Epstein-Barr virus antibody in childhood Hodgkin's disease

Fifteen patients with childhood onset of Hodgkin's disease were studied for prevalence and quantity of Epstein-Barr virus (EBV) antibody to learn about the relationship between infection with EBV and Hodgkin's disease. Findings indicated that, compared with normal child control subjects, prevalence of EBV antibody is not increased in Hodgkin's disease, but the quantity of antibody increases as the duration of Hodgkin's disease increases. It seems that EBV plays no role in the cause of Hodgkin's disease and that production of greater amounts of antibody relates to immunoregulatory defects associated with Hodgkin's disease.     

Second malignant tumours in childhood Hodgkin's disease

This study was undertaken to determine the treatment-specific incidence of second malignant tumours (SMT) in childhood Hodgkin's disease. The institutional databases at The Hospital for Sick Children, the Princess Margaret Hospital, and the Toronto-Bayview Regional Cancer Centre were reviewed for the years 1958–1993. Three hundred and forty-three consecutive newly diagnosed children were evaluated. The overall 30 year cumulative SMT incidence was 31%. The 20 year SMT incidence was greater for patients who relapsed (n = 129), 27%, compared with patients who remained relapse free (n = 214), 13%. For patients with stage 1–3B disease who remained relapse free, the 10 year SMT rate was 7% for patients who were surgically staged and treated with extended field radiation treatment (EF RT) (35 G), compared with 3% in clinically staged patients treated with MOPP (six cycles) and EF RT (25–30 G). To date there is no significant difference in the oncogenicity of these treatment protocols. However, EF RT alone was less effective in disease control. For stages 1–3B, 62% of patients relapsed after EF RT alone compared with 18% after bimodal treatment. Therefore treatment intensification due to relapse was more frequent in the former group. The overall 10 year SMT incidence for patients treated with these protocols was 11% and 3%, respectively. The 20 year SMT incidence following EF RT alone was 24%. We conclude that SMTs were a common late complication in childhood Hodgkin's disease and are a limiting factor in the achievement of cure. The incidence of SMTs was increased in children who required retreatment and was minimal in children who remained in a first complete remission. Therefore the initial treatment strategy in childhood Hodgkin's disease must be to minimize the risk of relapse, in order to avoid the morbidity and mortality associated with both relapse and SMT induction, and to achieve this objective with a primary treatment protocol of low oncogenicity. © 1996 Wiley-Liss, Inc.     

Chemotherapy and irradiation in childhood Hodgkin's disease.

Eighty children aged less than 16 years with newly diagnosed Hodgkin''s disease were treated between 1974 and 1982. Complete remission occurred in 95%, with actuarial five year overall survival of 94%, and relapse free survival of 82%: median follow up was 4.8 years. Sixty one children were staged clinically while 19 had staging laparotomies before treatment. Most received combined modality treatment with Ch1VPP chemotherapy (chlorambucil, vinblastine, procarbazine, and prednisolone) followed by irradiation of initial bulk disease. Nodular sclerosis predominated in both sexes, accounting for 60% of the total. Girls with stage IV disease, nodal sclerosis histology, and bulky mediastinal masses had a relatively poor prognosis. Ten children have relapsed, and three prolonged (6 to 7 years) second remissions have been observed. Four died of disease, and one from infection. Clinical staging, avoiding splenectomy, reduced the risk of serious infections. Our current policy is to treat stage IA disease with local irradiation and all other stages with chemotherapy, adding irradiation for bulky mediastinal disease.     

Hodgkin's disease and renal paraneoplastic syndromes in childhood

The purpose of this study was to investigate children followed as having both Hodgkin's disease (HD) and nephropathy and discuss the factors which might play roles in the pathogenesis of this association by reviewing the pertinent literature. Our experience among 661 children with HD revealed ten cases (1.5%) with nephropathy; eight of these were biopsy proven. Tissue diagnoses were amyloidosis (AA type) in four cases, and membranoproliferative glomerulonephritis and minimal change glomerulopathy in two cases each. Sex distribution was equal. There was a predominance of the mixed cellular (MC) histologic type in our patients with HD. Nephropathy was shown to antedate the diagnosis of HD in two cases and to herald a relapse in one. In brief, the development of a nephropathy in a patient with HD can be considered as a paraneoplastic phenomenon. Renal amyloidosis may already be present at the time of diagnosis of HD and must be kept in mind as a cause of proteinuria due to preexisting nephropathy. Developing renal paraneoplastic syndrome, even in early-staged HD, in children, may be a poor prognostic factor.     

Secondary Hodgkin's disease in childhood acute lymphoblastic leukemia

Improved survival in childhood acute lymphoblastic leukemia has led to the occurrence of second malignancies in these patients. Hodgkin's disease is very rare as a second malignancy. We report three patients with acute lymphoblastic leukemia in remission who developed Hodgkin's disease. Although all had received low-dose irradiation, none received alkylating agents as part of their chemotherapy. Review of our cases and of 11 reported in the literature revealed unique aspects of this association. There was a short median interval of 19 months to the development of the second malignancy. Over one-third of the patients had uncommon sites of involvement (lung, tonsil, small bowel). The distribution of histologic subtypes was unusual, as 5 of 14 cases had lymphocyte depletion or unclassifiable Hodgkin's disease. The results of therapy were excellent. Our three patients are alive, with both malignancies in continuing remission. Two patients are off all therapy for 4 and 6 years, respectively. The third remains on antileukemic treatment. Secondary Hodgkin's disease in childhood acute lymphoblastic leukemia does not appear to have a poor prognosis and long-term survival and possible cure of both diseases may be achieved.     

Gonadal function following chemotherapy for childhood Hodgkin's disease

Gonadal function was assessed in 101 postpubertal subjects after chemotherapy for childhood Hodgkin's disease. All had received ChIVPP (chlorambucil, vinblastine, procarbazine, and prednisolone) chemotherapy alone, with no radiotherapy below the diaphragm. Gonadotropin levels were available in 46 (79.3%) male and 32 (74.4%) female subjects. The mean age at diagnosis in the male cohort was 12.2 years (range 8.2–15.3) and in the females 13.0 years (9.0–15.2). The males and the females were studied at a median of 6 years (range 2.5–11.1) and 4.3 years (range 1.9–11.5) from diagnosis, respectively. Forty-one (89.1%) male subjects had elevated follicle-stimulating hormone (FSH) levels, confirming severe germinal epithelial damage. Germinal epithelial damage was seen in subjects up to 10 years out of therapy. Subtle Leydig cell dysfunction was identified in 24.4% with raised luteinizing hormone (LH) levels. All subjects, however, progressed spontaneously through puberty. Seventeen (53%) women had raised gonadotropin levels, with variable estradiol levels. Of these, 10 subjects presented with symptomatic ovarian failure and 6 received hormone replacement therapy (HRT). Nine women had 11 successful pregnancies, two of whom had previously had symptoms of ovarian failure with one requiring HRT. A much higher prevalence of ovarian failure has been observed, than has previously been considered in the prepubertal and pubertal female following combination chemotherapy. These conclusions have important implications for future counseling, management, and research in this population. © 1996 Wiley-Liss, Inc.     

Berger's disease in childhood]

Berger's disease or IgA nephropathy (NIgA) is the most common form of glomerulonephritis in the world. In children macroscopic haematuria is the first sign in about 80% of the patients. Renal failure appears in 20% of cases after twenty years of follow-up. The most important prognosis indicators are a nephrotic syndrome at the onset, a proteinuria > 1 g/24 hours, diffuse tubulo-interstitial lesions and extracapillary proliferation with crescents in more than 50% of the glomeruli. The pathogenic mechanisms are just emerging and involve a disrupted process of the systemic tolerance to mucosal antigen with abnormal mucosal gamma delta T cell repertoire, abnormally glycosylated IgA1 molecules and a down-regulation of Fc alpha receptors on blood cells. After IgA deposition, the mechanisms of mesangial cell damage and activation involve vascular factors as endothelin/nitric oxide system, cytokines and growth factors such as interleukine-6, platelet derived growth factor and transforming growth factor beta. There is no curative treatment but steroids are useful in diffuse proliferative extracapillary forms, when histological activity score is high with a short delay between diagnosis and treatment, or for moderately severe NIgA with normal renal function.     

Treatment of childhood Hodgkin's disease with ABVD without radiotherapy

Seventeen previously untreated children with Hodgkin's disease were treated with six courses of the combination adriamycin, bleomycin, vinblastine, and DTIC (ABVD), without radiotherapy, from 1984–1987. In all patients, complete remission was attained. After a median follow-up period of 73.5 months (range 59–98 months), five patients had a relapse after 4, 5, 11, 21, and 34 months, respectively, from attainment of complete remission. In 12 patients with stages I and II, two relapses occurred. Three out of five patients with stage III and stage IV developed a relapse. Based upon these results, we conclude that ABVD might be an appropriate treatment for newly diagnosed children with Hodgkin's disease stages I and II. However, for children with stages III and IV, more intensive treatment is needed. Radio-therapy should be withheld for children with refractory disease, residual disease, or relapse. © 1996 Wiley-Liss, Inc.     

Sonography in the diagnosis of Hodgkin's disease in childhood and adolescence

We are reporting about the results of the staging by ultrasound in 11 children with Hodgkin's disease. Sonography stands the test as a method that reliably predicts abdominal involvement in patients with Hodgkin lymphoma. Only in a few cases an indication for an additional computerized tomography is given. A demonstration of typical ultrasonic findings takes place.     

Gonadal function after combination chemotherapy for Hodgkin's disease in childhood.

The effect of quadruple chemotherapy (mustine, vincristine, procarbazine, and prednisolone) on gonadal function was investigated in 15 males and 2 females treated for Hodgkin''s disease during childhood. The 2 females have regular menstrual cycles with evidence of ovulation in one. Twelve of the males have shown normal progression of pubertal development since completing their treatment. Nine out of 10 late pubertal or adult subjects had small testes but only one developed gynaecomastia. All 4 prepubertal subjects had normal basal and peak gonadotrophin responses to luteinising hormone-releasing hormone. Nine of the 12 subjects studied during puberty or adulthood had either an increased basal serum follicle-stimulating hormone (FSH) level or an exaggerated FSH response to luteinising hormone-releasing hormone. Each of the 6 males who provided semen for analysis was azoospermic after an interval of between 2.4 and 8 (mean 5.3) years after completion of treatment. We conclude that severe testicular damage is common after treatment with mustine, vincristine, procarbazine, and prednisolone in childhood. The germinal epithelium is particularly vulnerable and the resultant azoospermia is likely to be irreversible. The Leydig cells are less susceptible to cytotoxic-induced damage. Pubertal development is normal and there is no indication for androgen replacement therapy.     

Management of childhood lymphomas—Hodgkin's disease and non-Hodgkin's lymphomas

Hodgkin's disease can be cured in greater than 70% of the children diagnosed. Overall 5-year survival rates now approach 90% and approximotely 80% for 10-year survival. Combination chemotherapy along with irradiation has decreased the relapse rate in all stages of Hodgkin's disease. Intensive chemotherapy and irradiation therapy is associated with long-term complications including development of second malignant tumors. Optimum therapy is the minimum therapy associated with uncomplicated care. In 80 to 90% of children with non-Hodgkin's lymphoma the disease is widerspread when obvious clinically at diagnosis, and the first site of relapse is commonly the bone marrow or central nervous system (CNS). Combined chemotherapy, irradiation and CNS prophylaxis has resulted in 50% to 80% 3-year, disease-free survival. Patients with mediast'nal or extensive intrabdominal disease have a poor prognosis.     

Perineal lesions in childhood Crohn disease]

BACKGROUND: Perineal lesions (PAL) usually evolve together with bowel disease and often constitute a serious and disabling complication of Crohn's disease. PATIENTS: Forty-three children (47%) with Crohn's disease developed PAL in a retrospective study of 92 patients ranging in age from 4 to 20 years. RESULTS: PAL occurred at the mean age of 11.4 +/- 0.7 years, prior to diagnosis in 25% or subsequently in 21%. PAL were severe: complex fistulae (15%), rectovaginal fistulae (2%), anal raggedness (13%); moderate: subcutaneous fistulae (11%), abscesses (19%), cavitating ulcers (9.5%) and stricture formations (5.7%); or mild: eczema (6.7%), fissures (57%) and skin tags (17%). An association with these various features has been observed in 31%. The extent of involvement of the gastrointestinal tract was rectosigmoid (72%), ileal and colonic (41%), ileal with pancolitis (12%). Two PAL course profiles were observed: one with exacerbation and remissions (52%), the other without remission (48%), especially anal raggedness (100%), cavitating ulcers (80%) and skin tags (61%). Medical treatment included steroids (54%), metronidazole (53%), salicylates (51%), nutritional support (44%), azathioprine (17%). PAL healed in 41%. Surgical treatment was performed in 27% with 83% of healing. Relapses occurred in 35% after medical treatment and 86% after surgery.