Myeloproliferative neoplasms in children

Hofmann, Inga

doi:10.1007/s12308-015-0256-1

Cited by 45 publications

(56 citation statements)

References 86 publications

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“…The BCR‐ABL1 ‐negative classical MPNs appear to be extremely rare in children, with PV and ET estimated to occur in one to two cases per 10 000 000 children annually . Recent efforts, however, suggest that with increasing awareness, the precise incidence is higher .…”

Section: Introductionmentioning

confidence: 99%

Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

Mughal

Pemmaraju

Radich

et al. 2019

Hematological Oncology

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The 60th American Society of Hematology (ASH) held in San Diego in December 2018 was followed by the 13th Post‐ASH chronic myeloproliferative neoplasms (MPNs) workshop on December 4 and 5, 2018. This closed annual workshop, first introduced in 2006 by Goldman and Mughal, was organized in collaboration with Alpine Oncology Foundation and allowed experts in preclinical and clinical research in the chronic MPNs to discuss the current scenario, including relevant presentations at ASH, and address pivotal open questions that impact translational research and clinical management. This review is based on the presentations and deliberations at this workshop, and rather than provide a resume of the proceedings, we have selected some of the important translational science and treatment issues that require clarity. We discuss the experimental and observational evidence to support the intimate interaction between aging, inflammation, and clonal evolution of MPNs, the clinical impact of the unfolding mutational landscape on the emerging targets and treatment of MPNs, new methods to detect clonal heterogeneity, the challenges in managing childhood and adolescent MPN, and reflect on the treatment of systemic mastocytosis (SM) following the licensing of midostaurin.

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Section: Introductionmentioning

confidence: 99%

Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

Mughal

Pemmaraju

Radich

et al. 2019

Hematological Oncology

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“…Children with Down syndrome have a higher risk of developing acute megakaryoblastic leukemia with myelofibrosis (MF) while pediatric myelodysplastic syndromes (ped‐MDS) with MF (ped‐MDS‐MF) and primary myelofibrosis (ped‐PMF) are rare . In general, MF secondary to myeloid neoplasms is thought to be a surrogate of a more advanced disease stage.…”

Section: Introductionmentioning

confidence: 99%

“…MF is graded from 0 (no MF: scattered linear reticulin corresponding to normal bone marrow) to 3 (diffuse and dense increase of reticulin with extensive intersections with bundles of collagen and osteosclerosis) . In young patients, MF grade 3 is thought to be rare and usually MF grade 1 (loose network of reticulin) or grade 2 (dense network of reticulin with extensive intersections) are detectable . The molecular mechanisms which induce MF are unknown, but it is likely that neoplastic cells stimulate fibroblasts via cytokines .…”

Section: Introductionmentioning

confidence: 99%

Molecular profile of inflammatory and megakaryocytic factors in pediatric myelodysplastic syndrome with acute myelofibrosis

Hussein

Suttorp

Stucki-Koch

et al. 2018

Pediatric Blood & Cancer

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Pediatric fibrotic myelodysplastic syndromes (ped-MDS-MF) and pediatric primary myelofibrosis (ped-PMF) are rare, and the molecular changes which mediate fibrosis have never been investigated. Histology and gene expression profile of 119 fibrosis/angiogenesis/inflammation/megakaryopoiesis-related factors in bone marrow biopsies were performed (two ped-MDS-MF and one ped-PMF). In one progressive ped-MDS, comparison of MF grade 0 (no myelofibrosis) and MF grade 2 (dense network of reticulin fibres) after 4 months showed that expression of fibrosis-related transcripts increased and dysplastic megakaryocytes formed a dense net of CD42b proplatelets. These changes were not observed in another ped-MDS-MF, whereas ped-PMF showed a similar proplatelet pattern. These findings indicate that fibrotic changes in ped-MDS may involve proplatelet-related and unrelated pathways.

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“…For a more thorough overview, the reader is referred to several reviews published recently. [3][4][5][6][7] Low-grade MDS MDS with less than 2% blasts in peripheral blood (PB) or less than 5% blasts in the bone marrow (BM) are classified as refractory cytopenia of childhood (RCC) or low-grade MDS. 1,2 The majority of the children with RCC have a hypoplastic BM, which resembles aplastic anemia.…”

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confidence: 99%

Myelodysplastic and myeloproliferative disorders of childhood

Hasle

2016

Hematology

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Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions. RCC is often hypoplastic and may respond to immunosuppressive therapy. In case of immunosuppressive therapy failure, hypercellular RCC, or RCC with monosomy 7, hematopoietic stem cell transplantation (HSCT) using reduced-intensity conditioning regimens is indicated. Almost all patients with refractory anemia with excess blasts are candidates for HSCT; children age 12 years or older have a higher risk of treatmentrelated death, and the conditioning regimens should be adjusted accordingly. Unraveling the genetics of JMML has demonstrated that JMML in patients with germ line PTPN11 and CBL mutations often regresses spontaneously, and therapy is seldom indicated. Conversely, patients with JMML and neurofibromatosis type 1, somatic PTPN11, KRAS, and most of those with NRAS mutations have a rapidly progressive disease, and early HSCT is indicated. The risk of relapse after HSCT is high, and prophylaxis for graft-versus-host disease and monitoring should be adapted to this risk. Learning Objectives• To recognize the challenges in making a diagnosis of MDS in children • To know the different therapeutic strategies in low-grade and advanced MDS • To understand the genetics of JMML and how it may be used for treatment stratification Myelodysplastic and myeloproliferative disorders are rare in children and have different morphologic features, cytogenetic findings, prognostic factors, and therapeutic aims than in adults. Therefore, there is a need for a pediatric approach to the classification of these disorders 1 as integrated in the 2008 version of the World Health Organization classification 2 that recognizes the specific features of diseases in children vs those in adults (Table 1).The diseases are divided into low-grade myelodysplastic syndrome (MDS), advanced MDS, and juvenile myelomonocytic leukemia (JMML). The myeloid leukemia of Down syndrome represents a specific entity that should not be included in series of MDSs and will not be discussed in this review. There is an increasing recognition that more children have an underlying genetic predisposition for the development of MDS or JMML. For a more thorough overview, the reader is referred to several reviews published recently. 3-7Low-grade MDS MDS with less than 2% blasts in peripheral blood (PB) or less than 5% blasts in the bone marrow (BM) are classified as refractory cytopenia of childhood (RCC) or low-grade MDS.1,2 The majority of the children wit...

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Myeloproliferative neoplasms in children

Cited by 45 publications

References 86 publications

Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

Molecular profile of inflammatory and megakaryocytic factors in pediatric myelodysplastic syndrome with acute myelofibrosis

Myelodysplastic and myeloproliferative disorders of childhood

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