Treatment of acute leukemia in older patients

The median age of patients with acute leukemia is more than 60 years, and the incidence of the disease increases with age. There are several unfavorable biologic and clinical factors in older patients with acute leukemia, the remission rate and their survival are much worse than in younger adults. The poor performance score and any other concomitant disease and the poor reserve capacity of their bone marrow represent significant difficulties to deliver the proper remission induction and postremission therapy. The poor biologic factors like acute leukemia following myelodysplasia, unfavorable cytogenetic abnormalities and multidrug resistance among elderly patients are more common comparing to younger patients. The authors summarize the international data and attempt to define the proper therapy namely who are candidates for induction and intensive postremission therapy, what is the role of palliative cytostatic treatment or supportive care for these patients.     

Prognostic impact of karyotype in de novo acute myeloid leukemia: study of 139 cases

A group of 139 patients with de novo acute myeloid leukemia were investigated to determine the prognostic significance of karyotype on early death, complete remission, continuous complete remission and survival. There were 27 children and 112 adults. Mean age was 32 years. t(15;17) was found associated with a high rate of early death and a diploid karyotype with long continuous complete remission. The presence of a structural change was predictive of shorter survivals. The study of the prognostic impact of recurrent anomalies reveals a good prognostic impact for normal karyotype (1 year survival probability: 40%), followed by t(8;21) (1 year survival probability: 24%), and by t(15;17) (1 year survival probability: 9%).     

Treatment results with ALL-BFM-95 protocol in children with acute lymphoblastic leukemia in Hungary

BACKGROUND: In Hungary children (from 1 to 18 years of age) with de novo acute lymphoblastic leukemia were treated from January 1996 to October 2002, according to protocol ALL-BFM-95. AIM: The aim of this study was to evaluate the experience with this protocol, the treatment results according to the risk groups and to compare the Hungarian data with the international results. METHODS: Patients were stratified into 3 risk groups, based on initial white blood cell count, age, immunology, cytogenetics and response to treatment: standard, medium and high risk group. RESULTS: Three hundred sixty eight children entered the study (male-female ratio was 1.27:1, median age 6 years and 4 months). 110 (29.9%) children were in the standard, 210 (57.1%) in the medium and 48 (13%) in the high risk group. Duration of the chemotherapy was 2 years, except of the boys in the standard risk group, their maintenance therapy was 1 year longer. The overall complete remission rate was 93.2%. 20 (5.4%) children died in induction and 5 (1.4%) were non-responders. The 5-year overall survival for all patients was 78.5%, in the standard risk group 93.2%, in the medium risk group 78.4% and in the high risk group 44.5% with a minimum follow up of 1.19 years and median follow up of 4.85 years. From the 368 patients 272 (73.9%) are still in their first complete clinical remission and other 18 children are alive after relapse. In 14.7% of the patients relapse was diagnosed; the most common site was the bone marrow. In one patient second malignancy occurred. The 5-year event free survival for all patients was 72.6%, in the standard risk group 87.6%, in the medium risk group 72.1% and in the high risk group 39.9%. CONCLUSION: The treatment outcome of children with acute lymphoblastic leukemia improved remarkably over the last decades. 78% of children suffering from acute lymphoblastic leukemia could be cured with the ALL-BFM-95 protocol. The Hungarian results are comparable to those achieved by other leukaemia study groups in the world regarding the ALL-BFM-95 protocol.     

Imatinib therapy in chronic myeloid leukemia

Chronic myeloid leukemia is a malignant clonal alteration of the pluripotent hemopoietic stem cell. The genetic hallmarks of the disease are the t(9,22) (Philadelphia chromosome), registered by conventional cytogenetics in more than 90% of all chronic myeloid leukemia cases and the active tyrosine kinase protein encoded by bcr-abl fusion gene. The constitutively active tyrosine kinase is currently accepted to be the cause of chronic myeloid leukemia. The introduction of imatinib has considerably changed the treatment of chronic myeloid leukemia. Prior studies demonstrated high rates of cytogenetic responses in all phases of the disease. METHODS: The authors evaluated the cytogenetic and molecular responses of 21 chronic phase chronic myeloid leukemia patients who were consecutively admitted to their center. 13 of them were primarily treated with imatinib, and the other 7 were heavily pretreated with interferon alfa, cytarabine, all-trans-retinoic acid. Hydroxiurea pretreatment was routinely introduced in all patients until complete hematologic remission. Peripheral blood sample in every 3 months were collected for quantitative real-time polimerase chain reaction, and bone marrow aspirate in every 6 months for conventional cytogenetics. Results: Hematologic remission could have been achieved with hydroxiurea pretreatment in each patient. Complete cytogenetic remission at the 6th month and major molecular response at the 12th month were observed in each patient. CONCLUSIONS: Imatinib treatment caused complete cytogenetic response and major molecular response in each chronic phase chronic myeloid leukaemia patient in our group. Hydroxiurea might have some effect on the rapid and deep cytogenetic and molecular responses, observed in the primary imatinib-treated group.     

成人急性白血病178例临床特点及治疗效果探讨

目的 总结成人急性白血病临床特点及治疗经验。方法 收集1994年1月-2004年10月收治的178例成人急性白血病病历，进行回顾性分析。结果 成人急性白血病院内感染发生率为53．4％，早期病死率为11．8％，常规治疗完全缓解率（CR）为43．8％，5年生存率为15．7％，急性髓细胞白血病（肌）和急性淋巴细胞白血病（ALL）两种类型间患者的缓解情况及5年生存率均无显著性差异（P〉0．05），以早幼粒细胞白血病（M3）的治疗效果最好。结论 成人急性白血病临床表现不典型，感染发生率较高，常规化疗后总体预后不理想，提倡采用个体化治疗方案。     

长期生存急性髓性白血病23例临床分析

目的总结分析我院收治的生存五年以上急性髓性白血病23例(AML)患者的临床情况,并探讨其影响预后的多种相关因素。方法分析1990～2003年167例中长期生存5年以上23例AML患者的临床及实验室资料。结果23例生存5年以上者,M1 1例,M2 5例,M3 13例,M4 1例,M5 3例,达完全缓解时间较短,完全缓解后坚持强化,化疗时间为3～5年。结论白血病细胞类型、达初次缓解的疗程和时间、年龄、个体化治疗是影响急性白血病患者生存的重要原因。     

急性混合细胞白血病实验室特征与临床相关性研究

目的探讨急性混合细胞白血病(HAL)的实验室特征及其与诊断分型和临床治疗的相关性.方法对27例HAL住院患者的临床及实验资料进行回顾性分析.结果HAL患者临床上易合并肝、脾、淋巴结肿大及各种浸润症状.外周白细胞数高,易合并重度贫血.免疫表型中双系列较双表型多见.诱导缓解治疗缓解率为25.0%.以兼顾急性淋巴细胞白血病(ALL)和急性非淋巴细胞白血病(AML)方案及针对ALL的方案缓解率高.形态学表现为髓系白血病,合并重度贫血者以及有细胞遗传学异常者化疗缓解率低;而免疫表型、外周血白细胞数、血小板是否正常、是否合并浸润症状对化疗有效率无影响.化疗后易合并肺部细菌和霉菌混合感染,预后差.结论HAL病情凶险,临床有一定特点,但诊断应进行以免疫表型为主的MICM分型.形态学表现为髓系白血病,合并重度贫血者以及有细胞遗传学异常者诱导缓解治疗效果不佳.治疗应首选兼顾ALL和AML的方案或针对ALL的方案.     

Chronic neutrophilic leukemia: a long-term analysis of seven cases and review of the literature

Chronic neutrophilic leukemia is an uncommon hematological entity. According to the WHO classification it is recognized as part of the family of myeloproliferative disorders. In the last 20 years seven patients have been diagnosed with chronic neutrophilic leukemia at our department. All but one had splenomegaly, two patients developed severe anaemia and in one case thrombocytosis was present at the time of diagnosis. White blood cell count ranged between 39 x 10(9)/1-71 x 10(9)/l with 80% of neutrophils and striking myeloid hyperplasia were present in the bone marrow without evidence of any dysplasia resembling chronic myelocytic leukemia. Granulocyte alkaline phosphatase scores were increased except one case and both cytogenetics (Philadelphia chromosome) and molecular biologic analysis (bcr/abl) revealed no alteration of any. Four patients have been followed up. Three of them died due to progression of chronic neutrophilic leukemia. One patient, initially receiving hydroxyurea + interferon therapy and showing progression, developed complete hematological remission with an eight week imatinib mesylate (Glivec) treatment. Beside of their own experiences the authors review the current literature and discuss differential diagnostic and therapeutic challenges, as well.     

Immunophenotyping in acute leukemia: detection of minimal residual disease

Immunophenotyping improves both accuracy and reproducibility of the acute leukaemia classification and is considered particularly useful for identifying poorly differentiated subtypes of acute myeloid leukaemia and lineage association of acute lymphoid leukaemia. Immunological studies of leukaemic blasts has become critical also identifying biphenotypic leukaemias and acute myeloid leukaemia expressing lymphoid associated markers. At present, while the prognostic value of individual antigen expressions is still controversial, the immunologic detection of minimal residual disease seems to be important in monitoring the acute leukaemia patients in remission. In the present study immunophenotyping of bone marrow samples of 42 patients with acute myeloid leukaemia and 13 patients with acute lymphoid leukaemia was analysed. Patients were assessed both before and after treatment by immunophenotyping, cytogenetics and polymerase chain reaction amplification. The immunophenotyping have allowed more sensitive definition of acute leukaemia relapse, but molecular genetic methods are recommended for detection of elimination of residual disease.     

Treatment of chronic myeloid leukemia with interferon-alpha

The authors have treated 38 patients with chronic phase chronic myeloid leukemia in their single center in the last five years. Conventional chemotherapy provided about 40-50% hematological response, interferon-alpha seems to be more effective, complete hematological remission occurred in 65%. Interphase cytogenetics and fluorescein in situ hybridisation technique was used to measure the cytogenetic response. They observed complete cytogenetic remission in two cases (8%), major response in 11 (39%), minor response in 4 (15%) and minimal response in 4 cases (15%). Interferon-alpha is an effective, well-tolerated medicine in the treatment of chronic myeloid leukemia.     

Acute leukemia in the elderly patient. Forty case reports

Between 1989 and 1996, 40 cases with acute leukemia (16 males and 24 females) were diagnosed in our institution. Median age was 65 years (range, 56-88 years). Leukocyte count was more than 30.109/l in 42% of cases. According to the French-American-British (FAB) criteria, 11 cases were classified lymphoblastic and 29 myeloblastic. Sixteen patients have received palliative treatment because of there age and there bad performance status. Only 24 patients have received curative treatment. Complete remission was achieved in 12 cases (50%), 5 cases (20%) failed to respond and 7 (30%) died during induction. Relapse was observed in 8 cases. The 2-year survival rate was 10% confirming the worse prognosis of the acute leukemia in elderly.     

大剂量阿糖胞苷治疗急性髓细胞白血病疗效观察

目的：探讨大剂量阿糖胞苷治疗急性髓细胞白血病的临床疗效。方法：回顾性分析笔者所在医院治疗的36例急性髓细胞白血病患者的临床资料。按照随机方式分为观察组和对照组,对照组采取DA、HA或DAE方案诱导至完全缓解,观察组在对照组治疗的基础上,以大剂量阿糖胞苷静脉滴注巩固强化治疗4个疗程,比较两组患者治疗后1、2、3年无病生存率（VVS）。结果：观察组1、2、3年无病生存率均明显优于对照组（P〈0．05）。结论：大剂量阿糖胞苷巩固强化治疗,能够安全有效地延长患者生命,减少并发症,提高患者生存质量,临床治疗效果良好。     

Leukemia cell types and agricultural practices in Nebraska

The risk of specific histologic types of leukemia among farmers was investigated using mortality records from Nebraska for the years 1957-1974. The frequency of farming as an occupation listed on the death certificates among 1,084 leukemia deaths was compared to the corresponding frequency for 2,168 controls for calculation of odds ratios (OR). The elevated OR for chronic lymphatic leukemia among farmers was statistically significant (OR = 1.67), while elevated ORs for acute lymphatic leukemia (OR = 1.34), acute monocytic leukemia (OR = 1.94), and acute unspecified leukemia (OR = 2.36) were not. Farmers who died at younger ages or who were born in more recent years were at greater risk of acute lymphatic, acute myeloid, chronic myeloid, acute unspecified, and unspecified leukemia than other farmers. Certain cell types were related to agricultural characteristics of the subject's county of residence, although few were statistically significant. Farmers from counties with large cattle inventories and significant dairy activity were at higher risk of chronic lymphatic leukemia. Farmers from major corn-producing, hog- and chicken-raising, and pesticide- and fertilizer-using counties tended to be at higher risk of acute lymphatic, acute myeloid, chronic myeloid, and acute unspecified leukemia than farmers from counties less involved in the production or use of these agricultural factors.     

Acute myeloblastic leukemia in adults: evaluation of the AML 06/96 protocol

The treatment of acute myeloid leukemia (AML) permits in a population of 25 to 60 years, a complete remission (CR) about 60 to 85% with relapse free survival at 5 years from 45 to 60%. We report our therapeutic results during two years, from june 1996 to december 1998. 104 patients with the novo AML treated according to AML 06/96 protocol, the mean age was 32.5 years old, from 16 to 55 years old. The hyperleucocytar form (GB > 50,000 elts/mm3) represented the third of the cases, only 98 patients received the induction. 6 patients died before treatment. The whole rate of CR was 55%. The rate of failure was 16%, the deaths was about 15.5%, the relapse represented 30.6% with mean delay about 14.1 months, from 4 to 35 months. The CR has been maintained in 9 patients with mean recession of 53 months, from 36 months to 62 months. The overall survival at 5 years was 9%. Our results are still unsufficient in comparison with the literature and could be improved by recess of ARA-C and donorubicin doses in induction and consolidation, as well as a good knowledge about the cytogenetical aspect of the treated population.     

儿童急性白血病缓解期微量元素和营养相关蛋白的变化

目的 探讨儿童急性淋巴细胞白血病和急性粒细胞白血病缓解期某些微量元素及营养相关蛋白的变化.方法 应用原子吸收光谱法、散射比浊法、干化学法和化学发光法等,对上海儿童医学中心43例急性淋巴细胞白血病和19例急性粒细胞白血病缓解期患儿(缓解组)和30名体检正常儿童(正常对照组)红细胞计数、血红蛋白含量、血清总蛋白、白蛋白、铁、铁蛋白、转铁蛋白、乳酸脱氢酶、铜蓝蛋白、铜、锌及铜/锌比值等指标进行检测,并对缓解组和正常对照组之间的差异进行比较.结果 缓解组与正常对照组相比,血清总蛋白(P=0.454)、铁(P=0.769)、转铁蛋白(P=0.903)和锌(P=0.343)差异均无统计学意义.缓解组血清铁蛋白(P=0.000)、乳酸脱氢酶(P=0.000)、铜蓝蛋白(P=0.000)、铜(P=0.002)和铜/锌比值(P=0.003)均显著高于正常对照组,而红细胞计数(P=0.000)、血红蛋白含量(P=0.000)和白蛋白(P=0.046)均显著低于正常对照组.缓解组中急性淋巴细胞白血病和急性粒细胞白血病相比,除乳酸脱氢酶(P=0.025)外,其他指标差异均无统计学意义(P均>0.05).结论 在儿童急性淋巴细胞白血病和急性粒细胞白血病的疾病缓解期,血清中微量元素与营养相关蛋白含量正逐步恢复正常,重建原有的平衡状态.

Abstract：

Objective To investigate the changes of serum trace elements and nutritional proteins in children with acute lymphoblastic leukemia and acute myeloid leukemia at the stage of remission.Methods Erythrocyte count,hemoglobin,serum levels of total protein,albumin,iron,ferritin,transferrin,lactate dehydrogenase,ceruloplasmin,cuprum,zinc and their ratio were measured in 43 patients with acute lymphoblastic leukemia,19patients with acute myeloid leukemia at stages of remission(remission groups),and 30 healthy controls(control group)enrolled from Shanghai Children's Medical Center using atomic absorption spectrometry,nophelometry assay,dry chemical method,and chemiluminescence method.The differences of these indicators between remission groups and control group were analyzed.Results Serum levels of total protein(P=0.454),iron(P=0.769),transferrin(P=0.903),and zinc(P=0.343)were not significantly different between the remission groups and the control group.Serum levels of ferritin(P=0.000),lactate dehydrogenase(P=0.000),ceruloplasmin(P=0.000),cuprum(P=0.002),and Cu/Zn ratio(P=0.003)in the remission groups were significantly higher than those in control group.On the contrary,erythrocyte count(P=0.000),hemoglobin(P=0.000)and albumin(P=0.046)were significantly lowerin remission groups than those of control group.Serum levels of all detected indicators were not significantly different between the acute lymphoblastic leukemia remission group and acute myeloid leukemia remission group(P>0.05)except for lactate dehydrogenase(P=0.025).Conclusion At the remission stage of acute lymphoblastic leukemia and acute myeloid leukemia,serum levels of some trace elements and nutritional proteins gradually returned to normal,and the original balance is established again.     

儿童急性白血病缓解期微量元素和营养相关蛋白的变化

目的 探讨儿童急性淋巴细胞白血病和急性粒细胞白血病缓解期某些微量元素及营养相关蛋白的变化.方法 应用原子吸收光谱法、散射比浊法、干化学法和化学发光法等,对上海儿童医学中心43例急性淋巴细胞白血病和19例急性粒细胞白血病缓解期患儿(缓解组)和30名体检正常儿童(正常对照组)红细胞计数、血红蛋白含量、血清总蛋白、白蛋白、铁、铁蛋白、转铁蛋白、乳酸脱氢酶、铜蓝蛋白、铜、锌及铜/锌比值等指标进行检测,并对缓解组和正常对照组之间的差异进行比较.结果 缓解组与正常对照组相比,血清总蛋白(P=0.454)、铁(P=0.769)、转铁蛋白(P=0.903)和锌(P=0.343)差异均无统计学意义.缓解组血清铁蛋白(P=0.000)、乳酸脱氢酶(P=0.000)、铜蓝蛋白(P=0.000)、铜(P=0.002)和铜/锌比值(P=0.003)均显著高于正常对照组,而红细胞计数(P=0.000)、血红蛋白含量(P=0.000)和白蛋白(P=0.046)均显著低于正常对照组.缓解组中急性淋巴细胞白血病和急性粒细胞白血病相比,除乳酸脱氢酶(P=0.025)外,其他指标差异均无统计学意义(P均>0.05).结论 在儿童急性淋巴细胞白血病和急性粒细胞白血病的疾病缓解期,血清中微量元素与营养相关蛋白含量正逐步恢复正常,重建原有的平衡状态.     

Survival of patients with aggressive non-hodgkin's lymphoma: no difference between first line treatment in a prospective randomised phase III clinical trial and first line treatment according to routine clinical practice

OBJECTIVE: To compare survival of patients with disseminated aggressive non-Hodgkin's lymphoma (NHL) who were treated either as part of a clinical trial or in routine clinical practice. DESIGN: Retrospective. METHOD: The survival was studied of patients with disseminated NHL of an intermediate or high degree of malignancy who were treated in the Meander Medical Centre, Amersfoort, the Netherlands, in the years 1994-2001 with chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). This took place either in routine clinical practice (RCP) or as part of a clinical trial where patients < or = 60 years of age received intensified CHOP and patients > 60 years received CHOP with growth factors. Treatment data, the response to therapy, survival and prognostic factors according to the International Prognostic Index for aggressive NHL were collected by a review of the patient records. RESULTS: Fifty-nine patients were eligible for this analysis: 32 men and 27 women with a median age of 63 years (range 30-83). Of these, 35 were treated within a clinical trial and 24 were treated in RCP. The patient characteristics in the two groups were comparable. There was no difference in median survival between the trial and RCP groups, this being 27 months for all patients, 34 months for the younger patients, 20 months for the elderly patients, and 42 months for patients who achieved complete remission following chemotherapy. CONCLUSION: No difference in overall survival was found between patients with disseminated aggressive NHL who underwent treatment according to either RCP or as part of a clinical trial. It demonstrates that both patients in clinical trials and patients treated according to RCP received equally effective therapy. Recent developments in NHL treatments are promising, and therefore participation in clinical trials should be encouraged.     

Acute lymphoblastic leukemia in adults. Apropos of 42 cases

Between 1989 and 1995, 42 cases with acute lymphoblastic leukemia (18 males and 24 females) were diagnosed in our institution. Median age was 38.5 years (range, 16-88 years). Leukocyte count was more than 30.10(9)/l in 54% of cases. According to the French-American-British (FAB) criteria, 67% were classified L1 and 33% L2. Sixteen patients were treated with 12LA80 protocol, 14 patients with LALA 85 protocol, 6 patients with LALA 87 protocol and 6 patients with EORTC protocol. Complete remission was achieved in 22 cases (52%), 8 cases (20%) failed to respond and 12 (28%) died during induction. Relapse was observed in 10 cases. The 4-year survival rate was 28% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.     

Practical considerations and questions in the treatment of chronic lymphocytic leukemia

Understanding the pathogenesis and refine the treatment of chronic lymphocytic leukemia have been tremendously improved in the past decade. Treatment outcome and estimated prognosis have become more accurate due to the advanced molecular biological techniques and the classical prognostic markers. Incorporation of fludarabine and rituximab into the standard protocols fundamentally improved treatment outcome in chronic lymphocytic leukemia. Chemoimmunotherapy has improved not only the remission rates but had a significant impact on overall survival, as well. Eliminating residual leukemia and achieving complete hematological remissions at such high rates establish potential background for cure. Still, a great deal of dispute has been emerged regarding everyday clinical practice. Authors present their institutional experiences and review the literature.