Hodgkin's disease in Indian children: outcome with chemotherapy alone

BACKGROUND: To assess the efficacy of chemotherapy alone, using four cycles of COPP alternating with four cycles of ABVD in all stages of childhood Hodgkin's disease (HD). PROCEDURE: Between January 1991 and February 2001, 148 previously untreated patients were investigated, treated, and analyzed for remission and survival. RESULTS: There were 134 boys and 14 girls with a median age of 8 years, 75% were less than 10 years old. 63.5% had advanced stage disease (IIB-IV). B symptoms were present in 54.4% of cases; bulky mediastinal mass in 18 cases (12.2%); spleen and bone marrow involvement in 22 (14.9%) and four cases (2.7%), respectively. Mixed cellularity (MC) subtype was found in 86.0%. Response to treatment was evaluated in 133 patients: complete remission (CR) was achieved in 121 patients (91.0%), partial remission (PR) in seven (5.3%), progression occurred in two (1.5%), and three (2.3%) died on therapy. Four patients with mediastinal residual disease were given additional involved field radiotherapy. Out of 111 patients analyzable, five (4.5%) have relapsed 6-30 months after completing chemotherapy, and were treated with additional cycles of ABVD and low-dose involved field radiotherapy. The 5-year actuarial overall survival (OS) and event-free survival (EFS) are 91.5 and 87.9%, respectively. Advanced stage, B symptoms, anemia, spleen, and marrow involvement were adverse prognostic factors for survival. CONCLUSIONS: Chemotherapy alone with alternating COPP/ABVD, without additional radiotherapy, provides high rates of durable remission and is an effective therapy in childhood HD, even in case of large mediastinal mass and peripheral or abdominal bulky disease.     

Cyclical combination chemotherapy and thyroid function in patients with advanced hodgkin's disease

Clinical and biochemical assessment of thyroid function was undertaken in patients with Hodgkin's disease at designated points following diagnosis. At diagnosis, two of 20 patients had either abnormally low routine thyroid indices, or elevated thyroid stimulating hormone (TSH) levels that were not due to iodine-based investigations. Following lymphography, 76.5% of patients had TSH levels that remained elevated for a median period of 3 months. No detectable thyroid dysfunction was induced during chemotherapy. Fifty-four patients were studied at a median time of 35 months after chemotherapy. One euthyroid patient had a nodular goitre, and one had abnormal thyroid indices. TSH levels were elevated in 44% of patients, although the median TSH level for the group was normal. Half the patients had abnormal TRH stimulation tests. Sixty patients were studied after irradiation and chemotherapy. Four patients had clinical thyroid dysfunction, and 10% of routine thyroid indices were abnormal. TSH levels were abnormal in 80%, with a markedly elevated median level. All thyroid releasing hormone stimulation tests were abnormal.     

Comparison of the clinical course of hodgkin's disease in children and adolescents

In this study the clinical features and response to therapy of 34 children, 4–10 years of age, and 54 adolescents, 11–20 years of age, were compared. The therapeutic response in patients in this series entered on a formal protocol was compared with nonstudy patients. The 2 age groups had similar sex ratios, characterized by male predominance, and age was not a determining factor in the extent of disease at diagnosis. By contrast, the distribution of histopathology varied between children and adolescents: mixed cellularity was most prevalent in the 4–10-year group (14/34), while nodular sclerosis predominated in the older patients (23/55). Remission induction and duration were not age dependent, but remission duration did differ between study and nonstudy patients. Forty-five of 57 patients in the former group remain in continuous complete remission compared to 7 of 31 in the latter group. From these results we conclude that the clinical course of Hodgkin's disease is similar in children and adolescents and that the aggressive therapy combined with careful staging used so successfully in adults should be adhered to in younger patients.     

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.     

Hodgkin's disease in children

From 1921 to 1973, 106 children with Hodgkin's disease under the age of 17 years were seen at Roswell Park Memorial Institute and were analyzed retrospectively. Evaluation was separated into three eras: 1921–1949 (early era), 1950–1964 (middle era), and 1965–1973 (recent era). In the early era, suboptimal radiation therapy was employed. In the middle era, radiation therapy techniques were improved, and single-agent chemotherapy was introduced. In the recent era, multiagent chemotherapy routines were frequently used; aggressive external megavoltage radiation therapy became routine in conjunction with improvement in staging procedures. The best survival was observed in the recent era where five-year survival of 96% was noted in early stage disease. Favorable prognostic features included: younger age group (5–9 years), female sex, lymphocytic predominant histology, early stage disease, and complete response to therapy. Nodular sclerosing and mixed cell types had an equal prognosis. The concept of involved area radiotherapy along with combination chemotherapy appears a reasonable approach in children and should be tested in a randomized study against more extensive radiotherapy techniques in early stage disease.     

Randomized study for the treatment of adult advanced Hodgkin's disease: Epirubicin,vinblastine, bleomycin,and dacarbazine (EVBD) versus mitoxantrone,vinblastine, bleomycin,and dacarbazine (MVBD)

Seventy patients with previously untreated advanced Hodgkin's disease and without bulky disease were entered in a prospective randomized clinical trial comparing epirubicin in combination with vinblastine, bleomycin, and dacarbazine (EVBD) with a regimen containing mitoxantrone, vinblastine, bleomycin, and dacarbazine (MVBD). Both groups were comparable for the variables of age, sex, stage, and presence of B symptoms and histology. Thirty-one (88%) of EVBD-treated patients achieved a pathologically documented complete remission (CR) compared to the 24 cases (68%) of the MVBD-treated group. After a median follow-up of 36 months, duration of CR is better in the EVBD-treated patients with an actuarial 5-year duration of CR of 80%, statistically different to the MVBD group: 53% (P < 0.01). Both regimens ahowed the same gastrointestinal toxicity, but the patients treated with the MVBD regimen shown most and severe hematological and cardiac toxicities. Also, biochemical alterations in hepatic test were observed in these patients. The alternative use of epirubicin in combination chemotherapy appears to be as effective in advanced Hodgkin's disease without bulky disease, with reduced clinical toxicity. Mitoxantrone containing regimen was not found to have an equivalent efficacy and clinical toxicity was most frequent and severe. We feld that mitoxantrone could be consider a second-line drug in the treatment of advanced Hodgkin's disease. © 1994 Wiley-Liss, Inc.     

Combination chemotherapy of advanced previously treated Hodgkin's disease with streptozotocin,CCNU, adriamycin and bleomycin

Seventeen patients with advanced, previously treated Hodgkin's disease received therapy with a combination of streptozotocin 500 mg/m² /day i.v. days 1–5, CCNU 100 mg/m² orally day 1, adriamycin 45 mg/m² i.v. day 1, and bleomycin 15 mg/m² i.m. days 1 and 8 at 28-day intervals (SCAB). The overall response rate was 59% with six patients (35%) achieving complete remission and four patients (24%) entering partial remissions. No maintenance therapy was given and the median duration of complete remission was 8+ months (range 2+–18+ months), while the median duration of partial remission was only 2 months (range 2–3 months). The median duration of survival from the start of therapy for the complete responders was 16+ months (range 5+–25+ months) while the median survival for the partial and nonresponders was only 5 months (range 2–13 and 3–11+ months, respectively). Toxicity was a major problem with this drug combination. Myelosuppression occurred regularly and was severe after 25% of courses. There were two death directly related to drug-induced myelosuppression. Other serious toxicities included bleomy cin-induced pulmonary toxicity in three patients, with one death; renal tubular dysfunction secondary to streptozotocin in three patients; hepatic dysfunction in three patients and severe weight loss in three patients. SCAB has proven to be an active although toxic combination which is not cross-resistant to MOPP-type regimens. Alterations in drug dosages and scheduling are being evaluated in an effort to ameliorate toxicity and preserve efficacy.     

Treatment of Hodgkin's disease in children with alternating mechlorethamine,vincristine, procarbazine,and prednisone (MOPP) and adriamycin,bleomycin, vinblastine,and dacarbazine (ABVD) courses without radiotherapy

Since the introduction of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, children with Hodgkin's disease (HD) have been treated with chemotherapy alone. The occurrence of side effects related to irradiation (especially secondary solid tumors) is less likely to occur. Alkylating agents in the MOPP chemotherapy combinations are, however, known for their late effects, i.e., gonadal dysfunction and secondary malignancies. Combination with non-alkylating and non-cross-resistant drugs (as in the adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] combination) may give superior treatment results and possibly a decrease in the occurrence of side effects. From 1988 to 1993 all children presenting with HD were treated with alternating MOPP and ABVD courses (3 × MOPP, 3× ABVD). Twenty-one children (7 females, 14 males), ages 5–18 years (median 14 years) were included; their clinical stages were 1, 7 patients; II, 8 patients; III, 5 patients; IV, 1 patient. Their pathology revealed 2 lymphocytic predominance, 17 nodular sclerosis, 1 mixed cellularity. In 1 patient only cytology was done and thus histopathologic subclassification was not possible. Two children have relapsed; disease-free survival is 90%. Analysis of toxicity revealed no decrease in cardiac function by ultrasound examination and no pulmonary effects noted by carbon monoxide diffusion. In 1 of the 10 children tested, mild hypogonadism was noted. No secondary tumors occurred. From this small population of children with HD we conclude that treatment with MOPP/ABVD for 6 cycles without radiotherapy may be adequate. The occurrence of gonadal dysfunction may be less frequent than with 6 cycles of MOPP. However, more patients and further follow-up are needed. Med. Pediatr. Oncol. 29:23–27, 1997. © 1997 Wiley-Liss, Inc.     

Results of a randomized study of early stage Hodgkin's disease using ABVD,EBVD, or MBVD

From January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse-free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen. Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone-containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease. © 1995 Wi1ey-Liss Inc.     

Epstein-barr virus (EBV) latent membrane protein (LMP) in tumor cells of Hodgkin's disease in pediatric patients

Twenty-nine out of 31 consecutive pediatric patients with Hodgkin's disease treated at our hospital from 1988 to 1992 were studied. The selection criterion was the availability of sufficient formalin-fixed, paraffin-embedded tissue for analysis. Patient age ranged from 3 to 15 years with a median age of 7 years. Lymph node biopsies were examined for the presence of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP) in malignant cells by peroxidase immunolabeling. LMP positivity was present in 10/15 (67%) of mixed cellularity, 1/6 (17%) of lymphocyte predominance, 0/7 (0%) of nodular sclerosis, and 1/1 (100%) of lymphocyte depletion. Positive cases by age range were: 10/12 (83%) for 3–6 years and 2/17 (11%) for 7–15 years. The association between EBV and Hodgkin's disease in children appeared to be more frequent in patients with mixed cellularity and those in the 3–6 age range, though examples of EBV-positive tumors were found in other histologic subtypes, stages and ages. Findings indicate that Hodgkin's disease in children is at least as strongly linked to EBV as in adults. Furthermore, we suggest that the EBV is associated with a subgroup of patients which can be defined on the basis of the age at diagnosis. © 1995 Wiley-Liss, Inc.     

Simultaneously occurring alopecia areata and Hodgkin's lymphoma: Complete remission of both diseases with MOPP/ABV chemotherapy

A 43-year-old man presented with simultaneously occurring alopecia areata and stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's disease were present for 6 months, and rapidly developing patchy hair loss of the scalp was present for 2 weeks prior to presentation. The patient was treated with eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of Hodgkin's disease. Four months after the completion of chemotherapy, the patient had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may be an autoimmune disease and may respond to chemotherapy. © 1992 Wiley-Liss, Inc.     

Castleman's disease of the mesentery in a child: A case of seven years' duration without typical x-ray findings

This report describes a 9-year-old boy with intermediate variant type of giant lymph node hyperplasia or Castleman's disease (CD) originating from the mesentery. He had symptoms and signs related to the disease for seven years before the final diagnosis. The patient's general condition remained good, except for periods of fever and abdominal pain. Pallor and slow growth were the only abnormal findings on physical examination during the follow-up. Laboratory measurements showed worsening microcylic anemia, low serum iron level, and low iron stores in bone marrow samples. The erythrocyte sedimentation rate (ESR) increased to 110 mm/h, and the serum levels of C-reactive protein varied between 80 and 120 mg/l. The level of serum albumin was low, 25–28 g/l, and serum immunoglobulin G was somewhat elevated, varying between 17–13 g/l. The radiologic examination of intestine gave pathological results suggesting a small bowel disease, but no tumor was detected. The abnormal laboratory values and symptoms of the patient resolved completely after surgical removal of the mass. Med. Pediatr. Oncol. 28:362–365, 1997. © 1997 Wiley-Liss, Inc.     

Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine and etoposide (DBVE) and radiation: a Pediatric Oncology Group (POG) study

PURPOSE: The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD). PATIENTS AND METHODS: Between August 1992 and December 1993, 51 eligible children < or =21 years of age, 31 male and 20 female, were enrolled in this study which was designed for low stage (IA, IIA, IIIA1) HD. Laparotomy and surgical staging was optional. Five postpubertal patients with Stage IA and IIA disease received only involved-field radiation therapy. The other 46 patients, who form the basis of this report, received combined modality therapy consisting of four courses of doxorubicin, bleomycin, vincristine, and etoposide (DBVE) followed by 2,550 cGy involved-field irradiation. RESULTS: With a median follow-up of 8.4 years, the 6-year overall and event-free survival rates for the 46 patients treated with combination therapy were 98 +/- 2% and 91 +/- 5%, respectively. All patients achieved remission after completion of therapy. There have been four recurrences and a remission death due to gunshot wound. Combined modality therapy was well tolerated. Predominant side effects were gastrointestinal and hemopoietic. There have been no clinically significant cardio-pulmonary side effects so far. CONCLUSION: In clinically staged children with early-stage HD, DBVE and low-dose involved-field irradiation was effective therapy with tolerable side effects and reduced potential for long-term adverse events.     

Hodgkin's disease and non-Hodgkin's lymphoma in children and young adults: A clinicopathologic study of 127 cases

One hundred twenty-seven cases of non-Hodgkin's lymphoma and Hodgkin's disease in children and young adults at the University of Wisconsin Hospital between 1969 and 1980 have been reviewed. Nodular sclerosing was the most frequent histologic type in patients with Hodgkin's disease. Malignant lymphoblastic lymphoma (MLLB) was the most common type of non-Hodgkin's lymphoma. The relationship of the histological pattern to age and sex as well as clinical behavior and survival are discussed.     

Late recurrence in Hodgkin's disease: A report of two cases

Two cases of Hodgkin's disease are described who relapsed 22 and 19 years after regional radiation therapy. One of the patients also developed a carcinoma of the large bowel soon after first relapse. The importance of long follow-up and documentation of cause of death in Hodgkin's disease is stressed.     

儿童克罗恩病诊断和治疗的10年临床经验总结

目的分析儿童克罗恩病（Crohn’s disease,CD）临床特点、总结10年来的诊治经验,促进对儿童CD的认识,提高诊断治疗水平。方法对1996至2005年诊断为CD的9例患儿的临床资料及诊治结果进行分析。结果本组9例,男8例,女1例,年龄6—13岁。平均病程10个月。病变单独累及小肠者3例,小肠和大肠同时受累者6例。腹痛和腹泻是最常见的胃肠道症状。主要的肠道外表现为体重下降、低蛋白血症、轻度贫血、发热和低钙血症。结肠镜下主要的病变有溃疡、节段性病变、鹅卵石样改变、多发性息肉和肛周病变。1例行胶囊内镜检查见典型纵形裂隙样溃疡和鹅卵石样改变。内镜活检组织病理检查以非特异性黏膜慢性炎症为主,2例见非干酪样肉芽肿（22．2％）。2例手术标本均未检出非干酪样肉芽肿。7例患儿予5氨基水杨酸（5-ASA）口服,部分加用抗生素和营养治疗,2例加用肾上腺皮质激素。现3例患儿维持长期缓解。结论儿童CD诊断需特别强调排除感染性腹泻。CD患儿常见的体重下降和营养障碍可为诊断提供重要线索。合适的剂型和较大剂量的5-ASA[30—50mg／（kg·d）]对诱导和维持缓解有较好疗效。     

Epstein-Barr virus infection,Hodgkin's disease,non-Hodgkin's lymphoma,and reactive follicular hyperplasia in Japanese children: Evaluation of paraffin-embedded specimens using polymerase chain reaction and immunohistochemistry

Epstein-Barr virus (EBV) infections are common in Japanese children, with infections by EBV type 1. The relationships between EBV infection and lymphadenopathies in Hodgkin's disease (HD), non-Hodgkin's lymphomas (NHL), reactive follicular hyperplasia (RFH), and infectious mononucleosis (IM) in 37 Japanese children were evaluated. Formalin-fixed, paraffin-embedded lymph node specimens that were obtained at surgical resection or biopsy were evaluated for the presence of EBV DNA and the latent membrane protein-1 (LMP-1) using polymerase chain reaction (PCR) and immunohistochemical staining. The PCR detected EBV DNA in nine of 13 (69.2%) patients with RFH, including a case of IM, all three (100%) patients with HD, and one of 21 (4.8%) patients with NHL. All EBV-positive samples contained EBV type 1. Reed-Sternberg's cells in HD were immunohistochemically positive for LMP-1, whereas all cases of RFH and NHL were negative for LMP-1. Results suggest that EBV infection may be related to HD. Although no proof exists that EBV infection contributes to the transformation of cells, thus causing RFH or NHL, the present authors suggest that the EBV-positive cases in Japanese children demonstrate a relationship between the clinical and histopathological features of the lymphadenopathy and EBV-type 1 infection.