than 2 months and clinical signs of pulmonary, renal, or hepatic embarrassment. These data confirm the need for prompt intervention in the infant who is suffering from compression of these vital structures by the enlarged liver. Radiation therapy is to be preferred for this purpose, because of the often severe toxicity that is associated with chemotherapy in infants. One, and possibly two babies in this series died of chemotherapy-related complications.
In this retrospective multicentric study, we report on early deaths (ie, those that occurred during the first month of treatment) in a total of 943 newly diagnosed ALL pediatric patients registered from 1976 to 1981 at 21 centers of the AIL- AIEOP . Objectives of this study were as follows: (1) to verify the incidence and the cause of early death in a wide population of children with ALL and (2) to elucidate factors associated with early death and therefore to identify "high-risk" groups of patients. Out of the 943 ALL patients, 39 (4.1%) early deaths were registered. Main causes were infection, 20 patients (51.3%); hemorrhage, 11 patients (28.3%); uric acid nephropathy, 2 patients (5.1%); cardiac failure, 3 patients (7.6%); syndrome of inappropriate antidiuretic hormone secretion, 1 patient. Two patients died during the first week of unknown cause. Thirteen factors measured at diagnosis and possibly influencing the early death rate were analyzed. Using the chi-square test, only three of these factors (age, mediastinum status, surface markers) appear to have any significant influence on the early death rate. We also tried to determine how therapy influences this process by analyzing variations in the early death rate, other factors being equal. Significant differences in the early death rates were encountered in AIEOP protocols using different induction regimens.
PTC, a mixture of oligopeptides of m-L-sarcholysin, acting primarily as an alkylating agent, was utilized as initial therapy following diagnosis in 80 children with nonlocalized neuroblastoma. Of the 67 evaluable patients (21 Stage III, 41 Stage IV and five Stage IV-S), 51 had measurable lesions allowing to evaluate PTC activity; objective tumor responses to the drug were recorded in 45 of these 51 cases (88.2%); 5/5 Stage III, 37/41 Stage IV, 3/5 Stage IV-S. Complete responses were obtained in seven patients (13.7%), partial responses in 32 (62.7%), objective improvement in six (11.8%). Four patients (7.8%) had either no tumor change, or tumor progression. There have been two early drug-related deaths (3.9%). Stage III and IV patients responding to PTC were then treated by irradiation + VCR, followed by cycles of a combination of ADriamycin, vincristine, and cyclophosphamide. Stage IV-S patients received no further therapy. Thirteen of 21 Stage III (61.9%), five of 41 Stage IV (12.2%) and four of five Stage IV-S (80%) are presently alive from 19-48 months (median, 27 months). PTC is an effective agent in advanced neuroblastoma. However, the results of this report do not indicate that its addition to a "standard" treatment, at least in the schedule adopted in this protocol, has improved the final outcome of children with nonlocalized disease.
Thirty-four infants under 1 year of age with Wilms' tumor were diagnosed and treated in 14 Italian pediatric oncology units during 1970-79. The 3-year survival rates decreased with higher group unilateral tumors: 95% in group I Wilms' tumor, 75% in group II and 20% in group III. The survival rates for children with group I and II Wilms' tumor were similar for those who were treated with surgery and chemotherapy and those who also received postoperative radiotherapy. During 1975-79 fewer patients with group I Wilms' tumor received radiotherapy (1 of 11) than during 1970-74 (4 of 6, p less than 0.05). All these children are alive at this writing.
Hereditary neuroblastoma in a pair of identical twins is reported. In one of the twins the tumor occurred in fetal life and caused death of the twin before birth; in the other one, the tumor occurred at two months of life as IV-S neuroblastoma in the liver with primary tumor undetected. The unusual clinical course of the latter case is described: twice there was tumor regression, but in spite of treatment, fatal uncontrolled growth occurred. The family history, characterized by neoplasms of dissimilar cell types but without additional cases of neuroblastoma, is also detailed.
A phase II evaluation of vindesine (VDS) was carried out in 46 patients with hematologic malignancies refractory to conventional chemotherapy. Two VDS schedules were employed (at random): (A) a weekly bolus (5 mg/m2 i.v. X 4); (B) fractionated daily injections (0.5 mg/m2 i.v. q.12 h X 10, course to be repeated after 10-15 days). Complete and partial remissions were observed in acute lymphocytic leukemia (3/14 patients), acute non-lymphocytic leukemia (2/12 patients), chronic myelocytic leukemia in blastic crisis (4/12 patients) and non-Hodgkin's lymphoma (4/8 patients). Responses were seen with higher frequency in patients treated with the weekly bolus (42.8 vs 16%). Myelosuppression was the most relevant side effect in both schedules. Neurotoxicity occurred infrequently and was generally mild in degree. Further trials with VDS in combination with other drugs are recommended in hematologic malignancies.
Among 727 children with acute lymphocytic leukemia (ALL) observed at eight pediatric clinics in Italy in the years 1967-1974, 200 (27.5%) survived for more than five years after diagnosis. The proportion of long-term survivors rose significantly during the years 1970-1974 when aggressive therapeutic programs with curative intent were uniformly adopted in Italy (19.8% vs. 29.4%; P less than 0.05). Clinical and laboratory data at diagnosis of the 200 long-term survivors were analyzed and compared with that of the 527 nonsurvivors. We found that, besides a leukocyte count greater than 50,000 cells/mm3, other factors such as early central nervous system CNS leukemia and the presence of mediastinal mass were predictive of a poorer prognosis for long-term survival. Life-table analysis revealed that the chance of long-term survival was significantly higher in those children who have survived for five years without relapse (82.9% vs. 24.1%; P less than 0.01). Although late initial relapse is always possible, if a child with ALL remains in continuous complete remission for at least nine years, it is likely that the patient is cured.
From June 1976 to May 1980, 25 previously untreated children with non-Hodgkin's lymphoma (NHL) were studied and treated with a protocol modified from the one (LSA2L2) proposed by Wollner [8]. Stage III and IV had, in addition, prophylactic treatment of the central nervous system (CNS) with cranial irradiation (2,400 rad plus intrathecal methotrexate). The complete remission rate is 96%. Of these patients, 76% are disease free surviving after a median observation time of nearly two years. The disease-free actuarial survival is 100% for 6 children with Stage I-II disease and 68% for 19 Stage III-IV children after median observations times respectively 25 + and 19 + months. None of the 19 high-risk patients developed CNS disease after prophylactic treatment. Mediastinal involvement and leukemia conversion at diagnosis were not unfavorable prognostic factors, but primary skeletal or subcutaneous disease and Burkitt-tupe histology were ominous features in patients treated by this regimen. It is concluded that good results are obtained when an aggressive multimodal and multiple drug regimen like the LSA2-L2 is coupled with CNS prophylaxis and is used assiduously to maintain complete remission during the first 12 months of treatment.
The results of discontinuing therapy in children with acute lymphocytic leukemia observed at four associated institutions are presented. Of the 247 patients who achieved complete remission, 122 (49.3%) reached the point of discontinuing therapy after 2-4 years of continuous remission. The median period off therapy was 13 months with a range of 1-69 months. Of the 122 children removed from therapy, 27 (22.1%) relapsed, mainly in the bone marrow; relapses occurred 1-32 months after cessation of therapy (median ten months) with only two relapses occurring later than two years. By actuarial analysis, 57% of the patients are projected in continuous remission after five years from cessation of therapy. Neither selected features at diagnosis nor single modalities of treatment were found to predict whether relapse would occur after discontinuing therapy. Long-term remission and possibly cure can be expected in over one-third of newly diagnosed children with ALL after 2-4 years of antileukemic treatment.