Childhood non-Hodgkin's lymphoma and "leukemia-lymphoma syndrome": long-term results with the modified LSA2-L2 protocol

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.     

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.     

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%.     

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.     

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.     

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.     

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］     

Results of the LMT81 protocol,a modified LSA2L2 protocol with high dose methotrexate,on 84 children with non-B-cell (lymphoblastic) lymphoma

From May 1981 to June 1989, 84 children with non-B-cell lymphoma (82 lymphoblastic, 1 T-cell immunoblastic, 1 unclassified diffuse lymphoma) were treated in the pediatric department of the Institut Gustave Roussy according to a protocol called LMT81, which was derived from the LSA₂L₂ protocol of Wollner and modified by the adjunction of 10 courses of high dose methotrexate to improve the CNS prophylaxis. No planned irradiation was performed except in cases of initial testis (2 patients) or CNS (5 patients) involvement and residual mass (2 patients). Sixty patients had mediastinal involvement; for the others, primaries were in the head and neck (7), nodes (2), (sub)cutaneous (4), bone (7), and elsewhere (2). According to Murphy's staging system, there were 2 stage I, 6 stage II, 33 stage III, and 43 stage IV. Among the stage IV patients, 41 had bone marrow involvement, 24 of them with more than 25% blast cells in bone marrow and 19 with blast cells in blood; 7 hadCNS involvement. Three patients did not achieve complete remission, 4 died in remission (two measles, one post-transfusion AIDS, one unexplained definitive aplasia) and 13 relapsed at 2 to 29 months (median-13 months). Among the 77 patients without initial CNS involvement, there was only one isolated CNS relapse. With a median follow-up of 57 months (10-106 months), the event-free survival is 75% (SE 2.5) for the 84 patients with a plateau at 29 months, 73% (SE 8) for stage I and II patients, 79% (SE 4) for stage III, and 72% (SE 4) for stage IV patients. Survival was similar in each stage group. Reasons for failure of treatment, however, were different, being toxic deaths in stage II; initial therapy resistance, early relapses, and toxic deaths in stage III; and tumor failures in stage IV. In conclusion, this protocol is efficacious on T and non-T, non-B childhood lymphoma with a low incidence of CNS relapse. A future study will seek to diminish toxicity and long-term sequellae while at least maintaining the same cure rate of patients.     

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.     

Pediatric hodgkin's disease in costa rica: Twelve years' experience of primary treatment by chemotherapy alone,without staging laparotomy

This is a prospective and nonrandomized study in which 86 children with previously untreated Hodgkin's disease (HD) were clinically staged (CS) and treated with chemotherapy (CT) alone. Fifty-two (CS IA-38, IIA-7, IIB-3, IIIA-4) received six courses of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP). Ten (CS IA with peripheral nodes) received only three courses of CVPP with a reinforcement of C on day 8. Twenty-four (CS IIIB-18, IVA-2, IVB-4) received six courses of CVPP alternating with six courses of epirubicine, bleomycine, and vincristine (EBO). Surgical staging was not performed in any patient. Two patients (CS IIIB) had partial remission and died from progressive disease. Seventy out of 86 children have not relapsed and are in complete remission with a median follow-up of 65 months (range 13-156 months); 14 children relapsed seven to 37 months from diagnosis (median 16 months); one of them (IV B) died of disease. Thirteen are in second and third remission (median 55 months). Actuarial five year survival rates and relapse-free survival rates are 100% and 90% for CS I to IIIA and 81% and 60% for CS 1MB and IV, respectively. As a result of this study, we can conclude that in developing countries most of the children with HD staged by noninvasive diagnostic techniques can be cured with CT alone as primary treatment and thus will not suffer from the late effects of radiotherapy (RT) and the morbidity of laparotomy and splenectomy. RT alone or with other CT combinations should be considered for children who develop relapse of HD. © 1994 Wiley-Liss, Inc.     

Benign proliferative lesions mimicking recurrence of Hodgkin's disease

Salvage treatment in patients with recurrent Hodgkin's disease is more effective when tumor burden is minimal. That is why more intensive follow-up strategies, including frequent imaging tests, have been recently developed for the detection of early relapse. However, as screening procedures become more sensitive, there is an increasing risk of false-positive results, demonstrating nonmalignant proliferative disorders. We describe three young patients who had lymphocyte-predominant or mixed-cellularity Hodgkin's disease and were in clinical complete remission for 2.5–3 years after a combined treatment with chemotherapy and radiation. Imaging tests revealed new gallium-avid lymphadenopathy in the chest in two cases. Pathologically enlarged pelvic lymph nodes were identified in another case, after a diagnosis of recurrent disease in axilla. Those findings were interpreted as relapse, and the patients underwent thoracotomy and laparotomy, respectively, for histologic confirmation. The results showed progressively transformed germinal centers and sarcoid-like lesions, two benign proliferative disorders. When patients with Hodgkin's disease in remission show new lymphadenopathy, even with positive gallium scan, it seems mandatory to obtain tissue for histologic examination, even through invasive procedures such as laparotomy and thoracotomy, to avoid wrong diagnosis and unnecessary treatment. Med. Pediatr. Oncol. 28:187–190 © 1997 Wiley-Liss, Inc.     

Intracranial Hodgkin's disease in two patients with familial Hodgkin's disease

Intracranial Hodgkin's disease is very rare and is often a terminal event. The case of a 33-year-old man who relapsed in the anterior pituitary gland without other evidence of disease 6 months after extended field radiation therapy for Stage IIA Hodgkin's disease is presented. He remains well with no evidence of disease five years after surgery and chemotherapy for intracranial relapse. The case of a 16-year-old boy with a dural relapse of Hodgkin's disease associated with positive cerebrospinal fluid cytology is also presented. These two patients are members of different families each with multiple cases of Hodgkin's disease. Central nervous system involvement with Hodgkin's disease may be more frequent in familial Hodgkin's disease in which immune deficiency is common. Med. Pediatr. Oncol. 28:255–258. © 1997 Wiley-Liss, Inc.     

Results of the LMT81 protocol, a modified LSA2L2 protocol with high dose methotrexate, on 84 children with non-B-cell (lymphoblastic) lymphoma.

From May 1981 to June 1989, 84 children with non-B-cell lymphoma (82 lymphoblastic, 1 T-cell immunoblastic, 1 unclassified diffuse lymphoma) were treated in the pediatric department of the Institut Gustave Roussy according to a protocol called LMT81, which was derived from the LSA2L2 protocol of Wollner and modified by the adjunction of 10 courses of high dose methotrexate to improve the CNS prophylaxis. No planned irradiation was performed except in cases of initial tests (2 patients) or CNS (5 patients) involvement and residual mass (2 patients). Sixty patients had mediastinal involvement; for the others, primaries were in the head and neck (7), nodes (2), (sub)cutaneous (4), bone (7), and elsewhere (2). According to Murphy's staging system, there were 2 stage I, 6 stage II, 33 stage III, and 43 stage IV. Among the stage IV patients, 41 had bone marrow involvement, 24 of them with more than 25% blast cells in bone marrow and 19 with blast cells in blood; 7 had CNS involvement. Three patients did not achieve complete remission, 4 died in remission (two measles, one post-transfusion AIDS, one unexplained definitive aplasia) and 13 relapsed at 2 to 29 months (median-13 months). Among the 77 patients without initial CNS involvement, there was only one isolated CNS relapse. With a median follow-up of 57 months (10-106 months), the event-free survival is 75% (SE 2.5) for the 84 patients with a plateau at 29 months, 73% (SE 8) for stage I and II patients, 79% (SE 4) for stage III, and 72% (SE 4) for stage IV patients. Survival was similar in each stage group. Reasons for failure of treatment, however, were different, being toxic deaths in stage II; initial therapy resistance, early relapses, and toxic deaths in stage III; and tumor failures in stage IV. In conclusion, this protocol is efficacious on T and non-T, non-B childhood lymphoma with a low incidence of CNS relapse. A future study will seek to diminish toxicity and long-term sequellae while at least maintaining the same cure rate of patients.     

Autologous bone marrow transplantation for pediatric Wilms' tumor: The experience of the European bone marrow transplantation solid tumor registry

This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary. © 1994 Wiley-Liss, Inc.     

Cerebral non-Hodgkin's lymphoma discovered when treating Hodgkin's disease

Case report of the appearance of a highly malignant cerebral non-Hodgkin's lymphoma of a diffuse large cell type, type B, occurring at the immediate onset of chemotherapy for a stage IV (mediastino-pulmonary) Hodgkin's disease (nodular sclerosis) diagnosed in a 16-year-old boy. The treatment of this cerebral lymphoma associated primary chemotherapy with high dose methotrexate, high dose aracytine, etoposide, and ifosfamide. The chemotherapy proved to be highly efficient, producing complete remission. Thoracic and abdominal irradiation for Hodgkin's disease was performed concomitantly with chemotherapy for the non-Hodgkin's lymphoma. This treatment was followed by 36 Gy of cerebral irradiation. Thirty-six months after the discovery of the cerebral non-Hodgkin's lymphoma the patient was still disease-free and doing well. © 1993 Wiley-Liss, Inc.     

Results of neuroblastoma treatment in Austria (1979-1984)

During the period from 1979 until 1984 55 children were registered: 4 in Evan-stage I, 13 in stage II, 16 in stage III, 18 in stage IV and 4 in stage IV-S. 39 of these 55 patients have been followed for a minimum of two years. The current two year survival rate is 10/10 in stages I and II, 6/13 in stage III, 3/14 in stage IV and 2/2 in stage IV-S. These results demonstrate but a slight improvement in patients with stage II since the last Austrian statistic 1974. Despite modern chemotherapy the chance for survival of children with stage III or IV neuroblastoma is poor and better treatment modalities should be searched for.     

The 2000 Burkitt lymphoma trial in Malawi

BACKGROUND: We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity. METHODS: All Malawian children admitted to Queen Elizabeth Central Hospital, from 03/08/2000 to 12/03/2002 with confirmed BL were eligible. A fine needle aspirate, bone marrow aspirate, cerebrospinal fluid cytology, haemoglobin (Hb), white cell count (WCC), malaria smear, ELISA for HIV, and abdominal ultrasound were performed routinely. Murphy staging was used. The first dose of chemotherapy (COP1) consisted of 300 mg cyclophosphamide (CPM), 1 mg vincristine, and 60 mg prednisone given on day 1 and followed by COP2 on day 8 (only for patients with larger tumour volumes, stage III or IV disease). The vincristine dose in COP2 was 2 mg. COMP1 and 2 given on days 22 and 36 consisted of 500 mg CPM, 2 mg vincristine, 60 mg prednisone, and 2 g methotrexate. All doses were calculated per body surface area. Intrathecal methotrexate and hydrocortisone were given with COP1 and 2. RESULTS: Forty-two patients, 30 boys and 12 girls median ages 6 and 7.5 years, respectively, had Murphy stage I(n5), II(n8), III(n21), and IV(n8) disease. The face was involved in 74%, abdomen in 55%, bone marrow in 14%, kidneys in 24%, and 12% had paraplegia. Fourteen children died during or shortly after completion of chemotherapy. Three of these were disease related. Twelve patients suffered a local relapse after 57-328 days, and one a CNS relapse at 76 days. The projected EFS at 12 months is 50% in stage I, 50% in stage II, 24% in stage III, 25% in stage IV, and 33% for all patients. The cumulative mean dose of CPM was 62 mg/kg in survivors and 64 mg/kg in children who relapsed. One third of patients experienced significant marrow suppression, and infections after COMP1. CONCLUSIONS: Thirty-three percent of children are in first remission at 12 months. The morbidity and mortality of treatment was high. The high relapse rate in all stages may be due to the low cumulative dose of CPM.     

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.     

High-dose melphalan, vincristine, and total-body irradiation with autologous bone marrow transplantation in children with relapsed neuroblastoma: a phase II study

Seven children with neuroblastoma who had relapsed on or after conventional therapy (3 originally stage IV, 3 stage III, 1 stage II) were entered on a study of "massive therapy" with purged autologous bone marrow rescue. In 5 patients attempts were made to reinduce remission with alternative chemotherapy, and a partial or complete response was achieved in 3. The massive therapy regimen comprised melphalan, vincristine, and total-body irradiation. Of 6 patients with measurable disease, all showed objective response to high-dose therapy (5 partial, 1 complete remission), but the median duration of remission was only 5 months (range 1/2 to 10). One patient remains disease-free at 18 months post graft. This patient was the only one treated in second complete remission. These data confirm the high response rate achieved by high-dose melphalan, total-body irradiation regimens, but it appears unlikely that a single high-dose chemoradiotherapy procedure will cure patients after relapse, particularly if they are unresponsive to conventional salvage regimens. Such protocols may, however, have a role as consolidation in first remission. The use of double-autograft procedures is an alternative that warrants further investigation in patients with relapsed neuroblastoma.