CDV与CiE两种方案联合术前化疗治疗晚期儿童神经母细胞瘤的近期疗效观察

目的观察CDV(环磷酰胺+柔红霉素+长春新碱)与CiE(顺铂+足叶乙甙)联合术前化疗治疗晚期神经母细胞瘤患儿的近期疗效及相关毒性。方法回顾分析27例IV期神经母细胞瘤患儿临床资料,年龄1岁2个月至8岁,原发部位腹部21例,后纵隔4例,盆腔2例,骨髓转移23例,多发性骨转移12例。均经CDV方案3疗程及CiE方案2疗程化疗。应用神经母细胞瘤治疗反应评价标准和美国国立癌症研究所通用不良反应分级标准对化疗近期疗效和相关毒副反应进行评价。结果27例患儿经术前化疗,总有效率为82%;辅助化疗后24例患儿接受手术治疗,完全切除原发肿瘤14例(58%),部分切除10例(42%)。化疗相关毒副反应主要是骨髓抑制,27例患儿粒细胞下降均为IV级;血红蛋白下降III级7例(26%),IV级20例(74%);血小板下降III级2例(7%),IV级25例(93%)。所有患儿均出现不同程度的感染,经积极的抗感染治疗可以控制。消化道、肝脏、肾脏损害多为Ⅰ、Ⅱ级,经治疗可恢复。2例(7%)出现Ⅰ级神经毒性病例。无心功能受损病例。结论CDV与CiE联合术前化疗方案治疗IV期神经母细胞瘤有转好的疗效,可为手术治疗创造条件。     

以CDV和CiE持续静脉滴注为诱导方案治疗晚期神经母细胞瘤

目的研究CDV和CiE方案治疗晚期神经母细胞瘤的短期疗效及患儿耐受性。方法选择IV期神经母细胞瘤6例,年龄4～7岁。诱导方案CDV4疗程,CiE2疗程。用药:Ⅴ:长春新碱0.67mg/(m2·24h),第1、2、3天,持续滴注72h;D:柔红霉素:25mg/(m2·24h),第1、2、3天,持续72h;C:环磷酰胺2.1g/(m2·24h),第1、2天,持续滴注48h;Ci:顺铂50mg/(m2·24h),持续1h,第1、2、3天;E:足叶乙甙200mg/(m2·24h),持续2h,第1、2、3天。结果6例转移病灶全部消失,包括骨髓、骨组织、眼球后。化疗后白细胞降低明显,至(0.1～0.2)×109/L,3～4周恢复至3×109/L,每例患儿在化疗不同疗程中出现38°C～39°C的发热1～2次,持续3～8d。2例血培养大肠杆菌阳性各1次,CRP升高分别为25mg/L、32mg/L,其余血培养阴性,用亚胺培等感染控制。结论晚期神经母细胞瘤可较好的耐受CDV和CiE强烈诱导化疗,近期疗效较好。     

CEM为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤相关毒性及疗效观察

目的　观察以CEM (卡铂 +VP 16 +马法兰 )为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤患儿的毒性和疗效。方法　研究经大剂量放、化疗及手术治疗达完全缓解的IV期神经母细胞瘤患儿 6例 ,采用CEM预处理方案 (卡铂每日 4 2 5mg/m2 共 4d ,VP 16每日 338mg/m2 共 4d ,马法兰每日 70mg/m2 共 3d)的自体外周血造血干细胞移植 ,并依据Bearman标准对预处理毒性进行评价 ,对其造血重建、并发症及预后进行观察。结果　预处理后髓外毒性除 1例为I级肝损害外 ,主要表现在口腔粘膜 (I级 6例 )和胃肠道 (I级 5例 ,II级 1例 )损害。白细胞于移植后 3± 0 .5d达到 0 ,移植后 33± 3.1d稳定于 1× 10 9/L以上。除 1例患儿移植后 11个月颅内转移外 ,余 5例患儿均健康存活。随诊时间分别为 8、10、2 3、36及 4 8个月。结论　以CEM为预处理方案的自体外周血造血干细胞移植可以安全、有效的治疗IV期神经母细胞瘤。     

低体质量儿童外周血干细胞的动员和采集

目的通过评价环磷酰胺+吡柔比星+长春新碱(CDV)、吡柔比星+长春新碱+环磷酰胺+顺铂(AVCP)、卡铂+替尼泊苷+长春新碱(CTV)动员方案对低体质量儿童神经母细胞瘤和原始神经外胚层肿瘤/横纹肌肉瘤/视网膜母细胞瘤自体外周血造血干细胞移植动员采集的临床效果,探讨安全有效地动员和采集低体质量儿童(体质量<20 kg)外周血干细胞的方法。方法在采用CDV/AVCP/CTV方案化疗+粒细胞集落刺激因子(G-CSF)动员后使用CS-3000 Plus血细胞分离机(美国Baxter公司),专用SVSC分离槽和SVCC收集槽,并选择儿童单个核细胞收集程序进行外周血干细胞采集。结果20例(神经母细胞瘤13例,视网膜母细胞瘤3例,横纹肌肉瘤2例,原始神经外胚层肿瘤2例)体质量小于20 kg患儿采用CDV/AVCP/CTV方案动员,化疗第4-9天(平均6 d)WBC<2×109L-1,应用G-CSF第6-15天(平均9 d)开始采集外周血造血干细胞,20例均采集到足够的单个核细胞数(MNC)和CD34+细胞,采集次数1~4次,平均2.1次,MNC:(6.1±1.2)×108kg-1,CD34+细胞为(3.9±0.8)×106...     

晚期儿童肝母细胞瘤的预后分析

目的：探讨晚期儿童肝母细胞瘤（hepatoblastoma,HB）的预后情况。方法回顾性分析首都医科大学附属北京同仁医院儿科2006年4月-2014年7月收治的103例患儿中随访3年以上的30例晚期HB患儿的临床资料,总结其临床疗效和预后情况。结果（1）POG／CCG临床分期：III期12例,完全缓解（CR）10例（83％）;IV期18例,CR 8例（44％）,两组CR率无显著差异（P＝0.08）;（2）血清AFP：30例患儿中28例明显升高,占93％;（3）术前化疗：提高了69％的肿瘤完全切除率;（4）疗效与预后：30例患儿5年总体生存率为58％。胎儿型、POG／CCG III期和肿瘤完全切除患儿生存率明显提高（P＜0.05）。结论儿童晚期HB经综合治疗预后尚可。胎儿型预后较好,但肿瘤未完全切除,POG／CCG IV期及伴有远处转移尤其是肺转移患儿预后仍较差,应尽可能地早期诊断及治疗。     

大剂量化疗造血干细胞移植治疗IV期神经母细胞瘤的长期疗效研究

目的：目前IV期神经母细胞瘤患儿无论采用何种方法治疗均疗效差,长期生存率低,需要探索新的治疗途径。该文采用大剂量化疗、自体外周血造血干细胞移植及13-顺式维甲酸治疗等方法,试图提高IV期神经母细胞瘤的长期疗效。方法：选择IV期神经母细胞瘤患儿28例,年龄2.1~11.5岁,平均3.3±1.9岁,发病时间1~7个月,平均3.1±0.7个月。原发部位:肾上腺23例,胸部3例,胸腹联合1例,骶骨1例。强烈化疗6疗程,期间进行外周血造血干细胞采集、手术切除,然后进行自体外周血造血干细胞移植,术后行局部放疗及13-顺式维甲酸治疗,定期随访。结果：28例患儿诱导化疗结束时13例取得完全缓解,11例取得部分缓解,4例化疗中病情进展。完全缓解及部分缓解的24例患儿完成治疗进入本研究。随访3.5±0.7年,两组4年无病生存率29.2%。完全缓解组中位无复发生存时间4.1±0.7年;部分缓解组中位无复发生存时间2.8±0.5年,两组中位无复发生存时间差异有显著性(t=3.9,P<0.01)。结论：大剂量化疗、自体外周血造血干细胞移植及13-顺式维甲酸治疗IV期神经母细胞瘤可取得较好疗效,4年无病生存率29.2%,移植前达到完全缓解时可取得更好疗效     

大剂量化疗造血干细胞移植治疗IV期神经母细胞瘤的长期疗效研究

目的目前IV期神经母细胞瘤患儿无论采用何种方法治疗均疗效差,长期生存率低,需要探索新的治疗途径。该文采用大剂量化疗、自体外周血造血干细胞移植及13-顺式维甲酸治疗等方法,试图提高IV期神经母细胞瘤的长期疗效。方法选择IV期神经母细胞瘤患儿28例,年龄2.1~11.5岁,平均3.3±1.9岁,发病时间1~7个月,平均3.1±0.7个月。原发部位:肾上腺23例,胸部3例,胸腹联合1例,骶骨1例。强烈化疗6疗程,期间进行外周血造血干细胞采集、手术切除,然后进行自体外周血造血干细胞移植,术后行局部放疗及13-顺式维甲酸治疗,定期随访。结果28例患儿诱导化疗结束时13例取得完全缓解,11例取得部分缓解,4例化疗中病情进展。完全缓解及部分缓解的24例患儿完成治疗进入本研究。随访3.5±0.7年,两组4年无病生存率29.2%。完全缓解组中位无复发生存时间4.1±0.7年;部分缓解组中位无复发生存时间2.8±0.5年,两组中位无复发生存时间差异有显著性(t=3.9,P<0.01)。结论大剂量化疗、自体外周血造血干细胞移植及13-顺式维甲酸治疗IV期神经母细胞瘤可取得较好疗效,4年无病生存率29.2%,移植前达到完全缓解时可取得更好疗效     

术前多基因联合检测指导化疗对进展期神经母细胞瘤儿童手术切除率及预后的影响

目的 探索术前多基因联合对进展期神经母细胞瘤(NB)患儿手术切除率及预后的影响.方法 收集2013年1月至2015年l月本院收治的采取手术治疗的进展期(Ⅲ、Ⅳ期) NB 患儿 46例,均经病理确诊.根据INSS 分期及COG危险度分层,本组病例Ⅲ期 19 例 (41.3%) ,Ⅳ期 27 例 (58.7%) ,中危15例(32.6%),高危31例(67.4%).46例患儿均行术前新辅助化疗及手术治疗.依据术前是否行多基因联合检测分为多基因联合检测化疗组和常规化疗组.多基因联合检测组患儿,根据药敏结果参考选择化疗方案,如常规方案中有一种药物敏感,则可选择该方案进行化疗.如常规方案中无敏感药物或化疗两个疗程后评估提示化疗效果欠佳,则根据药敏结果选用包含至少一个敏感药物的化疗方案.结果 3例ERCC阴性中危患者最初使用方案无铂类药物,肿瘤缩小不满意,后根据药敏检测更换包含铂类药物方案后肿瘤缩小明显,均在更换方案后2~3个疗程行手术,其余4例中危患儿均提示TOPOIIα高表达,选用了OPEC方案及卡铂+足叶乙甙/阿霉素轮换.高危患儿中5例TOPOI阴性患儿最初均使用CT方案,第二或三个疗程时根据药敏结果换用OPEC方案.其余患儿检测结果提示对铂类、足叶乙甙或蒽环类其中之一敏感,使用OPEC方案化疗.多基因联合检测组术前化疗3~6个疗程,平均 4.6个疗程,常规化疗组术前化疗4~8个疗程,平均 5.6个疗程.多基因联合检测组患儿肿瘤瘤体缩减率明显高于常规化疗组.两组患儿手术切除率差异无统计学意义.本资料所有患儿均获得随访,随访时间14~30个月,平均21个月,总体生存率为60.9%,中危组患儿2年生存率为80%,高危组期患儿2年生存率51.6%.多基因联合检测化疗组2年生存率为中危85.7%,高危53.8%,总生存率为65%,常规化疗组2年生存率为中危75%,高危50%,总生存率为57.7%.两组相比差异无统计学意义.结论 进展期神经母细胞瘤患儿联合检测ERCC1、TOPOI 和TOPOIIα表达指导个体化化疗,有效率有所提高,化疗不良反应减少,改善了患儿生活质量.     

神经母细胞瘤规范化诊治的初步经验

目的 总结按日本研究会方案治疗神经母细胞瘤的经验体会.方法 2000年至2006年间诊治新发小儿神经母细胞瘤98例,年龄12 d～144个月,经影像学、24 h尿香草扁桃酸、骨穿和手术病理确诊.按INSS分期,Ⅰ期3例、Ⅱ期13例、Ⅲ期31例、Ⅳ期48例、Ⅵs期3例.治疗方案按日本研究会神经母细胞瘤综合治疗方案98年修订版进行.结果 本组术前新辅助化疗缓解率为49.2%(29/59),手术肉眼完整切除率为60.8%.总体2年生存率为73.4%,总体5年生存率为47.8%,其中Ⅲ期分别为75.0%和58.8%,Ⅳ期分别为64.1%和20.0%.结论 规范化治疗是提高神经母细胞瘤治疗效果的重要手段.日本研究会方案是较为可行的方案之一,可有效提高患儿的生存率.肿瘤肉眼完整切除是神经母细胞瘤综合治疗的重要部分,外科医师参与并掌握治疗方案,是规范化治疗得以执行的保证.     

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］     

45例儿童神经母细胞瘤预后因素分析

目的 分析影响儿童神经母细胞瘤（NB）的临床预后因素,期望通过综合性诊断治疗方案改善NB的预后。方法研究对象为1998年10月至2003年12月新诊断为NB患儿,根据年龄及分期分为高、中、低危3组,各组采用包括不同化疗强度的NB综合治疗方案。方案包括确切分期分组,Ⅲ、Ⅳ期患儿延迟或二次肿瘤根治术,不同强度的化疗方案和完成化疗后全顺维甲酸诱导分化治疗,高危组在化疗结束时接受自身造血干细胞移植（ASCT）。结果年龄6个月至11岁,共45例。I期9例,Ⅱ期1例,Ⅲ期8例,Ⅳ期26例,1Vs期1例。6例在≤2个疗程后好转中放弃治疗;39例按计划治疗,11例接受了ASCT。获得完全缓解（CR）31例（80％）,获得部分缓解（PR）8例（20％）。中位随访期21个月（14个月至64个月）;末次随访时CR24例（62％）,中位CR时间为22个月;带病生存病情稳定4例,总生存率（SR）72％。疾病进展、复发或已死亡11例（28％）。大于18个月、Ⅲ期及Ⅳ期明显影响预后,P分别为0．04、0．003。不同危险组预后不同,P为0．003。肿瘤原发于后腹膜,Ⅲ、Ⅳ期患儿手术未能完全切除肿瘤和未能接受ASCT者预后差,但未达统计学有效水平,P=0．092、0．55和0,60。结论NB综合整体治疗方案较为合理。年龄大于18个月、Ⅲ期及Ⅳ期为预后不良因素。肿瘤原发于后腹膜、手术未能完全切除肿瘤和未能接受ASCT预后差,但P未达统计学有效水平。     

High-risk neuroblastoma in Ontario: a report of experience from 1989 to 1995

PURPOSE: We did a population-based study of children with high-risk neuroblastoma to determine their survival and look for factors that had an impact on survival. METHODS: We carried out a retrospective cohort study of patients diagnosed in Ontario from 1989 to 1995. 162 cases of neuroblastoma were diagnosed in the province with 70 (43%) considered high-risk: all were older than one year of age, with 15 patients classified as International Neuroblastoma Staging System (INSS) stage 3, and 55 INSS stage 4. RESULTS: Stage 3 patients did significantly better than Stage 4 patients with a 5-year overall survival of 67.7% and 22.7% respectively (P = 0.015). In stage 4 patients achieving at least a partial response to up-front therapy and surviving for at least 9.5 months after diagnosis (the median time to transplant), there was no difference in survival between the 19 transplant patients and the 17 treated with chemotherapy alone (P = 0.75). However, patients transplanted by peripheral stem cell (PSC) collection did significantly better than both the bone marrow transplantation (P = 0.002) and chemotherapy-alone group (P = 0.047). There was a significant difference in up-front chemotherapy and use of radiation in the three groups (P < 0.001 and P = 0.01 respectively), but no difference in the incidence of bone and bone marrow metastases, MYCN amplification or unfavorable histology. CONCLUSIONS: In this nonrandomized study, we found that stage 4 neuroblastoma patients alive more than 9.5 months after diagnosis, with at least a partial response to initial therapy, did significantly better with PSC transplant compared with bone marrow transplantation or chemotherapy alone.     

强烈化疗和自体外周血造血干细胞移植及维甲酸治疗晚期神经母细胞瘤

目的 探讨强烈化疗、自体造血干细胞移植及维甲酸对晚期神经母细胞瘤的治疗效果方法 研究Ⅳ期神经母细胞瘤患儿6例,年龄4～8岁,发病时间1个月～1年;原发部位腹部5例、胸部1例,均有骨髓转移,1例有多发性骨转移及球后病变。成立多学科参与的治疗小组,采用术前化疗、手术切除、强烈化疗、局部放疗、自体外周血造血干细胞移植及维甲酸生物治疗等。结果 经综合治疗造血干细胞移植前6例均达到完全缓解,骨髓中肿瘤细胞消失,骨转移及球后病变被控制。化疗中骨髓抑制明显,血象恢复较慢,达3～4周。感染明显,三分之一疗程后发热,用头孢他定(商品名复达欣)、亚胺培南(商品名泰能)等感染被控制。造血干细胞移植过程顺利。术后随诊4～18个月疾病处于完全缓解状态,心、肝、肾器官功能正常,骨髓恢复正常或在恢复中。结论 强烈化疗、自体外周血造血干细胞移植及维甲酸是治疗Ⅳ期神经母细胞瘤的有效方法。     

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group

BACKGROUND: High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. PROCEDURE: In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. RESULTS: Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). CONCLUSIONS: In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified. Because they are more toxic, complex, and costly these combination megatherapy regimens should be compared with single agent melphalan in randomised clinical trials.     

Oral topotecan for refractory and relapsed neuroblastoma: a retrospective analysis

PURPOSE: Among patients with multiply relapsed neuroblastoma refractory to conventional chemotherapy, oral topotecan has often been used for palliation. Although toxicity was generally thought to be mild, the efficacy of such an approach remains unproven. METHODS: The authors retrospectively analyzed patients with multiply relapsed or refractory neuroblastoma who were treated with oral topotecan for palliation. Each course was generally 1 mg/m2/d in two divided doses, for 21 consecutive days, repeated after a 1-week rest in patients without symptoms of progressive disease. Disease status was assessed by radiographic studies, urine catecholamine levels, and multiple bone marrow aspirations and biopsies. RESULTS: Twenty patients between the ages of 3 and 34 (median 13 years) received 1 (n = 7), 2 (n = 3), 3 (n = 4), 4 (n = 2), 6 (n = 2), and 12 courses (n = 2). Prior treatments included multiple cycles of high-dose alkylator-based chemotherapy (n = 20), high-dose intravenous topotecan (n = 8), myeloablative chemotherapy or radioimmunotherapy (n = 10), or experimental biologic agents (n = 16). Anti-neuroblastoma effects were seen in five patients lasting 6 to 12 months; two additional patients remained stable for 4 months. Thirteen patients had progressive disease (11 after one or two cycles). Toxicity included diarrhea (n = 12) requiring a dose adjustment in three patients and discontinuation of the drug in a fourth, and myelosuppression (n = 11) requiring transfusion and/or granulocyte-colony stimulating factor support.CONCLUSIONS: Oral topotecan therapy has antitumor activity in a small percentage of patients with relapsed or refractory neuroblastoma. Toxicities, including diarrhea and myelosuppression, may necessitate a dose adjustment in this patient population. Low-dose oral topotecan may have utility in the treatment of neuroblastoma.     

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.