Idiopathic Myelofibrosis in Children

Slone, Jeremy S.; Smith, Megan; Seegmiller, Adam C.; Sidonio, Robert F.; Yang, Elizabeth

doi:10.1097/mph.0b013e31829cdea0

Cited by 10 publications

(4 citation statements)

References 8 publications

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“…However, around one-fifth of the paediatric PMF regress completely on supportive therapy without the need for HSCT. Clinical, laboratory characteristics and supportive therapy details are not available therefore it is speculative whether these cases were transfusion-dependent or not 3 5. Also, HSCT was associated with high treatment-related mortality, with the largest paediatric series reporting 5/17 (30%) and 4/9 (45%) death in the HSCT group 3 4.…”

Section: Discussionmentioning

confidence: 99%

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Complete resolution of primary myelofibrosis in an infant with steroids and hydroxyurea

Khera,

Misra,

Singh

et al. 2023

BMJ Case Rep

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Paediatric primary myelofibrosis (PMF) is exceedingly rare and distinct compared with adult PMF. It is characterised by peripheral blood cytopenias, leucoerythroblastosis, reticulin fibrosis, extramedullary haematopoiesis and hepatosplenomegaly. In the absence of laid down diagnostic criteria, the diagnosis is largely of exclusion. Though early haematological stem cell transplant (HSCT) remains the treatment of choice, spontaneous remission or remission with steroids and/or cytoreductive agents is described in around 20% of cases of paediatric PMF. Moreover, HSCT in paediatric PMF is associated with high mortality (30%–45%). Therefore, it may be prudent to consider a trial of steroids and/or cytoreductive agents in all transfusion-dependent paediatric PMF while considering HSCT and ongoing bone marrow donor search. We describe one such infant with PMF who had complete remission of clinical and haematological parameters with a combination therapy of steroids and hydroxyurea.

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Section: Discussionmentioning

confidence: 99%

“…Unlike adults, the guidelines on risk-based management of paediatric PMF are not robust. Authors have recommended early haematological stem cell transplant (HSCT) based on prognostic criteria, although spontaneous remissions are described 1 4 5. HSCT in paediatric PMF is associated with high mortality rates 3 4.…”

Section: Introductionmentioning

confidence: 99%

Complete resolution of primary myelofibrosis in an infant with steroids and hydroxyurea

Khera,

Misra,

Singh

et al. 2023

BMJ Case Rep

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“…Occasional cases of spontaneous remissions, long-term stable disease and resolution after a course of steroids have been described [3, 15, 17, 39, 41, 54, 58, 63, 64, 69], suggesting that some of the cases diagnosed as PMF might in fact have been primary or secondary AIMF. While there are some recent case studies comparing PMF to AIMF and proving guidance differentiating the two conditions, this differential remains challenging in children[87].…”

Section: Primary Myelofibrosismentioning

confidence: 99%

Myeloproliferative neoplasms in children

Hofmann

2015

J Hematopathol

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Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders characterized by aberrant proliferation of one or more myeloid lineages often with increased immature cells in the peripheral blood. The three classical BCR-ABL-negative MPNs are: 1) polycythemia vera (PV), 2) essential thrombocythemia (ET), and 3) primary myelofibrosis (PMF), which are typically disorders of older adults and are exceedingly rare in children. The diagnostic criteria for MPNs remain largely defined by clinical, laboratory and histopathology assessments in adults, but they have been applied to the pediatric population. The discovery of the JAK2 V617F mutation, and more recently, MPL and CALR mutations, are major landmarks in the understanding of MPNs. Nevertheless, they rarely occur in children, posing a significant diagnostic challenge given the lack of an objective, clonal marker. Therefore, in pediatric patients, the diagnosis must rely heavily on clinical and laboratory factors, and exclusion of secondary disorders to make an accurate diagnosis of MPN. This review focuses on the clinical presentation, diagnostic work up, differential diagnosis, treatment and prognosis of the classical BCR-ABL-negative MPNs (PV, ET and PMF) in children and highlights key differences to the adult diseases. Particular attention will be given to pediatric PMF, as it is the only disorder of this group that is observed in infants and young children, and in many ways appears to be a unique entity compared to adult PMF.

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“…Although CALR , JAK2 , and MPL have been described as causative genes in adult PMF, the causes of childhood PMF remain elusive. Among the three pediatric PMF cases reported by Slone and colleagues, only one case possessed a JAK2 -V617F mutation and exhibited blindness, whereas the other two cases showed clinical courses that are rarely observed in adult PMF patients and thus remained agnogenic [16]. Therefore, the mechanisms underlying the pathogenesis of childhood PMF remain a mystery.…”

Section: Introductionmentioning

confidence: 98%

Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis

Ding

Zhang

Yang

et al. 2017

Genomics, Proteomics &Amp; Bioinformatics

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Primary myelofibrosis (PMF) is a chronic myeloproliferative disorder in human bone marrow. Over 50% of patients with myelofibrosis have mutations in JAK2, MPL, or CALR. However, these mutations are rarely detected in children, suggesting a difference in the pathogenesis of childhood PMF. In this study, we investigated the response to drug treatment of a monozygotic twin pair with typical childhood PMF. The twin exhibited different clinical outcomes despite following the same treatment regimen. The transcriptomic profiles of patient samples after drug treatment (E2 and Y2) were significantly different between the twin pair, which is consistent with the observation that the drug treatment was effective only in the younger brother, despite the twin being genetically identical. Bioinformatics analysis of the drug-responsive genes showed that the JAK-STAT pathway was activated in the cured younger brother, which is opposite to the pathway inhibition observed in adult PMF cases following treatment. Moreover, apoptosis and cell cycle processes were both significantly influenced by drug treatment in the sample of younger brother (Y2), implying their potential association with the pathogenesis of childhood PMF. Gene mutations in JAK2, MPL, or CALR were not observed; however, mutations in genes including SRSF2 and SF3B1 occurred in this twin pair with childhood PMF. Gene fusion events were extensively screened in the twin pair samples and the occurrence of IGLV2-14-IGLL5 gene fusion was confirmed. The current study reported at transcriptomic level the different responses of monozygotic twin brothers with childhood PMF to the same androgen/prednisone treatment regimen providing new insights into the potential pathogenesis of childhood PMF for further research and clinical applications.

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Idiopathic Myelofibrosis in Children

Cited by 10 publications

References 8 publications

Complete resolution of primary myelofibrosis in an infant with steroids and hydroxyurea

Complete resolution of primary myelofibrosis in an infant with steroids and hydroxyurea

Myeloproliferative neoplasms in children

Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis

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