High incidence of treatment failure with vincristine, etoposide, epirubicin, and prednisolone chemotherapy with successful salvage in childhood Hodgkin disease

BACKGROUND AND PROCEDURE: In an attempt to further reduce the long-term toxicity of chemotherapy for childhood Hodgkin disease (HD), the Australian and New Zealand Children's Cancer Study Group between 1990 and 1996 enrolled 53 children with biopsy-proven and imaging-staged HD into a chemotherapy-only treatment regimen using 5-6 courses of vincristine, etoposide, epirubicin, and prednisolone (VEEP). RESULTS: There were 23 events in these children with 3 progressive disease (PD), 8 partial remissions (PR), and 12 relapses. In the stage I patients, there were 8 events (35%). There was no association between the number of events and the stage of HD. Massive mediastinal disease at diagnosis was present in 16 patients, 11 of whom had an event with 3 PD, 3 PR, and 5 relapses. For all patients with an event at 6-24-month follow-up, all but two patients were salvaged with either alkylating agent-based chemotherapy alone or with irradiation and chemotherapy. The event-free survival for the whole group with median follow-up of 33 months was 59%, but only 31% for massive mediastinal disease. Disease-free survival was 78% and overall survival at 60 months was 92%, with one death due to drug-induced aplasia and another from acute myeloid leukemia. CONCLUSIONS: We conclude that VEEP chemotherapy in childhood HD used as the only treatment modality has an unacceptably high treatment failure rate in patients with massive mediastinal disease and 35% incidence of treatment failure in stage I disease.     

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.     

Results of Treatment of 18 Children With Hodgkin Disease With MOPP Chemotherapy as the Only Treatment Modality

Eighteen children with Hodgkin disease (16 previously untreated; two relapsed) were treated with MOPP chemotherapy (nitrogen mustard, vincristine, prednisone, procarbazine) only. Ten had clinical stage I and II disease, four had stage III, and four had stage IV. In ten patients, the clinical stage was confirmed by staging laparotomy. Six courses of MOPP were given to eight stage I and II patients and two stage IV patients. Between 7 and 12 courses were given to two stage I and II, and six stage III and IV patients. Dose reduction of 75-50% was required in 13% and delay of treatment in 22% of the first six courses of MOPP. Hematologic toxicity, minor and major viral infections, and nausea and vomiting were the major complications. Complete remission (CR) was obtained in 17 patients. Of these 17, there has been one death in CR, and one relapse. Sixteen patients have discontinued treatment and have been observed off treatment for 8 months to 7.5 years. The actuarial disease-free survival with a median follow-up of 28 months is 80% and overall survival is 92%.     

Hodgkin's disease in children: Treatment with MOPP and low-dose,extended field irradiation without laparotomy late results and toxicity

The 10 year results of a trial of bimodal treatment of Hodgkin's disease in children with 6 cycles of MOPP and low-dose extended field irradiation, without staging laparotomy, were for 57 children in all stages as follows: survival 85%, relapse-free survival 80%, and survival-free of second relapse 86%. There were three fatal toxic events, two due to viral infection and one to a second malignant tumor (NHL). Three other patients developed a second malignant tumour, and one developed a thyroid adenoma. No patient developed acute leukemia. These results are compared with the results of treatment of surgically staged children by extended field irradiation alone, with bimodal treatment reserved for relapse or advanced disease at diagnosis. Initial bimodal treatment improved the overall 10 year survival free from a second relapse rate by 20% (86% vs. 66%). No major difference in treatment toxicity between these two groups has emerged during the first 10 years of follow-up. We conclude that, except for favourable CS-1 presentations, children with Hodgkin's disease confined to the lymphatic system should be given bimodal treatment, but that the least morbid effective combination remains to be determined.     

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.     

MOPP therapy in children with Hodgkin's disease

Between 1979 and 1987, 28 children with Hodgkin's disease were treated with MOPP (nitrogen mustard, Oncovin, prednisone, procarbazine) combination chemotherapy without radiotherapy. Twenty-four were staged clinically. Splenectomy was performed in four only. Staging was as follows: nine (32%) in stage I, five (18%) in stage II, nine (32%) in stage III, and five (18%) in stage IV. Histologic types were lymphocytic predominance in five (18%), mixed cellularity in 15 (54%), nodular sclerosis in seven (25%) and lymphocytic depletion in one (4%). All children achieved complete remission. Two in stages III and IV relapsed and were salvaged with additional chemotherapy and radiotherapy. Twenty-six are in continuous relapse-free remission for periods ranging from 2 to 9 years. The relapse-free survival rate of 92% and survival rate of 100% compares favorably with results obtained using combined modality treatment.     

5岁以上神经母细胞瘤患者的临床特点及疗效分析

目的 总结5岁以上神经母细胞瘤（NB）患儿的临床特点及疗效,为改善其预后提供理论基础。方法 回顾性分析54例初治NB患儿临床资料,进行临床特点、疗效总结以及Kaplan-Meier生存分析。结果 54例患儿中男36例、女18例,均为3、4期。以腹膜后占位最多见（76%,41/54）,其次为纵隔占位（18%,10/54）、椎管内占位（4%,2/54）和盆腔占位（2%,1/54）。截止至随访日期,54例患儿中存活30例（56%）：无病生存23例（77%,其中9例为复发再度化疗后完全缓解）、肿瘤部分缓解6例（20%,均为复发再度化疗患儿）、进展1例（3%,为复发再度化疗后进展）;死亡24例（44%）,其中22例为复发再度化疗后死亡、2例为初治期间多脏器衰竭死亡;治疗、随访期间共38例复发。Kaplan-Meier生存分析提示：54例患儿平均生存时间53.8个月;3期患儿总生存率（OS）为80%,高于4期患儿（53%）,差异具有统计学意义（P < 0.01）;复发患儿平均生存时间（51.68个月）低于无复发病例（62.57个月）,差异有统计学意义（P < 0.01）。结论 年长儿NB临床分期多属晚期,但规律治疗仍可提高疗效,应增加患儿信心,坚持规范治疗。     

儿童霍奇金淋巴瘤34例临床分析

目的 认识儿童霍奇金淋巴瘤(HL)的病理及临床特点,总结根据危险度分层治疗即化疗联合低剂量受累野放疗的疗效,探讨治疗相关毒性作用.方法 前瞻性研究2003年1月至2009年4月我院治疗的34例霍奇金淋巴瘤患儿;全部行活检病理形态及免疫组化检查,参照世界卫生组织(WHO)2001病理分型标准诊断、按霍奇金淋巴瘤An arbor分期标准分期.根据患儿不同的危险因素及对治疗反应将患儿分成低危、中危、高危3个治疗组.结果 男28例,女6例;以Ⅲ期、Ⅳ期居多.22例为经典混合细胞型(64.7%).侵犯部位广泛;巨大瘤块18例(52.9%);大于4个淋巴结区受累16例;B组症状15例.25例行EB病毒感染指标即潜伏膜蛋白(LMP)或EB病毒编码RNA(EBER)染色,100%阳性.随访时间(26.1±16.3)个月.低危组0例,中危组14例,高危组20例.总体生存率100%、预计5年无事件生存率94.1%;中、高危患儿Ⅲ、Ⅳ度血液学不良反应累积发生率分别为40.0%和70.8%.结论 儿童时期霍奇金淋巴瘤男多于女,与EB病毒相关,病理以混合细胞型居多,预后相对较好,根据疾病危险度进行联合化疗及低剂量受累野放疗方案的近期疗效可靠,但随访时间尚短,需进一步观察远期不良反应.     

NASAL-PARANASAL-ORONASOPHARYNGEAL LYMPHOMAS IN CHILDHOOD: The Role of Staging System on Prognosis

Most of the patients with nasal-paranasal and oropharyngeal-nasopharyngeal (NPONP) lymphomas had early-stage disease according to the Murphy system. But the survival rates are not correlated with the stages. Treatment results were analyzed to see the effects of the staging in NPONP lymphomas. Fifty-five children (median age 8 years, M/F: 4.5) with NPONP lymphoma were included in this study. The Murphy staging system was used at diagnosis and all cases were restaged according to the TNM system: primary tumor, regional lymph node, and metastasis. The survival rates were analyzed by grouping the patients according to the treatment and stages. The disease was located in Waldeyer's ring, the sinonasal region, and the nasopharynx in 45.4, 27.3, and 27.3% of patients, respectively. Thirty-nine patients had stage I or II disease according to the Murphy system. When the TNM system was used, 92% of these patients were upstaged to stage III-IV. Five-year overall and event-free survival rates were 52.1 and 50.4%, respectively, for the whole group. Five-year event-free survival rates for Murphy stage I, II, and III disease were 66.7, 56.9, and 45.4%, respectively. The rates for TNM stage III and IV patients were 64.3 and 43.8%. Treatment protocols were intensified in most of the early-stage disease treated with modified LSA2-L2 regimen and better survival rates were obtained in these patients. The intensification of the treatment by using intrathecal treatment and doxorubicin in patients with early-stage disease at NPONP location seems effective. In conclusion, the Murphy staging system is not suitable for the staging of NPONP lymphomas. It should be revised to predict the prognosis and decision-making for treatment.     

Precocious puberty as initial presentation in mediastinal tumour

Numerous disorders can cause precocious puberty in children, and germ cell tumours (GCT) are one of the rare causes. We report two cases of mediastinal malignant GCTs who presented with precocious puberty. Both patients had bulky and advanced disease, were aggressively treated with neo-adjuvant chemotherapy and surgery, and are surviving and free of disease.     

TESTICULAR GERM CELL TUMORS IN PREPUBERTAL CHILDREN

Pediatric testicular germ cell tumors are rare. Fifteen children, all less than 5 years of age, were evaluated and treated during February 1987 to July 1996. The median age was 18 months (range, 4-60 months). All were staged according to the Pediatric Oncology Group/Children's Cancer Study Group staging system. Seven patients had stage III disease. Histologically, 9 patients had pure endodermal sinus tumor, 1 had endodermal sinus tumor with embryonal carcinoma, 1 had embryonal carcinoma alone, 2 had immature teratoma, and 2 had mature teratoma. Six children were kept on surveillance. All others received chemotherapy with cisplatin, bleomycin, and vinblastine. The 10-year actuarial overall survival rate was 86.7%.     

How curable is relapsed Wilms' tumour? The United Kingdom Children's Cancer Study Group.

Three hundred and eighty one children with Wilms'' tumour were treated on the United Kingdom Children''s Cancer Study Group WT1 Study (1980/6). Seventy one patients relapsed during or after treatment, which included surgery and chemotherapy, with irradiation depending on stage and histology. Despite treatment with various combinations of chemotherapy, surgery, and radiotherapy there were only 17 survivors. For unfavourable histology, any stage, only two of 20 survive. We conclude that, after relapse, even for patients who have had localised disease and favourable histology, the ''salvage'' rate is little more than 50% and for all others the likelihood of cure is very small. Three of 41 children who relapsed less than 12 months from diagnosis survive, compared with 14 of 30 who relapsed later. It is essential that even with this ''good prognosis'' tumour initial treatment is optimal and given by centres experienced in management of children''s cancer. Furthermore, there is a clear need for additional effective chemotherapeutic agents for relapsed patients.     

Involved field (IF) irradiation with or without chemotherapy in the management of children with Hodgkin's disease

The present policy at Memorial Sloan Kettering Cancer Center (MSKCC) of treating children with Hodgkin's disease [HD] is as follows: involved field (IF) irradiation only (3,600 rad) for Stages IA and IIA; IF irradiation (2,400 or 2,000 rad) combined with multidrug chemotherapy (MDP) protocol for all other stages. A somewhat higher recurrence rate is accepted for Stages IA and IIA in view of the good salvage rate for these recurrences and in view of side effects of more aggressive types of radiation treatment. One hundred forty-two patients with HD, 2-19 years of age, were treated at MSKCC between 1970 and 1981; 98 of these were treated according to the present policy (SP group), and 44 (NP group) were treated differently. All SP patients underwent staging laparotomy. The follow-up time was 12 to 146 months with a median of 65 months; two patients were lost to follow-up. For the SP group, all stages, 10-year disease-free survival is 77%, and 10-year survival is 93%. By comparison, in the NP group 10-year disease-free survival is 64%, and 10-year survival is 80%. The disease-free survival of SP patients in Stages IA and IIA treated with IF radiation alone is 72%, and survival is 95%. The disease-free survival of SP patients in advanced stages treated with combined radiation and chemotherapy is 87%; the salvage rate of recurrent disease in these stages is poor. The survival was apparently better (P = 0.07) in the SP group as compared to the NP group. All 6 patients of the SP group who died had a nodular sclerosing type of HD. None of the patients in the SP group have developed secondary malignancies, and no severe bone growth retardations or late effects to other organs were observed. In our opinion, IF irradiation alone might at present be suitable treatment for children in Stages IA and IIA of Hodgkin's disease, and addition of IF radiation with low doses of MPD improves the survival of patients in advanced stages.     

Significance of splenomegaly in childhood Hodgkin disease

OBJECTIVES: Spleen involvement in childhood Hodgkin disease (HD) has not been described extensively. The authors' purpose was to study the clinicoradiologic features and prognostic significance of splenomegaly and that of splenic involvement in childhood HD. METHODS: One hundred forty-one children presenting with HD between January 1991 and February 2001 and treated with chemotherapy alone (4 COPP/4 ABVD) were included in the study. Radiotherapy was given in four patients with residual mediastinal disease. Patients were staged clinically and assessed for splenic deposits by computed tomography, ultrasonography, or both. RESULTS: Splenic involvement was seen in 22 children (15.6%). On univariate analysis, spleen deposits were significantly correlated with constitutional symptoms (P = 0.02), splenomegaly on physical examination (P < 0.001), involvement of three or more lymph node areas (P = 0.006), involvement of subdiaphragmatic lymph nodes (P = 0.01), mediastinal involvement (P = 0.001), and bulky disease (P = 0.005). Multivariate analysis retained enlarged spleen, involvement of three or more lymph node areas, and bulky disease as significant risk factors for spleen involvement. Relapse occurred significantly more in children with splenic involvement (P = 0.04) and in those with splenomegaly (P = 0.04). Presence of splenic deposits was an adverse prognostic factor for 5-year event-free survival (67.5% vs. 93.0%, P = 0.01). CONCLUSIONS: Enlarged spleen, involvement of three or more lymph node areas, and bulky disease are predictable risk factors for HD splenic deposits. Splenic involvement on computed tomography scan or ultrasonography is significantly associated with relapse and contributes to a poorer outcome of HD in children treated with chemotherapy alone.     

Prognosis of Hodgkin’s disease in india

In a study of 388 patients with proved Hodgkin’s disease, peak age incidence was found to be between 10 to 30 years. Mixed cellular pattern was the most common pattern on histopathology which is more common in India than in Western countries where nodular sclerosis is seen in greater number of patients. Of 388 patients 149 were subjected for exploratory laparatomy and splenectomy for proper staging. Patients were treated with extended radiotherapy for stage I and II disease, and 84% and 73% of patients respectively had 5years survival period. In stage III and IV disease combined chemotherapy regime led to cure in 19–40% of cases. The newer developments have changed the total outcome of the disease which was considered as fatal illness only two decades ago.     

Treatment of pediatric Hodgkin disease avoiding radiotherapy: excellent outcome with the Rotterdam-HD-84-protocol

BACKGROUND: To reduce radiotherapy (XRT) induced toxicity of treatment of children with Hodgkin disease (HD) while maintaining a high cure rate, we introduced a risk-adapted protocol consisting of chemotherapy (CT) alone in 1984. PROCEDURE: The outcome of 46 children treated for HD from 1984 until 2000 according to the Rotterdam-HD-84-protocol was determined. Children with stage I-IIA disease (n = 23), were treated with six courses of epirubicin, bleomycin, vinblastine, and dacarbazine (EBVD). Children with stage IIB-IV disease (n = 23), were treated with three to five alternating cycles of EBVD and mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). RESULTS: At a median follow-up time of 8.6 years (range 2.6-18.3 years), the 10-year overall survival (OS) is 95% and the event-free survival (EFS) 91%. In 5/46 patients XRT was administered because of residual mediastinal mass. Four children relapsed, two of them died. Up until now only one patient developed hypothyroidism; no symptomatic cardiac or pulmonary dysfunction, no second malignancy has been diagnosed. CONCLUSIONS: Risk-adapted treatment consisting of CT alone is highly efficacious for children with HD and toxicity is low. XRT was administered in only a small minority of children with HD. CT should be the first choice for HD in children and XRT should preferably be used for those with refractory or histologically proven residual disease or relapse.     

Long-term control of central nervous system leukaemia.

Seventy-four children with acute lymphoblastic leukaemia had one or more episodes of central nervous system (CNS) leukaemia. 5 children had CNS involvement at diagnosis; 4 survived for less than one year. In 35 children who had not had a previous bone marrow relapse on treatment and who received combination chemotherapy, the median duration of haematological remission from the time of first CNS relapse was almost 3 years. 5 children received full dose (2400 rads) craniospinal irradiation after their first CNS relapse; 4 have remained in CNS and haematological remission for 2 1/2 years or more. 18 children who had a CNS relapse after irradiation received 4-weekly intrathecal methotrexate; in 8 children this was given via an intraventricular reservoir. The median duration of CNS remission in children receiving intrathecal methotrexate was 2 years. Systemic and intrathecal treatment was stopped in 7 children after 2 1/2 years in continuous remission and in 2 children after 2 years. 4 of these 9 children remain in remission at intervals from 41 to 69 weeks off treatment but one is severely retarded. These results show that CNS disease is compatible with prolonged survival, but illustrate the difficulties of eradicating established CNS leukaemia.     

14例肝母细胞瘤患儿的临床疗效观察

目的：通过对儿童肝母细胞瘤患儿的临床治疗结果的回顾总结,对ICE化疗方案的有效性和安全性进行评估。方法：自2000年6月至2008年6月,14例初发患儿入选,男7例,女7例,中位年龄：1.33岁（范围0.25～8.25岁）。临床分期：Ⅰ期6例,Ⅱ期1例,Ⅲ期5例,Ⅳ期2例。诊断时血甲胎蛋白（AFP）水平显著升高13例,1例AFP正常。采用多科室协作模式进行治疗,其中一期手术8例,3例进行了二期手术。化疗方案采用ICE方案,14例患儿共接受了73个疗程化疗,其中术前化疗25个疗程。结果：14例患儿治疗后有效12例（85.7%）,其中完全缓解10例（71.4%）,部分缓解2例,2例无效。随访至2008年7月31日,疾病处于长期完全缓解者9例（64.3%）,中位随访时间为35个月（范围：16～96个月）。5年总生存率（OS）为：（70.71±12.37）%,5年无事件生存率（EFS）为：（64.29±12.81）%。1例患儿复发,2例失访。结论：ICE化疗方案联合手术治疗能有效并且安全地治疗儿童肝母细胞瘤,Ⅳ期患儿的治疗有待于进一步研究。［中国当代儿科杂志,2009,11（8）：659-662］     

Mediastinal germ cell tumors: clinical aspects and outcomes in 7 children.

BACKGROUND: Mediastinal germ cell tumors presenting during childhood are extremely rare. Publications on this entity are very scarce. This paper reports on the clinical presentations, method(s) of treatment, complications, results and outcomes in a series of children with mediastinal germ cell tumors. METHODS: A retrospective chart review of 7 children treated between 1971 and 2001 for mediastinal germ cell tumor was carried out. Age at diagnosis and symptoms were recorded. Each patient's surgical treatment, peri- and postoperative complications, histological staging and final outcome were analysed. RESULTS: The median age of the 4 boys and 3 girls was 3 years (range 21 months-15 years). The most frequent symptoms were respiratory distress, persistent coughing, thoracic pain and anorexia/weight loss. Four patients had histologically benign tumors (mature teratoma). Their sole treatment consisted of complete surgical excision of the tumor and (part of) the thymus using either median sternotomy or left-sided thoracotomy. Recovery was uneventful. No recurrences have been observed. All four are alive with no evidence of disease, between 2.5 and 29 years after treatment. Malignant tumors were observed in three patients (1 yolk sac tumor, 1 choriocarcinoma and 1 malignant teratoma). Treatment consisted of either biopsy or debulking followed by chemotherapy (and radiotherapy in 1 case). Two of them died from uncontrollable metastatic disease. The patient with yolk sac tumor survived; he is now in remission, 4 years after diagnosis. CONCLUSIONS: Both this study and the literature review testify to the extreme rarity of mediastinal germ cell tumors in childhood. Children with this type of tumor usually are severely symptomatic. Histologically benign tumors carry an excellent prognosis provided surgical excision is complete. Histologically malignant tumors, on the other hand, have a worse prognosis. However, the use of platinum-based combination chemotherapy has considerably increased the survival rates.     

Hodgkin's disease. Treatment of the young child.

Age of a patient when afflicted with Hodgkin's disease is an important prognostic factor. Although there are histologic and stage differences as a function of age, the younger a patient is when diagnosed, the better the cure rate. Youngsters less than age 10 years have a freedom from relapse of 80% at 26 years follow-up examination; adolescents in the 11 to 16 age group have a freedom from relapse or 74%; and adults aged 17 years or older have a freedom from relapse of 64%. These differences translate into significant survival differences as well, with children aged 10 years or younger and those aged 11 to 16 years having a 26-year survival of 74%, as compared to adults, who have a 37% survival (P = 0.003). These differences remain significant when comparing those with stage I and II disease, as opposed to those with advanced stage III and IV disease. Children present the greatest challenges with respect to staging and treatment. The older child with localized disease can be managed appropriately as an adult. However, for the younger child the use of low-dose radiation and multiagent chemotherapy is widely accepted. Using this approach, survival rates of 85% or greater are reported from many large institutional and cooperative group experiences. The goals of treatment today are cure of disease, with maximal quality of life and minimal complications from the treatment. The late effects of greatest importance to the youngest children are skeletal and bone growth abnormalities, sterility, and malignant tumor induction. Treatment programs today should be directed towards refining therapy to minimize sequelae while maximizing quality of life. These goals are best achieved when children are managed in regional centers with demonstrated expertise in the management of children with Hodgkin's disease. Whereas cure can be achieved in a large majority of children diagnosed with Hodgkin's disease, our challenge is cure, with the least sequelae and the greatest quality of life. "Children are not simply micro-adults, but have their own specific problems."