Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia

The relationship between the level of retinoblastoma protein (RB) expression and the survival of 113 newly diagnosed acute myelogenous leukemia (AML) patients was studied. Western blotting was used to determine the level of RB protein present in peripheral blood leukemia cells and results were confirmed in 26 patients by immunohistochemistry. The leukemic cells from 22/113 AML patients (19%) contained RB protein at levels that were equal to or less than the level of RB observed in the mononuclear cell fraction of peripheral blood from normal individuals (Low RB). Levels of RB greater than that of normal blood (Elevated RB) were seen in 91 patients (81%). The median survival of patients with low RB was significantly shorter than that seen in patients with elevated RB, 12 weeks versus 40 weeks (P = .02). Remission induction frequency was 36% in low RB patients compared with 68% in AML patients with elevated RB (P = .01). Multivariate analysis showed that low RB protein level was an independent prognostic factor predictive or poor survival after allowing for other known prognostic factors. These data suggest that a low level of the RB protein at the time of diagnosis is associated with shortened survival in AML patients because of inferior response to conventional therapy. Monitoring of the RB level could identify a subgroup of AML patients with an extremely poor prognosis when treated with chemotherapy alone, who would be eligible for alternative therapeutic strategies.     

Plasma cell leukemia: a highly aggressive monoclonal gammopathy with a very poor prognosis

Plasma cell leukemia (PCL) is an aggressive variant of multiple myeloma and is characterized by the presence of >20% and/or an absolute number of greater 2 × 10(9)/L plasma cells circulating in the peripheral blood. PCL represents approximately 2–4% of all MM diagnosis and exists in two forms: primary PCL (PPCL, 60% of cases) presents de novo, whereas secondary PCL (SPCL, accounts for the remaining 40%) consists of a leukemic transformation in patients with a previously diagnosed MM. Because the mechanisms contributing to the pathogenesis of PCL are not fully understood, immunophenotyping, genetic evaluation (conventional karyotype, FISH, GEP and array-CGH), and immunohistochemistry are really important tools to investigate why plasma cells escape from bone marrow and become highly aggressive. Since treatment with standard agents and steroids is poorly effective, a combination of new drugs as part of the induction regimens and bone marrow transplant (autologous and allogeneic approaches) could nearly overcome the poor prognosis exhibited by PCL patients.     

High-dose cytosine arabinoside for acute nonlymphocytic leukemia

Eighteen patients with acute nonlymphocytic leukemia (ANLL), aged 17-73 years, were treated with high-dose cytosine arabinoside (HD-Ara-C) using 3 g/m2 IV q 12 hours X 12 doses. Seven patients were treated for relapse and four (57%) obtained a complete remission with a median duration of 19.5 weeks. In nine patients, refractory to conventional chemotherapy, no complete responders were observed. Treatment failure was most commonly due to drug resistance. Two elderly patients with ANLL not previously exposed to chemotherapy died during the initial induction. Recent data on the HD-Ara-C experience in ANLL are presented and compared with this study.     

Calcitonin-related peptides in patients with acute leukemia: association of human calcitonin with poor prognosis

Elevated serum levels of peptides hormones in patients with acute leukemia and production of these agents by the leukemic blasts have been described. In 77 patients with acute leukemia the influence of common risk factors and elevations of serum levels of calcitonin-related peptides on clinical outcome was evaluated. By multivariate analysis, only age and elevated serum level of h-CT were found to be significantly correlated to survival. CGRP and s-CT showed no influence on outcome. Closer inspection of the clinical course of these patients showed that patients with elevated h-CT are not likely to survive the first 4 weeks after diagnosis. The possibility that this hormone may influence the biological behavior of the leukemic cells is discussed.     

难治性急性髓性白血病治疗进展

难治性急性髓性白血病的治疗,仍是当今临床血液学一个难以突破的棘手问题,国内外多种治疗效果均不满意.本文就新型化疗药的应用、传统药物的新用、靶向治疗、造血干细胞移植等方面内容作一综述.     

The treatment of patients with newly diagnosed poor prognosis acute myelogenous leukaemia: response to treatment and treatment failure

The failure of poor prognosis patients with newly diagnosed AML to enter remission is usually due to two phenomena: a high mortality rate and resistance of the leukaemia to chemotherapy. We conducted a pilot study of a regimen designed to overcome these two types of treatment failure. Patients were carefully selected for therapy on the basis of their likelihood of surviving. Chemotherapy consisted of high dose cytosine arabinoside (HDaraC) with the doses modified on the basis of patient age so as to reduce the risk of toxicity. Finally, daunorubicin was administered only to those patients for whom HDaraC was not likely to produce sufficient antileukaemia effects to produce a remission. The median patient age was 67 years and 69/88 (78%) patients had a history of preleukaemia and/or toxic exposure. Only 11/84 (13%) patients died during remission induction therapy and 40/84 (48%) entered CR. Patients with only one risk factor had a higher CR rate than those with more than one risk factor (56% v. 30%, P = 0.02) and also had longer durations (222 d v. 113.5 d, P = 0.035). Two types of resistance to chemotherapy were observed: 'classical resistance' (the failure of chemotherapy to produce substantial killing of leukaemia cells) and the rapid regrowth of leukaemia cells subsequent to a level of cytoreduction which otherwise would have been sufficient to produce a CR.     

老年急性髓系白血病的治疗现状

急性髓系白血病（AML）随着年龄的增长发病率逐渐升高。由于老年AML患者化疗完全缓解率低,治疗相关死亡率高,长期生存率低,预后差,尚缺乏统一有效的治疗策略。本文就目前老年AML治疗现状作简单综述,探讨传统化疗、造血干细胞移植及新的靶向药物在老年AML治疗中的应用。     

急性髓系白血病细胞表面抗原CD11b的表达与其预后的关系

目的:探讨急性髓系白血病(AML)细胞表面抗原表达与预后的关系.方法:回顾性分析90例初治AML患者,流式细胞仪检测骨髓白血病细胞表面抗原的表达情况,按染色体危险分层分为好、中、差3组,x2分析骨髓白血病细胞表面抗原阳性率的差异;Kaplan- Meier生存分析和COX回归分析骨髓白血病细胞表面抗原的阳性率与患者预后...     

Therapy for acute myeloid leukemia in 119 adults: A comparison of two treatment protocols

Summary Of 119 patients with acute myeloid leukemia, 69 were treated with Adriamycin, Vincristine and Cytosine Arabinoside (Therapy 1) and 50 with Daunorubicin, Cytosine Arabinoside and 6-Thioguanine (Therapy 2) as well as a consolidation therapy. The maintenance therapy with Cytosine Arabinoside and 6-Thioguanine was the same for both groups. The complete remission rate was 44% for Therapy 1 and 68% for Therapy 2 (p<0.05). — The median values for remission duration were 7 and 13 months respectively (p=0.10); for survival time the median values were 18 and 19 months. These figures show in retrospect that high remission rates can be attained through intensive induction therapy and that longer remission duration is correlated with more aggressive induction therapy. A mild form of maintenance therapy seems to have little effect on the duration of complete remission.     

Cytogenetic and hematological spontaneous remission in a case of acute myelogenous leukemia

Several cases of spontaneous remission (SR) interrupting the invariably progressive course of untreated acute myeloblastic leukemia (AML) have been reported so far. We shall add to this series the hematological and cytogenetic SR occurring in a 72-yr-old man affected by AML following myelodysplastic syndrome. At diagnosis cytogenetic analysis showed the 48, xy, del (6) (p22-pter), +13, +14 karyotype. Owing to a lobar pneumonia, the chemotherapy was deferred and a broad spectrum antibiotic therapy was established. Supportive care included red cells and platelet transfusions and low-dose corticosteroid. Two months later, after the pneumonia had completely disappeared, a complete remission, lasting about 5 months, was documented on bone marrow morphological and cytogenetical examination, although some degree of myeloid dysplasia persisted. Possible mechanisms of the various SRs described during the course of AML are discussed with a review of the literature.     

Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia

Background

In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study.

Design and Methods

Having reported feasibility previously, we hereby report the efficacy of escalated imatinib (200 mg, 400 mg, 600 mg or 800 mg) in combination with two cycles of intravenous cytarabine (200 mg/m² or 1000 mg/m² days 1 to 7) in 162 patients with chronic myeloid leukemia.

Results

With a median follow-up of 55 months, the 5-year cumulative incidences of complete cytogenetic response, major molecular response, and complete molecular response were 89%, 71%, and 53%, respectively. A higher Sokal risk score was inversely associated with complete cytogenetic response (hazard ratio of 0.63; 95% confidence interval, 0.50–0.79, P<0.001). A higher dose of imatinib and a higher dose of cytarabine were associated with increased complete molecular response with hazard ratios of 1.60 (95% confidence interval, 0.96–2.68, P=0.07) and 1.66 (95% confidence interval, 1.02–2.72, P=0.04), respectively. Progression-free survival and overall survival rates at 5 years were 92% and 96%, respectively. Achieving a major molecular response at 1 year was associated with complete absence of progression and a probability of achieving a complete molecular response of 89%.

Conclusions

The addition of intravenous cytarabine to imatinib as upfront therapy for patients with chronic myeloid leukemia is associated with a high rate of complete molecular responses (Clinicaltrials.Gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00028847","term_id":"NCT00028847"}}NCT00028847).     

慢性粒细胞白血病急变为急性巨核细胞白血病1例

急性巨核细胞白血病(AMLK)占所有急性髓系白血病中发生率的0.5%~1.2%,其中慢性粒细胞白血病(CML)转化为AMLK的比例报道不一。现报道1例以骨髓纤维化(MF)首诊的AMLK,最终通过电镜、免疫分型以及分子生     

Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia

Deregulation of signal transduction pathways (STPs) may promote leukemogenesis by conferring cell proliferation and survival advantages in acute myelogenous leukemia (AML). Several agents targeting STPs are under development; however, redundancy and cross-talk between STPs could activate multiple downstream effectors and this could negate the effect of single-target inhibition. The frequency of concurrent activation of multiple STPs in AML and the prognostic relevance of STP activation in AML are unknown. STP protein expression (PKCalpha, ERK2, pERK2, AKT, and pAKT) was measured by Western blot in samples from 188 patients with newly diagnosed, untreated AML. In univariate and multivariate analysis high levels of PKCalpha, ERK, pERK, and pAKT, but not AKT, were adverse factors for survival as was the combination variable PKCalpha-ERK2&pERK2-pAKT. Survival progressively decreased as the number of activated pathways increased. Patients were more likely to have none or all 3 pathways activated than was predicted based on the frequency of individual pathway activation, strongly suggesting that cross-activation occurred. Simultaneous activation of multiple STPs is common in AML and has a progressively worse adverse effect on prognosis. It is thus likely that only combinations of agents that target the multiply activated STPs will be beneficial for patients with AML.     

Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population

Background

Biphenotypic acute leukemia is a rare disorder that is difficult to diagnose. It displays features of both myeloid and lymphoid lineage. There is still a lack of studies in biphenotypic acute leukemia in a Chinese population. We present here a comprehensive investigation of the clinical and biological characteristics, and outcome of biphenotypic acute leukemia in our hospital in over a seven year period.

Design and Methods

We retrospectively analyzed 452 adult acute leukemia patients diagnosed according to French-American-British (FAB) classification and biphenotypic acute leukemia diagnosed according to European Group for the Immunological Characterization of Leukemias (EGIL) classification, respectively. Biological characteristics, response to treatment, and outcome were examined in biphenotypic acute leukemia patients and compared with that in acute myeloid leukemia and acute lymphoblastic leukemia patients with complete follow-up profiles diagnosed in the same period.

Results

Of 452 acute leukemia patients, 21 cases (4.6%) were diagnosed as biphenotypic acute leukemia. Among them, 14 (66.7%) were B lymphoid and myeloid, 5 (23.8%) were T lymphoid and myeloid, one (4.8%) was T/B lymphoid and one (4.8%) was trilineage differentiation. When compared with acute myeloid leukemia and acute lymphoblastic leukemia, patients with biphenotypic acute leukemia showed significantly higher incidence of CD34 antigen expression, unfavorable karyotypes, and extramedullary infiltration (p<0.05). In this cohort of patients with biphenotypic acute leukemia, t(9;22) was the most common abnormality in chromosome structure. The median disease-free survival and overall survival in biphenotypic acute leukemia patients was five months and ten months, respectively, significantly shorter than those in acute myeloid leukemia and acute lymphoblastic leukemia patients (p<0.05).

Conclusions

The prognosis of biphenotypic acute leukemia patients is poor when compared with de novo acute myeloid leukemia or acute lymphoblastic leukemia. Biphenotypic acute leukemia patients showed a much higher incidence of CD34 antigen expression, complex abnormal karyotype, extramedullary infiltration, relapse, and resistance to therapy after relapse.     

Arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: a single center experience

Arsenic trioxide (As(2)O(3)) has been found effective in the treatment in the treatment of acute promyelocytic leukemia (APML). Most studies with As(2)O(3) involve patients with APML who have relapsed following standard therapy. Between January 1998 and July 2000, 14 patients were recruited for an ongoing trial of As(2)O(3) in the treatment of newly diagnosed APML. Arsenic trioxide was administered at a dose of 10 mg/day until complete remission (CR) was achieved. Afterward, a consolidation course and a maintenance schedule consisting of As(2)O(3) as a single agent were administered over 6 months. There were 3 early deaths related to intra-cerebral hemorrhage: two on day 3 and one on day 4. Of the 11 evaluable patients, one died on day 21 secondary to uncontrolled sepsis, while the remaining 10 (91%) have attained CR. The average time to CR was 52.3 days (range: 34-70 days). One patient developed an isolated central nervous system (CNS) relapse and subsequently went into a second CR following therapy with triple intrathecal chemotherapy, cranial irradiation, and an additional 4-week course of systemic As(2)O(3). This patient, as well as the remaining nine, has continued to remain in CR at a median follow up of 15 months (range: 2-33 months). Eight out of 10 patients achieved molecular remission at variable periods during their consolidation and maintenance schedules. One patient developed an ATRA syndrome and was administered daunorubicin (40 mg/day) for 2 days. The side effects with this therapy were minimal and did not require cessation of therapy in any patient. There was no significant hepatic toxicity. In our experience, arsenic trioxide is effective in inducing and maintaining remission in patients with APML with minimal side effects. The optimal regimen and total dose required need to be defined.     

改良CHG方案治疗成人高白细胞性急性髓系白血病

目的:观察改良CHG方案治疗初诊成人高白细胞性急性髓系白血病(HAML)的疗效及不良反应。方法:23例初诊成人HAML患者接受改良CHG方案化疗:高三尖杉酯碱(HHT)2 mg/d,静脉滴注;阿糖胞苷(Ara-C)10 mg/(m2·d),皮下注射,1次/12h,共14 d,化疗过程中,WBC10×109/L时予粒细胞集落刺激因子(G-CSF)300μg/d,皮下注射,直至中性粒细胞绝对值(ANC)≥1.5×109/L时停用。结果:15例(65.2%)获得完全缓解(CR),2例(8.7%)部分缓解(PR),总有效率(OR)73.9%。早期死亡2例,病死率8.7%。WBC计数降至10×109/L以下所需时间为6(4~10)d。化疗期间主要不良反应为骨髓抑制,表现为粒细胞缺乏及继发感染、出血。结论:改良CHG方案治疗初诊成人高白细胞性急性髓系白血病有效率高,不良反应可控制。     

急性非淋巴细胞白血病MIC分型及其与预后的关系

目的：探讨急性非淋巴细胞白血病（ANNL）MIC分型及其与预后关系。方法：43例ANLL患者进行形态学分型,采用流式细胞术检测白血病细胞免疫类型,骨髓短期培养,G显带技术分析染色体核型,分析比较MIC结果及其与预后的关系。结果：ANLL患者髓系系列CD13、CD33和MPO的表达最为常见,阳性率分别为100．00％、95．38％和53．49％;干／祖细胞CD38、HLA—DR和CD34的阳性率分别为83．72％、74．42％、74．42％,各系列单抗在FAB各亚型原始细胞的表达水平不同,其中CD34和CD7分别在急性混合细胞白血病（HAL）和M5高表达;细胞遗传学检查染色体异常率为53．49％,其中复杂异常的患者CR率明显低于其他组。2例FAB分型为Mo的患者免疫分型为HA1,3例M5和2例M4为伴淋巴系抗原表达的ANLL。结论：形态学结合免疫分型和细胞遗传学检查可以准确地了解白血病细胞的生物学性质,指导临床治疗和判断预后,尤其对于形态学特征不明显的HAL等患者更有价值。     

血清Hcy、D-D、FIB联合预测急性肺血栓栓塞患者远期预后不良的价值探讨

目的探讨血清同型半胱氨酸(Hcy)、D-二聚体(D-D)、纤维蛋白原(FIB)联合预测急性肺血栓栓塞(PTE)患者远期预后不良的价值。方法回顾性分析2018年3月~2019年10月本院收治的142例急性PTE经常规治疗后出院患者的临床资料,随访6个月,统计远期预后不良发生情况;对比预后不良组和预后良好组治疗前后血清Hcy、D-D、FIB水平及变化率;制作受试者工作特征曲(ROC),分析血清Hcy、D-D、FIB变化率及三者联合对急性PTE患者远期预后不良的预测效能。结果本研究中急性PTE患者预后不良的发生率为21.83%(31/142);治疗后2组患者血清Hcy、D-D、FIB水平均降低(P<0.05),且预后良好组较预后不良组均更低(P<0.05),预后不良组血清Hcy、D-D、FIB变化率均明显低于预后良好组(P<0.05);ROC分析显示,血清Hcy、D-D、FIB变化率预测急性PTE患者远期预后不良的最佳截断点分别为18.01%、55.43%、20.64%,血清Hcy、D-D、FIB变化率三者联合的特异度高于血清Hcy、D-D、FIB变化率单独进行预测的特异度(P<0.05),且血清Hcy、D-D、FIB变化率三者联合预测急性PTE患者远期预后不良的曲线下面积(AUC)为0.932,高于血清Hcy、D-D、FIB变化率单独预测的AUC(P=0.067、P=0.153、P=0.021)。结论血清Hcy、D-D、FIB联合预测急性PTE患者远期预后不良的预测效能较高,三者变化率联合适用于对急性PTE患者远期预后不良进行预测。