Smoldering acute myelogenous leukemia in the elderly.

Out of 75 consecutive elderly AML patients who did not receive anti-leukemic treatment (52 pts) or failed to respond to differentiating agent (23 pts), 6 patients had survivals of 13.2 to 98 months with treatment restricted to supportive care. This cut-point is far longer than the median survival of the 235 elderly patients (3.5 mo.), either untreated (med. survival: 1 mo.) or treated (with treatment ranging from conventional induction to palliative chemotherapy) (4 mo.), admitted to our department within the same period of time. These cases of smoldering AML (4 women, 2 men) were all of AML2 FAB subtype (4 de novo, 2 post MDS) and presented with a significantly better performance status, lower WBC and circulating blast counts, higher platelet counts and with lower bone marrow infiltration than AML cases with more rapid progression. Cytogenetical analysis when available (3 pts) showed normal karyotypes and clonogenic assay performed in 3 of these patients showed a lack of (2 pts) or reduced in vitro leukemic cell growth (1 pt). The identification of specific characteristics of smoldering leukemia in the elderly might be an important development in the understanding of the physiopathology of acute leukemia and a tool for helping decision-making when selecting the time and intensity of cytotoxic treatment in these older patients.     

Administration schedule of daunorubicin for elderly patients with acute myelogenous leukemia: a single-institute experience

We evaluated the efficacy of daunorubicin (40 mg/m(2)/day for 5 days, 200 mg/m(2)/cycle) combined with standard dose of cytarabine (100 mg/m(2)/day for 7 days) for acute myelogenous leukemia patients aged 65-74 years as induction therapy. Complete remission (81.3%) was achieved in 13 of 16 patients following the therapeutic program. The median duration of recovering absolute neutolophilic counts over 1000/μl and platelet counts over 100 000/μl were 33 days and 27 days, respectively. None of the patients had any adverse cardiac complications or died during administration of the induction therapy. Patients achieving complete remission received post-remission therapy consisting of two regimens other than induction therapy. The 3-year disease-free and overall survival rates were 36.9 and 50.0%, respectively. Extending the total period of the daunorubicin therapy might be an alternative to increasing the daily dose of daunorubicin in the induction therapy for elderly patients who were candidates for receiving intensified chemotherapy.     

Treatment of acute myelogenous leukemia in the elderly

Current data indicate that most elderly patients with acute myelogenous leukemia should be treated with intensive chemotherapy. Most should receive remission induction chemotherapy using cytarabine 100 to 200 mg/m2/d by constant intravenous infusion for five to seven days plus daunorubicin greater than or equal to 30 mg/m2/d for three days. Patients in good overall condition with a near-normal performance status may benefit from a more intensive regimen. Patients achieving remission should receive one to three courses of consolidation chemotherapy. Highly debilitated patients have poor results with any form of therapy, and there has been no apparent advantage for low-dose chemotherapy compared to standard treatment regimens. The intensity of chemotherapy treatment must be individualized to the requirements of the patient.     

Low-dose ara-C therapy for acute myelogenous leukemia in elderly patients

Forty-four evaluable patients with untreated acute myelogenous leukemia received twice-daily subcutaneous injections of low-dose ara-C (10 mg/m2) for less than or equal to 42 days. The median age was 72 years (range 53-87); 42 of 44 patients were greater than or equal to age 60. Ten patients (23%) had complete responses with a median duration of 9.9 months. Median survival was 3 months (range 0.6-31.2+) for all patients, and 19.5 (range 7.9-31.2+) for patients who attained complete responses. Cytoreduction occurred slowly with low-dose ara-C and five of ten patients who achieved complete remission did not develop marrow aplasia. Toxicity was predominantly related to infections associated with granulocytopenia. Nonhematologic toxicity was limited. Low-dose ara-C as used in this trial results in a complete response rate and a duration of response similar to those achieved with other treatments in elderly patients, but with reduced toxicity.     

Remission of acute myelogenous leukemia in elderly patients with prior refractory dysmyelopoietic anemia

Refractory dysmyelopoietic anemia (RDA) is a myeloproliferative disorder usually of elderly patients which often evolves into acute myelogenous leukemia (AML). AML in such patients is usually considered untreatable with standard aggressive chemotherapy in part because these patients are often elderly, but primarily because of the concern that the bone marrow of these patients no longer has a residual stem cell to repopulate the bone marrow following chemotherapy-induced aplasia. The authors treated three patients (ages 72, 69, and 62 years, respectively) with intensive chemotherapy after RDA evolved into AML. Each patient had been pancytopenic for 3 to 15 months prior to their transition to AML. At the onset of therapy for AML, all were severely pancytopenic with greater than 50% myeloblasts in the bone marrow. All patients had bone marrow aplasia by day 14 after chemotherapy with a complete bone marrow remission and normal peripheral counts by day 26. These data suggest that intensive chemotherapy of AML with prior RDA may result in complete bone marrow remission.     

Prognostic factors in elderly patients with acute myelogenous leukemia: a single center study in Japan

We retrospectively analyzed data of 47 patients aged 60 years or older, hospitalized in our institution with the diagnosis of acute myelogenous leukemia (AML), and searched for prognostic factors. Induction with anthracyclines significantly correlated with better complete remission (CR) rate (P = 0.0016) and overall survival (OS) (P < 0.001). Another factor significantly affecting CR rate was higher age (> 70 years) (P = 0.042). Therapy-non-related factors predictive for shorter OS in univariate analyses were age older than 70 years (P = 0.003), percentage of blasts in bone marrow more than 80% (P = 0.048), serum lactate dehydrogenase level higher than 250 U l(-1) (P = 0.032). In stepwise cox proportional hazard regression model, all the four factors predictive for poor OS remained to be independently and significantly prognostic for shorter OS. Only two patients receiving anthracyclines died within 30 days and the frequency was not different from that in patients not receiving anthracyclines. The use of anthracyclines as induction therapy is recommended even in the elderly patients.     

Early deaths in acute myelogenous leukemia.

In a series of 84 patients with acute myelogenous leukemia, 24 died within 6 weeks of starting treatment. Twenty of the 24 patients had failed to achieve remission at the time of death. Death was due to infection in 20 patients and in 17 of these to septicemia; but whereas severe local infection with septicemia accounted for 12 deaths, only five patients died of septicemia without local infection. Bleeding was the direct cause of death in only four patients and an associated terminal event in another three; of these four patients three had disseminated intravascular coagulopathy. Surprisingly, in this group of patients age and overall clinical status at the time of admission were of no prognostic value in the first 6-week period. The importance of drug resistent disease associated with intractable local infection as a major cause of early death is emphasized.     

Management of acute myeloid leukemia in elderly patients.

Acute myeloid leukemia (AML) at older age is associated with several biologic and clinical characteristics. Hence, it may arise from an early level of hematopoietic stem cells and has a high frequency of blast cells with multidrug resistance glycoprotein MDR1 expression and particularly a high incidence of poor prognostic karyotypes. These factors, rather than age per se, underlie the poorer outcome as compared with younger cases. Prospective randomized studies clearly demonstrate, however, that elderly patients benefit from more intensive induction therapy and particularly from full-dose application of anthracyclines and possibly also cytarabine. Hematopoietic growth factors accelerate the recovery from treatment-induced neutropenia and may improve the remission rate, remission duration, and even overall survival. New treatment strategies need to be developed, however, for poor-prognosis AML subtypes in order to further improve the therapeutic perspectives for elderly patients with AML.     

中剂量阿糖胞苷用于老年急性髓系白血病患者巩固强化治疗的临床观察

目的 分析初治老年急性髓系白血病(AML)患者诱导缓解后应用中剂量阿糖胞苷(MDAC)巩固治疗的临床效果及不良反应.方法 61例2个疗程内达完全缓解(CR)的老年AML(M3除外)患者,分别应用MDAC和常规剂量阿糖胞苷(SDAC)进行巩固强化治疗,对其临床资料进行回顾性分析.结果 MDAC组26例,SDAC组35例,MDAC组与SDAC组的无复发生存(RFS)时间分别为42.7和16.0个月(P=0.002),总生存(OS)时间分别为44.6和18.2个月(P=0.004),累积复发率分别为26.9%(7/26)和54.3%(19/35)(x2=4.567,P=0.033),3年生存率分别为23.1%(6/26)和8.6%(3/35)(x2=2.496,P=0.114).两组不良反应发生率差异均无统计学意义(均P>0.05).结论 老年AML患者应用MDAC巩固强化治疗,可延长早期达CR患者的RFS及OS时间,不良反应发生率与SDAC相似.     

Prognostic value of immunophenotyping in elderly patients with acute myeloid leukemia: a single-institution experience

BACKGROUND: The poor prognosis for elderly patients with acute myeloid leukemia (AML) raises questions regarding the benefit of treating them with intensive chemotherapy. The impact of initial characteristics on prognosis has been addressed previously in elderly patients; however, very few data are available regarding the prognostic value of immunophenotypic characteristics in this setting. METHODS: The authors investigated expression of the membrane antigens CD13, CD15, CD33, and CD34 by flow cytometry in elderly patients with newly diagnosed AML and analyzed whether these parameters had clinical or prognostic relevance to help physicians in their choice of therapy. RESULTS: Immunophenotyping was performed in 273 patients aged > or =60 years (median age, 69 years). CD13 was expressed in 73% of patients, CD15 was expressed in 43% of patients, CD33 was expressed in 64% of patients, and CD34 was expressed in 66% of patients. Complete remission was obtained in 157 patients (58%). The median overall survival was 8.1 months, and the 3-year survival rate was 14%. Three risk groups were defined based on CD34 and CD33 antigen expression: The poor-risk group included patients with CD34-positive/CD33-positive or CD34-negative/CD33-negative disease, the intermediate-risk group included patients with CD34-positive/CD33-negative disease, and the favorable-risk group included patients with CD34-negative/CD33-positive disease. After cytogenetic analyses, immunophenotype was the most significant prognostic factor in terms of survival in a multivariate analysis (P = .03 and P < .0001, respectively). When immunophenotypic and cytogenetic parameters were combined, patients were classified into 4 prognostic groups: Group A (3-year survival rate, 33%) included patients with favorable and normal karyotypes who had a favorable immunophenotype, Group B (3-year survival rte, 28%) included patients with normal karyotypes who had an intermediate immunophenotype, Group C (3-year survival rate, 8%) included patients with intermediate or normal karyotypes who had an unfavorable immunophenotype, and Group D (3-year survival rate, 2%) included all patients who had unfavorable cytogenetics. CONCLUSIONS: Immunophenotypic characteristics appeared to be a major prognostic factor in this population of elderly patients with AML. By using 2 simple parameters assessed at the time of diagnosis, the authors devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.     

The role of allogeneic transplantation in high-risk acute myelogenous leukemia.

Patients with high-risk acute myelogenous leukemia (AML) in first remission are at increased risk for disease recurrence and are often considered for allogeneic bone marrow transplantation (BMT) if there is a suitable HLA-identical sibling donor. Analysis of results from randomized clinical trials comparing different treatment strategies for patients with AML (chemotherapy, autologous BMT, and allogeneic BMT) suggests that allogeneic BMT may be a superior treatment modality for patients in the high-risk subgroup. Interpretation of clinical trial results, however, is problematic due to poor compliance with transplant options, absence of studies specifically designed to addresses this question, and ongoing redefinition of the high-risk subgroup. Alternative allogeneic transplant approaches to reduce toxicity from graft-versus-host disease and enhance graft-versus-leukemia reactivity may offer therapeutic promise in this patient population.     

Testicular relapse in adult acute myelogenous leukemia.

Testicular relapse (TR) in adult acute myelogenous leukemia (AML) is uncommon, occurring in only 1-2% of patients with bone marrow relapse. TR in the absence of systemic relapse has been reported previously in 2 adults and 12 children, of which 67% were monocytic variants of AML. This article presents the case of a 29-year-old man with AML that relapsed in his testicle without evidence of bone marrow relapse. This patient and the two previously mentioned adults experienced bone marrow relapse within 2 months and died within 7 months of their TR. TR in adult myelogenous leukemia should be considered a harbinger of systemic relapse and suggests a need for aggressive local and systemic therapy.     

Cell cycle studies in acute myelogenous leukemia.

Since the proliferative characteristics of leukemia cells play an important role in determining response to therapy, one may assume that an alteration of these characteristics could be therapeutically beneficial. To this end appropriate methods should be used to evaluate the effects of bioactive agents on leukemia cells in vivo in patients.     

Clinical management of prolactinomas: A ten-year experience

A ten-year experience on 36 patients bearing macroprolactinomas (MP) and 86 others bearing microprolactinomas (mP) is reported in this study. Different therapeutical approaches were used: 1) trans-sphenoidal surgery in 24 patients with MP and in 25 with mP; 2) medical therapy with the oral form of bromocriptine (BRC) in all the 24 patients with MP previously subjected to surgery, in 48 patients with mPab initio, and in 16 out of 25 patients with mP previously subjected to surgery; 3) medical therapy with the long-acting injectable forms of BRC in 12 MP-and 13 mP-bearing patients, and 4) conventional radiotherapy in 12 of the 24 patients with MP previously subjected to surgery. The follow-up, performed five years after surgery, showed that: a) all the 24 patients with MP but one had normal PRL levels during BRC administration, with a rebound of hyperprolactinemia in all cases after withdrawal; b) during the treatment BRC caused normalization of PRL in 15 of the 16 mP-bearing patients surgically treated and in all the 48 mP-bearing patients only treated with BRC; c) in 20 of the 25 patients the treatment with injectable retard BRC caused the normalization of plasma PRL and the shrinkage of the tumor mass in all the patients with MP but one, as revealed by seriate CT scans. In conclusion, the surgical treatment of prolactinomas was ineffective to normalize plasma PRL levels in most patients whereas BRC, in standard or in retard forms, was able to normalize plasma PRL levels, reduce the tumoral mass and preserve the pituitary residual tissue. BRC should be, therefore, used as first choice therapy both for MP and mP.     

New agents for acute myelogenous leukemia.

New agents for the treatment of acute myelogenous leukemia are discussed that reflect different treatment mechanisms. These include histone acetylation, angiogenesis inhibition, protein kinase inhibitors, and a novel retinoid. Efficacy and safety in phase I and phase II trials reviewed, as well as the problems involved in crossing over from treatment of solid tumors to blood disorders.     

Epidemiology of acute myelogenous leukemia

The epidemiologic literature suggests that environmental exposures, familial susceptibility, and cytogenetic changes affect AML risk in childhood and adulthood. Unfortunately, many studies are limited by inadequate sample sizes, imprecise case definition, or inadequate exposure measurement. Few studies have singled out AML alone, either because of insufficient numbers or because methods of case ascertainment made it difficult to distinguish specific cell types. Studies of total leukemia or all acute leukemias offer insights into potential risk factors for AML, but may also be misleading in instances when few AML patients were actually included. Future studies should include adequate numbers of patients with AML. At the same time, further refinement of case definition through parameters such as specific cytogenetic changes may make risk factor identification in epidemiologic studies more likely.     

Treatment of acute myelogenous leukemia in older adults.

The overall strategy for the treatment of older adults is summarized in Table 8. Soon after the birth of effective chemotherapy for acute leukemia, the perspective for all patients was summarized as follows: 'With all humility it may be claimed that there are, at least, grounds for hope and encouragement in this recently acquired ability occasionally to halt for a while the formerly unrelenting malignant process known as acute leukemia'. In reviewing the overall survival data for older adults one may feel that we are at a similar juncture in assessing the outcome for this particular population. It is hoped that some of the potential advances may provide greater hope and improved results over the next decade.