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Blood Advances Jan 2022Acute promyelocytic leukemia (APL) is associated with a favorable long-term prognosis if appropriate treatment is initiated promptly. Outcomes in clinical trials and...
Acute promyelocytic leukemia (APL) is associated with a favorable long-term prognosis if appropriate treatment is initiated promptly. Outcomes in clinical trials and population-based registries vary; potential explanations include a delay in treatment and lower adherence to guideline-recommended therapy in real-world practice. We used the Vizient Clinical Data Base to describe demographic characteristics, baseline clinical characteristics, and treatment patterns in patients newly diagnosed with APL during the study period of April 2017 to March 2020. Baseline white blood cell count was used to assign risk status and assess treatment concordance with National Comprehensive Cancer Network guidelines. Logistic regression models examined adjusted associations between patient, hospital, disease characteristics, and adverse outcomes (in-hospital death or discharge to hospice). Among 1464 patients with APL, 205 (14.0%) experienced an adverse outcome. A substantial subset (20.6%) of patients did not receive guideline-concordant regimens. Odds of adverse outcomes increased with failure to receive guideline-concordant treatment (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.43-3.75; P = .001), high-risk disease (OR, 2.48; 95% CI, 1.53-4.00; P < .001), and increasing age (≥60 years: OR, 11.13; 95% CI, 4.55-27.22; P < .001). Higher hospital acute myeloid leukemia (AML) patient volume was associated with lower odds of adverse outcome (OR, 0.44; 95% CI, 0.20-0.99 [for ≤50 vs >200 AML patients per year]; P = .046). In conclusion, in this large database analysis, 14.0% of patients newly diagnosed with APL died or were discharged to hospice. A substantial proportion of patients did not receive guideline-concordant therapy, potentially contributing to adverse outcomes.
Topics: Hospital Mortality; Humans; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Middle Aged; Odds Ratio; Prognosis; United States
PubMed: 34724703
DOI: 10.1182/bloodadvances.2021005642 -
Hematology/oncology and Stem Cell... Jun 2018Pathologic increase in bone marrow reticulin fibrosis can be present in many malignant hematopoietic diseases. In acute leukemia, one-third of patients have some degree... (Review)
Review
Pathologic increase in bone marrow reticulin fibrosis can be present in many malignant hematopoietic diseases. In acute leukemia, one-third of patients have some degree of marrow reticulin fibrosis at presentation, which is thought to be related to cytokine release from blasts. Marrow fibrosis is particularly common in acute megakaryoblastic leukemia, while this change is rarely seen in acute promyelocytic leukemia. Six case reports of acute promyelocytic leukemia with marrow reticulin fibrosis have been described so far in the literature. Herein, we present three cases of classical acute promyelocytic leukemia with increased marrow reticulin fibrosis encountered in our institution, summarizing their clinicopathologic features, treatment, and outcome to date. Awareness of the features of acute promyelocytic leukemia with marrow reticulin fibrosis is important as it may guide treatment options.
Topics: Adult; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Primary Myelofibrosis
PubMed: 27614232
DOI: 10.1016/j.hemonc.2016.08.001 -
Tidsskrift For Den Norske Laegeforening... May 2014Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid leukaemia (AML) with unique biological and clinical features and unique therapeutic requirements. The... (Review)
Review
BACKGROUND
Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid leukaemia (AML) with unique biological and clinical features and unique therapeutic requirements. The article provides a brief description of the development, pathophysiology, diagnosis and treatment of APL.
METHOD
The article is based on the authors' own experience and reviews of key articles and national and international guidelines.
RESULTS
The disease is caused by a single genetic event, namely the translocation t(15;17), which gives rise to the oncoprotein PML-RARA. Clinical and morphological characteristics arouse suspicion of the disease, and the diagnosis is verified by detecting the translocation. At the time of diagnosis most patients have severe coagulopathy and the predominant clinical manifestation is bleeding. Early mortality is due to severe haemorrhage, usually intracranial. Early treatment start with all-trans retinoic acid (ATRA) on suspicion of APL is essential to reduce this early mortality. ATRA is also an important part of continued treatment, in combination with anthracycline-based chemotherapy and possibly arsenic. After this treatment, the prognosis for disease-free long-term survival is > 90%. There are also safe and effective treatment options for elderly patients with complex comorbidities.
INTERPRETATION
With APL it is particularly important to start disease-targeting therapy in the form of ATRA quickly because of the high risk of serious haemorrhages and high early mortality. If serious haemorrhages are avoided, the prognosis is very good.
Topics: Antineoplastic Agents; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Humans; Leukemia, Promyelocytic, Acute; Oncogene Proteins, Fusion; Translocation, Genetic; Tretinoin
PubMed: 24865730
DOI: 10.4045/tidsskr.13.1508 -
Annals of Laboratory Medicine Mar 2022
Topics: Humans; Leukemia, Plasma Cell; Leukemia, Promyelocytic, Acute; Tretinoin
PubMed: 34635620
DOI: 10.3343/alm.2022.42.2.278 -
BMC Cancer Feb 2023The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance.
BACKGROUND
The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance.
METHODS
Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers.
RESULTS
APL occurred in 374 males and 387 females at a median age of 44 (1-97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 10/L, diagnosis during 1991-2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14-161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 10/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010-2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens.
CONCLUSIONS
There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754).
Topics: Male; Female; Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Arsenic Trioxide; Leukemia, Promyelocytic, Acute; Neoplasms, Second Primary; Neoplasm Recurrence, Local; Tretinoin; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Oxides; Arsenicals
PubMed: 36765318
DOI: 10.1186/s12885-023-10612-z -
Annals of Hematology Feb 2024The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We...
The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.
Topics: Humans; Adult; Leukemia, Promyelocytic, Acute; Tretinoin; Neoplasms, Second Primary; Incidence; Retrospective Studies; Treatment Outcome; Risk Factors; Pathologic Complete Response; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38110588
DOI: 10.1007/s00277-023-05582-y -
Internal Medicine (Tokyo, Japan) Aug 2019Acute promyelocytic leukemia (APL) in human immunodeficiency virus (HIV)-infected individuals is very rare. There is currently no consensus regarding the use of... (Review)
Review
Acute promyelocytic leukemia (APL) in human immunodeficiency virus (HIV)-infected individuals is very rare. There is currently no consensus regarding the use of anti-cancer drugs with highly active anti-retroviral therapy (ART) in these patients due to their small number. We herein report two cases of APL with HIV-infected patients. Both cases received all-trans-retinoic acid-containing chemotherapies and achieved complete remission. ART was continued throughout the treatment course. The clinical course of these cases suggests that it is preferable to perform standard chemotherapy for APL with ART if patients have an adequate performance status.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Leukemia, Promyelocytic, Acute; Male; Remission Induction; Treatment Outcome; Tretinoin
PubMed: 31118366
DOI: 10.2169/internalmedicine.1662-18 -
Blood Sep 2021Most patients with acute promyelocytic leukemia (APL) can be cured with combined all-trans retinoic acid (ATRA) and arsenic trioxide therapy, which induces the...
Most patients with acute promyelocytic leukemia (APL) can be cured with combined all-trans retinoic acid (ATRA) and arsenic trioxide therapy, which induces the destruction of PML-RARA, the initiating fusion protein for this disease. However, the underlying mechanisms by which PML-RARA initiates and maintains APL cells are still not clear. Therefore, we identified genes that are dysregulated by PML-RARA in mouse and human APL cells and prioritized GATA2 for functional studies because it is highly expressed in preleukemic cells expressing PML-RARA, its high expression persists in transformed APL cells, and spontaneous somatic mutations of GATA2 occur during APL progression in mice and humans. These and other findings suggested that GATA2 may be upregulated to thwart the proliferative signal generated by PML-RARA and that its inactivation by mutation (and/or epigenetic silencing) may accelerate disease progression in APL and other forms of acute myeloid leukemia (AML). Indeed, biallelic knockout of Gata2 with CRISPR/Cas9-mediated gene editing increased the serial replating efficiency of PML-RARA-expressing myeloid progenitors (as well as progenitors expressing RUNX1-RUNX1T1, or deficient for Cebpa), increased mouse APL penetrance, and decreased latency. Restoration of Gata2 expression suppressed PML-RARA-driven aberrant self-renewal and leukemogenesis. Conversely, addback of a mutant GATA2R362G protein associated with APL and AML minimally suppressed PML-RARA-induced aberrant self-renewal, suggesting that it is a loss-of-function mutation. These studies reveal a potential role for Gata2 as a tumor suppressor in AML and suggest that restoration of its function (when inactivated) may provide benefit for AML patients.
Topics: Animals; CRISPR-Cas Systems; Cell Line, Tumor; Disease Progression; GATA2 Transcription Factor; Gene Expression Regulation, Leukemic; Genes, Tumor Suppressor; Humans; Leukemia, Promyelocytic, Acute; Mice; Mutation
PubMed: 34125173
DOI: 10.1182/blood.2021011758 -
Turkish Journal of Haematology :... Dec 2022
Topics: Humans; Leukemia, Promyelocytic, Acute; Leukemia, Myeloid, Acute; Nuclear Proteins
PubMed: 35965415
DOI: 10.4274/tjh.galenos.2022.2022.0220 -
Blood Oct 1993
Review
Topics: Drug Resistance; Humans; Leukemia, Promyelocytic, Acute; Retinoids; Tretinoin; Tumor Cells, Cultured
PubMed: 8400247
DOI: No ID Found