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American Journal of Hematology Nov 2018
Topics: Adolescent; Adult; Aged; California; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Risk Factors; Treatment Failure; Young Adult
PubMed: 30105792
DOI: 10.1002/ajh.25252 -
Clinical and Applied... 2022Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic...
INTRODUCTION
Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL.
MATERIALS AND METHODS
31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated.
RESULTS
All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively).
CONCLUSION
Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED.
Topics: Adult; Blood Coagulation Tests; Female; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Male; Reference Values; Thrombelastography
PubMed: 35942712
DOI: 10.1177/10760296221119809 -
Haematologica Apr 2011We report the clinical features and treatment outcome of 33 patients with multiple sclerosis who developed acute promyelocytic leukemia. Thirty patients were previously...
We report the clinical features and treatment outcome of 33 patients with multiple sclerosis who developed acute promyelocytic leukemia. Thirty patients were previously exposed to mitoxantrone. The median latency period between treatment initiation and acute promyelocytic leukemia diagnosis was 32 months. The PML-RARA bcr1 iso-form was identified in 87% of cases. Twenty-nine (90%) patients achieved hematologic remission after all-trans retinoic acid and chemotherapy (n = 31) or arsenic trioxide and all-trans retinoic acid. Consolidation included modified chemotherapy or arsenic trioxide. At a median follow up of 26 months, 23 patients are in complete remission, 4 relapsed and one developed secondary leukemia. The 5-year cumulative incidence of relapse and overall survival were 23% and 68%, respectively. Although treatment heterogeneity and suboptimal post-remission therapy must be taken into account, overall results and development of secondary leukemia in one patient suggest that effective and less toxic agents like arsenic trioxide warrants further investigation in this context.
Topics: Adult; Aged; Antineoplastic Agents; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Multiple Sclerosis; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 21193421
DOI: 10.3324/haematol.2010.036657 -
Haematologica Jun 2017
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; DNA Mutational Analysis; Female; Gene Expression Profiling; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Mutation; Recurrence; Time Factors; Translocation, Genetic; Young Adult
PubMed: 28341736
DOI: 10.3324/haematol.2016.162206 -
Cancer Reports (Hoboken, N.J.) Mar 2024Recent advances in the treatment of acute promyelocytic leukemia (APML) have seen unprecedented improvements in patient outcomes. However, such rapid growth in... (Review)
Review
BACKGROUND
Recent advances in the treatment of acute promyelocytic leukemia (APML) have seen unprecedented improvements in patient outcomes. However, such rapid growth in understanding often leads to uncertainty regarding superiority among candidate treatment regimens, especially when further scrutinized from an epidemiological perspective.
AIMS
The aim of this systematic review with epidemiological analysis was to identify and compare commonly utilized protocols for standard-risk APML with a particular focus on complete remission (CR), overall/disease-free survival (DFS), and reported adverse events.
METHODS AND RESULTS
Medline, Scopus, and CINAHL were interrogated to identify studies utilizing all-trans retinoic acid (ATRA) in addition to arsenic trioxide (ATO) and/or anthracyclines such as idarubicin (IDA) in the treatment of de-novo APML. After collation of studies, an epidemiological analysis was subsequently performed to compare protocols with regards to outcomes of interest using number needed to benefit (NNB) and number needed to harm (NNH) measures. Seventeen articles, describing 12 distinct trials, were included in the analysis. These trials made use of three unique protocols; CR rates were 94%-100% for ATO/ATRA regimens, 95%-96% for ATO/ATRA/anthracycline regimens, and 89%-94% for ATRA/anthracycline regimens. Epidemiological analysis demonstrated NNB for CR was 9.09 (ATO/ATRA vs. ATRA/IDA) and 20.00 (ATO/ATRA vs. ATO/ATRA/IDA), NNH for neutropenia was -3.45 (ATO/ATRA vs. ATRA/IDA), and NNH for infection was -3.13 (ATO/ATRA vs. ATRA/IDA) and -1.89 (ATO/ATRA vs. ATO/ATRA/IDA).
CONCLUSION
The ATO/ATRA regimen is superior to chemotherapy-containing protocols at inducing remission and promoting survival in patients with APML. The regimen is better tolerated than the proposed alternatives with fewer adverse events. Future research opportunities include quantifying APML epidemiology and pursuing oral arsenic as an option for simplification of therapeutic protocols.
Topics: Humans; Leukemia, Promyelocytic, Acute; Anthracyclines; Arsenicals; Oxides; Treatment Outcome; Tretinoin; Antibiotics, Antineoplastic; Pathologic Complete Response
PubMed: 38507294
DOI: 10.1002/cnr2.2035 -
Cancer Medicine Sep 2023The innovative combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic...
BACKGROUND
The innovative combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated.
METHODS
In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA-ATO-containing regimens.
RESULTS
Patients with ACA had markedly decreased hemoglobin levels than that without ACA (p = 0.021). Risk stratification in the ACA group was significantly worse than that in the non-ACA group (p = 0.032). With a median follow-up period of 62.0 months, worse event-free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (p = 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (p = 0.017; p = 0.037).
CONCLUSIONS
To sum up, ACA remains the independent prognostic value for EFS, we should build risk-adapted therapeutic strategies in the long-term management of APL when such abnormalities are detected.
Topics: Humans; Leukemia, Promyelocytic, Acute; Progression-Free Survival; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Tretinoin; Chromosome Aberrations; Oxides; Arsenicals; Treatment Outcome
PubMed: 37584196
DOI: 10.1002/cam4.6398 -
Postepy Higieny I Medycyny... Nov 2013During last decades acute promyelocytic leukemia, once considered the deadly disease, has evolved to the most treatable of all subtypes of acute myeloid leukemias. The... (Review)
Review
During last decades acute promyelocytic leukemia, once considered the deadly disease, has evolved to the most treatable of all subtypes of acute myeloid leukemias. The intense clinical and basic research has led to a rational approach to treatment in which the use of the differentiating agent all-trans-retinoic acid has proven to be effective first-line therapy. Arsenic trioxide, used for relapsed disease, further improved the survival rate of patients. The classical model presented the therapeutic success as a result of over-coming of the differentiation block characteristic of neoplastic cells. However, the resent in vivo and ex vivo studies, seem to show that the induction of differentiation process is not required to cure acute promyelocytic leukemia. Rather than inducing differentiation, targeting clonogenic leukemia initiating cells or destroying PML-RARa fusion protein may represent a more effective therapeutic goal in this type of leukemia.
Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Humans; Leukemia, Promyelocytic, Acute; Oncogene Proteins, Fusion; Oxides; Secondary Prevention; Survival Rate; Tretinoin
PubMed: 24379249
DOI: 10.5604/17322693.1077467 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2023Early death is a major factor of treatment failure in acute promyelocytic leukemia (APL), however, the recent trends in the incidence of early death based on the...
BACKGROUND
Early death is a major factor of treatment failure in acute promyelocytic leukemia (APL), however, the recent trends in the incidence of early death based on the population-level are not clear. Hence, this study is aimed at describing the incidence, recent trends, causes and characteristics of early death in APL based on the real world.
MATERIALS AND METHODS
APL patients diagnosed from 1986 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) dataset were enrolled, and categorized based on gender, age, year of diagnosis, race, marital status, resident county and socioeconomic status (SES). The risk factors for all-cause and acute myelocytic leukemia (AML) specific early death were determined by univariate and multivariate logistic regression analyses, and stratified analysis was conducted by age.
RESULTS
Overall, 3212 APL patients were included in analysis between 1986 and 2015, of which a total of 683 (21.3%) patients were noted for early death. Significant differences were recognized for patient distribution by age, year of diagnosis, marital status, and SES. The early death rate of APL patients diagnosed during 2006-2015 was significantly lower than that of the early stage, but this trend was not evident in juvenile patients. At the same time, older age, and lower SES score were independent risk factors for early death in the multivariate analysis.
CONCLUSION
We established that the early death trend in APL has decreased over the past few years, but the early death rate remains high, especially in older patients and those with lower SES.
Topics: Humans; Aged; Leukemia, Promyelocytic, Acute; Leukemia, Myeloid, Acute; Risk Factors; Multivariate Analysis; Incidence
PubMed: 36567214
DOI: 10.1016/j.clml.2022.11.005 -
Indian Journal of Cancer 2020Early death is still the characteristic feature of acute promyelocytic leukemia (APL) despite the advances in the treatment regimen. Analyzing the incidence of early...
BACKGROUND
Early death is still the characteristic feature of acute promyelocytic leukemia (APL) despite the advances in the treatment regimen. Analyzing the incidence of early death would prove beneficial as no much substantial information is available pertaining to the rural population. The present study analyzed the incidence of APL-associated early death, its clinical characteristics, and outcome among acute myeloid leukemia patients.
METHODS
This retrospective study included patients catering to the rural areas of Vijayawada (Andhra Pradesh, India) from January 2013 to June 2017. Chi-square test, Fisher's exact test, independent sample median test, and Kaplan-Meier test for probability of survival were used.
RESULTS
Of the 204 acute myeloid cases, 24% cases (median age = 30 years; range=8 to 68 years) were identified as APL. Early death rate was 34.6%, who expired within 30 days from diagnosis with 65% suffering high disease risk. The median time from admission to death was 2 days (range 0-18). Cause of early death was majorly due to hemorrhage (64%). Moreover, 47.1% of early death patients received no prior antileukemic treatment. The overall 5-year cumulative disease-free survival rate among patients with APL was 76% where high disease risk patients had the least disease-free survival (65%-75%), whereas intermediate and low-risk patients had >80% and 100% disease-free survival rate, respectively.
CONCLUSION
Early diagnosis and timely intervention might help to prevent early death as our findings clearly indicate poor awareness of disease and lack of early intervention among the rural population.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Follow-Up Studies; Humans; India; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Prognosis; Retrospective Studies; Rural Population; Survival Rate; Young Adult
PubMed: 33078753
DOI: 10.4103/ijc.IJC_177_19 -
Technology in Cancer Research &... 2020Acute promyelocytic leukemia, a subtype of acute myeloid leukemia, is highly curable. In subgroup of patients with non-high-risk acute promyelocytic leukemia,... (Meta-Analysis)
Meta-Analysis
Acute promyelocytic leukemia, a subtype of acute myeloid leukemia, is highly curable. In subgroup of patients with non-high-risk acute promyelocytic leukemia, intravenous arsenic trioxide plus all-trans-retinoic acid is considered the preferred regimen for acute promyelocytic leukemia. Recently, there are interests in the use of the oral form of arsenic, named the Realgar-Indigo naturalis formula, but the data on its efficacy and safety are still relatively limited. The current study was conducted with the aims to identify and summarize the results of all available randomized-controlled studies. A systematic review was conducted in the 2 major databases, utilizing the terms for arsenic and acute promyelocytic leukemia. Eligible studies had to be randomized-controlled studies that compared efficacy and/or adverse effects of oral arsenic versus intravenous arsenic for treatment of patients with acute promyelocytic leukemia. The Mantel-Haenszel method was used to pool the effect estimates and 95% confidence intervals of the included studies together. A total of 4 randomized controlled studies with 482 patients with acute promyelocytic leukemia (258 in Realgar-Indigo naturalis formula group and 224 in intravenous arsenic trioxide group) were included in the meta-analysis. The chances of achieving complete remission were numerically higher in the Realgar-Indigo naturalis formula group but the difference was not statistically significant (pooled odds ratio: 4.59, 95% CI: 0.74-28.57, = 0%). Similarly, other efficacy outcomes, including 30-day mortality rate, overall survival, and event-free survival, also tended to favor the Realgar-Indigo naturalis formula group but the difference was not statistically significant. There was no significant difference in the chance of developing differentiation syndrome, cardiac complications, grades 3 to 4 liver toxicity, grades 3 to 4 renal toxicity, and infection between the 2 groups. The results may suggest that all-trans-retinoic acid plus oral Realgar-Indigo naturalis formula regimen is, at minimum, not a worse alternative to the standard all-trans-retinoic acid plus intravenous intravenous arsenic trioxide regimen for treatment of acute promyelocytic leukemia, especially for patients with low-to-intermediate risk.
Topics: Administration, Intravenous; Administration, Oral; Antineoplastic Agents; Arsenic Trioxide; Drug-Related Side Effects and Adverse Reactions; Humans; Leukemia, Promyelocytic, Acute; Prognosis; Randomized Controlled Trials as Topic
PubMed: 32583728
DOI: 10.1177/1533033820937008