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Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia.

ABSTRACT: The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76.8%), grade 1 in 16 patients (19.5%), and grade 0 in 3 patients (3.7%). Grade 2 fibrosis was associated with reduced hemoglobin levels (median 9.75 vs 11.0 g/dL in grade 0/1; p?=?0.04) and increased percentages of ringed sideroblasts (7.5 vs 0%; p?=?0.008). In multivariable analysis, grade 2 fibrosis was an independent predictor of poor overall survival (OS; 95% CI 1.32-6.35; HR 2.90; p?=?0.008), but not event-free survival (EFS; 95% CI 0.62-2.67; HR 1.28; p?=?0.50). Absolute neutrophil count (ANC) was found to impact OS (95% CI 1.01-1.09; HR 1.05; p?=?0.009), while both ANC (95% CI 1.00-1.07; HR 1.04; p?=?0.04) and peripheral blood blast percentage (95% CI 1.02-1.32; HR 1.16; p?=?0.02) impacted EFS. These results implicate fibrosis grade is an important indicator of prognosis, with high-grade fibrosis predicting inferior survival. Given the prevalence of marrow fibrosis in CMML, fibrosis grading should be incorporated into prognostic assessment and therapeutic decision-making.

SUBMITTER: Khan M

PROVIDER: S-EPMC6506234 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia.

Khan Maliha M Muzzafar Tariq T Kantarjian Hagop H Badar Ifra I Short Nicholas N Wang Xuemei X Chamoun Kamal K Jain Preetesh P DiNardo Courtney C Pemmaraju Naveen N Bose Prithviraj P Borthakur Gautam G Cortes Jorge J Verstovsek Srdan S Garcia-Manero Guillermo G Estrov Zeev Z

Annals of hematology 20180320 7

The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identif ...[more]

PMID: 29557496

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Project description:Prior studies have investigated patients' characteristics, treatments, and outcomes for older adults with myelodysplastic syndromes, but most failed to distinguish chronic myelomonocytic leukemia. Recognizing potentially important differences between the diseases, we undertook a population-based comparison of baseline characteristics, treatments, and outcomes between older adults with chronic myelomonocytic leukemia and myelodysplastic syndromes. The patients' data were obtained from Surveillance Epidemiology and End Results registry data from 2001-2005, linked to Medicare claims. Baseline characteristics, treatment (red blood cell transfusions, hematopoietic growth factors, hypomethylating agents, chemotherapy or transplantation), progression to acute myeloid leukemia, and overall survival were compared using bivariate techniques. Multivariate logistic regression estimated differences in treatments received. Cox proportional hazard models estimated the effects of chronic myelomonocytic leukemia relative to myelodysplastic syndromes on progression-free survival. A larger proportion of patients with chronic myelomonocytic leukemia (n=792), compared to patients with myelodysplastic syndromes (n=7,385), failed to receive any treatment (25% versus 15%; P<0.0001), or only received red blood cell transfusions (19.8% versus 16.7%; P=0.037). A larger percentage of patients with chronic myelomonocytic leukemia progressed to acute myeloid leukemia (42.6% versus 15.5%, respectively; P<0.0001), with shorter time to progression. Chronic myelomonocytic leukemia patients had a shorter median survival (13.3 versus 23.3 months; P<0.0001) and lower 3-year survival rate (19% versus 36%; P<0.0001). Adjusted estimates, controlling for baseline characteristics and selected treatments, indicate that chronic myelomonocytic leukemia was associated with an increased risk of progression to acute myeloid leukemia or death (HR 2.22; P<0.0001), compared to myelodysplastic syndromes. In conclusion, chronic myelomonocytic leukemia is less frequently treated in older adults and is associated with worse outcomes, even after controlling for the patients' baseline characteristics and selected treatments. Our data suggest the need for continued evaluation of the biological differences between these diseases and clinical trials targeting chronic myelomonocytic leukemia.

Dataset Information

Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia.

Publications

Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia.

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