急性淋巴细胞白血病免疫分型及临床疗效的研究

 目的 研究急性淋巴细胞白血病（ALL）的免疫分型及与预后的相关性。方法 采用骨髓涂片染色进行细胞形态学检查,采用单克隆抗体（McAb）和流式细胞术（FCM）进行免疫表型检测。参照白血病协作方案进行诱导化疗及强化、巩固维持治疗。结果 形态学符合ALL诊断后行免疫分型检查,21例儿童ALL患者中,15例为B系表达,4例为T系表达,1例为B系、髓系混合表达,1例为T系、B系混合表达。9例成年人ALL患者中,5例为B系表达,2例为T系表达,1例为T系、B系混合表达,1例为B系、髓系混合表达。儿童初治ALL的平均完全缓解（CR）率是85.71 ％,显著高于成年人（66.67 %）;随访儿童ALL复发率16.67 %,成年人为50.00 ％。结论 结合免疫分型与细胞形态学分型,确定ALL类型,对其治疗及预后有重要意义。     

大剂量甲强龙联合方案治疗复发或高危儿童急性淋巴细胞白血病的临床研究

 目的 评估大剂量甲强龙（HDMP）为主的联合化疗方案对复发或高危儿童急性淋巴细胞白血病（ALL）的疗效和毒副作用。方法 选择2003年6月至2006年2月收治的复发和高危ALL患儿19例，年龄3～16岁，中位年龄7岁；其中男14例，女5例，16例为复发和多次复发，3例为初诊高危组且泼尼松预治疗反应不佳，全部接受大剂量甲强龙联合方案治疗。结果 19例HDMP方案再诱导治疗者，CR 17例，CR率94 %，NR1例，早期死亡1例。患者不良反应主要有感染、血压增高、肌无力、消化道反应和凝血功能异常。结论 HDMP为主的联合化疗方案对复发或高危儿童ALL的疗效显著，在加强支持对症治疗下不良反应可以控制。     

HyperCVAD方案治疗复发成年人急性淋巴细胞白血病18例

 目的　观察HyperCVAD化疗方案治疗复发成年人急性淋巴细胞白血病（ALL）的疗效。方法　18例复发成年人ALL,采用HyperCVAD作为再诱导化疗方案,同时给予对症支持治疗。结果　1个疗程化疗总有效率达72 %,达完全缓解（CR）的中位时间为19 d,中性粒细胞＞1.0×109／L所需时间为21 d,血小板＞20×109／L所需时间为17 d。结论　HyperCVAD是治疗复发成年人ALL的有效化疗方案。     

Hyper CVAD B方案治疗难治性和复发性急性淋巴细胞白血病12例

 目的　观察Hyper CVAD B方案治疗难治性和复发性急性淋巴细胞白血病（ALL）的疗效及患者不良反应。方法　选择12例难治性复发性ALL患者，应用Hyper CVAD B方案，具体根据患者年龄、体表面积、合并症进行调整用药剂量和用药间期，若1个疗程未达到完全缓解（CR）或部分缓解（PR），则进行第2个疗程，方案同前，2个疗程未达CR则换用其他方案。结果　12例患者中获得CR 8例，PR 2例，NR 2例，总有效率83.3 %。主要的不良反应是骨髓抑制、胃肠道反应、口腔溃疡，无严重的心肝肾功能改变和神经系统并发症。结论　Hyper CVAD B方案可作为难治性和复发性ALL的挽救治疗方案，患者不良反应可耐受。     

米托蒽醌联合治疗儿童难治性复发性急性白血病的临床疗效观察

 目的 观察总结米托蒽醌（MTZ）联合治疗儿童难治性复发性急性白血病（RRAL）的疗效。方法 RRAL 12例,急性淋巴细胞白血病（ALL）9例,急性髓性白血病（AML）3例;ALL用VMLP／Dex方案（长春新碱、米托蒽醌、左旋门冬酰胺酶、泼尼松／地塞米松）2～4周;AML用MAE方案（米托蒽醌、阿糖胞苷、依托泊苷）或大剂量阿糖胞苷+依托泊苷。结果 9例ALL,CR 7例,PR 1例,1例未复查;3例AML,CR 2例,NR 1例。总CR率为81.8 %（9／11）,总有效率90.9 %（10／11）。用药后骨髓抑制较明显,大部分病例ANE≤0.1×109／L持续1～2周,轻微肝功能损害,未见药物相关的心脏损害。结论 MTZ不失为治疗儿童难治性复发性急性白血病的有效药物之一,用药后要注意预防和治疗骨髓抑制后出现的各种感染和出血。     

XIAP及其相关因子1在急性淋巴细胞白血病中表达意义

目的：探讨X染色体连锁凋亡抑制蛋白（XIAP）及其相关因子（XAF1）在急性淋巴细胞白血病（ALL）中的表达及其临床意义,并评估其在临床治疗及预后中的价值。方法：采用病例对照研究,应用实时荧光定量聚合酶链反应（RQ-PCR）检测85例ALL患者骨髓标本中XIAP及XAF1的mRNA表达水平。结果：XIAP mRNA表达水平初诊ALL组高于CR组和对照组（P〈0.05）,而低于复发组（P〈0.05）,CR组表达水平高于对照组（P〈0.05）;而XAF1在ALL时呈低表达或不表达,CR组表达高于ALL其它组（P〈0.05）,与对照组差异无统计学意义（P〉0.05）。XIAP及XAF1二基因表达水平在T系ALL与B系ALL,成人与儿童,男女性别之间表达水平差异无统计学意义（P〉0.05）。XIAP/XAF1比值在ALL患者中初诊组和复发组明显高于对照组和缓解组（P〈0.05）,缓解组高于对照组（P〈0.05）。结论：ALL患者XIAP基因高表达,而XAF1呈现低表达或不表达,提示XIAP可能通过抑制白血病细胞凋亡参与了ALL的发生发展,并与预后不良及治疗反应相关。ALL中XIAP与XAF1表达水平的不平衡,可能是ALL预后不良及复发的一项重要因素之一。抑制XIAP及上调XAF1基因来治疗ALL,将为ALL的基因治疗提供新思路。     

FLAG方案治疗难治复发急性白血病的临床分析

 目的 观察FLAG方案治疗难治复发急性白血病的临床效果。方法 17例复发难治急性白血病患者接受FLAG方案治疗,包括：氟达拉滨（Flud）30 mg·m- 2·d-1,阿糖胞苷（Ara-C）0.5～2.0 g／d,粒细胞集落刺激因子（G-CSF）250～300 μg／d,连用5 d。结果 原发耐药组7例中有4例CR;早期复发组6例中2例CR,1例PR;晚期复发组4例中1例CR,1例PR。不同疾病类型中,急性非淋巴细胞白血病（ANLL）组10例有7例获得CR;急性淋巴细胞白血病（ALL）组共7例, 1例CR,1例PR。按接受Ara-C剂量不同将患者分为两组,标准剂量组（Ara-C 1.5～2.0 g／d）7例,CR6例;降低剂量组（Ara-C 0.5～1.0 g／d）10例,仅1例获得CR,2例PR。在不良反应方面,粒细胞缺乏中位持续时间为21.5 d（16～34 d）;从化疗开始直至血小板＞20×109／L的中位时间为22 d（14～32 d）。在非血液学不良反应中,主要为感染（15／17）,其次为药物热（5／17）。在减低剂量C组中,各种不良反应发生没有明显下降。 结论 FLAG对难治性ANLL有较好的疗效,且不良反应较轻。降低Ara-C剂量会显著降低治疗有效率,且患者不良反应没有明显减少。     

FLAG方案治疗小儿复发难治性急性白血病临床研究

目的探讨FLAG方案（氟达拉滨,阿糖胞苷,粒细胞集落刺激因子）治疗小儿复发难治性急性白血病的疗效。方法采用FLAG方案[氟达拉滨30mg／（m^2·d）X5＋阿糖胞苷2g／（m^2·d）×5d＋粒细胞集落刺激因子5μg/（kg·d）]治疗21例2—13岁的小儿复发难治性急性白血病,其中急性非淋巴细胞性白血病（AML）15例,急性淋巴细胞性白血病（ALL）6例。首次复发（R1）后首选FLAG方案者8例,次选10例,原发难治2例,第三次缓解（CR3）后FLAG巩固治疗1例。结果21例患儿中1例作为缓解后巩固治疗,1例因化疗后感染死亡而无法评估FLAG应用后缓解率;其他19例可评估患儿中9例（47％）获完全缓解（CR）,3例（16％）部分缓解（PR）,7例（37％）无效（NR）,总有效率63％。其中AMLCR率57％,ALL为20％;R1后首选FLAG方案者CR率为57％,次选为20％。应用FLAG后患儿中性粒细胞〉0．5×10^9／L的中位时间为21（12～36）天,血小板〉20×10^9/L的中位时间为19．4（13～30）天。21例患儿中18例合并感染（86％）,除1例死亡外其余均得到有效控制,治疗相关死亡率为4．76％。FLAG治疗后7例患儿进行了造血干细胞移植治疗,目前2例无病存活,分别已移植后无病生存14个月和56个月,其他4例死于移植相关并发症,1例死于移植后复发。另外14例非移植患儿中1例因FLAG相关感染死亡,7例因NR而放弃治疗或合并感染死亡,FLAG治疗有效的6例患儿中2例放弃治疗,4例复发死亡。本组患儿FLAG治疗后中位生存时间5个月。结论FLAG方案治疗小儿复发难治性白血病疗效肯定,毒副作用可以耐受;AML选择FLAG的疗效优于ALL;复发后首选FLAG治疗效果好于次选者。     

米托蒽醌联合用药治疗成人急性白血病临床观察

目的：观察米托蒽醌（MTZ）治疗初治、复发急性白血病（AL）的临床疗效和毒副作用。探索以MTZ为主要药物作为一线治疗药物的可行性。方法：急性髓细胞白血病（AML）诱导治疗采用MTZ和阿糖胞苷（Ara-C)。急性淋巴细胞白血病（ALL）诱导治疗采用长春新碱（VCR）、MTZ、异环磷酰胺（IFO）和强的松（Pred),条件允许时加用左旋门冬酰胺酶（L－ASP）。结果：37例患者中29例取得完全缓解（CR）,CR率78．4％。对20例AML患者进行了随访,治疗多于6疗程以上的10例患者,有8例持续CR（CCR）,中位缓解期为15．5月。结论：米托蒽醌联合用药治疗急性白血病有较好的疗效,其毒副作用可以耐受。该方案可以作为一线方案用于AL的诱导治疗。     

去甲氧柔红霉素为主的联合化疗治疗急性白血病

 目的　分析去甲氧柔红霉素（IDA）和柔红霉素（DNR）治疗急性白血病（AL）的疗效和毒副作用。方法　59例AL患者,初治43例,复发难治16例。急性非淋巴细胞白血病（ANLL）39例,用IA方案化疗;急性淋巴细胞白血病（ALL）18例,用IDA联合长春新碱、异环磷酰胺、泼尼松方案化疗;急性混合细胞白血病（MAL）2例,用IDA联合长春新碱、环磷酰胺、阿糖胞苷方案化疗。同期48例患者采用DNR为主的方案治疗。结果　IDA为主方案的完全缓解（CR）43例,部分缓解（PR）4例,总有效率79.7 %;初治43例中,CR 34例,PR 3例,总有效率86.1 %;复发难治16例中,CR 9例,PR 1例,总有效率62.5 %;39例ANLL中,CR 28例,PR 3例,总有效率79.5 %;18例ALL中,CR 15例,PR 1例,总有效率88.9 %;DNR为主方案的总有效率为80.4 %。结论　IDA是疗效确切、安全、可靠的抗白血病药物。     

Treatment of Refractory and Relapsed Adult Acute Leukemia Using a Uniform Chemotherapy Protocol

Twenty-nine adult patients with relapsed (21) or refractory (8) de novo acute leukemia (12 ALL and 17 ANLL) were treated with a remission-induction salvage chemotherapeutic protocol including vindesine, mitoxantrone, cyclophosphamide, intermediate-dose cytosine arabinoside, prednisolone and methotrexate. Ten of seventeen (59%) ANLL and 8/12 ALL (67%) achieved complete remission (CR). Seven of eight (86%) cases refractory to first-line remission-induction therapy (3/4 ANLL and 4/4 ALL) entered complete remission. The most frequent non-hematologic side effects were gastrointestinal. All patients experienced severe pancytopenia, with median times to recovery of granulocyte and platelet counts of 28 and 29 days, respectively. Nine of twenty-nine (31%) patients suffered febrile episodes of unknown origin and 13/29 (45%) suffered documented infections. Five patients (17%) died while aplastic, four from infection and one from cardiotoxicity. Four patients who entered CR were submitted to a bone marrow transplantation (BMT), two autologous and two allogeneic BMT. Sixteen of the 18 patients who entered CR relapsed, with a median remission duration of 3.5 ± 2.9 months. Two patients remain in remission at 5+ and 17+ months. These results suggest that this protocol is an effective remission-induction salvage therapy for adult acute leukemias.     

Phase II clinical trial of carboplatin in relapsed and refractory leukemia.

Carboplatin is a second-generation platinum complex drug which has demonstrated activity against a variety of neoplasms including acute leukemia, particularly when given by continuous intravenous (i.v.) infusion. Adults with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), either refractory or in first or second relapse, were given a continuous i.v. infusion of carboplatin at a dose of 315 mg/m2 daily for 5 days. A second course was given if the bone marrow at day 14 showed persistent leukemia. If the marrow was hypoplastic, treatment was delayed until marrow recovery was documented. Those with residual leukemia were given a second course. Those achieving complete remission (CR) were given an additional course as consolidation. Of the 46 eligible patients entered (36 AML and 10 ALL) eight achieved CR (17%) of which 6 were AML and 2 ALL. Of nine primary refractory patients, two achieved CR, one AML and one ALL. Excluding the inevaluable patients (protocol violations, patient refused further therapy, early deaths prior to day 14, the CR rate was eight of 28 (29%). All except two CRs required two courses of induction. The non-hematologic toxicity was minimal except for renal and auditory toxicity. Renal toxicity greater than grade 2 was seen in 17 patients and was associated with concomitant use of nephrotoxic antibiotics. In two patients, renal failure was a major factor in the cause of death. Ototoxicity was observed in 11 patients, but was grade 3 in only three. There were 18 deaths during the study. Fourteen died of infection, two died of infection and hemorrhage, one died of hemorrhage while aplastic, and one died of other causes. This trial indicates that carboplatin is an active agent in acute leukemia and warrants further investigation.     

Report on the fourth Japanese-German workshop on molecular and cellular aspects of carcinogenesis

To evaluate the incidence of second malignant tumors in a cohort of subjects previously treated for childhood cancer, we analyzed data from the Off-Therapy Registry (OTR) of the Italian Association of Pediatric Hematology/Oncology, which collects information on children treated for Hodgkin's disease, non-Hodgkin's lymphoma, Wilms' tumor, acute lymphoblastic leukemia (ALL) and acute non-lymphatic leukemia and who had been removed from treatment in the absence of clinical signs of disease, i.e. the off-therapy stage. Second malignant tumors (SMT), diagnosed before December 31, 1988, were identified through a special enquiry to the 36 institutions cooperating in the registry. Observed cases were compared to expected numbers estimated from age- and sex-specific incidence rates derived from the Cancer Registry of the Province of Varese. In a total of 3,310 study subjects, 27 SMTs have been registered. The Cumulative Risk (CR) of SMT was 2.9% 15 years after the end of treatment and the Standard Incidence Ratio (SIR) was 10.8. The ALL sub-cohort had the highest risk of SMT (SIR 13.6) and 9 cases of CNS tumor occurred in this group (SIR 58.9). All 9 had received prophylactic cranial radiotherapy (CRT) and 5 had been treated on one protocol, characterized by low-dose intrathecal methotrexate (IT MTX) given monthly for 2 years after CRT. The Off-Therapy Registry has unique criteria for inclusion; direct comparisons with similar studies are therefore somewhat problematic. However, our data suggest that the risk of SMT in childhood ALL cancer survivors may be greater than previously reported, and that CNS tumors are the most common SMT in this group. The administration schedule of IT MTX may be an important risk factor. © 1994 Wiley-Liss, Inc.     

Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period.

Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follow-up data. The analysis included data on 351 patients treated by standard chemotherapy according to 11 different successive and/or concomitant regimens. Complete remission (CR) was achieved in 299 patients (79%). Initial performance status, LDH level, immunophenotype, age, and risk group (defined according to Hoelzer's criteria) at diagnosis were of significant prognostic value for CR achievement. Median leukemia-free survival (LFS) was 14 months with a 3-year, a 5-year, and an 8-year LFS at 30%, 26%, and 24%, respectively. LFS was better in T cell lineage ALL than in B cell lineage ALL (P = 0.05). Younger age was also a favorable prognostic factor for LFS (P = 0.001). Philadelphia-positive (Ph+) ALL displayed a poor outcome since median LFS was 7 months with only 13% of survival at 3 years. Median overall survival (OS) of the entire cohort was 18 months with a 3-year, a 5-year, and an 8-year OS at 32%, 24%, and 22% respectively. Favorable prognostic factors for OS were younger age (P < 0.0001), and T cell lineage ALL (P = 0.001). Among non-T cell lineage ALL, standard-risk ALL confirmed a significant better outcome than high-risk ALL (P = 0.0003). It was apparent from this analysis that hazard rates for death and relapse were greatest in the first year, decreased substantially between years 1 and 2, then decrease further between years 2 and 3. Rates of death and relapse were quite low after 3-4 years. All patients relapsing after 3 years of CR were B or non-B non-T cell lineage ALL. Long-term survivors (LTS), defined as survival in CR > or =3 years, represented 23% of evaluable patients. Eighty-three patients remain alive in initial CR at >3 years, while only three were LTS after a second CR. Overall, no significant improvement was shown in terms of CR achievement and survival duration over the years. However, regarding survival, a significant improvement was demonstrated in T cell lineage ALL (P = 0.03). Furthermore, patients (aged less than 50 years) transplanted while in first CR did significantly better than those receiving only chemotherapy as post-remission therapy (P < 0.0001). The 3-year OS, after allogeneic transplantation in first CR, was 74% in T cell lineage ALL, while it was less than 50% in B cell lineage ALL. This single center study on a large cohort of ALL patients reflects the degree to which ALL treatment remains unsuccessful in adults. Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR.     

复方苦参注射液联合NP方案治疗晚期非小细胞肺癌的临床研究

  目的 比较复方苦参注射液（岩舒）联合NP方案与NP方案对初治Ⅲb ~ Ⅳ期非小细胞肺癌（NSCLC）患者的疗效、毒性及生活质量的改善情况。方法 A组（34例）接受复方苦参注射液联合NP方案治疗；B组（36例）接受NP方案治疗。两组均以4周为1周期，重复3个周期。客观疗效与不良反应按WHO标准进行评价，生活质量根据临床受益疗效来评价。结果 A、B两组客观疗效（CR+PR）分别为26.5 %及22.2 %（P＞0.05）；中位生存期A组32周，B组27周（P＜0.01）；白细胞减少及恶心呕吐反应B组均较A组明显（P＜0.01）；两组均未发现其他严重的不良反应。临床受益疗效A组高于B组（P＜0.05）。结论 复方苦参注射液联合NP方案与单纯NP方案治疗晚期NSCLC的客观疗效差异无统计学意义，但A组患者不良反应小，中位生存期长，患者生活质量改善明显。     

中/大剂量阿糖胞苷方案序贯化疗后自体造血干细胞移植治疗成年人急性白血病69例分析

 目的 观察第1次完全缓解（CR1）期成年人急性白血病（AL）患者中／大剂量阿糖胞苷（I／HIDAC）序贯强烈化疗后自体造血干细胞移植（ASCT）的安全性及移植疗效。方法 回顾性分析CR1期无HLA匹配同胞供者的成年人AL患者,早期接受I／HIDAC序贯强烈化疗并ASCT治疗。观察其毒副作用、移植相关死亡率（TRM）及总生存率（OS）和无白血病生存率（LFS）等。结果 69例患者接受I／HIDAC强化治疗中位2（1 ~ 3）疗程。患者均发生WHOⅢ ~ Ⅳ级造血系统毒性,常见的非造血系统毒性为胃肠道、皮肤、黏膜毒性、发热及感染等,多为轻微到中等程度。患者均采集到足量的骨髓和／或外周血干细胞。1例预处理后早期死亡,余患者移植后均完全造血重建。中位随访80.5个月,TRM 10.14 %。预期移植后5年OS在AML和ALL分别为（55.36±3.69）%和（56.90±3.56）%,而5年LFS分别为（55.51±3.70）%和（58.09±3.14）%。结论 成年人AL在取得CR1后早期进行以I／HIDAC为基础的强化／巩固治疗后进行ASCT,患者耐受性良好,可获得较好的长期OS和LFS。     

Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia: a single-centre experience.

Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA-identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy-TBI (n = 15), VP16-Cy-TBI(n = 12), CBV (n = 1) and Bu-Cy (n = 1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease-free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4-years DFS of 42.3 per cent. Three patients died of transplant-related complications before 100 days. Relapse occurred in 11 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment-related complications. There were 13 survivors (median follow-up 38 months, range 12-98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p = 0.39). No long-term DFS is obtained from patients with resistant disease (n = 4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p = 0.29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA-matched siblings, the option of BMT should be considered in light of local consolidation survival results.