Adult Acute Nonlymphocytic Leukemia Research Articles

CAGE regimen in the treatment of adult refractory acute non-lymphocytic leukemia

Objective: To observe the effect of CAGE regimen in the treatment of adult refractory acute non-lymphocytic leukemia. Methods: In this experiment, 86 adult patients with refractory acute non-lymphocytic leukemia who were treated between January 2018 and January 2022 were selected as experimental subjects and were divided into two groups, the observation group and the control group, according to different treatment methods, with 43 patients in each group. The observation group was treated with the CAGE regimen, whereas the control group was treated with conventional therapy. The disease remission rate and incidence of adverse reactions were observed. Results: The comparison of disease remission rates between the two groups showed that there was no significant difference in the results of the first course of treatment and the second course of treatment between the two groups (P > 0.05), but the incidence of adverse reactions in the observation group was lower than that in the control group (P < 0.05). Conclusion: The CAGE regimen has a significant therapeutic effect in the treatment of adult refractory acute non-lymphocytic leukemia. It improves the treatment advantage of patients during the treatment process, thus alleviating the condition of patients and improving their quality of life.

Adult leukemia risk and personal appliance use: a preliminary study.

The hypothesis that use of personal electric appliances may be associated with increased risk of acute nonlymphocytic leukemia in adults was tested using interview data from a previously completed case-control study of 114 cases and 133 controls conducted between 1981 and 1984. Cases were obtained from a population-based cancer registry in western Washington state, and controls were obtained from the same area by random digit dialing. Of 32 electrical home appliances for which data on use were available for adult acute nonlymphocytic leukemia cases and controls, three motor-driven personal appliances (electric razors, hair dryers, and massage units) were selected a priori because their use represents exposure to higher peak magnetic fields than that from most other home appliances. When compared on an "ever used" versus "never used" basis, use of one or more of these appliances was not associated with increased risk of leukemia in the population studied (odds ratio (OR) = 0.71, 95% confidence interval (CI) 0.41-1.24). When the appliances were considered individually, massage units were more likely to have been used by cases than by controls (OR = 3.00, 95% CI 1.43-6.32), while hair dryers were more likely to have been used by controls than cases (OR = 0.38, 95% CI 0.22-0.66). There was a nonsignificant tendency for electric razor use to differentiate the cases from controls (OR = 1.33, 95% CI 0.80-2.23). When reported daily time of use was stratified, there was no overall increased risk with increased time of use except for electric razors (p < 0.05). In addition to the analysis of appliance use data from the case-control study, the authors obtained several models of these motor-driven personal appliances and characterized the magnetic fields they produce. Magnetic field flux density, or the B-field, and spectral measurements showed that partial body exposure from such appliances may exceed 0.5 mTesla (root mean squared) at rates-of-change exceeding 10 Tesla/sec. These epidemiologic data must be interpreted cautiously because the number of cases is limited and because of proxy reporting of appliance use for deceased cases. Nevertheless, the authors believe these data indicate that peak magnetic field exposure from personal appliances warrants further investigation as a possible risk factor for acute nonlymphocytic leukemia in adults.

Relation between platinum-DNA adducts and complete remission in adult acute nonlymphocytic leukemia

The purpose of this study was to determine the relationship between platinum-DNA adducts in leukemic cells and the success of remission induction therapy in adult patients with acute nonlymphocytic leukemia (ANLL). Freshly isolated cells from pre-treatment bone marrow aspirates of 14 patients were incubated with cisplatin in vitro and the amount of platinum bound to DNA was determined using a competitive ELISA procedure and an antibody directed against platinum-modified DNA. Platinum-DNA adduct levels discriminated well between complete remission (CR) and remission failure (RF) patients, treated with mitoxantrone, cytosine arabinoside ± carboplatin.

Ubenimex in the treatment of acute nonlymphocytic leukemia in adults

A multi-institutional randomized study for the evaluation of ubenimex (Bestatin) in the treatment of adult acute nonlymphocytic leukemia was performed. One hundred and ninety-five patients were registered from February 1988 to December 1990. Patients who had reached complete remission by one or two courses of remission induction chemotherapy were divided into the ubenimex group or the control group by randomization. Patients of the ubenimex group started to receive 30 mg ubenimex orally once a day when maintenance therapy began and continued as long as possible. Remission duration and survival were analyzed based on the data as of August 31, 1991. Remission duration of the ubenimex group was superior to that of the control group (generalized Wilcoxon test: p = 0.0338). Fifty percent remission duration was 508 days in the ubenimex group and 386 days in the control group. There has been no statistical difference in survival between the two groups as yet.

Review of ubenimex (Bestatin): clinical research

An immunomodulating agent, ubenimex (Bestatin) has low toxicity even after long-term oral administration and brings about significant modifications in immunological response. In a cooperative randomized controlled study of Bestatin immunotherapy for adult acute nonlymphocytic leukemia, prolongation of remission duration and survival was achieved with Bestalin immunotherapy combined with remission maintenance chemotherapy. The significant prolongation of remission duration and survival was seen in the Bestatin group, especially in the elderly patients. Randomized controlled studies of Bestatin immunotherapy were performed in solid tumors including malignant melanoma, carcinoma of the lung, stomach, bladder, head and neck and esophagus, and therapeutic benefits regarding disease free-interval or survival were observed in certain types of the above-mentioned cancers; however, Bestatin immunotherapy for these cancers should be further investigated in large-scale controlled studies to confirm its activity. Bestatin/ubenimex/immunotherapy/leukemia/cancer

High-dose cytosine arabinoside and L-asparaginase therapy for poor-risk adult acute nonlymphocytic leukemia. A retrospective study

The effectiveness and toxicities of high-dose cytosine arabinoside with L-asparaginase (HiDAC-ASNase) were evaluated in 41 patients with "poor risk" acute nonlymphocytic leukemia (ANLL). Twenty-four patients had either refractory or relapsed primary ANLL, and 17 had ANLL secondary to prior cytotoxic chemotherapy or an underlying hematologic disorder. The overall complete remission (CR) rate was 37%. The CR rates for primary and secondary ANLL were almost identical. Furthermore, advanced age alone did not adversely influence the CR rate. The median CR duration was 302 days with no differences between primary and secondary ANLL. The induction death rate was 24%. Predictors for induction deaths included poor initial performance status, fever at the time of presentation, low cholesterol and/or albumin, and an initial bone marrow aspirate with greater than 50% blasts. These data indicate that HiDAC-ASNase is a moderately effective regimen for patients with poor prognosis ANLL including secondary ANLL.

Expression of the multidrug resistance gene in myeloid leukemias

The human multidrug-resistance gene ( MDR1) encodes an energy-dependent multidrug efflux protein responsible for the cross-resistance of cultured cells to natural product chemotherapeutic agents such as the anthracyclines and vinca alkaloids. RNA transcript levels were measured in leukemia cells obtained from 15 adult acute nonlymphocytic leukemia (ANLL) cases and 15 cases of chronic myelogenous leukemia (CML). Expression of MDR1 RNA was common in ANLL, and appears to be most frequent in leukemic cells of patients with the poorest response to chemotherapy. Expression of the MDR1 gene was not detectable in the peripheral white blood cells of any of the CML cases during the chronic phase, but was detectable in the immature cells present during this phase of the disease. The cells of the three blastic crisis patients contained detectable levels of MDR1 RNA. These studies support the idea that expression of the MDR1 gene contributes to drug resistance in ANLL, and may play a role in some instances in the drug-resistance of CML in blastic crisis. In contrast, studies of the level of expression of anionic glutathione transferase and DNA polymerase B failed to show any relationship between the RNA transcript levels of these enzymes and responsiveness to chemotherapy.

Randomized controlled study of chemoimmunotherapy with bestatin of acute nonlymphocytic leukemia in adults

A new immunomodulating agent, bestatin (INN: Ubenimex has low toxicity even after long-term oral administration and has significant modifications in immunological response. A cooperative randomized controlled study of bestatin immunotherapy in combination with remission maintenance chemotherapy for adult acute nonlymphocytic leukemia (ANLL) was performed. After induction of complete remission, patients were randomized to the bestatin group (30 mg bw per os (po) daily) and the control group. The 101 eligible cases (bestatin: 48, control: 53) were analyzed; the bestatin group achieved longer remission than the control group and a statistically significant longer survival. Though this prolongation of remission was not significant in the bestatin group compared to the control group in the 15–49 yr age group, in the 50–65 yr age group it was significantly longer. Bestatin is shown to be a clinically useful drug for immunotherapy of adult ANLL, since it has prolonged survival and remission especially in elderly patients, with few side-effects.

Results and Prognosis of Acute Non-Lymphocytic Leukemia in Adults

Between 1977-87, 319 patients with AML were admitted to Hannover Medical School. At all 41 of these patients were not treated (median duration of survival 0.6 months). Among the 278 treated patients, there was a CR rate of 53.6%, the median duration of remission was 10.1 months and the median duration of survival 7.0 months. The patients with FAB-classification M4-M5 had a worse prognosis than those with M1-M3. Patients under 50 years of age had a significant higher remission rate and survival time than those over 50 years. In the last 10 years, the remission rate rose from 37.3% to 61.0% (p = 0.1776). There was a rise in median duration of survival from 5.9 months (1977-79) to 8.0 months (1984-85) (p less than 0.001). The median remission time decreased from 15.8 months (1977-79) to 12.0 months (1984-85) (p less than 0.001). After the first reinduction therapy, the remission rate (46.6%), duration of remission (5.3 months), and duration of survival (4.1 months) was lower than after primary therapy. After the second reinduction therapy the CR rate was 69.2%, and the remission time 2.9 months. The CR rate after the third reinduction therapy was 22.2%.

Serum lactate dehydrogenase fails to predict response to treatment and survival in acute non-lymphocytic leukemia.

Total serum lactate dehydrogenase (LDH) activity was measured in 514 adult patients with de novo acute non-lymphocytic leukemia (ANLL) prior to any treatment and was compared with several disease features, with response to induction treatment, and with relapse-free survival. LDH was higher in the M4 and M5 FAB cytological subtypes and was positively correlated with the white blood cell count (WBC). The proportion of remissions, of deaths during induction, and of failure, and the duration of relapse-free survival, were clearly unrelated to LDH activity, in the whole series as well as in different age groups (below 40 years, and 40 to 60 years) and in any FAB cytological subtype. Multivariate analysis showed that only WBC and sex (female better than male) were marginally related with relapse-free survival. These data provide conclusive evidence that LDH does not help in defining the prognosis of adult ANLL, either because enzyme activity fails to reflect the number and proliferation rate of leukemic cells efficiently, or because with current standard treatment these features are of borderline importance, in contrast with acute lymphocytic leukemia and malignant lymphomas.

Adult Acute Nonlymphocytic Leukemia in Saudi Arabia: Experience at King Khalid University Hospital in Riyadh

Twenty-two adult patients with acute nonlymphocytic leukemia (ANLL) were analyzed. There were 15 males (68%) and 7 females (32%). Their median age was 42 years. Thirty-six percent had acute myelomo...

The Curative Treatment of Adult Acute Nonlymphocytic Leukemia

The Curative Treatment of Adult Acute Nonlymphocytic Leukemia

A Consolidation Therapy For Adult Acute Nonlymphocytic Leukemia Aiming at a Short Term Treatment

A Consolidation Therapy For Adult Acute Nonlymphocytic Leukemia Aiming at a Short Term Treatment

Next-of-kin attitudes regarding participation in an epidemiologic case-control study.

We assessed next-of-kin's attitudes about participating in an epidemiologic case-control study of adult acute nonlymphocytic leukemia. Responses from a mailed questionnaire indicated that 95 per cent were glad they participated. While 74 per cent benefited, 18.5 per cent were bothered in some way. Results concerning the need to obtain physician permission before contacting next-of-kin were inconclusive; however, 8 of 10 females contacted by the case's physician considered consent necessary.

Acute nonlymphocytic leukemia and residential exposure to power frequency magnetic fields.

Recent research has suggested that nonionizing radiation in the form of power-frequency magnetic fields may play some role in carcinogenesis in general and in acute nonlymphocytic leukemia in particular. Much of the epidemiologic evidence is preliminary in nature and the methods of previous studies have been criticized. In order to further evaluate this hypothesis, a population-based case-control study of adult acute nonlymphocytic leukemia and residential exposure to power-frequency magnetic fields was carried out in western Washington state. Analyses were based on 114 cases who were newly diagnosed from 1981 to 1984 and identified from a population-based cancer registry, and 133 controls who were chosen from the study area by random digit dialing. Magnetic field exposure was estimated from external electrical wiring configurations within 140 ft (42.7 m) of each subject's residence. In addition, magnetic fields were measured inside the subject's residence at the time of interview. Neither the directly measured magnetic fields nor the surrogate values based on the wiring configurations were associated with acute nonlymphocytic leukemia.

Cigarette Smoking and Leukemia: Cancer, Vol. 60, No. 2, July 15, 1987, pp. 141–144

Cigarette smoking has not been consistently associated with the subsequent development of leukemia. However, many of the earlier epidemiologic studies of leukemia have not considered specific histologic subtypes separately. The association between cigarette smoking and adult acute nonlymphocytic leukemia was examined in a case-control study of 114 patients and 133 controls. Cigarette smoking was associated with a significantly increased risk of acute myelocytic leukemia (relative risk estimate = 1.78, 95% confidence interval = 1.01 to 3.15) along with a significant (P less than 0.001) dose-response based on the total number of years of cigarette smoking. Since this is a preliminary study, more analyses of other epidemiologic studies are needed before it can be concluded that there is a causal association.

Hyperleukocytosis in adult acute nonlymphocytic leukemia: impact on remission rate and duration, and survival.

The clinical courses of 353 patients with acute nonlymphocytic leukemia (ANLL) treated between 1971 and 1982 at the Baltimore Cancer Research Program (BCRP) of the National Cancer Institute were reviewed and examined for the impact of presenting WBC count on the initial course and overall outcome of these patients. Group A (WBC greater than 100,000/microL) had significantly more deaths during the first week of therapy than did group C (WBC less than 50,000/microL) (P = .0003). CNS hemorrhage was responsible for a significantly greater number of deaths in group A compared with group C (P less than .004). The group B (WBC 50,000 to 100,000/microL) death rate was intermediate. These findings are consistent with other reports of complications of leukostasis. Rapid intervention with antileukemic therapy and cranial irradiation may have decreased the risk of CNS hemorrhage in group A. If early deaths are removed from analysis, the complete remission rate among patient groups is not significantly different (group A, 59%; group B, 68%; group C, 65%). However, further analyses of patients achieving remission demonstrate significant differences among patient groups based on presenting WBC count. The median complete remission duration of patients in group A (4.2 months) is shorter than that of patients in group B (8.0 months) or C (8.0 months), P = .07. In addition, remission duration has improved with modern aggressive antileukemic therapy in groups B (median before 1977, 7.0 months; after 1977, 22.0 + months) and C (before 1977, 6.0 months; after 1977, 16.0 + months). No such improvement has occurred in group A, in which the median duration of remission was 4.2 months before and after 1977. The same findings are demonstrated in an analysis of survival, with improvement occurring only in groups B (median before 1977, 16.5 months; after 1977, 26.0 + months) and C (before 1977, 13.5 months; after 1977, 24.0 + months). Long-term follow-up (minimum of 4 years) of these patients has allowed an analysis of the effect of presenting WBC count on the overall outcome of adult patients with ANLL.

Cigarette smoking and leukemia.

Cigarette smoking has not been consistently associated with the subsequent development of leukemia. However, many of the earlier epidemiologic studies of leukemia have not considered specific histologic subtypes separately. The association between cigarette smoking and adult acute nonlymphocytic leukemia was examined in a case-control study of 114 patients and 133 controls. Cigarette smoking was associated with a significantly increased risk of acute myelocytic leukemia (relative risk estimate = 1.78, 95% confidence interval = 1.01 to 3.15) along with a significant (P less than 0.001) dose-response based on the total number of years of cigarette smoking. Since this is a preliminary study, more analyses of other epidemiologic studies are needed before it can be concluded that there is a causal association.

Acute nonlymphocytic leukemia in adults: pathophysiology, status of current therapy, and new approaches.

Recent information concerning the cell biology of leukemias has provided new insights into the pathophysiology and pathogenesis of acute leukemia, involving the detection of leukemia viruses, oncogenes and their products, and the discovery of factors supporting clonal leukemic growth. Murine, avian, and cat leukemia viruses are well characterized. To date, only HTLV I appears to be a likely candidate as a human leukemia virus. For both avian and murine viruses, there is a fundamental classification distinction between long-latency viruses (LLV) and acute transforming viruses (ATV). The ATV are replication defective and must be propagated with a helper virus. They have within their genome an identifiable oncogene. The LLV do not contain such an oncogene and presumably act by “promotor insertion”, e.g., a retroviral long terminal repeat (LTR inserted 5’ to the cellular oncogene. Acutely appearing neoplasms are probably not clonal, but reflect infection of multiple target cells. Long-latency neoplasms, however, are clonal and probably reflect expansion of a random oncogenic event. There are usually differences between in vitro and in vivo target cell specificities for these viruses. Furthermore, pathogenicity in the animal is greatly affected by animal age, inoculum route, and the genetics of the recipients. Target cell specificities will hopefully be classified by new in vitro culture techniques for hematopoietic cells. Three avian ATV are interesting because of their apparent target cell specificity:AEV (erythroblastosis virus), AMV (myeloblastosis virus), and MC 29 (myelocytomatosis virus). Relative numbers of target cells appear to differ for these viruses: 50 for AEV, 700 for AMV, and 3500 for MC 29. AEV (V-erb B) affects erythroid precursors (presumably BFU-E), AMV (Vmyb), early myeloid precursors, and MC 29 (V-myc), macrophage-like cells. In vitro AEV and MC 29, but not AMV, transform fibroblasts.KeywordsAcute Myeloid LeukemiaHairy Cell LeukemiaCytosine ArabinosideAcute Myeloblastic LeukemiaErythroblastosis VirusThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Evidence favoring lineage fidelity in acute nonlymphocytic leukemia: absence of immunoglobulin gene rearrangements in FAB types M4 and M5

The concept of lineage fidelity in acute leukemia has recently been challenged by the finding of rearrangements of the immunoglobulin heavy chain genes in a leukemic cell line and in a small number of sporadic cases of acute nonlymphocytic leukemia with a monocytic phenotype. We therefore screened leukemic blood or bone marrow samples of 33 adult patients with acute nonlymphocytic leukemia of FAB types M4 (23 patients) and M5 (10 patients); 28 were obtained at diagnosis and 5 at relapse. All cases were well characterized pathologically and histochemically. Cytogenetic analysis performed in each case demonstrated karyotypes that were representative of those generally seen in these types of leukemia, with a clonal abnormality present in all except 9 of 32 patients who were successfully studied. DNA prepared from each sample was digested with the restriction enzyme BamH1 and analyzed by Southern blot hybridization to probes for the JH region of the immunoglobulin heavy chain. All 33 cases had DNA retained in the germline configuration with no evidence of rearrangement. This finding supports the concept of lineage fidelity, and suggests that true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in adult acute nonlymphocytic leukemia.