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CR8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.     

FLAG方案治疗难治及复发急性淋巴细胞白血病13例

目的 观察氟达拉滨(Flu)、阿糖胞苷（Ara-C）及粒细胞集落刺激因子(G-CSF)(FLAG方案)治疗复发及难治性急性淋巴细胞白血病( ALL)的临床疗效及安全性。方法对13例复发及难治性ALL患者给予1～3个疗程FLAG方案化疗，观察其疗效及患者不良反应。结果FLAG方案治疗总有效(OR)率为76.92％(10/13)。患者主要不良反应为骨髓抑制和继发感染。结论FLAG方案对于复发及难治性ALL患者是一种有效的治疗选择，不良反应大多能够耐受。     

以下肢静脉血栓为主要表现的成年人急性淋巴细胞白血病一例并文献复习

目的 提高对初发急性淋巴细胞白血病(ALL)静脉血栓形成机制及其治疗的认识.方法 分析1例以下肢静脉血栓为主要表现的成年ALL病例资料并复习相关文献.结果 该患者予VCDLP方案化疗并联合低分子肝素治疗后达完伞缓解,患肢水肿明显减轻.结论 以静脉血栓形成为主要表现的成年人ALL非常罕见,可由多种原因导致.在安全有效的抗凝治疗支持下,可不必停用左旋门冬酰胺酶等化疗药物,临床医生处理血栓形成应根据美国胸科医师学会指南,个体化治疗.     

大剂量甲氨蝶呤治疗急性淋巴细胞白血病血药浓度及不良反应观察

目的 探讨大剂量甲氨蝶呤(HD-MTX)治疗急性淋巴细胞白血病(ALL)的血药浓度与患者不良反应的关系.方法 分析12例完全缓解期的ALL患者HD-MTX化疗后不良反应.结果 HD-MTX化疗后患者以骨髓抑制(7/12)、胃肠道反应(8/12)、肝损害(5/12)为常见的不良反应.化疗后24 hMTX血药浓度为(23.688±9.607)μmol/L,经甲酰四氢叶酸钙(CF)解救后,44、68 h血药浓度降低为(0.338±0.247)μmol/L,(0.045±0.033)μmol/L.结论 HD-MTX治疗时保证充分水化、碱化,正确使用CF解救是保证HD-MTX方案顺利进行的关键因素.     

左旋门冬酰胺酶治疗儿童急性淋巴细胞白血病的不良反应及防治

目的 探讨左旋门冬酰胺酶(L-ASP)治疗儿童急性淋巴细胞白血病(ALL)的不良反应及可行的防治方法.方法 对50例ALL患儿应用L-ASP治疗的171个疗程进行回顾分析.结果 171个疗程中有77个疗程中出现1种或1种以上不良反应:过敏反应6例次(12%)(维持期)、凝血功能障碍13例次(26%)(诱导缓解期20%,维持期6%)、胰腺炎4例次(8%)(诱导缓解期)、药物性肝炎23例次(46%)(诱导缓解期16%,维持期30%)、胃肠反应40例次(80%)(诱导缓解期60%,维持期20%),高血糖症9例次(18%)(诱导缓解期6%,维持期12%),经及时正确防治无一例死亡.结论 积极预防可减少L-ASP的不良反应,保证化疗顺利进行;及时诊断和处理可减少严重并发症的发生,提高ALL患儿的无病生存率.     

HAG预激化疗作为诱导缓解方案治疗老年人急性髓系白血病和骨髓增生异常综合征的临床观察

目的 观察HAG预激化疗作为诱导缓解方案在治疗老年急性髓系白血病(AML)和骨髓增生异常综合征-难治性贫血伴原始细胞增多型(MDS-RAEB)患者中的疗效.方法 对应用HAG预激方案治疗的21例AML和9例MDS-RAEB患者(≥60岁)的临床资料进行回顾性总结,包括疾病完全缓解(CR)率、有效率以及不良反应.结果 21例老年AML患者中,HAG诱导缓解的有效率为66.7%(14/21),其中CR率为47.6%(10/21);9例老年MDS-RAEB患者中,CR率为55.6%(5/9):HAG预激化疗的主要不良反应为因骨髓抑制继发的感染,调整化疗方案后所有患者均能耐受.结论 HAG预激化疗作为诱导缓解方案适用于老年AML和MDS-RAEB患者.     

小儿急性淋巴细胞白血病血清CD3+ CD4- CD8- T细胞和T细胞亚群的变化及其临床意义

目的 探讨小儿急性淋巴细胞白血病(ALL)外周血CD3+ CD4- CD8- T细胞(DNT细胞)及T淋巴细胞亚群的变化及意义.方法 采用免疫荧光流式细胞术检测30例ALL患儿及24例健康小儿外周血DNT细胞及T淋巴细胞亚群CD3+ T细胞、CD3+ CD4+ T细胞及CD3+ CD8+ T细胞水平.结果 DNT细胞、CD3+ T细胞、CD3+ CD4+ T细胞百分比均明显低于对照组,分别为(4.93±3.75)%比(8.19±3.21)%(t=3.4,P<0.01):(49.99 ±11.70)%比(64.13 ±11.39)%(t=4.1,P<0.01);(28.30 ±7.56)%比(34.61 ±6.43)%(t=3.2,P<0.01);而CD3+ CD8+ T细胞百分比明显高于对照组,为(31.19±9.89)%比(24.33 ±4.24)%(t=3.1,P<0.01).结论 ALL患儿外周血DNT细胞及T亚群的变化提示患儿体内存在免疫功能紊乱,这可能与ALL的发病机制有关.     

序贯诱导法治疗高危急性非淋巴细胞白血病

目的 探讨小剂量HA(LD-HA)方案及标准方案序贯诱导法治疗高危急性非淋巴细胞白血病(ANLL)的疗效.方法 对50例不适合常规诱导的高危ANLL患者(LD-HA组)进行了序贯诱导.第1个周期诱导方案为LD-HA,首次诱导仍未缓解者,更换为标准方案(DA或HA)诱导.选择同期以DA或HA方案诱导治疗的23例ANLL患者(DA/HA组)作为对照,最多诱导2个周期.结果 LD-HA组患者完全缓解率为80.0%(40/50),诱导过程死亡2例;中位无瘤生存时间为19.6个月,中位生存时间为12.2个月;1、3、5年生存率分别为57.0%、24.1%、18.8%.DA/HA组共17例完全缓解,缓解率为73.9%;中位无瘤生存时间为19.8个月,中位生存时间为12.1个月;1、3、5年生存率分别为56.58%、27.1%、27.1%,两组相比,1、3、5年生存率差异无统计学意义(x2值分别为0.009、0.237、1.807,P值均＞0.05).结论 以LD-HA及标准方案序贯诱导高危ANLL患者,可获得较高的完全缓解率及长期生存率.     

MT方案治疗急性单核细胞白血病的疗效及其与染色体核型的关系

目的 研究米托蒽醌联合替尼泊苷(MT)方案在急性单核细胞白血病(M5)诱导缓解中的疗效及患者不良反应,并观察疗效与白血病染色体核型的关系.方法 将33例M5患者按治疗史分两组:初治组23例(A组)、DA(柔红霉素联合阿糖胞苷)或HDA(三尖杉酯碱、柔红霉素和阿糖胞苷)1个疗程无效组10例(B组).按核型预后分两组:预后中等组29例(C组),预后不良组4例(D组),均采用MT方案2个疗程诱导缓解,分别统计4组的临床疗效及患者不良反应.结果 MT方案对A、B组的M5诱导完全缓解(CR)率分别为83%(19/23)及60%(6/10),有效率达91%(21/23)及70%(7/10).C、D组CR率分别为83%(24/29)及25%(1/4),有效率为88%(26/29)及50%(2/4),其中复杂核型CR率为0(0/3),非复杂核型的11q23染色体异常患者一次化疗达CR率100%(4/4).MT方案对M5化疗后白细胞最低点在第(7±3)天出现,为(0.4±0.2)×109/L,白细胞<1×109/L时间达(8±5)d,未见化疗相关死亡病例.结论 MT方案简单有效、较安全,是治疗M5的较佳化疗方案,对1个疗程DA、HDA方案无效者亦可试用.MT方案化疗疗效与核型预后分组有关,对11q23染色体异常的M5患者疗效较好,对复杂核型患者疗效欠佳.     

全反式维甲酸、三氧化二砷、化疗联合治疗急性早幼粒细胞白血病疗效观察

目的 评估全反式维甲酸(ATRA)、三氧化二砷(As2O3)、化疗联合治疗初诊急性早幼粒细胞白血病(APL)的疗效和患者不良反应.方法 对40例采用ATRA、As2O3、化疗三联疗法治疗的APL患者的临床资料进行回顾性分析,观察其疗效及不良反应.结果 总体CR率92.5%(37/40),完全缓解所需中位时间27(22～61)d;白细胞≥10×109/L组CR率72.7%(8/11),白细胞<10×109/L组CR率100%(29/29),差异有统计学意义(x2=8.550,P=0.004);治疗过程中无严重不良反应,仅1例发生维甲酸综合征.结论 ATRA、As2O3、化疗联合应用可作为APL患者的首选治疗方案.     

Identification and partial characterization of two steroid 5 alpha-reductase isozymes in the canine prostate

BACKGROUND AND OBJECTIVE: Intensive induction and post-remission therapies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensification therapy in the overall results of treatment has not been consistently evaluated. The objective of this study was to analyze the results of a multicenter prospective protocol, PETHEMA ALL-89, in which, after intensive induction and consolidation therapy, randomization to receive delayed intensification treatment was performed. DESIGN AND METHODS: One hundred and eight adults (age > or = 15 years) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the end of the first year were randomized to receive one six-week cycle of late intensification therapy. Uni- and multivariate analyses of early response to treatment, complete remission (CR), leukemia-free survival (LFS) and overall survival (OS) were performed. RESULTS: The median (range) age of the series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34 months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-year probability 47% (34-59%). There were no differences in either LFS and OS between patients who did or did not receive delayed intensification therapy. Prognostic factors for CR attainment were advanced age and slow response to therapy. These two features were, in addition to high leukocyte counts, the parameters with negative influence in both LFS and OS. INTERPRETATION AND CONCLUSIONS: The results of PETHEMA ALL-89 are similar to those referred in other chemotherapy-based protocols in adult ALL. Delayed intensification has not improved the length of remission and survival. Efforts to improve the prognosis of adult ALL patients must be mainly focused in early intensification treatment.     

The GIMEMA ALL 0183 trial: analysis of 10-year follow-up. GIMEMA Cooperative Group, Italy

We report the 10-year follow-up of the GIMEMA ALL 0183 trial. From 1983 to 1987, 358 adults with acute lymphoblastic leukaemia (ALL) were entered into this trial, which included a mild induction, an early intensive consolidation, a post-consolidation phase randomized in conventional maintenance (arm A) and in more intensive regimen (arm B). CNS prophylaxis did not include CNS irradiation. The overall complete remission (CR) rate was 79.3% (284/358); 212 patient were randomized (110 in arm A and 102 in arm B). The median overall CR duration was 20 months and the median overall survival (OS) 21 months; both curves reach a plateau after 6 years; at 10 years 25% of patients were projected to be in long-term remission and survivors. The median disease-free survival (DFS) was 17 months, at 10 years 27% and 28% of patients were DFSs in arm A and in arm B respectively. In multivariate analysis age, WBC count and L2 FAB subtype were found to significantly influence OS and DFS. With regard to our previous report OS appears to linearly correlate with initial WBC count and age (P = 0.0002 and P = 0.042 respectively). 195 (68.7%) patients relapsed (only 25 had isolated CNS). The overall second CR rate was 56.5%; 23 patients underwent transplantation (12 BMT and 11 ABMT). Post-relapse survival was found to be influenced by the duration of first CR.     

Results of the CCLSG high risk ALL 874 protocol in childhood acute lymphoblastic leukemia. Children's Cancer and Leukemia Study Group

One hundred and eighty eight children with acute lymphoblastic leukemia (ALL) were treated in a Children's Cancer and Leukemia Study Group high-risk ALL 874 study from April, 1987 to September, 1991. These patients received a four-drug induction regimen followed by the early consolidation regimen, cranial irradiation at 6 months of remission and three years of continuation therapy with rotational administration of four drugs. The patients were randomized into two regimens. In regimen A, the consolidation chemotherapy consisted of the intermediate dose cytosine arabinoside (Ara-C), cyclophosphamide (CPM) plus 6MP, and in regimen B, it consisted of high-dose Ara-C plus CPM. Regimen A was given to 106 patients and 82 patients received regimen B. The complete remission induction rate for regimen A and B was 89.4% (93/104) and 98.7% (78/79), respectively. The 3-year event-free-survival (EFS) rate was 70.6% for regimen A, which was higher than the 56.7% for regimen B. The 3-year EFS rate was 44.4% for the 53 patients with an initial leukocyte count > or = 10 x 10(4)/microliters and 72.2% for 132 patients with a leukocyte count < 10 x 10(4)/microliter. We considered that Ara-C plus L-asp, added to the conventional high-risk ALL 811 protocol, improved the prognosis of the high risk ALL patients. However, further intensive chemotherapy was required for improvement of the outcome of the patients with hyperleukocytosis (> or = 10 x 10(4)/microliters).     

Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer

PURPOSE: Patients with cancer and chronic inflammatory disorders have used shark cartilage (SC) preparations for many years. Preclinical studies that support their beneficial effects are scanty, and reports of clinical trials have been anecdotal. The proposed mechanisms of antitumor action include direct or indirect inhibition of angiogenesis. Because of the emerging use of SC as an alternative to conventional cancer therapy, this trial was launched to evaluate the safety and efficacy of SC. PATIENTS AND METHODS: Sixty adult patients with advanced previously treated cancer (breast, 16 patients; colorectal, 16 patients; lung, 14 patients; prostate, eight patients; non-Hodgkin lymphoma, three patients; brain, one patient; and unknown primary tumor, two patients) were enrolled. Eligibility criteria included confirmation of diagnosis, resistance to conventional therapy, objective measurable disease, life expectancy of 12 weeks or greater, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, no recent or concomitant anticancer therapy, no prior SC, and informed consent. Patients underwent evaluation of the extent of disease, quality-of-life score (Functional Assessment of Cancer Therapy-General [FACT-G] scale), and hematologic, biochemical, and selected immune function studies at baseline and after 6 and 12 weeks of SC therapy. The dose of SC was 1 g/kg daily orally in three divided doses. Standard criteria were used to evaluate adverse events and response. RESULTS: Ten of 60 patients were lost to follow-up(LTFU) or refused further treatment (RFT) before the 6-week evaluation and were not assessable for toxicity and response. Three patients with stable disease at 6 weeks were LTFU or RFT thereafter. Of the 47 fully assessable patients, five were taken off study because of gastrointestinal toxicity or intolerance to SC. Progressive disease (PD) at 6 or 12 weeks occurred in 22 and five patients, respectively. Five patients died of PD while undergoing SC therapy. No complete (CRs) or partial responses (PRs) were noted. Median time to tumor progression in the entire study population was 7+/-9.7 weeks (mean, 11.4 weeks; range, 3.7 to 45.7 weeks). Ten (20%) of 50 assessable patients, or 16.7% of the 60 intent-to-treat patients, had stable disease (SD) for 12 weeks or more. The median time to tumor progression was 27 weeks, the mean was 28.8+/-9.9 weeks, and the range was 18.6 to 45.7 weeks. In this subset, FACT-G scores improved in four patients, were unchanged in four patients, and declined in two patients. Twenty-one adverse events (grade 1, eight events; grade 2, seven events; and grade 3, six events) were recorded, 14 of which were gastroenterologic (nausea, vomiting, constipation). CONCLUSION: Under the specific conditions of this study, SC as a single agent was inactive in patients with advanced-stage cancer and had no salutary effect on quality of life. The 16.7% rate of SD was similar to results in patients with advanced cancer treated with supportive care alone.     

Secondary haematological neoplasm after treatment of adult acute lymphoblastic leukemia: analysis of 1170 adult ALL patients enrolled in the GIMEMA trials. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto

Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs. The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died. The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively. The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.     

低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

目的 观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤(MM)患者的疗效及安全性.方法 35例初治及难治复发MM患者,硼替佐米1.1 mg/m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg/d开始逐渐加量至150 mg/d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案.28 d为1个疗程,每例患者至少接受2个疗程以上治疗.达到部分缓解(PR)及以上疗效的患者应用沙利度胺150 mg/d或患者能够耐受的最大剂量维持治疗.采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应.结果 中位随访20个月,35例患者治疗总有效率82.8%,其中完全缓解(CR)率48.6%,良好的部分缓解(VGPR)率17.1%,PR率17.1%.3年预计无进展生存(PFS)和总生存(OS)率分别为60.92%和72.41%.达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义(P=0.004).初治及难治复发患者客观缓解率(ORR)及OS率差异无统计学意义.Ⅲ～Ⅳ度非血液学毒性主要包括乏力(3/35)、恶心、呕吐(8/35)、便秘(4/35)和周围神经病变(3/35).Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏(10/35)和血小板减少(8/35).结论 低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间.     

Long-term survival and quality of life in patients treated with a national all protocol 15-20 years earlier: IDM/HDM and late effects?

In a follow-up matched control study the 93 (70.5%) survivors of 132 children treated with a national protocol for acute lymphoblastic leukemia (ALL) and 5 survivors of the other 21 cases of ALL in childhood diagnosed in the same period were evaluated. Thus it was also a population-based study. The national treatment protocol was used in the period 1975-1980. Methotrexate (MTX) infusions combined with intrathecal MTX were used as prophylaxis against neuroleukemia instead of irradiation. Neither doxorubicin (Adriamycin) nor cyclophosphamide was used in the protocol. A questionnaire covering demographic data, number of offspring, learning problems, level of athletic performance, education, and work status as well as medical information was used. Forms were received from 94 (96%) of the 98 adult surviving cases and corresponding controls in the family. Interviews were performed in the remaining four cases (4%). There were no statistical differences between the two groups with respect to physical and mental health and quality of life. Hospital records of all patients were also checked for possible late effects. There was no definite case of secondary malignant neoplasm; however, there was one case of prolactinoma and only one case of serious sequelae (hemiparesis during therapy), probably due to intrathecal and intravenous MTX.     

Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.