-
Ugeskrift For Laeger Jan 2018Acute promyelocytic leukaemia has changed from being a highly fatal to a highly curable disease. Over time, key discoveries have identified the genetic and molecular... (Review)
Review
Acute promyelocytic leukaemia has changed from being a highly fatal to a highly curable disease. Over time, key discoveries have identified the genetic and molecular abnormalities, which cause the disease. First choice of treatment has now changed from all-trans retinoic acid (ATRA) and chemotherapy to a chemo-free combination of arsenic trixoide and ATRA. This new regimen has shown equal responses and overall cure rates compared with the previous standard of care containing conventional chemotherapy, but with much lower toxicity. This will pave the way for better and easier treatment for elderly and frail patients.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Disseminated Intravascular Coagulation; History, 20th Century; Humans; In Situ Hybridization, Fluorescence; Leukemia, Promyelocytic, Acute; Tretinoin
PubMed: 29336301
DOI: No ID Found -
Haematologica Apr 2011
Topics: Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Humans; Leukemia, Promyelocytic, Acute; Neoplasms, Second Primary; Oxides; Radiotherapy, Computer-Assisted
PubMed: 21454880
DOI: 10.3324/haematol.2011.041970 -
Biomedical and Environmental Sciences :... Jun 2022Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.
OBJECTIVE
Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.
METHODS
Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b.
RESULTS
MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients.
CONCLUSION
This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.
Topics: Animals; Humans; Leukemia, Promyelocytic, Acute; Mice; MicroRNAs; Oncogene Proteins, Fusion
PubMed: 35882408
DOI: 10.3967/bes2022.067 -
Oncology (Williston Park, N.Y.) Jul 2012The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the... (Review)
Review
The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the most curable subtype of acute myeloid leukemia (AML). Patients who do not survive generally succumb within the first 30 days after presentation or diagnosis, often from intracranial or pulmonary hemorrhage caused by the characteristic coagulopathy associated with this disease. For the majority of patients who avoid hemorrhagic complications, the goals of decreasing the side effects of diagnosis and treatment-including pain, inpatient hospital days, and late sequelae of cytotoxic chemotherapy-have emerged as paramount. Here, we discuss novel and provocative observations regarding diagnostic and treatment strategies for APL that are likely to emerge as standards of care in the next 5 years, and that may improve the rate of early hemorrhagic death and decrease diagnosis- and treatment-related morbidity.
Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Arsenic Trioxide; Arsenicals; Biopsy, Fine-Needle; Bone Marrow; Clinical Trials as Topic; Dexamethasone; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Oxides; Practice Guidelines as Topic; Prognosis; Pulmonary Edema; Remission Induction; Respiratory Insufficiency; Tretinoin
PubMed: 22888564
DOI: No ID Found -
Scientific Reports Feb 2023While optical microscopy inspection of blood films and bone marrow aspirates by a hematologist is a crucial step in establishing diagnosis of acute leukemia, especially...
While optical microscopy inspection of blood films and bone marrow aspirates by a hematologist is a crucial step in establishing diagnosis of acute leukemia, especially in low-resource settings where other diagnostic modalities are not available, the task remains time-consuming and prone to human inconsistencies. This has an impact especially in cases of Acute Promyelocytic Leukemia (APL) that require urgent treatment. Integration of automated computational hematopathology into clinical workflows can improve the throughput of these services and reduce cognitive human error. However, a major bottleneck in deploying such systems is a lack of sufficient cell morphological object-labels annotations to train deep learning models. We overcome this by leveraging patient diagnostic labels to train weakly-supervised models that detect different types of acute leukemia. We introduce a deep learning approach, Multiple Instance Learning for Leukocyte Identification (MILLIE), able to perform automated reliable analysis of blood films with minimal supervision. Without being trained to classify individual cells, MILLIE differentiates between acute lymphoblastic and myeloblastic leukemia in blood films. More importantly, MILLIE detects APL in blood films (AUC 0.94 ± 0.04) and in bone marrow aspirates (AUC 0.99 ± 0.01). MILLIE is a viable solution to augment the throughput of clinical pathways that require assessment of blood film microscopy.
Topics: Humans; Leukemia, Promyelocytic, Acute; Bone Marrow; Deep Learning; Leukemia, Myeloid, Acute; Hematologic Tests
PubMed: 36781917
DOI: 10.1038/s41598-023-29160-4 -
PloS One 2019Acute Promyelocytic Leukemia (APL) is a rare and potentially lethal condition in which risk-based therapy often leads to better outcomes. Because of its rarity and... (Clinical Trial)
Clinical Trial
Acute Promyelocytic Leukemia (APL) is a rare and potentially lethal condition in which risk-based therapy often leads to better outcomes. Because of its rarity and relatively high overall survival rate, prospective randomized trials to investigate alternative APL treatment schedules are challenging. Mathematical models may provide useful information in this regard. We collected clinical data from 38 patients treated for APL under the International Consortium on Acute Leukemia (ICAL) protocol and laboratory data during induction therapy. We propose a mathematical model that represents the dynamics of leukocytes in peripheral blood and the effect of ICAL treatment on the disease's dynamics. We observe that our cohort presents demographic characteristics and clinical outcomes similar to previous clinical trials on APL. Over a follow-up period of 41.8 months, the relapse-free survival and overall survival at two years are both found to be 78.7%. For two selected patients, the model produces a good fit to the clinical data. Information such as the response to treatment and risk of relapse can be derived from the model, and this may assist in clinical practice and the design of clinical trials.
Topics: Adult; Disease-Free Survival; Follow-Up Studies; Humans; Leukemia, Promyelocytic, Acute; Leukocyte Count; Male; Middle Aged; Models, Biological; Survival Rate
PubMed: 31415632
DOI: 10.1371/journal.pone.0221011 -
Annals of Hematology Sep 2013Despite substantial progress in the management and outcome of acute promyelocytic leukemia (APL) during the last decades, older age remains a prominent negative... (Review)
Review
Despite substantial progress in the management and outcome of acute promyelocytic leukemia (APL) during the last decades, older age remains a prominent negative prognostic factor. The improvement of long-term stabilization and cure of older APL patients is therefore a particular challenge. Data of unselected population-based studies suggest a high rate of exclusion from clinical trials in older age. The comparison of registry and study data indicates that study patients represent a positive selection. Older APL patients seem as sensitive to therapy as younger patients. With conventional therapy, based on all-trans retinoic acid (ATRA) and chemotherapy, over 50 % of older APL patients can probably be cured. Special problems of advanced age are the high rate of early death before or during induction therapy and the high frequency of death in remission with negative influence on the outcome. Both may be related in part to a higher vulnerability against the common treatment with ATRA and chemotherapy. Alternative less toxic approaches including arsenic trioxide (ATO) with or without ATRA and combinations with gemtuzumab ozogamicin or with reduced chemotherapy can induce long-lasting remission in all stages of APL. Considering the high curative potential and the excellent tolerance of ATO in newly diagnosed and relapsed APL, older patients are probably a particular target group for a chemotherapy-free approach with ATO.
Topics: Aged; Aged, 80 and over; Arsenic Trioxide; Arsenicals; Clinical Trials as Topic; Disease Management; Humans; Leukemia, Promyelocytic, Acute; Oxides; Treatment Outcome; Tretinoin
PubMed: 23694997
DOI: 10.1007/s00277-013-1788-z -
Journal of Cancer Research and... 2023Acute promyelocytic leukemia (APL) comprises approximately 10% of acute myeloid leukemia (AML) cases.
BACKGROUND
Acute promyelocytic leukemia (APL) comprises approximately 10% of acute myeloid leukemia (AML) cases.
MATERIAL AND METHODS
Both options of treatment (ATRA-ATO and ATRA-chemotherapy) were discussed with patients with low- and intermediate-risk APL, pros and cons explained in details, and treatment regimen selected after getting informed written consent.
RESULTS
Total 71 patients were included in the study; among these patients, 3 were negative for both FISH for t (15,17) and RT-PCR for promyelocytic leukemia retinoic acid receptor alpha, and 36 patients with APL had white blood cell count at diagnosis >10 × 10/l. Total 30 patients with newly diagnosed as low- and intermediate-risk-APL fulfilled all inclusion criteria, treated and followed for a minimum period of 2 years up to June, 2016. Fifteen patients liked to be treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), while rest of the 15 patients preferred treatment with ATRA and chemotherapy.
CONCLUSION
Combination of ATRA and ATO is equally effective, less toxic, and more feasible in comparison to ATRA and chemotherapy for patients with low- and intermediate-risk APL and is a viable option for this subset of patients, especially in countries with limited resources.
Topics: Humans; Leukemia, Promyelocytic, Acute; Arsenicals; Oxides; Tertiary Care Centers; Arsenic Trioxide; Tretinoin; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37787311
DOI: 10.4103/jcrt.jcrt_436_21 -
Blood Mar 2013In this issue of Blood, Rego and colleagues describe the exciting accomplishments of the International Consortium on Acute Promyelocytic Leukemia (IC-APL), an initiative...
In this issue of Blood, Rego and colleagues describe the exciting accomplishments of the International Consortium on Acute Promyelocytic Leukemia (IC-APL), an initiative of the International Members Committee of the American Society of Hematology (ASH).(1) The purpose of this initiative is to create a network of institutions in developing countries that will work in partnership with cooperative groups in the United States and Europe in order to close the gap in quality of care and outcomes in acute promyelocytic leukemia (APL) between developed and developing countries.
Topics: Community Networks; Developing Countries; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Quality Improvement
PubMed: 23493766
DOI: 10.1182/blood-2012-12-470757 -
Blood May 2021The retinoic acid receptors (RARA, RARB, and RARG) are ligand-regulated nuclear receptors that act as transcriptional switches. These master genes drew significant... (Review)
Review
The retinoic acid receptors (RARA, RARB, and RARG) are ligand-regulated nuclear receptors that act as transcriptional switches. These master genes drew significant interest in the 1990s because of their key roles in embryogenesis and involvement in a rare malignancy, acute promyelocytic leukemia (APL), in which the RARA (and very rarely, RARG or RARB) genes are rearranged, underscoring the central role of deregulated retinoid signaling in leukemogenesis. Several recent provocative observations have revived interest in the roles of retinoids in non-APL acute myeloid leukemia (AML), as well as in normal hematopoietic differentiation. We review the role of retinoids in hematopoiesis, as well as in the treatment of non-APL AMLs. From this perspective, broader uses of retinoids in the management of hematopoietic tumors are discussed.
Topics: Animals; Hematopoiesis; Humans; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Receptors, Cytoplasmic and Nuclear; Retinoids
PubMed: 33651885
DOI: 10.1182/blood.2020010100