Etoposide-related acute promyelocytic leukemia

The development of therapy-related acute myeloid leukemia (t-AML) has become a growing concern over the past decade, because of the increase in the percentage of long-term survivors of primary malignancy. We reviewed 17 cases with etoposide-related acute promyelocytic leukemia (APL) reported in the literature. The close association between treatment with etoposide for Langerhans cell histiocytosis (LCH) and the development of etoposide-related APL was demonstrated among Japanese and Italians. Our data on the breakpoints (b/ps) of the PML and RARalpha genes are presented. It is suggested that chromatin structure might be more important than specific consensus sequence in the distribution of b/ps in etoposide-related APL.     

Epidemiology of acute promyelocytic leukemia

BACKGROUND: The estimated incidence of acute promyelocytic leukemia (APL) is approximately 6 cases per 10 million people per year with no apparent differences between sexes. The age of APL cases is younger than that of other acute myeloid leukemias (AML). Spatial and temporal clusters of APL have been reported. These observations suggest a possible selective role for environmental and/or occupational factors in APL development. METHODS: A multicenter case-control study was carried out on risk factors for acute leukemias and preleukemias. In this report data related to APL are selectively analyzed from the larger study to identify specific risk factors. RESULTS: The case-control study on 38 cases of APL showed a strong association with shoemaking (odds ration 6.3, 95% confidence interval 1.3-31.1). A moderate leukemogenic effect from living in houses built with tuff, a polous building material containing gamma-emitting radionuclides and having a high radon concentration, and from using hair dyes was also suggested. CONCLUSIONS: These data, together with the reported spatial and temporal clustering of APL, support the hypothesis of specific environmental and/or occupational risk factors for APL among other AML subtypes and indicate the need for additional ad hoc multicenter studies.     

Cytogenetic studies of acute promyelocytic leukemia

Translocation t(15;17) is reported in bone marrow cells from six of seven patients with active acute promyelocytic leukemia (APL). One patient who showed t(15;17) at final relapse did not show it in directly prepared or cultured cells taken from a previous relapse. Bone marrow samples from two patients showed only cells with a normal karyotype in the direct preparation, whereas more than 60% of cells cultured for 24 hr showed t(15;17). R-Banding, G-banding, and an attempt at high-resolution banding indicated the break points t(15;17)(q24;21) for one of our patients.     

All-trans-retinoic acid in acute promyelocytic leukemia

We performed a retrospective analysis of all patients admitted to our institution with a diagnosis of infantile hypertrophic pyloric stenosis (IHPS) during a 10-year period from 1985-95 in order to assess the possible association between IHPS and urinary tract infections (UTIs). All 285 patients with IHPS had radiological or ultrasonographic confirmation of that diagnosis and underwent the Ramstedt procedure. Those who continued to be symptomatic were evaluated for UTI by urine analysis and culture. Positive cases were further evaluated for urinary system anomalies. The male:female ratio of IHPS was 3.4:1. Concomitant UTI was diagnosed in 8 patients by suprapubic aspiration or bladder catheterization. The prevalence of UTI in this series was 2.8%, 20-fold higher than the expected prevalence. Three of the 8 patients with UTI (37.5%) had urinary tract anomalies. These findings suggest an association between IHPS and UTI. We recommend that all IHPS patients be evaluated for UTI and positive cases undergo further evaluation for urinary anomalies.     

All-trans-retinoic acid in acute promyelocytic leukemia

BACKGROUND: All-trans-retinoic acid induces complete remission in acute promyelocytic leukemia. However, it is not clear whether induction therapy with all-trans-retinoic acid is superior to chemotherapy alone or whether maintenance treatment with all-trans-retinoic acid improves outcome. METHODS: Three hundred forty-six patients with previously untreated acute promyelocytic leukemia were randomly assigned to receive all-trans-retinoic acid or daunorubicin plus cytarabine as induction treatment. Patients who had a complete remission received consolidation therapy consisting of one cycle of treatment identical to the induction chemotherapy, then high-dose cytarabine plus daunorubicin. Patients still in complete remission after two cycles of consolidation therapy were then randomly assigned to maintenance treatment with all-trans-retinoic acid or to observation. RESULTS: Of the 174 patients treated with chemotherapy, 120 (69 percent) had a complete remission, as did 124 of the 172 (72 percent) given all-trans-retinoic acid (P=0.56). When both induction and maintenance treatments were taken into account, the estimated rates of disease-free survival at one, two, and three years were 77, 61, and 55 percent, respectively, for patients assigned to chemotherapy then all-trans-retinoic acid; 86, 75, and 75 percent for all-trans-retinoic acid then all-trans-retinoic acid; 75, 60, and 60 percent for all-trans-retinoic acid then observation; and 29, 18, and 18 percent for chemotherapy then observation. By intention-to-treat analysis, the rates of overall survival at one, two, and three years after entry into the study were 75, 57, and 50 percent, respectively, among patients assigned to chemotherapy, and 82, 72, and 67 percent among those assigned to all-trans-retinoic acid (P= 0.003). CONCLUSIONS: All-trans-retinoic acid as induction or maintenance treatment improves disease-free and overall survival as compared with chemotherapy alone and should be included in the treatment of acute promyelocytic leukemia.     

Retinoic acid syndrome in acute promyelocytic leukemia

This article, the first of two, reports the evaluation of a minor injuries clinic. The authors describe the background to the service and the methodology and results of the study. Some 20,000 patients attended the clinic during its first two years, at an average cost of 33 pounds per patient. Waiting times were low and 67 per cent of patients were discharged. Independent clinical audit rated 98 per cent of cases as satisfactorily treated. The clinic has generally been accepted by the local medical community and was funded permanently in late 1996.     

High frequency of acute promyelocytic leukemia among Latinos with acute myeloid leukemia

A high frequency (24%) of acute promyelocytic leukemia (APL) was noted among acute myelocytic leukemia (AML) cases at the Los Angeles County-University of Southern California (LAC-USC) Medical Center, in comparison with the expected frequency of 5% to 15%. Because of the high proportion of Latinos in this center, we questioned if APL is more common in this ethnic group. The proportion of APL among the 80 AML patients of Latino origin was significantly higher (30; 37.5%) when compared with the 62 non-Latinos (4; 6.5%) (P = .00001). In an attempt to verify this finding on a larger group of patients, we analyzed 276 pathologically verified cases of AML in patients aged 30 to 69 years from the entire County of Los Angeles, registered on an ongoing population-based epidemiologic study of AML. APL was more frequent among the 47 Latinos (24.3%) than in the 229 non-Latinos (8.3%) (P = .0075). APL is seen in younger patients with AML, but Latino AML patients also had a higher frequency of APL after accounting for their younger age (age-adjusted odds ratio for APL among Latinos in LAC-USC Medical Center, 9.4 [95% confidence interval (CI) 2.9, 30] P = .0002; among Latinos in the population-based study, 3.0 [95% CI 1.3 to 6.9] P = .01). The different ethnic distribution of AML was found to be due to a higher proportion of APL cases per se, and not to a lower proportion of any other French-American-British subtype (P = .0004). These results, from two different populations of AML patients, indicate that Latinos with AML have a higher likelihood of the APL subtype of disease, which may suggest a genetic predisposition to APL and/or exposure to distinct environmental factor(s).     

治疗急性早幼粒细胞白血病的几个问题

急性早幼粒细胞白血病(APL)为急性髓系白血病的一个亚型,以进展快,易发生弥散性血管内凝血(DIC)和死亡率高为特征.95%以上APL患者有典型染色体易位t(15;17)形成PMLRARα融合基因.1986年以来,中国首创以全反式维甲酸(ATRA)和亚砷酸(ATO)治疗APL,使APL的转归大大改观,成为仅用药物可治愈的AML.结合作者经验讨论治疗APL中的有关问题.     

Jumping translocations of 3q in acute promyelocytic leukemia

Jumping translocation is a rare phenomenon, seldom reported to occur in cancer. A complex four-way translocation involving chromosomes 3, 9, 15, and 17 was identified in the chromosome study on a patient with a history of an acute promyelocytic leukemia (APL). In the follow-up studies, the same complex rearrangement exhibited a jumping translocation between chromosomes 3 and 9 in one clone and 3 and 6 in another clone. This is the first reported case of jumping translocation in APL.     

Ultrastructural observations on a variant of acute promyelocytic leukemia

A patient with acute leukemia is presented in whom the leukemic cells, as seen by light microscopy were typical promyelocytes. The cells had normal or slightly invaginated nuclei with typical cytoplasmic granules and the diagnosis was confirmed by cytochemistry. The clinical course was rapid and the patient died of disseminated intravascular coagulation and urosepsis within a few days of diagnosis. However, electron microscopic examination showed cells with extremely convoluted and lobulated nuclei with nuclear pockets and cytoplasmic bridges as well as the complete absence of cytoplasmic granules in the majority of the cells. Furthermore, the urine lysozyme (muramidase) was elevated. These findings suggest that the leukemia in this patient may be classified as a hypogranular variant of acute promyelocytic leukemia (APL), with monocytoid ultrastructural appearances.     

Chronic myelogenous leukemia and acute promyelocytic leukemia: new bone marrow transplantation options

PURPOSE/OBJECTIVES: To describe new bone marrow transplantation (BMT) options for chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL), as well as their applications and prognoses, and to describe the role of the oncology nurse in caring for the BMT recipient and options for future nursing research. DATA SOURCES: Published articles, book chapters, and personal experience. DATA SYNTHESIS: Various pretransplant agents and methods are under investigation to improve the outcome and reduce the costs of allogeneic and autologous BMT and peripheral blood progenitor cell (PBPC) transplants. Preliminary results of current studies indicate that autologous BMTs and PBPC transplants have merit as a treatment option in patients with AML and require further research. For patients with APL, BMT usually is reserved for those who fail to achieve or relapse after achieving remission with chemotherapy. Preliminary data show that patients with CML and APL who receive a PBPC transplant engraft more rapidly with decreased morbidity and mortality. CONCLUSIONS: BMT options for patients with CML and APL continue to evolve as advances in pretransplant methods and symptom management become capable of improving the outcome, decreasing costs, and shifting patient care to the outpatient and homecare settings. IMPLICATIONS FOR NURSING PRACTICE: Understanding the marrow transplant options available to patients with CML and APL is essential for nurses. They must stay informed about ongoing improvements in pretransplant processes and symptom-management procedures that reduce BMT morbidity and mortality. Inpatient and outpatient nurses need to collaborate and participate in nursing research to find better ways of providing the best care possible for patients.     

CD95 predicts responsiveness to tretinoin in acute promyelocytic leukemia

We describe a predictive marker (CD95) for the responsiveness to tretinoin (RA) in acute promyelocytic leukemia (APL). Functional CD95 expression during RA treatment have been observed only in those patients who responded to RA. Expression of CD95 (Fas antigen), which plays a major role in apoptosis, was determined by fluorescence activated cell sorter (FACS) analysis. APL cases in which no enhancement of CD95 expression was observed showed no response to RA and did not obtain complete remission. We propose that CD95 can predict the clinical response to RA probably due to differentiation.     

Use of trans-retinoic acid in the treatment of acute promyelocytic leukemia

OBJECTIVE: To discuss acute promyelocytic leukemia (APL) and review the literature concerning differentiation treatment of APL with trans-retinoic acid (t-RA). DATA SOURCES: English-language articles concerning APL or its treatment with t-RA were identified with a MEDLINE search. STUDY SELECTION: All studies available at the time of article preparation, which addressed t-RA treatment in APL, were selected. DATA EXTRACTION: Data extraction and assessment were performed subjectively by the authors. An extensive discussion of specific study details is included in the article. DATA SYNTHESIS: APL is a unique subset of acute myelogenous leukemia and is typified by an accumulation of malignant promyelocytes in the bone marrow. Within the granulocyte cell cycle of a patient with APL, differentiation has been halted at the level of the promyelocyte, preventing formation of mature granulocytes. Upon treatment with traditional cytotoxic chemotherapy, complete remission rates of approximately 70 percent, with a five-year survival ranging from 25 to 40 percent have been achieved. In most patients with APL, a characteristic chromosomal t(15q+;17q-) translocation has been found, which may be responsible for the production of an aberrant retinoic acid receptor-alpha. Therefore, t-RA induction therapy has been investigated and has produced promising results. Administration of t-RA in dosages of 45-100 mg/m2/d has induced complete remissions. The apparent mechanism of t-RA is the induction of promyelocyte differentiation and maturation. The most common adverse effects noted have been dry skin, cheilitis, and headaches. CONCLUSIONS: Upon consideration of the initial trials, t-RA appears to be a promising and unique treatment for APL.