Improved outcome for acute lymphoblastic leukemia in children of a developing country: results of the Chilean National Trial PINDA 87.

BACKGROUND: The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. PROCEDURE: From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12-18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 instead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. RESULTS: Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% +/- 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5-9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. CONCLUSIONS: We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series.     

Treatment of acute lymphoblastic leukemia in childhood and adolescence: results of the multicenter therapy study ALL-BFM 81

In therapy study ALL-BFM 81 633 previously untreated patients with acute lymphoblastic leukemia (ALL) less than 18 years of age have been recruited from April 1, 1981 to September 30, 1983 and treated in 37 institutions throughout West-Germany and Austria. Here only therapy results of 611 patients with non-B-ALL are presented. Patients with ALL of B-type are described elsewhere. In this fourth consecutive trial of the BFM study group three major questions have been asked: 1. Is it possible to assess the individual risk for relapse more accurately by the use of a risk factor rather than by the risk score which was the discriminator in studies ALL-BFM 76 and ALL-BFM 79? Does this risk factor discriminate more precisely patients at the highest risk for relapse? Offers more intensive risk-adapted therapy to this patient group a better chance for disease-free survival? 2. In patients at a standard risk for relapse with a risk factor below 1.2--approximately 60% of patients with non-B-ALL--can radiotherapy for prevention of CNS disease effectively be replaced by chemotherapy (intermediate dose Methotrexate)? 3. It is possible to reduce duration of maintenance therapy by 6 months to a total duration of 18 months with no unfavorable effect? To assess the radiation problem in standard risk patients and to evaluate the importance of duration of maintenance therapy two randomisations have been utilized. After a median duration of study ALL-BFM 81 of 4 1/2 years and 3 1/4 years after the study had been closed (date of evaluation January 1, 87) the answers are as follows: 1. For the majority of patients risk-adapted therapy had a curative effect. The probability for event-free survival (EFS) in standard risk patients in slightly above 70%, in medium risk patients 67%. In high-risk patients risk-adapted therapy did not improve prognosis, the EFS being still in the order of 50%. A good assessment of the individual risk for relapse is possible by the newly introduced risk factor. This principle is superior to the risk score used in former studies ALL-BFM 76 and ALL-BFM 79 because a low risk group (risk factor below 0.8) could be identified including approximately 25% of all patients with non-B ALL. Selection, quality, and timing of therapy elements remain the decisive prognostic factors, however. 2. Standard risk patients with a risk factor below 0.8 can effectively be protected for CNS relapse by treatment with intermediate dose Methotrexate.(ABSTRACT TRUNCATED AT 400 WORDS)     

儿童急性淋巴细胞白血病的临床分析

目的 分析初诊儿童急性淋巴细胞白血病的临床特征及远期疗效情况,提高急性淋巴细胞白血病患儿的总生存率（overall survival,OS）和无事件生存率（event-free survival,EFS）.方法 收集2005年至2010年住院治疗的初诊急性淋巴细胞白血病80例患儿的临床资料,采用急性淋巴细胞白血病IC-BFM2002为基础的化疗方案,运用Kaplan-Meier法统计分析患儿的5年OS和EFS.结果 80例患儿,男女比例1.22∶1,中位年龄4岁3个月,标危33例（41.2％）,中危37例（46.3％）,高危10例（12.5％）,白细胞（WBC≥20×109/L）22例（27.5％）,BCR/ABL阳性3例（3.8％）;MLL基因重排1例（1.3％）;TEL/AML阳性17例（21.3％）.完全缓解79例（98.8％）,5年OS和EFS分别为（85.9±4.0）％和（79.2±4.7）％,其中标危组5年EFS（86.6±6.4）％,中危组5年EFS （81.1±6.4）％,高危组5年EFS（48.0±16.4）％,组间比较差异有统计学意义（x2=7.03,P＜0.05）.复发12例（15.o％）,中位时间23.5个月.死亡11例（13.8％）,中位时间13个月.结论 初诊儿童急性淋巴细胞白血病患儿的疗效好,标准的分型诊断及危险度分层治疗有利于提高患儿的生存质量.     

Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone

PURPOSE: The cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL) were compared in a group of patients who received dexamethasone during the intensification and maintenance phases of therapy with those in a historical control group for whom antileukemia therapy was similar, except that the corticosteroid component of therapy was prednisone. METHODS: Patients treated for ALL on Dana-Farber Cancer Institute protocols 87-01 (n = 44) and 91-01 (n = 23) were evaluated by standard cognitive and achievement tests. Corticosteroid therapy was delivered in 5-day pulses given every 3 weeks during intensification and continuation phases of therapy for a total of 2 years. RESULTS: Children treated on protocol 87-01 received prednisone at a dose of 40 mg/m2/d (standard risk, SR) or 120 mg/ m2/d (high risk, HR); those treated on protocol 91-01 received dexamethasone at a dose of 6 mg/m2 per day (SR) or 18 mg/m2 per day (HR). Children treated on protocol 91-01 performed less well on cognitive testing. Subsample analysis indicated that cranial radiation therapy and methotrexate dose did not account for differences in cognitive outcomes. CONCLUSIONS: The findings of this preliminary study are consistent with the hypothesis that dexamethasone therapy can increase risk for neurocognitive late effects in children treated for ALL and indicate that further investigation of this question is warranted.     

Corticosteroid-dependent reduction of leukocyte count in blood as a prognostic factor in acute lymphoblastic leukemia in childhood (therapy study ALL-BFM 83)

In therapy study ALL-BFM 83 a total of 630 patients with acute lymphoblastic leukemia (ALL) have prospectively been evaluated for initial response on therapy with corticosteroids. It was the aim to qualify the in vivo cytoreduction as a new predictor for therapy failure. All patients were exposed for 7 days to prednisone before combination chemotherapy at day 8 has been started. At day 0 one additional dose of Methotrexate was given intrathecally. Therapy for all patients with non-B-ALL has been stratified according to initial tumor burden (risk factor) providing four therapy branches: standard risk low (SR-L), standard risk high (SR-H), medium risk (MR), high risk (HR). After a median duration of study of 21 months, event-free survival (EFS) is for all 630 patients 73%, 81% for SR-L, 76% for SR-H, 69% for MR, and 35% for HR patients (date of evaluation Jan. 1, 1987). In this prospective study, a small subgroup of patients (n = 48; 7.6% of total group) is characterized by greater than 1000 leukemic blasts/mm3 peripheral blood at day 8 after exposure to prednisone. In this subgroup the EFS is only 43% in contrast to 76% in the complementary group of 582 patients with less than 1000 leukemic blasts/mm3 peripheral blood at day 8. Patients of that risk group are derived from therapy branches SR-H, M and HR, the latter contributing relatively most patients. In this negatively selected group all patients with an initial high white blood count, CNS disease at diagnosis, immune subtypes as prae-T-ALL (n = 6), T-ALL (n = 18), null-ALL (n = 5), and males clearly dominate. Of 48 patients with greater than 1000 blasts/mm3 at day 8 4 subsequently failed to enter remission and 8 were qualified as lateresponders. 18 patients relapsed, most of them earlier compared to those of the complementary group. The initial in vivo response on corticosteroid therapy is considered a supplementary prognostic predictor for early failure. It will be utilized in trial ALL/NHL-BFM 86 to qualify patients at the highest risk for relapse. This group of patients is supplemented in addition by non- and lateresponders and children with acute undifferentiated leukemia (AUL). The in vivo corticosteroid test is simple, generates early and reliable results and can be obtained almost always. Thus it may be recommended for use in a multicenter trial.     

CNS late-effects after ALL therapy in childhood. Part III: neuropsychological performance in long-term survivors of childhood ALL: impairments of concentration, attention, and memory

PURPOSE: To date, the event free survival (EFS) after treatment of childhood acute lymphoblastic leukemia (ALL) attains 80%. The survivor group is growing steadily. Therefore, the primary purpose of our study is to define the neuropsychological function and to describe which central nervous system (CNS) functions are impaired following the German ALL-BFM and COALL protocols for CNS-negative patients.Patients and METHODS: In a cross-sectional multicenter study 121 subjects, long-term survivors of childhood ALL in first continuous complete remission were investigated. Seven years ago, the subjects were treated as standard or medium risk patients according to ALL-BFM 81, ALL-BFM 83, or COALL 82 protocols, receiving comparable treatments. According to different CNS-prophylaxes, two subgroups were compared in the study: the non-cranially irradiated MTX-group (methotrexate-group) (n = 38) and the cranially irradiated RT-group (radiotherapy-group) (with MTX i.th.) (n = 83). Intellectual and cognitive abilities of these groups were evaluated using standardized psychometric techniques. The Kaufman factors Verbal Comprehension, Perceptual Organisation and Freedom from Distractibility were calculated. Demographical and clinical data collected at the time of the diagnosis were compared between both groups. The different prognoses for patients within both groups were taken into account using a defined risk factor. Analysis of variance was conducted to relate intellectual performance to age, gender, and CNS-treatment. RESULTS: The RT-group exhibited a lower Full Scale IQ than the MTX-group (101.2 +/- 15.9 vs. 109.9 +/- 14.9, P = 0.031). Particularly for the Kaufman factor Freedom from Distractibility the RT-group showed the lower scores (96.9 +/- 14.1 vs. 105.5 +/- 12.6, P = 0.037). Significant interactions between gender and CNS prophylactic treatment were observed for Full Scale IQ (P = 0.008), Verbal IQ (P = 0.012), Performance IQ (P = 0.024), Verbal Comprehension (P = 0.004), and Perceptual Organisation (P = 0.032). CONCLUSIONS: Cranial irradiation in combination with MTX therapy was associated with deficits in attention, concentration, and the ability of sequencing and processing, measured by the Kaufman factor Freedom from Distractibility. Our results support the strategy of avoiding prophylactic CNS irradiation in low risk patients.     

Outcome of acute lymphoblastic leukemia in children with AL90 regimen: impact of response to treatment and sex difference on prognostic factors

BACKGROUND: In our previous studies, the outcome of high-risk ALL was still poor. In the present study, all children with ALL were classified into three groups and treated with a new regimen (AL90). PATIENTS AND METHODS: Between 1990 and 1996, 220 children with ALL, treated with the AL90 regimen, were classified into three risk groups: low, intermediate, and high: LR, IR, and HR, respectively. The protocol consisted of three- to five-drug induction, consolidation with intermediate-dose methotrexate and/or cytarabine, mercaptopurine and cyclophosphamide, four-drug intensification, and sequential maintenance therapies. Only intrathecal chemotherapy was used for CNS prophylaxis in the LR group, whereas cranial irradiation was added for the IR and HR groups. RESULTS: The number of eligible patients was 91: LR group, 71: IR group, and 58: HR group. Complete remission (CR) was obtained in > 98% of the LR and IR groups, while only 88% achieved CR in the HR group. The 5-year event-free survival (EFS) rate was 67.4% in all patients: 70.4% in the LR group, 71.7% in the IR group, and 57.5% in the HR group. With respect to the previous study, EFS in the HR group who showed positive residual leukemia at 14 days was improved, whereas EFS in boys versus girls was significantly lower (48.8% : 85.7%, P = 0.02). CONCLUSIONS: In high-risk ALL, the rate of induction failure was high and boys had a worse outcome, calling for improvements in induction therapy and a specific approach for boys.     

CAMSBDH-ALL方案治疗儿童急性淋巴细胞白血病的中长期疗效观察

目的 回顾性分析CAMSBDH-ALL 方案治疗儿童急性淋巴细胞白血病（ALL）的中长期疗效。方法 1999 年1 月至2007 年12 月间初诊儿童ALL 共318 例,2002 年12 月前收治的83 例患儿采用CAMSBDH-ALL99 方案治疗,其中标危（SR）患儿48 例,高危（HR）患儿35 例;之后收治的235 例患儿采用CAMSBDH-ALL03 方案,其中SR 患儿131 例,HR 患儿104 例。99 方案采用传统化疗;03 方案在99 方案的基础上进行调整。结果 03 方案组中长期OS 率及EFS 率均明显高于99 方案组 （均P<0.01）;SR 及HR 患儿03方案组中长期OS 率及EFS 率亦均显著高于99 方案组（均P<0.01）;03 方案组复发率（28.9%）显著低于99方案组（50.6%）（P<0.05）,且病死率（28.5%）亦显著低于99 方案组（56.6%）（P<0.05）。结论 03 方案疗效明显优于99 方案,即能明显降低ALL 患儿复发率和病死率,提高患儿中长期生存率。     

Incidence, clinical markers and prognostic significance of immunologic subtypes of acute lymphoblastic leukemia (ALL) in children: experiences of the ALL-BFM 83 and 86 studies

In the therapy studies ALL-BFM 83 and 86, immunophenotyping of ALL by monoclonal antibodies was performed in a total of 1162 protocol patients (ALL-BFM 83 n = 578; ALL-BFM 86 n = 584). Both studies yielded similar results with respect to the incidence of immunological subtypes: CD10-negative pre-pre-B ALL (ALL-BFM 83: 3.6%; ALL-BFM 86: 5.3%), common ALL (80.1%; 77.9%), B-ALL (1.9%; 2.8%), pre-T/T-ALL (13.9%; 13.5%). Leukemic cells of 3 patients in the ALL-BFM 83 study lacked lymphoid and myeloid antigens (acute unclassifiable leukemia, 0.5%), and 3 patients in the ALL-BFM 86 study exhibited different blast populations with expression of either myeloid or lymphoid features (acute mixed-lineage leukemia, 0.5%). Coexpression of myeloid antigens (CD13 and/or CD33 and/or CDw65) on lymphoblasts (My-positive ALL) was identified in 35 of the 570 (6.1%) protocol patients prospectively analyzed in the ALL-BFM 86 study. The following associations were observed between the immunological subtype and the clinical risk factors: median age (years)-pre-pre-B 3.0, common 4.3, B- 7.9, pre-T/T-ALL 8.5 (pre-pre-B, common vs. pre-T/T-ALL p = 0.05); median leukocyte counts (x 10(9)/l)-pre-pre-B 80, common 9.1, B- 12.3, pre-T/T-ALL 68.1 (common, B- vs. pre-pre-B, pre-T/T-ALL p less than 0.05). The prognostic relevance of the immunophenotype was evaluated on the basis of the therapeutic results obtained in the ALL-BFM 83 study. A significant difference in the remission rate was only recognizable between patients with common ALL (99.1%) and those with pre-T/T-ALL (93.7%, p less than 0.001). After a median follow-up of 54 months, the probability of event-free survival is 71% for pre-pre-B ALL, 67% for common ALL, 56% for pre-T/T-ALL and 27% for B-ALL (common vs. B-, pre-T/T-ALL p less than 0.001), the prognosis in patients with pre-pre-B and common ALL being markedly influenced by the initial leukocyte counts and the age.     

ALL-BFM 95 Treatment in Turkish Children with Acute Lymphoblastic Leukemia—Experience of a Single Center

Little is known about the likelihood of curing children with high-dose chemotherapy regimens for treatment of childhood acute lymphoblastic leukemia (ALL) in Turkey. The authors here report their 13 years’ experience with original ALL-BFM (Berlin-Franfurt-Münster) 95 protocol in a cohort of 140 Turkish children with ALL. Complete remission rate was 97.7% with a relapse rate of 12.9% and death rate 17.9% during a median follow-up of 69 months. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) in these patients at 12 years were 75.0%, 87.1%, and 80.6%, respectively. These results show that ALL-BFM 95 protocol is equally applicable in the experienced centers, even in developing countries without substantial treatment-related toxicity. High rate of infection deaths are to be reduced with correct policies.     

提高化疗强度对伴IKZF1基因缺失儿童急性淋巴细胞白血病预后的影响

目的 总结伴IKZF1基因缺失儿童急性淋巴细胞白血病（ALL）的临床特征并观察提高化疗强度对其预后的影响。方法 2015年12月至2018年2月间确诊并按照中国儿童白血病协作组-ALL 2008（CCLG-ALL 2008）方案规范治疗的ALL患儿共278例,根据有无IKZF1基因缺失将其分为IKZF1基因缺失组和IKZF1基因正常组,IKZF1基因缺失组均接受CCLG-ALL 2008高危（HR）方案治疗,IKZF1基因正常组则按临床危险度分型接受不同强度化疗,比较两组的临床特征及无事件生存（EFS）率。结果 278例患儿中共24例（8.6%）检出IKZF1基因外显子大片段缺失。IKZF1基因缺失组初诊时WBC ≥ 50×10⁹/L、BCR-ABL1融合基因阳性、诱导缓解治疗第15天微小残留病≥ 10%、微小残留病-HR、临床危险度-HR所占比例均高于IKZF1基因正常组（P < 0.05）。IKZF1基因缺失组3年EFS率（76%±10%）低于IKZF1基因正常组（84%±4%）,但差异无统计学意义（P=0.282）;其中,IKZF1基因缺失组-非HR（实际按CCLG-ALL 2008 HR方案化疗）的预计3年EFS率为82%±12%,低于IKZF1基因正常组-非HR（86%±5%）,但差异无统计学意义（P=0.436）。结论 伴IKZF1基因缺失的儿童ALL早期治疗反应更差,提高化疗强度可能改善其预后。     

ALL-BFM 95 treatment in Turkish children with acute lymphoblastic leukemia-experience of a single center

Little is known about the likelihood of curing children with high-dose chemotherapy regimens for treatment of childhood acute lymphoblastic leukemia (ALL) in Turkey. The authors here report their 13 years' experience with original ALL-BFM (Berlin-Franfurt-Münster) 95 protocol in a cohort of 140 Turkish children with ALL. Complete remission rate was 97.7% with a relapse rate of 12.9% and death rate 17.9% during a median follow-up of 69 months. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) in these patients at 12 years were 75.0%, 87.1%, and 80.6%, respectively. These results show that ALL-BFM 95 protocol is equally applicable in the experienced centers, even in developing countries without substantial treatment-related toxicity. High rate of infection deaths are to be reduced with correct policies.     

Randomized comparison of rotational chemotherapy in high-risk acute lymphoblastic leukaemia of childhood — follow up after 9 years

A frequent change of drug combinations may circumvent drug resistance in the treatment of patients with acute lymphoblastic leukaemia (ALL). In study COALL 85/89 201 children with high-risk ALL were randomized to receive over a period of 8 months rotational chemotherapy with six drug combinations given either in slow rotation (SR) (each combination given twice in succession) or in rapid rotation (RR) (cach combination given once with a repetition of the drug combinations). Treatment of central nervous system leukaemia consisted of cranial irradiation and intrathecal methotrexate. Both SR and RR treatment groups were then given continuation chemotherapy of oral 6-mercaptopurine and methotrexate until 2 years after the date of diagnosis. The 9-year eventfree survival (EFS) rate for the whole group is 69%±3%, and the survival rate 75%±3% at a median follow up of 5.8 years. Failure to achieve remission at day 28 was the most important prognostic factor (EFS 12%±7% vs. 75%±3% in the remission group). In the RR group, 11/100 patients were not in remission at day 28 opposed to 7/101 patients in the SR group. Children aged <1 year (6/6 relapses) or aged >=10 years had a worse prognosis (EFS 64%±5% vs. 77%±4% in patients 1–10 years old). After 5 years EFS was inferior in the RR group attributable to a significantly higher relapse rate in children with a WBC>=100/nl. The EFS at 9 years for all patients, however, is similar in both groups (SR 72%±5% vs. RR 67±5%).     

MRD监测下88例儿童急性B淋巴细胞白血病长期疗效的分析

目的对88例儿童急性B淋巴细胞白血病（B—ALL）治疗的长期随访结果进行分析,探讨微小残留病（MRD）监测下儿童B—ALL的无事件生存率（EFS）。方法回顾性分析2005年1月．2008年5月接受儿童ALL诊疗建议（第三次修订草案）治疗的88例B．ALL患儿,应用流式细胞术（FCM）检测MRD,采用Kaplan—Meier方法评估患儿EFS,各临床危险度分组间患儿EFS差异用Logrank检验。结果88例患儿骨髓完全缓解（CR）率为97．7％,2年、3年、4年、5年EFS率分别为87．5％、86．4％、81．8％、77．2％,标危、中危、高危5年EFS率分别为86．2％、84．6％、63．1％。5例死亡,9例复发（10．5％）,复发中位时间为23（3—59）个月。结论采用儿童ALL诊疗建议（第三次修订草案）治疗CR率较高,在MRD监测下指导治疗,总体上B—ALL患儿的5年EFS提高。     

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。     

188例急性淋巴细胞性白血病患儿的疗效及预后分析

目的 对中南大学湘雅医院、广西医科大学第一附属医院急性淋巴细胞白血病(ALL)患儿的治疗结果及影响无事件生存率(EFS)的因素进行分析.方法 所有病例均采用中华医学会儿科学分会血液学组1998年第二次修正的小儿ALL诊疗建议(简称荣成方案)化疗,采用Kaplan-Meier方法评估依从治疗的188例患儿EFS,组间患儿EFS差异用Log-rank检验,用COX比例风险模型分析独立因素对EFS的影响.结果 374例接受诱导治疗儿童的完全缓解(CR)率为93.6%(354例),全程依从治疗的188例ALL的5年EFS为(68.1±5.6)%,标危、高危组5年EFS分别为(75.2±6.0)%、(47.6±11.6)%;总复发率为10.6%,复发的中位时间为13个月;188例患儿中共有29例死亡,死亡率15.4%;化疗相关死亡13例(7.0%).危险度分组、t(9;22)/bcr-abl融合基因和白细胞计数为独立的不良预后因素.结论 两家医院通过荣成方案治疗儿童ALL的总EFS接近70%,需要进行更加详细的危险因素评估和分组,降低治疗相关死亡率,提高儿童ALL治疗的依从性,以进一步提高EFS.     

儿童急性淋巴细胞白血病单中心临床研究

目的 初步评估所采用的2004全国小儿血液病学术会议关于儿童急性淋巴细胞白血病诊疗建议方案(简称04方案)的诊断、治疗效果.方法 对2004年10月-2007年6月282例急性淋巴细胞性白血病(简称急淋)患儿,参照04方案诊疗建议进行诊断、分型及治疗;按危险度分型进行统计并用SPSS统计软件对结果进行生存分析.结果 2004年10月-2007年6月88例新诊急淋患儿接受了04方案化疗,总完全缓解(CR)率为91.30%(63/69),标、中危组CR率均为100%(37/37),高危组CR率为81.25%(26/32);总4年无病生存率(EFS)为(59.73±7.22)%,标、中危患儿的EFS分别为(75.60±9.71)%和(65.50±11.69)%,高危组EFS为(44.03±12.36)%;总复发率为18.18%,骨髓复发占87.50%,单纯的中枢复发占12.50%;化疗相关死亡率为9.09%,其中诱导缓解治疗阶段因感染死亡7例(7.95%),真菌是主要病原菌.结论 应用04方案对儿童急淋进行诊治疗效满意;化疗第19天(d_(19))骨髓幼稚细胞数和临床危险度分型是独立的预后指标,大剂量甲氨蝶呤对中枢神经系统白血病的预防起到了重要作用;诱导期化疗过强,化疗相关死亡率高.     

儿童急性淋巴细胞白血病南方ALL99方案临床疗效分析

目的对82例儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)治疗结果进行分析,探讨如何提高儿童ALL无病生存率。方法应用南方ALL99方案治疗82例ALL患儿。该方案引进德国BFM95和香港-新加坡ALL97方案,作了少许改动,形成南方ALL99方案。改动方面包括将三联鞘注中的氢化可的松换成地塞米松,将外院不规则化疗过的标危患者按中危治疗,将每一疗程开始时的中性粒细胞和血小板的标准提高到中性粒细胞≥1×109/L,血小板≥100×109/L。采用SPSS软件进行寿命表法分析。结果对1999年4月至2003年9月收治的82例ALL患儿按南方ALL99方案进行治疗,78例获完全缓解(completeremission,CR),CR率为95%;13例患者因经济困难或其他原因失访。其中按南方ALL99方案坚持治疗的69例,预期2年无病生存率91%,预期5年以上无病生存率75%;因感染死亡3例(死亡率为4%),复发死亡6例。结论引进德国BFM95和香港-新加坡ALL97方案而成的南方ALL99方案治疗儿童ALL疗效好,化疗相关死亡率低,该方案对中国人耐受性好,值得推广应用。     

TREATMENT OF STANDARD-RISK ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN: The Results of Protocol AL841 from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan

A total of 62 patients with standard-risk acute lymphoblastic leukemia received three-drug induction consisting of vincristine, prednisolone, and L-asparaginase (l-Asp) followed by consolidation therapy with intermediate-dose methotrexate (MTX), intrathecal MTX, and 18 Gy of cranial irradiation. Maintenance therapy consisting of 6 drugs including daunorubicin (DNR, 450 mg/m2 in total) was continued for 3 years. Patients were randomized and half of them received weekly l-Asp during maintenance therapy as a late intensification. Complete remission (CR) was achieved in 61/62 (98.4%), and 11 of 61 patients relapsed. At 10 years, the event-free survival (EFS) was 80.6 5.0% and overall survival was 88.7 4.0%; median follow-up time was 9.3 years. The 10-year EFS of patients with additional l-Asp (84.8 6.2%) was superior to that without l-Asp (75.9 7.9%), although it was not statistically significant. No patients who received a full dose of DNR and maintained CR developed heart failure, although the shortening fraction decreased from 41.0% at diagnosis to 35.2% (median). The protocol AL841 provided good long-term disease control without severe late cardiac dysfunction.     

Childhood acute lymphoblastic leukemia in Turkey: factors influencing treatment and outcome: a single center experience

There is limited data about the long-term treatment outcome and prognosis of childhood acute lymphoblastic leukemia (ALL) in developing countries. Our study was designed to assess survival data and identify risk factors. Data of 142 children with ALL who were treated with a modified BFM 95 protocol between 1997 and 2007 were evaluated. The median age was 4.3 years. Complete remission (CR) rate after induction phase was 93.5%; with 2.1% induction-related mortality and 0.7% having resistance disease. Of complete responders, 67.1% are in continuous CR with a median follow-up of 63 months (range: 24 to 153 mo). Treatment-related mortality was 17.7% and the total rate of treatment abandonment was 3.5%. The probability of event-free survival was 67.3% (95% confidence interval 59.3-75.3) at 4 years and 63.2% (95% confidence interval 54.4-72.0) at 8 years. This report examines children with ALL treated with a modified ALL-BFM 95 protocol in a tertiary care center in Turkey with adequate follow up and demonstrates the need for improvements especially for patients with unfavorable risk group and strategies to reduce deaths from infection in CR to keep pace with cure rates in developed countries.