改良DAL-HX 83/90方案治疗儿童郎格罕细胞组织细胞增生症疗效分析

目的对DAL-HX83/90方案进行改良(强化),并对其远期疗效及耐受情况进行分析。方法2003年7月至2008年12月在中国武警部队总医院儿科住院经临床和病理确诊的郎格罕细胞组织细胞增生症(LCH)患儿11例,按DAL-HX83/90方案分三型治疗,按照国际组织细胞协会疗效判定标准进行疗效评价。结果11例随访时间为3个月至5年,中位随访时间47个月,治疗结束时治愈8例,好转2例,总有效率90.9%,复发率9.1%。除一过性白细胞降低、恶心、呕吐,Ⅲ型患儿有一过性肝功能损伤外无严重不良反应,全部患儿未发现后遗症。结论改良(强化)后的DAL-HX83/90方案疗效好,复发率低,患儿耐受良好。     

82例朗格罕斯细胞组织细胞增生症临床分析

目的 分析82例郎格汉斯细胞组织细胞增生症（LCH）患儿的治疗效果,旨在了解LCH的长期预后.方法 收集2001年6月-2011年5月我院收治的初治LCH患儿,其中2001年6月-2005年12月发病者按改良DAL-HX 83/90方案治疗,设为DAL-HX 83/90组,共27例;2006年1月-2011年5月发病者按LCH-Ⅲ方案治疗,设为LCH-Ⅲ组,共55例.所有患儿均按国际组织细胞协会疗效标准评价疗效.结果 82例患儿化疗结束后总有效率为87％,其中DAL-HX83/90组治疗总有效率为82％,LCH-Ⅲ组治疗总有效率为89％,两者比较差异无显著性（P=0.54）.82例患儿5年无事件生存率（EFS）为82％,5年总生存率（OS）为95％.DAL-HX 83/90组和LCH-Ⅲ组患儿复发率分别为22％和16％ （x2=0.12,P=0.73）,3年EFS分别为78％和84％（x2=0.14,P=0.71）.结论 采用改良DAL-HX 83/90方案和LCH-Ⅲ方案的近、远期疗效相仿,均可获得与国外研究近似的有效率和生存率.对有高危脏器累及、复发难治LCH患儿的治疗,仍是目前临床难题.     

儿童朗格汉斯细胞组织细胞增生症26例临床分析

目的 提高对儿童朗格汉斯细胞组织细胞增生症(LCH)临床特点的认识,探讨应用改良LCH-Ⅲ方案治疗的有效性和安全性.方法 26例LCH患儿均在确诊前完善必要的实验室检查、皮疹印片或组织病理检查,按Lavin-Osband法进行分级和分型.轻型者仅行局部治疗,其余病例共分为3组,分别按照改良LCH-Ⅲ方案进行化疗.结果 LCH病变可累及多个系统和脏器,可伴有不同程度功能障碍.26例患儿中,4例采用局部治疗,22例采用改良LCH-Ⅲ方案治疗(其中1例先采用局部治疗,病情进展再用此方案),6周时总有效率为72.7%,18个月时总有效率为86.4%.中位随访期36个月(24 ～ 50个月),治愈15例,稳定6例,进展或恶化3例,死亡2例.结论 LCH确诊时临床表现多样,病情轻重不一.改良LCH-Ⅲ方案可针对LCH临床分型和分级进行分层治疗,疗效满意,不良反应及治疗相关并发症少,值得临床推广应用.     

化疗治疗儿童骨嗜酸性肉芽肿的临床疗效观察

目的 探讨采用化疗治疗儿童骨嗜酸性肉芽肿(EGB)的疗效,提高该病的诊治水平,改善预后。方法 回顾性分析我院4年来22例经病理证实的儿童骨嗜酸性肉芽肿病例,其中10例采用了DAL-HX83／90化疗方案,对其疗效进行分析。结果 单发8例(36．4％),多发14例(63．6％),发病的部位不同,骨损害的影像学表现不一样。10例患儿接受了诱导和维持两个阶段的化疗,其中7例系单纯手术或局部治疗后复发或多发。6例治愈、3例病灶缩小或稳定,1例多发患者治疗不敏感,有播散和复发。结论 单纯手术治疗无法解决。EGB的“此起彼伏”现象,采用DAL-HX83／90方案化疗预防其远处播散或后期复发,目的是控制甚至治愈本病,可明显改善预后。     

儿童多系统受累朗格罕细胞组织细胞增生症53例临床分析

目的分析多系统受累朗格罕细胞组织细胞增生症(MS-LCH)患儿的临床特征及远期预后,评价改良DAL-HX83/90方案对MS-LCH患儿的疗效。方法回顾性病例分析。研究对象为2011年1月至2019年5月郑州大学第一附属医院儿童医院血液肿瘤科收治的53例MS-LCH患儿,初始化疗采用改良DAL-HX83/90方案,按是否累及危险器官分为无危险器官受累(RO-)组和累及危险器官(RO+)组,RO+组再分为Ⅰ组(仅肺受累)、Ⅱ组(肺外,伴或不伴肺受累),总结临床特征和随访结果,Kaplan-Meier生存分析法计算生存率,Log-Rank检验及Cox比例风险回归模型对年龄、性别、危险器官受累、6周诱导化疗反应进行单因素及多因素预后分析。结果53例MS-LCH患儿中男34例、女19例,发病年龄21月龄(3月龄至13岁),RO-组31例,RO+组22例,其中Ⅰ组12例、Ⅱ组10例。随访时间51(12~144)个月,6周诱导化疗有效率89%(47/53),进展复发率30%(16/53),5年无事件生存率(EFS)为(67±6)%,5年总生存率(OS)为(83±5)%。单因素分析发现6周诱导化疗有效者5年EFS、OS明显高于无效者[(76±6)%比0,(88±4)%比(41±22)%],差异均有统计学意义(χ²=34.743、10.608,均P<0.05)。RO-组5年EFS、OS明显高于RO+组[(80±7)%比(49±10)%,(93±4)%比(70±10)%],差异均有统计学意义(χ²=6.022、4.793,均P<0.05)。Ⅰ组5年EFS明显高于Ⅱ组[(83±10)%比(10±9)%],差异有统计学意义(χ²=9.501,P=0.002),年龄、性别与EFS、OS无明显相关性(均P>0.05)。Cox比例风险回归模型分析发现6周诱导化疗反应是影响EFS(HR=13.114,95%CI 3.759~45.742,P<0.01)、OS(HR=7.748,95%CI 1.542~38.920,P=0.013)的独立危险因素。结论采用改良DAL-HX83/90方案治疗无危险器官受累MS-LCH,患儿多数可获长期生存。但累及肝、脾或造血系统的MS-LCH患儿疾病进展和复发率较高。     

改良LCH-Ⅲ方案治疗郎格汉斯细胞组织细胞增生症临床观察

目的 观察国际组织细胞协会制定的LCH-Ⅲ方案的治疗效果,提高儿童郎格汉斯细胞组织细胞增生症(LCH)的疗效.方法 36例LCH患儿均经临床、实验室检查及活组织病理检查确诊,按疾病严重程度分为多系统高危险度(Ⅰ组)、多系统低危险度(Ⅱ组)及单系统多发和局限性特殊部位累及(Ⅲ组)3组,采用改良LCH-Ⅲ方案分别以不同化疗强度治疗,按国际组织细胞协会疗效标准进行评价.结果 Ⅰ组14例,Ⅱ组10例,Ⅲ组12例.化疗结束时完全缓解50.00%,好转33.33%.随访33例,复发4例(均为Ⅰ组),其中2例原方案再治疗缓解,2例放弃治疗死亡.另1例缓解期死于感染.目前持续缓解中14例,占38.89%.其中1组2例(14.29%),Ⅱ组8例(80.00070),Ⅲ组4例(33.33%).结论 改良LCH-Ⅲ方案疗效显著,多系统低危险度组(Ⅱ组)预后较好,多系统高危险度(Ⅰ组)患儿中有缓解后复发,复发患儿原方案治疗仍可能获缓解.     

伴t(8;21)/AML1-ETO的儿童急性髓系白血病的临床研究

目的探讨伴t(8;21)/AML1-ETO的儿童急性髓系白血病(AML)的临床及生物学特征。方法52例初治患儿,男34例,女18例,中位年龄12(4~18)岁,均进行了遗传学和/或AML1-ETO融合基因检测。诱导缓解治疗采用HA/DA/HAD方案,缓解后进行异基因造血干细胞移植或7~12疗程的联合化疗。结果24%的儿童AML伴t(8;21)/AML1-ETO,男女比例1·9,FAB分型为M250例(96%);初诊时伴中枢神经系统浸润7·7%(4/52);WBC17·2(1·8~146·3)×109/L,初诊时WBC大于10×109/L者50·0%(26/52),大于50×109/L者3·8%(2/52),血清乳酸脱氢酶升高者85·7%(36/42);细胞免疫分型CD19(44·4%),CD56(58·9%);单独为t(8;21)异常的13例(28·9%),Y染色体丢失22例,占男性患儿的64·7%;X染色体丢失3例,占女性患儿的16·7%,del(9q)6例;1疗程及2疗程完全缓解(CR)率分别为71·8%(28/39)和94·4%(34/36),4年的EFS率、DFS率和OS率分别为(25·4±9·6)%、(28·4±10·4)%和37·9±10·3)%。结论近1/4的儿童AML伴t(8;21)/AML-ETO,多见于FAB分型的M2型,男性居多,年长儿多发,易发生髓外浸润;高白细胞者少见,血清乳酸脱氢酶增高,细胞免疫分型较多表达CD19和CD56;细胞遗传学检查常伴有性染色体丢失和del(9q);诱导缓解治疗完全缓解率高,应用联合化疗进行巩固强化远期疗效好     

儿童朗格罕斯细胞组织细胞增生症34例临床分析

目的探讨儿童朗格罕斯细胞组织细胞增生症(LCH)的临床特点和预后,以期提高LCH诊疗水平。方法对34例初发LCH儿童患者进行回顾性分析。结果 34例患者中位年龄14.5个月(22 d至60个月),其中0~2岁的23例、2岁的11例;高危组17例,低危组17例。30例患者接受化疗,6周化疗总有效率67%(20/30),12个月总有效率87%(26/30),3年总生存(OS)率为86%±6%,3年无事件生存(EFS)率为64%±9%。高危组患者6周化疗有效率46.7%,3年OS为72%±12%,3年EFS为46%±13%,均低于低危组(86.7%、100%、82%±9%),差异均有统计学意义(P0.05)。高危组12个月化疗有效率(80%)与低危组(93%)的差异无统计学意义(P0.05);复发率和死亡率均为27%,而低危组无复发和死亡。结论 LCH总体生存率较高,但高危组6周化疗有效率低,远期预后较差。     

静脉注射多索茶碱佐治儿童支气管哮喘急性发作的临床研究

目的 观察多索茶碱治疗儿童支气管哮喘急性发作的临床疗效及安全性.方法 对符合诊断标准的90例支气管哮喘儿童随机分为多索茶碱治疗组52例和对照组38例.在常规治疗基础上,治疗组静脉滴注多索茶碱5 mg/(kg·d);对照组静脉滴注氨茶碱3～5 mg/(kg·d),观察其疗效和不良反应.结果 治疗组总有效率94.2%,对照组为73.9%,两组比较差异有显著性(P＜0.05).治疗组未发现明显不良反应.结论 多索茶碱治疗儿童支气管哮喘急性发作安全有效.     

CCLG-2008方案治疗儿童急性T淋巴细胞白血病单中心疗效分析

目的分析CCLG-ALL2008方案治疗儿童急性T淋巴细胞白血病(T-ALL)的单中心临床疗效。方法收集我科接受CCLG-ALL2008方案治疗的25例T-ALL患儿的临床资料,回顾性分析病人治疗效果及治疗相关毒副作用。结果 25例患儿,中危7例,高危18例;伴有中枢神经系统白血病(CNSL)3例;诱导缓解率96%。化疗期间发生严重感染7例(28%),并发可逆性后部脑病综合征(PRES)3例,继发第二肿瘤朗格罕斯细胞组织细胞增生症(LCH)1例,发生治疗相关死亡(TRM)1例。3年累积复发率为(17±0.08)%。CNSL 3年累积复发率为(4±0.04)%。单纯髓外白血病(EML)3年累积复发率为(10±0.07)%。本组病人的3年总体生存率(OS)为(87±0.07)%,3年无事件生存率(EFS)为(83±0.08)%。影响生存的主要因素是疾病复发和诱导期严重感染所致TRM。结论 CCLG-ALL2008方案治疗儿童T-ALL的单中心初步疗效好,CR率高,复发率低。     

Treatment of multisystem Langerhans cell histiocytosis. Results of the DAL-HX 83 and DAL-HX 90 studies. DAL-HX Study Group

BACKGROUND: The prognosis of children with multisystem Langerhans cell histiocytosis (LCH) has improved with the application of chemotherapy. However, treatment strategies used varied from conservative approach with treatment only during disease exacerbation to intensive chemotherapy starting immediately after diagnosis. No single drug or regimen has been proven to be superior to the others. Thus, optimal treatment of multisystem LCH remains still an unsolved problem. PATIENTS: Three hundred and twenty-four patients enrolled in the DAL-HX 83 and DAL-HX 90 studies were retrospectively re-evaluated by using the current definition for disease extent. Sixty-three patients fulfilling the criteria for multisystem LCH (involvement of > or = 2 organ systems) were object of the present study. These were 33 males and 30 females, median age at diagnosis 11.5 months (range, birth-13 years 2 months). The median observation time was 7 years 6 months (4 years-11 years 8 months). METHODS: All patients had morphologically confirmed diagnosis, which was additionally verified through demonstration of CD1a antigen, presence of Birbeck granules or central pathologic review. Uniform evaluation including a complete medical history and physical examination, laboratory tests (complete blood count, liver function tests, coagulation profile) and radiographic survey (skeletal survey and/or radionuclide bone scan) was performed in all patients. Additional investigations (bone marrow tap, CT, MRI etc.) were performed upon specific indications. The 63 patients with multisystem LCH were evaluated with respect to response to therapy, clinical course, outcome and development of permanent disabilities. The results of the DAL-HX studies were compared with the results of the first randomized international clinical trial on multisystem LCH (LCH-I). RESULTS: Response to 6 weeks of initial therapy showed a clear discrimination between responders and non-responders, with only 6% of the patients having intermediate response. When correlated to survival response to initial therapy appears to be a powerful prognosticator in multisystem LCH. There were some typical patterns of clinical course. Complete disease resolution at some point of the clinical course was documented in 50 (79%) patients. Thirty-five of them remained disease free, while 15 experienced one or more episodes of disease reactivation. Chronic reactivating course without complete disease resolution was observed in one patient. Deteriorating disease with fatal outcome was shown in 12 (19%) patients. The overall survival after 5 years of observation was 81%. One or more disease-related permanent disabilities were documented in 24 patients, in 4 of them these were shown at diagnosis and in 20 patients these developed after therapy had been commenced. Despite more intensive chemotherapy, the overall survival in DAL-HX 83/90 cohort was comparable with that in LCH-I studies. However, LCH-I compares unfavorably to DAL-HX 83/90 in some very important aspects. With respect to reactivation rate, reactivation free interval and development of permanent disabilities better results were achieved with the more intensive initial and prolonged continuation therapy concept of the DAL-HX studies. Even after extended analysis it remains unclear whether the superiority of the DAL-HX studies has to be attributed to the administration of continuous steroids, to the combination of vinblastine and etoposide, or to the prolonged continuation therapy including mercaptopurine. Answers to these questions are expected from the ongoing international clinical trial LCH-II.     

Diabetes insipidus in langerhans cell histiocytosi: Results from the DAL-HX 83 study

Diabetes insipidus (DI) in Langerhans cell histiocytosis (LCH) is a common complication of unclear etiology. The incidence varies among different publications from 15% to 50%. In the prospective DAL-HX 83 study, 19 out of 199 patients (9.5%) registered with newly diagnosed LCH were diagnosed to have DI. All patients were stratified according to uniform criteria. One hundred and six patients with disseminated disease were treated with standardized polychemotherapy promptly after diagnosis. At the time of diagnosis of LCH, DI was already established in 8 out of 199 patients (4%). After diagnosis, DI occurred in only one out of the remaining 91 patients with localized disease (1%) and in 10 out of 100 remaining patients with disseminated disease (10%). In 8 patients, the onset of DI was associated with other signs of active LCH. The cumulative risk to develop DI after a median observation time of 5 years 3 months was 11%. Retrospective analysis of clinical features revealed multisystem involvement, skull and orbital lesions, and in particular intracranial extension from osseous lesions to constitute risk factors for DI. Magnetic resonance imaging studies (MRI) were available in 12 patients and showed abnormalities of the pituitary region in 10 children. In none of the patients with established DI was it reversed or ameliorated by any treatment. However, the rapid institution of systemic chemotherapy for disseminated disease seems to prevent the occurrence of DI and may be responsible for the low frequency of DI in the DAL-HX 83 study. © 1995 Wi1ey-Liss Inc.     

Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator

BACKGROUND: Reliable prediction of prognosis allowing risk-adapted therapy remains a major issue in the management of multisystem Langerhans cell histiocytosis (LCH). In a recent publication of the International LCH Study Group, response to initial therapy appears to be a reliable outcome predictor. The aim of this study is to test this observation in a cohort of patients treated with more intensive initial therapy. Furthermore, we compare the predictive value of response to initial therapy to some other well-established stratification systems. PROCEDURE: Response to initial combination chemotherapy (prednisolone, vinblastine, and etoposide) at 6 weeks and its prognostic value was evaluated retrospectively in 63 patients with multisystem LCH from the DAL-HX 83 and 90 Studies, and correlated to some established scoring systems from the literature. RESULTS: After 6 weeks of therapy, 50/63 (79%) patients qualified as responders, 4/63 (7%) patients showed intermediate response, and 9/63 (14%) patients did not respond. Probability of survival at 5 years was 0.94 +/- 0.03 for responders, 0.75 +/- 0.22 for patients with intermediate response, and only 0.11 +/- 0.10 for non-responders. CONCLUSIONS: Response to initial therapy appears to be a reliable prognostic predictor. Compared to the published international LCH-I Study, our results suggest that more intensive initial treatment allows a better discrimination between responders and non-responders. This allows to identify a subgroup of patients with extremely poor prognosis (mortality rate 90%) relatively early in the disease course.     

Large cell anaplastic lymphoma in children--clinical experiences with a newly defined histologic entity

The clinical characteristics of 31 patients (pts.) (17 boys, 14 girls, median age 12 11/12 years) with large cell anaplastic lymphoma (LCAL) have been evaluated. 17 of these pts. had originally been diagnosed as suffering from "malignant histiocytosis" ("MH") and were therefore included in the DAL-Histiocytosis X 83 study. Another 14 pts. with Ki-1 lymphomas were enrolled in the BFM-NHL therapy studies. According to Murphyclassification 24 pts. (77%) had stage III or IV disease and in general presented in a severe condition. The lymphatic system was involved in 28 pts., 8 pts. (26%) had skin infiltration. With regard to lymphoma involvement of lung, bones and bone-marrow were unexpectedly frequent. CNS involvement was seen in just one pt. Despite rather heterogeneous therapy approaches (ALL-schedules, DAL-HX 83 protocol for treatment of "MH", combination of B-NHL-BFM and AML-BFM schedules, CHOP, BFM protocols for B-NHL) 30 out of 31 pts. achieved clinical remission (CR). The only nonresponder died during bone marrow transplantation of septicemia. 4 pts. relapsed during therapy. 3 of them died, 1 during a BMT. 1 pt. achieved 2nd CR with a BFM-B-NHL protocol. 3 pts. experienced a late relapse, 1 died, 1 2nd CR was achieved, the third pt. is still alive after 2 further relapses disease-free for 3 years. 23 pts. (74%, 13 out of 14 of BFM-NHL therapy study, 10 out of 17 of DAL-HX 83 study, 1 pt. after BMT) are in 1st CR with a median observation time of 2 9/12 years (range 5/12 to 17 9/12 years).(ABSTRACT TRUNCATED AT 250 WORDS)     

应用改良LCH-Ⅰ方案治疗郎格罕细胞组织细胞增生症疗效观察

探讨国际组织细胞协会制定的LCH-Ⅰ方案的治疗效果，提高重症郎格罕细胞组织细胞增生症 (LCH)患儿的疗效。方法17例LCH均经临床、实验室检查及活组织病理检查确诊。按hvin-Osband评分方 法将疾病严重程度分为4级。Ⅰ～Ⅳ级均采用改良LCH-Ⅰ方案，即先予大剂量甲基泼尼松龙冲击治疗，继以8 个疗程的鬼臼噻酚甙(VM26)完成整个治疗。按协会疗效标准进行评价。结果Lavin-Osband分级Ⅰ级8例、 Ⅱ级1例、Ⅲ级2例、Ⅳ级6例。短期疗效Ⅲ、Ⅳ级8例全部好转，有效率为100％；Ⅰ、Ⅱ级6例好转，有效率为 66.7％。追踪结果Ⅲ、Ⅳ级2例治愈、5例好转、1例恶化；Ⅰ、Ⅱ级6例好转，3例稳定，总有效率为76.5％ (13/17)。结论新的诊断标准明确，与国际标准接轨。LCH-Ⅰ方案疗效显著，尤对治疗时年龄＜1岁、病程＜ 3个月、病情重及S-100蛋白阳性者更显其优越性。     

Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study

BACKGROUND: Single-system (SS) disease is the most common presentation in Langerhans cell histiocytosis (LCH) with a heterogenous clinical picture and course. Mostly bone and rarely skin or lymph nodes are involved. PROCEDURE: One hundred and seventy patients with SS-LCH were registered in the DAL-HX 83/90 studies. They were diagnosed according to uniform diagnostic criteria and followed by a standardised schedule. RESULTS: Single bone lesions were most common (68%), followed by multiple bone lesions (19%), isolated skin disease (11%), and isolated lymph node involvement (4 patients). In the detection of bone lesions radiographic skeletal survey proved to be superior to bone scan (97% vs. 82%). Treatment comprised surgery, irradiation and local instillation of steroids, and standardised chemotherapy for multifocal bone disease. After initial therapy 81% of the patients remained disease free. Reactivations restricted to the skeleton occurred in 18% of both unifocal and multifocal bone disease. Two skin patients had a chronic course. Fatality occurred only in one infant with skin disease who progressed to multi-system disease. Twenty-five percent of all patients developed permanent consequences, which were already present at diagnosis in about half of these patients and comprised mainly orthopedic problems related to lesional sites. Diabetes insipidus occurred in 3% and anterior pituitary dysfunction in 2% of the patients. CONCLUSIONS: The course in SS%LCH was benign. In bone disease reactivations remained restricted to the skeleton and did not influence survival. However, reactivations had an impact on morbidity, as permanent consequences were mostly related to the site of disease activity. Med Pediatr Oncol 2001;37:108-114.     

Hungarian experience with Langerhans cell histiocytosis in childhood

The Langerhans cell histiocytosis (LCH) in children is relatively rare and the long-term analysis of therapy results has not been done yet in Hungary. The aim of this study was to investigate the incidence, clinical features, prognostic risk factors, and treatment results of children's LCH in Hungary in a 20-year period. Children less than 18 years of age with newly diagnosed LCH in Hungary were entered in this study. Clinical data of all children with LCH were reported to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The clinical files were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. Median follow-up duration of surviving patients is 10.98 years. Between January 1981 and December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The annual incidence of LCH in children younger than 18 years of age was 2.24/million children. The male-female ratio was 1.36:1; the mean age was 4 years 11 months. Thirty-eight children had localized disease and in 73 cases systemic dissemination was found already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation, and 5 children got only local irradiation. In 2 cases remission was achieved with local steroid administration. Seventy-five patients received chemotherapy. In the 20 years of the study 14 children died, 9 due to the progression of the disease. Sixteen patients had relapse with a mean of 2.16 ± 1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n = 111) was 88.3 ± 3.1% at 5 years and 87.3 ± 3.2% at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.     

Increased Risk of Secondary Leukemia After Single-Agent Treatment with Etoposide for Langerhans' Cell Hlstlocytosls

The study evaluated 139 patients diagnosed with Langerhans' cell histiocytosis (LCH) and enrolled in any protocol of the Italian Association of Pediatric Hematology/Oncology since 1982, Treatment was etoposide (VP-16) only in 50 patients, VP-16 and other drugs with an already established bukemogenic effect in 17 patients, only drugs with leukemogenic effect in 6 patients, other drugs in 35 patients, and surgery only in 31 patients. Median length of follow-up after diagnosis was 65 months (range, 1 to 126 months) for a total of 742.5 person-years at risk (PYRs). Three cases of acute myelogenous leukemia (AML) were reported; only 0.0044 case was expected. The standard incidence ratio (SIR) of AML in this cohort was 680.5 [95% confidence interval (CI), 140.2–1988.5], and the incidence rate per 1000 PYRs was 4.0 (95% CI, 0.8–11.8). For the subgroup treated with single-agent VP-16, the SIR after treatment was 2270.0 (95% CI, 275–8199), and the incidence rate after treatment was 14.7 (95% CI, 1.8–42.8). The study confirms a higher risk of leukemia after LCH and supports the hypothesis of an association between treatment-related acute nonlymphocytic leukemia and single-agent treatment with VP-16.