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Seminars in Diagnostic Pathology May 2023Myelodysplastic/ Myeloproliferative neoplasms (MDS/MPN) demonstrate overlapping pathologic and molecular features of myelodysplastic (MDS) and myeloproliferative (MPN)... (Review)
Review
Myelodysplastic/ Myeloproliferative neoplasms (MDS/MPN) demonstrate overlapping pathologic and molecular features of myelodysplastic (MDS) and myeloproliferative (MPN) neoplasms. Diagnosis is difficult based on morphology alone, requiring exclusion of various non-neoplastic causes for CBC abnormalities and morphologic findings and other myeloid neoplasms. Identifying a clonal abnormality by cytogenetics or molecular studies has vastly improved our ability to diagnose MDS/MPN and has been incorporated in the different classification schemas. Currently two separate classification systems are in use- The 5 edition WHO and international consensus classification. The two competing classifications emphasize genetic work-up and are similar on many levels; however, they do introduce diagnostic dilemma when diagnosing certain entities such as chronic myelomonocytic leukemia in the presence of NPM1 mutations. The genetic profile overlaps among different subentities; however, the combination and the incidence of mutations; together with the clinical features and morphology helps in further subclassification. In this review, we discuss the advances in molecular characterization of MDS/MPN. We attempt to summarize the differences between the various classification schemes, and highlight the changes made in the diagnostic criteria.
Topics: Humans; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; Mutation; Genomics; Neoplasms
PubMed: 37105794
DOI: 10.1053/j.semdp.2023.04.005 -
Blood Cancer Journal Jul 2023Leukemic transformation in myeloproliferative neoplasms (MPN), also referred to as "blast-phase MPN", is the most feared disease complication, with incidence estimates... (Review)
Review
Leukemic transformation in myeloproliferative neoplasms (MPN), also referred to as "blast-phase MPN", is the most feared disease complication, with incidence estimates of 1-4% for essential thrombocythemia, 3-7% for polycythemia vera, and 9-13% for primary myelofibrosis. Diagnosis of MPN-BP requires the presence of ≥20% circulating or bone marrow blasts; a lower level of excess blasts (10-19%) constitutes "accelerated phase" disease (MPN-AP). Neither "intensive" nor "less intensive" chemotherapy, by itself, secures long-term survival in MPN-BP. Large-scale retrospective series have consistently shown a dismal prognosis in MPN-BP, with 1- and 3-year survival estimates of <20% and <5%, respectively. Allogeneic hematopoietic stem cell transplant (AHSCT) offers the possibility of a >30% 3-year survival rate and should be pursued, ideally, while the patient is still in chronic phase disease. The value of pre-transplant bridging chemotherapy is uncertain in MPN-AP while it is advised in MPN-BP; in this regard, we currently favor combination chemotherapy with venetoclax (Ven) and hypomethylating agent (HMA); response is more likely in the absence of complex/monosomal karyotype and presence of TET2 mutation. Furthermore, in the presence of an IDH mutation, the use of IDH inhibitors, either alone or in combination with Ven-HMA, can be considered. Pre-transplant clearance of excess blasts is desired but not mandated; in this regard, additional salvage chemotherapy is more likely to compromise transplant eligibility rather than improve post-transplant survival. Controlled studies are needed to determine the optimal pre- and post-transplant measures that target transplant-associated morbidity and post-transplant relapse.
Topics: Humans; Blast Crisis; Retrospective Studies; Neoplasm Recurrence, Local; Myeloproliferative Disorders; Polycythemia Vera; Mutation; Chronic Disease
PubMed: 37460550
DOI: 10.1038/s41408-023-00878-8 -
Virchows Archiv : An International... Jan 2023The myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) category includes a heterogeneous group of diseases characterized by the co-occurrence of clinical... (Review)
Review
The myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) category includes a heterogeneous group of diseases characterized by the co-occurrence of clinical and pathologic features of both myelodysplastic and myeloproliferative neoplasms. The recently published International Consensus Classification of myeloid neoplasms revised the entities included in the MDS/MPN category as well as criteria for their diagnosis. In addition to the presence of one or more increased peripheral blood cell counts as evidence of myeloproliferative features, concomitant cytopenia as evidence of ineffective hematopoiesis is now an explicit requirement to diagnose the diseases included in this category. The increasing availability of modern gene sequencing has allowed better understanding of the biologic characteristics of these myeloid neoplasms. The presence of specific mutations in the appropriate clinicopathologic context is now included in the diagnostic criteria for some of MDS/MPN entities. In this review, we highlight what has changed in the diagnostic criteria of MDS/MPN from the WHO 2016 classification while providing practical guidance in diagnosing these diseases.
Topics: Humans; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; Mutation
PubMed: 36469102
DOI: 10.1007/s00428-022-03465-7 -
Acta Haematologica 2021Myeloproliferative neoplasms (MPNs) can transform into blast phase MPN (leukemic transformation; MPN-BP), typically via accelerated phase MPN (MPN-AP), in ∼20-25% of... (Review)
Review
BACKGROUND
Myeloproliferative neoplasms (MPNs) can transform into blast phase MPN (leukemic transformation; MPN-BP), typically via accelerated phase MPN (MPN-AP), in ∼20-25% of the cases. MPN-AP and MPN-BP are characterized by 10-19% and ≥20% blasts, respectively. MPN-AP/BP portend a dismal prognosis with no established conventional treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole modality associated with long-term survival.
SUMMARY
MPN-AP/BP has a markedly different mutational profile from de novo acute myeloid leukemia (AML). In MPN-AP/BP, TP53 and IDH1/2 are more frequent, whereas FLT3 and DNMT3A are rare. Higher incidence of leukemic transformation has been associated with the most aggressive MPN subtype, myelofibrosis (MF); other risk factors for leukemic transformation include rising blast counts above 3-5%, advanced age, severe anemia, thrombocytopenia, leukocytosis, increasing bone marrow fibrosis, type 1 CALR-unmutated status, lack of driver mutations (negative for JAK2, CALR, or MPL genes), adverse cytogenetics, and acquisition of ≥2 high-molecular risk mutations (ASXL1, EZH2, IDH1/2, SRSF2, and U2AF1Q157). The aforementioned factors have been incorporated in several novel prognostic scoring systems for MF. Currently, elderly/unfit patients with MPN-AP/BP are treated with hypomethylating agents with/without ruxolitinib; these regimens appear to confer comparable benefit to intensive chemotherapy but with lower toxicity. Retrospective studies in patients who acquired actionable mutations during MPN-AP/BP showed positive outcomes with targeted AML treatments, such as IDH1/2 inhibitors, and require further evaluation in clinical trials. Key Messages: Therapy for MPN-AP patients represents an unmet medical need. MF patients, in particular, should be appropriately stratified regarding their prognosis and the risk for transformation. Higher-risk patients should be monitored regularly and treated prior to progression to MPN-BP. MPN-AP patients may be treated with hypomethylating agents alone or in combination with ruxolitinib; also, patients can be provided with the option to enroll in rationally designed clinical trials exploring combination regimens, including novel targeted drugs, with an ultimate goal to transition to transplant.
Topics: Allografts; Blast Crisis; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Mutation; Myeloproliferative Disorders; Neoplasm Proteins
PubMed: 33882481
DOI: 10.1159/000512929 -
Hematology/oncology Clinics of North... Oct 2012Myeloproliferative neoplasm (MPN) animal models accurately re-capitulate human disease in mice and have been an important tool for the study of MPN biology and therapy.... (Review)
Review
Myeloproliferative neoplasm (MPN) animal models accurately re-capitulate human disease in mice and have been an important tool for the study of MPN biology and therapy. Transplantation of BCR-ABL transduced bone marrow into irradiated syngeneic mice established the field of MPN animal modeling. Genetically engineered MPN animal models have enabled detailed characterization of the effects of specific MPN-associated genetic abnormalities on hematopoietic stem and progenitor cells (HSPCs). Xenograft models have allowed the study of primary human MPN-propagating cells in vivo. JAK2V617F, the most common molecular abnormality in BCR-ABL negative MPN, has been extensively studied using retroviral, transgenic, knock-in and xenograft models.
Topics: Animals; Disease Models, Animal; Humans; Mice; Myeloproliferative Disorders
PubMed: 23009938
DOI: 10.1016/j.hoc.2012.07.007 -
Journal of Clinical Oncology : Official... Nov 2012Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of...
Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs.
PURPOSE
Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy.
PATIENTS AND METHODS
The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers.
RESULTS
MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P<.001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis, respectively. The MPN-SAF TSS strongly correlated with overall quality of life (QOL; r=0.59; P<.001) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) functional scales (all P<.001 and absolute r≥0.50 except social functioning r=0.48). No significant trends were present when comparing therapy subgroups. The MPN-SAF TSS had excellent internal consistency (Cronbach's α=.83). Factor analysis identified a single underlying construct, indicating that the MPN-SAF TSS is an appropriate, unified scoring method.
CONCLUSION
The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptom study to date. This new prospective scoring method may be used to assess MPN symptom burden in both clinical practice and trial settings.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Myeloproliferative Disorders; Prospective Studies; Quality of Life; Severity of Illness Index; Sickness Impact Profile; Surveys and Questionnaires; Young Adult
PubMed: 23071245
DOI: 10.1200/JCO.2012.42.3863 -
American Journal of Hematology Apr 2023
Topics: Humans; Blast Crisis; Myeloproliferative Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 36655312
DOI: 10.1002/ajh.26849 -
Leukemia Research Apr 2022Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare hematologic malignancy belonging to the category... (Review)
Review
Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare hematologic malignancy belonging to the category of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes. While certain clinical features, including anemia and thrombocytosis, are common to both the MDS and MPN disease components, the biologic consequences of the spliceosome mutation SF3B1 results in notable clinical exceptions. Importantly, both overall and leukemia free survival are shorter for MDS/MPN-RS-T when compared to essential thrombocythemia (ET). In the case of MDS/MPN-RS-T, thrombotic risk is not associated with the presence of JAK2V617F, nor history of prior thrombosis, but is associated with the presence of the mutated spliceosome gene SF3B1. In this review, we highlight the biology, pathology, risk stratification, and treatment approach to MDS/MPN-RS-T. In particular, we focus on clinical management concepts, which are largely borrowed from MDS and MPN, including the use of cytoreduction, bone marrow stimulating agents, and the role of allogeneic stem cell transplantation. We end by highlighting unmet needs and future research priorities in MDS/MPN-RS-T.
Topics: Anemia, Sideroblastic; Hematologic Neoplasms; Humans; Mutation; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; RNA Splicing Factors; Syndrome; Thrombocytosis
PubMed: 35279478
DOI: 10.1016/j.leukres.2022.106820 -
British Journal of Haematology May 2022Myeloproliferative neoplasm (MPN)-unclassifiable (MPN-U) or not otherwise specified represents a rare, poorly defined and heterogeneous group of MPNs. Disease incidence... (Review)
Review
Myeloproliferative neoplasm (MPN)-unclassifiable (MPN-U) or not otherwise specified represents a rare, poorly defined and heterogeneous group of MPNs. Disease incidence is difficult to define but likely represents close to 5% of all MPNs when strict World Health Organisation (WHO) criteria are applied. Dynamic review over time is required to assess if the disease can be re-classified into another MPN entity. A diagnosis of MPN-U leads to many challenges for both the patient and physician alike including lack of agreed monitoring and therapeutic guidelines, validated prognostic markers and licenced therapies coupled with exclusion from clinical trials. MPN-U has an inherent risk of an aggressive clinical course and transformation in some but who, and when to treat in the chronic phase, including identifying who may require more aggressive therapy at an earlier stage, remains elusive. Moreover, despite the significant thrombotic risk, there is no agreement on systematic primary thromboprophylaxis. We hereby provide a contemporary overview of MPN-U in addition to four illustrative cases providing our collective suggested approaches to clinical challenges.
Topics: Anticoagulants; Humans; Myeloproliferative Disorders; Neoplasms; Venous Thromboembolism
PubMed: 35191542
DOI: 10.1111/bjh.18087 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Oct 2022Classical myeloproliferative neoplasm (MPN) related thrombosis mainly affects elderly patients and often involves arterial circulation, while, MPN-visceral venous... (Review)
Review
Classical myeloproliferative neoplasm (MPN) related thrombosis mainly affects elderly patients and often involves arterial circulation, while, MPN-visceral venous thrombosis (SVT) mainly affects young women, and is closely associated with JAK2V617F mutation but not closely with CALR mutation. The pathogenesis of MPN-SVT is not only related to JAK2V617F mutation and vascular endothelial damage, but also needs further research to determine the machanism. JAK2V617F mutation is the most common in MPN-SVT clinically. Patients with non-cirrhotic SVT need to detect MPN mutation, while the detection of CALR or MPL mutation needs to be combined with clinical judgment. At present, the main treatment strategies of MPN-SVT are JAK inhibitors, supplementation of anticoagulants and treatment of portal hypertension. This article reviews the latest research progress on the epidemiology, pathogenesis, diagnosis and treatment strategies of MPN-SVT.
Topics: Aged; Anticoagulants; Female; Humans; Janus Kinase 2; Janus Kinase Inhibitors; Mutation; Myeloproliferative Disorders; Neoplasms; Thrombosis; Venous Thrombosis
PubMed: 36208278
DOI: 10.19746/j.cnki.issn.1009-2137.2022.05.052