Chronic myelomonocytic leukemia: molecularly contaminated, but not defined

Patnaik, Mrinal M.; Tefferi, Ayalew

doi:10.3109/10428194.2016.1169411

Cited by 3 publications

(3 citation statements)

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“…The prevalence rates of autoimmune diseases in patients with myeloid neoplasms ranges from 10%−30% [17–22], with a higher prevalence in patients with CMML (~20–30%). [23–26] In a large study of 377 CMML patients, autoimmune diseases were documented in 77 (20%), with 5 patients being diagnosed with ITP and one patient with AIHA. [25] In a large cohort of ITP patients (n=565), CMML related ITP was identified in 8 (1.4%) patients.…”

Section: Discussionmentioning

confidence: 99%

“…[7] While this finding is nonspecific, the sheer abundance of these monocyte derived cells raises questions about clonal infiltration and altered immune surveillance. [26] These foamy histiocytes were not detectable in the BM specimens of affected patients and while they remain an attractive predictive marker for possible platelet response after splenectomy, these findings needed to be validated in a larger study. The impact of gene mutations, especially RUNX1 on platelet responses have been previously described, however, due to small numbers we were not able to assess these correlations.…”

Section: Discussionmentioning

confidence: 99%

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Splenectomy in patients with chronic myelomonocytic leukemia: Indications, histopathological findings and clinical outcomes in a single institutional series of thirty‐nine patients

et al. 2018

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In a 28-year period, 39 (7%) patients with chronic myelomonocytic leukemia (CMML) (median age 66 years, 64% male) underwent a splenectomy at our institution. Primary indications for splenectomy were refractory thrombocytopenia (36%), progressive spleen related symptoms (33%), emergent splenectomy for splenic rupture (21%), refractory anemia (8%), and prior to allogeneic stem cell transplant (3%). Eleven (28%) patients had anemia at the time of splenectomy, of which 3 (27%) were autoimmune. The median time to splenectomy from CMML diagnosis was 6 months (0-40); perioperative morbidity and mortality rates were 43% and 13%, while the median postsplenectomy survival was 25 months (11-38). Durable remission in spleen related symptoms, thrombocytopenia, complications from splenic rupture, and anemia were achieved in 85%, 50%, 62%, and 21% of patients, respectively. Perioperative morbidity (n = 30) included infections/sepsis in 6 (20%), intraabdominal bleeding in 4 (13%), venous thromboembolism (VTE) in 3 (10%), and acute lung injury in 2 (7%) patients. The median duration of hospital stay was 6 days (1-25), with 5 deaths occurring secondary to respiratory failure (n = 2), multiorgan dysfunction (n = 2) and hemorrhagic shock (n = 1). There was no difference in overall survival between CMML patients that underwent splenectomy, in comparison to those that did not. Unlike in myelofibrosis, portal hypertension was not an indication for splenectomy and no patients developed post-splenectomy thrombocytosis. In conclusion, apart from being a lifesaving emergent modality in the event of splenic rupture, splenectomy has an important palliative role in patients with CMML, with significant and durable improvements in spleen related symptoms and refractory cytopenias.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Splenectomy in patients with chronic myelomonocytic leukemia: Indications, histopathological findings and clinical outcomes in a single institutional series of thirty‐nine patients

et al. 2018

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“…Cytogenetic abnormalities are seen in approximately one‐third cases (most commonly trisomy 8, followed by chromosome 7 deletion or rearrangements), while well‐established pathogenic gene variants are seen in >90% cases . In spite of the high frequency of gene mutations, there are no mutations specific to this disease . However, compared to cancers with high mutational burden such as melanoma with >1000 mutations per megabase of coding DNA (Mb), CMML is genetically more homogenous, with between 10‐15 somatic mutations in coding sequences per exome .…”

Section: Introductionmentioning

confidence: 99%

Advances in chronic myelomonocytic leukemia and future prospects: Lessons learned from precision genomics

Mangaonkar

Patnaik

2019

Adv Cell Gene Ther

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In the latest World Health Organization classification of myeloid neoplasms, chronic myelomonocytic leukemia (CMML) exists as a separate entity under the category of myelodysplastic/myeloproliferative (MDS/MPN) overlap syndromes. Outcomes remain uniformly poor with a median overall survival of ~2 years and an inherent risk of transformation into acute myeloid leukemia (15%‐20% over 5 years). Due to unique biologic characteristics such as overlapping features of myelodysplasia and myeloproliferation, and clinical diversity despite relative genomic homogeneity, CMML represents a unique model to study chronic myeloid tumor biology. Recent advances have focused on understanding the role of putative genomic abnormalities, in particular, clonal evolution of pathogenic alterations in genes regulating the epigenome (TET2), chromatin architecture (ASXL1), spliceosome complex (SRSF2, SF3B1), and cell signaling (NRAS, KRAS, CBL, JAK2). Disease prognostication has evolved from purely clinical prognostic models to those incorporating pathogenic gene variants. Therapeutic options in this disease remain dismal with only two agents approved by the United States Food and Drug Administration, namely 5‐azacitidine and decitabine. Allogeneic hematopoietic stem cell transplantation remains the sole curative option in this disease; however, is associated with substantial treatment‐related morbidity and mortality. Future areas of research include opportunities to further improve disease prognostication by employing novel technologies such as machine learning, incorporation of methylation and cytokine signatures, in addition to gene mutations; insights into clonal origins of this disease, and novel therapeutic strategies.

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Spectrum of autoimmune diseases and systemic inflammatory syndromes in patients with chronic myelomonocytic leukemia

Zahid

Barraco

Lasho

et al. 2016

Leukemia & Lymphoma

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Chronic myelomonocytic leukemia: molecularly contaminated, but not defined

Cited by 3 publications

References 12 publications

Splenectomy in patients with chronic myelomonocytic leukemia: Indications, histopathological findings and clinical outcomes in a single institutional series of thirty‐nine patients

Splenectomy in patients with chronic myelomonocytic leukemia: Indications, histopathological findings and clinical outcomes in a single institutional series of thirty‐nine patients

Advances in chronic myelomonocytic leukemia and future prospects: Lessons learned from precision genomics

Spectrum of autoimmune diseases and systemic inflammatory syndromes in patients with chronic myelomonocytic leukemia

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