Combination chemotherapy of Hodgkin's disease in children

Forty-five children with advanced Hodgkin's disease (stages III and IV) received combination chemotherapy in three schedules: MOPP (mustargen, Oncovin, procarbazine, prednisolone); COPP (cyclophosphamide was substituted for mustargen); and CVPP (cyclophosphamide, vinblastine, procarbazine, prednisone). The results showed the efficacy of all drug combinations (93% complete and partial remissions). However, the superiority of the MOPP program in prolonging the duration of the complete remission rate was demonstrated. Of 29 patients who showed complete response, 24 continued in complete remission from 8 to 53 months (median duration, 21 months). The other five patients relapsed within 2 to 6 months. Thirty-six of the 45 treated patients are still alive after an average period of follow-up of 19 months. The nine patients who died were followed for an average of seven months. The histologic type, prior chemotherapy, and the age of the patients influenced the results of treatment. The role of maintenance therapy is not discussed in this series     

Hodgkin's disease in two children of mother treated with nitrogranulogen

Hodgkin's disease was diagnosed in a 12-year old boy and a 2-year old his sister whose mother had been treated with repeated cycles of nitrogen mustard for optic neuritis. The mother received the first treatment two years prior to the boy's birth, and subsequently, in recurrent optic neuritis, three years prior to the birth of the girl.     

Treatment results for rhabdomyosarcoma in children

The results of treatment in 45 children with rhabdomyosarcoma was presented. Two-years survival was achieved in 63% and five-year in 45%. The importance of location and group of clinical progression discussed was importance prognostic factors in rhabdomyosarcoma.     

The results of radiotherapy managements in Hodgkin's disease (author's transl)

We reported the results of radiotherapy managements in Hodgkin's disease about 185 patients. From this study, it seems to appear possible to confirm or to note some particular facts: the real good prognosis of the forms begining in the right sus-clavicular fossa; the special staging of the long time survival patients (II Aa, type II); the small value in survival of chemotherapy done before and/or after radiotherapy in the I and II stages; in the other side, the true amelioration comming from chemotherapy in the III and IV stages; the value of irradiation by expanded fields; the particular interest of the total mode irradiation done at the beginning or during the course of the illness; the optimal dose of larger than or equal to 4 000 rads with a weekly dose of larger than or equal to 1 000 rads; the good tolerance of the radiotherapy. From this prelimary study, we hope dowing well in further with a greater number of patients.     

Clinical spectrum of chronic liver disease in north Indian children

Recent advances in serodiagnosis of hepatotropic viruses have revolutionized the approach to diagnosis and understanding of chronic liver disease (CLD). There are few studies on CLD in children from India. The present study was planned to define the clinical spectrum of CLD in children, its histopathology and seroepidemiology. Forty children with clinical features satisfying the criteria for diagnosing chronic liver disease were studied. All underwent routine laboratory investigations, liver function tests and ultrasound scan of the abdomen. Liver biopsy, upper GI endoscopy and other special investigations were done wherever indicated. The most common presenting features were jaundice (70%), fever (67%), and abdominal distention (60%). On examination hepatomegaly and icterus (80% each) and splenomegaly (67%) were the commonest findings. Serum transaminases were raised in 62.5% of children while prothrombin time was prolonged in 75% patients. Oesophageal and/or gastric varices were seen in 13 out of 29 patients subjected to upper GI endoscopy. Hepatitis B surface antigen (HbsAg) was positive in 5 children (12.5%) while 3 (7.5%) tested positive for anti HCV antibody. The commonest histopathological diagnosis was infantile cholangiopathy (20%) followed by cryptogenic cirrhosis and idiopathic chronic active hepatitis (17.5% each). The study suggests that the incidence of chronic hepatitis B and C is rather low in childhood. However larger and longer studies are required to delineate the exact incidence of these conditions in childhood and their progression in adolescence and early adulthood.     

Hodgkin's disease in children: clinico-roentgenologic features of the lesion in the chest

The roentgenologic features of Hodgkin's disease were studied in 105 patients under 14 years of age. The mediastinal and hilar nodes were involved in 64.7% of patients. Some consistency of extent and pattern of disease was observed in that mediastinal lymphatic lesions could be associated with cervico-supra-clavicular and retroperitoneal lesions. There was lung infiltration in 14.3% of patients and the frequency of this lesion dependent on the histological type. It was commoner in nodular sclerosis, mixed cellularity and lymphocytic depletion. Lung infiltration usually developed in continuity with the lymphatic gland lesion and only rarely in a metastasis-like form.     

Hodgkin's disease in siblings

An incidence survey of Hodgkin's disease in Greater Boston during 1959-1973 detected five sibling pairs under the age of 45. The expected number is 0.7; thus, siblings of young adults with Hodgkin's disease have about a sevenfold excess risk of the disease (P = 0.0008). Eight sibling pairs, not in the incidence series, were also identified. Among all 13 pairs, 12 were sex concordant; the number expected is 6.8 (P = 0.01). The literature includes 46 sibling pairs under 45 of which 30 are sex concordant. The expected number is 23.9 (P = 0.05). Combining the present and the literature series suggests that siblings of the same sex as an affected person have a risk of Hodgkin's disease double that of siblings of the opposite sex. The sex concordance suggests that the excess Hodgkin's disease among siblings of affected persons is due either to inter-personal transmission of an etiologic agent by prolonged or intimate contact or to common-source exposures.     

Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy in advanced Hodgkin's disease

The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy regimen with limited radiotherapy in relation to the promising preliminary data. Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered according to a schedule derived through hybridization, intensification, and shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46 of whom were in complete remission after chemotherapy. Remissions were complete in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor-specific, overall, relapse-free, and failure-free survival at 5 years were 0.89, 0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable, whereas nonhematologic side effects were fully acceptable. Most of the unfavorable prognostic factors lost their clinical weight. Only age and lymphocyte depletion histologic type were statistically correlated with major follow-up endpoints; performance status and bone marrow involvement were subordinate to age. Seven patients developed a second cancer (including 3 myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective regimen in advanced Hodgkin's disease. Early and late toxicity are no more severe than what would be expected with other alternating or hybrid regimens. A comparison with ABVD, which is currently considered the standard regimen for advanced Hodgkin's disease, is needed.     

Cytogenetics of Hodgkin's disease

Cytogenetic studies over the past 35 years have made a major contribution towards the understanding of the nature of Hodgkin's disease by demonstrating unequivocally the consistent presence of a clonal population of cells that have the cardinal features of malignancy e.g. more or less gross aneuploidy, frequently with complex chromosomal changes and showing considerable variation from case to case, thus comparable to the findings in carcinomas and other solid cancers. The mode is frequently in the triploid-tetraploid region, as we found in 17 of 27 cases studied in this laboratory by Feulgen microspectrophotometry, compared to only 10 cases with neardiploid modes. It is disappointing that no specific change, such as a translocation that could give a clue to the chromosomal location of a gene or genes involved in the etiology of Hodgkin's disease, has yet been found. Nevertheless it is clear that a number of nonrandom changes, including several that are also common in other malignancies including the non-Hodgkin's lymphomas, are frequently present, e.g., deletions of 1p, 6q, and 7q. Interestingly, deletions of 4q, with loss of 4q25 --> q27, that have also been reported may show some specificity for Hodgkin's disease.     

Fibrin deposits in Hodgkin's disease

Fibrin deposits were observed in the involved lymph nodes and/or spleens of 15 patients with Hodgkin's disease by specific immunofluorescence and by electron microscopy. Two basic patterns of fibrin deposition were observed: 1) intercellular deposits, chiefly associated with nonneoplastic-appearing lymphoid cells and 2) deposits associated with the collagen fibers of young connective tissue. In addition, coarse fibrin deposits were observed in areas of necrosis, presumably a non-specific finding. Fibronectin was also observed in intercellular areas, but staining was less intense than for fibrin. Fibrin deposits were also observed in 3 of 6 cases of non-Hodgkin's lymphoma, indicating that the finding is not an exclusive feature of Hodgkin's disease. The pathogenesis and possible significance of fibrin deposition in Hodgkin's disease are related to earlier observations of activation of the coagulation system on neoplasia and cell-mediated immunity and to the possible role of fibrin, fibronectin, and their breakdown products in angiogenesis and fibroplasia.     

Secondary amyloidosis in Hodgkin's disease

One case with secondary amyloidosis is described, manifested by a nephrotic syndrome, 13 years after the establishment of lymphogranulomatosis in a male, ages 46. Amyloidosis diagnosis with biopsy, after a long-term remission in a patient with a relatively restricted lymphogranulomatosis is of certain interest. The diagnostic difficulties of secondary amyloidosis in Hodgkin disease are discussed as well as the mechanism origination and the role of certain medicaments in amyloidosis origination and treatment.     

Telomerase activity in Hodgkin's disease

Telomere maintenance executed by the action of telomerase seems to be a prerequisite for immortalization. Telomerase is found in most cell lines and malignant tumors. A telomerase-independent mechanism for telomere maintenance in Hodgkin's disease has been proposed in the absence of detectable telomerase activity. In this study, telomerase activity was detected in 31 of 77 Hodgkin's disease samples and a strong correlation between eosinophilia and absence of detectable telomerase activity was found. Purified eosinophils and specifically eosinophil-derived neurotoxin and eosinophilic cationic protein, both ribonucleases, were found to degrade telomerase. Purified neutrophils also exhibited weak telomerase degradative activity. Reanalysis of previously telomerase-negative Hodgkin's disease samples with eosinophilia using ribonuclease inhibitors resulted in the detection of telomerase activity. Ribonuclease-containing cells in vivo thus have a considerable impact on the detectability of telomerase. In Hodgkin's disease samples without eosinophilia, 24 of 27 exhibited telomerase activity at decreased levels compared with non-Hodgkin's lymphomas and at increased levels compared with reactive nodes indicative of a telomerase positive tumor component in Hodgkin's disease. Telomerase positivity of the Hodgkin's and Reed-Sternberg cells in vivo was also supported by high levels of telomerase expression in Hodgkin's disease cell lines. Based on our data, Hodgkin's lymphomas are potential targets for antitelomerase therapy.     

Role of autotransplantation in Hodgkin's disease

Autologous bone marrow transplantation offers the opportunity for long-term disease-free survival in patients with Hodgkin's disease who might be considered incurable with other treatments. The appearance of late relapses in some reports is worrisome, but it is hoped that the majority of long-term survivors are indeed cured. Fundamental questions remain concerning the best conditioning regimen, the best rescue source, the optimal timing of transplantation, and ultimately whether transplantation is better than conventional salvage techniques. Some of these answers may be provided if long-term follow-up studies are reported and results are analyzed with reference to known prognostic factors. Ultimately, prospective trials will be needed to more clearly define the role of transplantation in Hodgkin's disease. It is hoped that ongoing trials will lead to higher remission rates, lower relapse rates, and diminished transplant-related mortality.