Clinical Significance of Bone Marrow Fibrosis in Patients with Polycythemia Vera

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5149-5149
Author(s):  
Aziz Nazha ◽  
Jorge E. Cortes ◽  
Zeev Estrov ◽  
Sherry Pierce ◽  
Hagop M. Kantarjian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Polycythemia Vera ◽  
Clinical Manifestation ◽  
World Health ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Md Anderson ◽  
The Impact ◽  
Marrow Fibrosis

Abstract Abstract 5149 Background: Polycythemia vera (PV) is a heterogeneous myeloproliferative disease characterized by expansion of morphologically normal red blood cells, granulocytes, and platelets with varying degrees of bone marrow fibrosis (BMF) during the disease course. BMF as a result of abnormal deposition of reticulin and collagen fibers in bone marrow stroma plays a role in the pathophysiology and clinical manifestation of myeloproliferative disorders in general. However, in PV, older age and previous history of thrombosis remain the only two major risk factors for consideration in decisions regarding therapy. Objectives: To investigate the characteristics associated with BMF and its prognostic impact on clinical manifestation, overall survival (OS), and transformation to primary myelofibrosis and acute leukemia in patients with PV. Methods: We conducted a retrospective chart review analysis of 115 patients who were diagnosed with PV according to World Health Organization criteria and were referred to MD Anderson Cancer Center between May 2000 and December 2009. Results of the first bone marrow biopsy done at MD Anderson were reviewed. BMF was documented according to the European consensus grading system (MF0-3), in which MF-3 is the most severe grade of fibrosis. Results: Of the 115 patients, 23 (20%) had MF-0, 46 (40%) MF-1, 36 (31%) MF-2, and 10 (9%) MF-3. Table 1 summarizes patient characteristics and outcomes by grade. Conclusion: Severe BMF was associated with higher risk of bleeding and thrombosis and larger spleen in patients with PV. There was no association between BMF severity and the demographic or symptoms of the disease. There was no association between BMF severity and the presence of JAK2 mutation or cytogenetic abnormalities. There was no impact of BMF on OS, EFS, or transformation to myelofibrosis or acute leukemia. However, longer follow-up is needed to investigate further the impact of BMF on OS and transformation-free survival. Disclosures: No relevant conflicts of interest to declare.

Prognostic Implications and Clinical Characteristics Associated with Bone Marrow Fibrosis in Patients with Myelofibrosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2824-2824
Author(s):  
Aziz Nazha ◽  
Zeev Estrov ◽  
Jorge E. Cortes ◽  
Sherry Pierce ◽  
Hagop M. Kantarjian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
World Health ◽  
Cancer Center ◽  
Bone Marrow Fibrosis ◽  
Jak2 Mutation ◽  
Hematopoietic Stem ◽  
Md Anderson ◽  
The Impact ◽  
Marrow Fibrosis

Abstract Abstract 2824 Background: Myelofibrosis (MF) is a heterogeneous, hematopoietic stem cell malignancy characterized by abnormal proliferation of myeloid cells with varying maturity and function. Bone marrow fibrosis (BMF), which results from abnormal deposition of stromal reticulin and collagen fibers, plays a major role in the pathophysiology of MF. Objectives: To investigate the characteristics associated with the extent of BMF and its implications on the clinical manifestation, overall survival (OS), event-free survival (EFS), and transformation to acute leukemia in patients with primary or secondary myelofibrosis. Methods: We conducted a retrospective chart review analysis of 514 patients who were diagnosed with myelofibrosis according to World Health Organization criteria (353 patients with primary myelofibrosis, 82 with post polycythemia vera [Post-PV] MF, and 79 with post essential thrombocythemia [Post-ET] MF) and were referred to MD Anderson Cancer Center between February 2005 and December 2009. Results of the first bone marrow biopsy done at MD Anderson were reviewed. BMF was documented according to the European consensus grading system (MF 0–3), in which MF-3 is the most severe grade of fibrosis. Result: Of 514 patients, 7 (1%) had MF-0, 44 (9%) had MF-1, 171 (33%) had MF-2, and 292 (57%) had MF-3. Table 1 summarizes patient characteristics and outcomes by grade. Conclusion: Severe bone marrow fibrosis was associated with lower Hgb, lower WBC count, larger spleen and abnormal cytogenetics. There was no association between JAK2 mutation and the severity of BMF. The OS, EFS and transformation to leukemia were similar among patients with various degrees of fibrosis. Similar results were achieved in patients with primary, post-PV MF, and post-ET MF. This might explain the heterogeneity of the disease course and its prognosis. Longer follow-up is needed to further investigate the impact of BMF on OS, EFS and PFS. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Bone Marrow Fibrosis in Polycythemia Vera: Validation of the IWG-MRT Study and Additional Observations

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3129-3129
Author(s):  
Daniela Barraco ◽  
Sonia Cerquozzi ◽  
Curtis A. Hanson ◽  
Rhett P. Ketterling ◽  
Animesh Pardanani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Polycythemia Vera ◽  
Univariate Analysis ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Abnormal Karyotype ◽  
Free Survival ◽  
Who Criteria ◽  
Marrow Fibrosis

Abstract Background Increased bone marrow (BM) reticulin fibrosis in polycythemia vera (PV) has been reported in 20% (Ann Hematol. 1999;78:495) to 51% (Eur J Haematol. 2011;86:148) of patients at diagnosis. In a previous report by the international working group for myeloproliferative neoplasms (MPN) research and treatment (IWG-MRT), the presence of BM fibrosis (≥ grade 1) at diagnosis was associated with a lower incidence of thrombosis during the clinical course and a higher risk of fibrotic progression while it did not affect overall (OS) or leukemia-free (LFS) survival (Blood. 2012;119:2239). The objectives for the current single center study of 262 PV patients were to validate the observations from the IWG-MRT and also identify other risk factors for myelofibrosis-free survival (MFFS) in PV. Methods Study patients were selected from our institutional database of MPN and fulfilled the 2016 World Health Organization (WHO) criteria for the diagnosis of PV (Blood. 2016;127:2391). Cytogenetic analysis and reporting was done according to the International System for Human Cytogenetic Nomenclature (Cytogenetic and Genome Research 2013;141:1-6). The degree of BM reticulin fibrosis was based on "real life" BM reports from Mayo Clinic hematopathologists and often in accordance with the European consensus scoring system (Haematologica 2005;90:1128). Statistical analyses considered clinical and laboratory parameters obtained at time of diagnosis. Results Patient characteristics: Analysis was conducted on 262 patients (median age 62 years; 50% males) who met 2016 WHO criteria for diagnosis of PV. Median (range) values were: hemoglobin 18 g/dl (14.8-24), leukocyte count 11.7 x109/L (4.3-59.3) and platelet count 454 x109/L (44-2747). Among informative cases, palpable splenomegaly was present in 27%, pruritus in 33% and erythromelalgia in 6%. Thrombosis history at diagnosis was documented in 28% of the patients and 23% experienced thrombotic events after diagnosis. Information on cytogenetics was available in 142 patients and karyotype was abnormal in 19%. BM reticulin fibrosis was reported to be absent in 135 patients (MF-0, 52%), grade 1 (MF-1) in 101 (39%), grade 2 (MF-2) in 22 (8%) and grade 3 (MF-3) in 4 (2%) patients. After a median follow up of 85 months, 107(41%) deaths, 30 (11%) fibrotic progression and 5 (2%) leukemic transformations were documented. Comparison of patients with and without bone marrow fibrosis A number of clinical and laboratory parameters were evaluated for possible association with the presence of ≥ grade 1 BM reticulin fibrosis and none, including age, sex, complete blood count, palpable splenomegaly, pruritus or erythromelalgia displayed a significant association. In univariate analysis, the presence of BM fibrosis (MF-0 versus MF-1 or greater) did not affect OS (p=0.5), LFS (p=0.2) or thrombosis-free survival (p=0.97) whereas a significant association was noted for MFFS (p=0.009; HR 2.9, 95% CI 1.3-6.7). Others risk factors for MFFS, in a univariate analysis, were leukocytosis ≥15 x 109/L (p=0.02; HR 2.7, 95% CI 1.17-6.48), presence of splenomegaly (p=0.02; HR 2.6, 95% CI 1.16-6) and abnormal karyotype (p=0.0005; HR 4.6, 95% CI 1.9-11). During multivariable analysis, not including karyotype, leukocytosis ≥15 x 109/L (p=0.04), presence of splenomegaly (p=0.04) and presence of BM reticulin fibrosis (p=0.01) remained significant; however, this significance for leukocytosis ≥15 x 109/L, presence of splenomegaly and BM reticulin fibrosis was lost when abnormal karyotype was added as covariate to each risk factor individually (p=0.4, p=0.1 and p=0.9, respectively). Conclusion We report a not infrequent (48% incidence) occurrence of ≥ grade 1 BM reticulin fibrosis at time of initial diagnosis of PV. In the current study, we did not find a prognostic impact for the presence of BM reticulin fibrosis, in terms of OS, LFS or thrombosis-free survival; however, a significant association was confirmed for MFFS that was independent of other non-genetic risk factors. The preliminary observation on the adverse prognostic impact of abnormal karyotype on MFFS requires additional studies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic impact of bone marrow fibrosis in polycythemia vera: validation of the IWG-MRT study and additional observations

2017 ◽  
Vol 7 (3) ◽  
pp. e538-e538 ◽  
Author(s):  
D Barraco ◽  
S Cerquozzi ◽  
C A Hanson ◽  
R P Ketterling ◽  
A Pardanani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Marrow Fibrosis

Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia

2016 ◽  
Vol 69 (9) ◽  
pp. 810-816 ◽  
Author(s):  
Eda Tanrikulu Simsek ◽  
Ahmet Emre Eskazan ◽  
Mahir Cengiz ◽  
Muhlis Cem Ar ◽  
Seda Ekizoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Imatinib Therapy ◽  
Imatinib Treatment ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Significant Difference ◽  
Grade Ii ◽  
Marrow Fibrosis

AimsBefore the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy.MethodsThe study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated.ResultsSevere MF (grade II–III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0–I) and severe (grade II–III) groups (p=0.278).ConclusionsAccording to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.

scholarly journals Impact of bone marrow fibrosis grade in post‐polycythemia vera and post‐essential thrombocythemia myelofibrosis: A study of the MYSEC group

2019 ◽  
Vol 95 (1) ◽  
Author(s):  
Barbara Mora ◽  
Paola Guglielmelli ◽  
Elisa Rumi ◽  
Margherita Maffioli ◽  
Daniela Barraco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Bone Marrow Fibrosis ◽  
Marrow Fibrosis

P112 Prognostic impact of bone marrow fibrosis in myelodysplastic syndromes (MDS)

2007 ◽  
Vol 31 ◽  
pp. S100
Author(s):  
S. Baghikar ◽  
S. Braunstein ◽  
P. Reinecke ◽  
S. Knipp ◽  
R. Haas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Marrow Fibrosis

scholarly journals Genetic and Clinical Features of Chronic Myelmonocytic Leukemia with Fibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5442-5442
Author(s):  
Mohammad O Hussaini ◽  
Jinming Song ◽  
Andrew T Kuykendall ◽  
David A Sallman ◽  
Eric Padron ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Risk Stratification ◽  
Gene Panel ◽  
World Health ◽  
Pathology Report ◽  
Monocyte Count ◽  
Bone Marrow Fibrosis ◽  
Worse Prognosis ◽  
Marrow Fibrosis ◽  
Severe Fibrosis

Introduction Chronic myelomonocytic leukemia (CMML) is an overlap syndrome with both myeloproliferative and myelodysplastic features. Clinical outcomes can be variable and risk stratification models such as GFM and Molecular Mayo Model (MMM) are useful. These models integrate age, WBC, anemia, thrombocytopenia, mutation status, monocyte count, and blast/promonocyte count, to segregate patients1. The presence of fibrosis in MDS (MF 2-3) is often associated with high grade disease, poor cytogenetics, and worse prognosis 2. The role of moderate to severe fibrosis in CMML (CMML-F) is not well studied. We investigated mutational landscape of CMML-F and whether CMML-F is associated with more aggressive disease thus warranting incorporation into risk models. Methods Total Cancer Care (TCC) and PathNet databases at Moffitt Cancer Center were queried for patients diagnosed with CMML between 2014 and 2017 with available Next Generation Sequencing (NGS) profiling (Genoptix 5-gene panel, Genoptix 21-gene panel, FoundationOne, Custom TrueSeq Myeloid). The cases were individually reviewed by a board-certified hematopathologist to confirm the diagnosis. The degree of reticulin fibrosis was manually collated from the pathology report and graded according to the World Health Organization (WHO) grading of bone marrow fibrosis (grade 0-3). Grade 1-2 or 2-3 fibrosis in the report were designated 1.5 and 2.5, respectively. CMML-F was defined as grade 2.5 or higher or collagen fibrosis. t-test and two tailed Fisher exact tests were performed for statistical analysis. Results Of 108 CMML patients (median age of 69.7 years), bone marrow fibrosis data was available for 91 individuals. The degree of fibrosis was as follows: Grade 0= 33, Grade 1= 34, Grade 1.5= 2, Grade 2= 15, Grade 2.5= 2, Grade 3=5 (of which 2 had collagen fibrosis). The CMML patients without fibrosis (MF<2.5) showed a longer median overall survival when compared to CMML-F (24.79 months versus 20.43 months; p=0.67), but it was not statistically significant. One of the 8 CMML-F patients had AML transformation (12.5%), similar to the 9 out of 82 CMML patients without fibrosis (11%). One of 2 patients (50%) with collagen fibrosis showed leukemic transformation, higher than the transformation rate in non-collagen fibrosis patients (11%; p=0.21). The most common mutations in CMML-F were: ASXL1 (25%), SRSF2 (25%), JAK2 (16.7%), and TET2 (16.7%). The most common mutations in non-CMML-F were: TET2 (60%), ASXL1 (45%), SRSF2 (38%), and RUNX1 (19%). Of note, TET2 mutations was less likely to occur in CMML-F (p=0.008). The average marrow blast percentage in CMML-F was 4.2% while in non-CMML-f was 8.6% (p=0.25). Conclusions: In this study we demonstrate that CMML-F is less likely to harbor TET2 mutations than CMML without fibrosis. However, unlike MDS, the presence of moderate-to-severe fibrosis does not correlate with worse prognosis in CMML. Large cohorts warranted to identify novel prognostic markers that could be incorporated into risk stratification schemas. Disclosures Kuykendall: Incyte: Honoraria, Speakers Bureau; Janssen: Consultancy; Abbvie: Honoraria; Celgene: Honoraria. Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Komrokji:JAZZ: Consultancy; Agios: Consultancy; Incyte: Consultancy; DSI: Consultancy; pfizer: Consultancy; celgene: Consultancy; Novartis: Speakers Bureau; JAZZ: Speakers Bureau.

The prognostic impact of bone marrow fibrosis in primary myelofibrosis

2016 ◽  
Vol 91 (10) ◽  
pp. E454-E455 ◽  
Author(s):  
Paola Guglielmelli ◽  
Alessandro M. Vannucchi ◽  
Keyword(s):  
Bone Marrow ◽  
Primary Myelofibrosis ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Marrow Fibrosis

Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome

Blood ◽  
2012 ◽  
Vol 119 (10) ◽  
pp. 2239-2241 ◽  
Author(s):  
Tiziano Barbui ◽  
Jürgen Thiele ◽  
Francesco Passamonti ◽  
Elisa Rumi ◽  
Emanuela Boveri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Clinical Course ◽  
Initial Diagnosis ◽  
World Health ◽  
Bone Marrow Fibrosis ◽  
Free Survival ◽  
Prognostic Relevance ◽  
Significant Difference ◽  
Health Organization

Abstract We examined the prevalence and prognostic relevance of bone marrow reticulin fibrosis in 526 patients with World Health Organization–defined polycythemia vera evaluated at the time of initial diagnosis. Seventy-four patients (14%) displayed mostly grade 1 reticulin fibrosis, with only 2 cases showing higher-grade fibrosis. Presenting clinical and laboratory characteristics, including JAK2V617F allele burden, between patients with and without fibrosis were similar for the most part, with the exception of a higher prevalence of palpable splenomegaly in patients with fibrosis (P < .01). Patients with fibrosis were less prone to experience thrombosis during their clinical course (1.1 vs 2.7 per 100 patient-years; P = .03) and more prone to develop post-polycythemia vera myelofibrosis (2.2 vs 0.8 per 100 patient-years; P = .01). There was no significant difference between the 2 groups in terms of overall or leukemia-free survival. The present study clarifies the incidence, degree, and prognostic relevance of bone marrow fibrosis obtained at time of initial diagnosis of polycythemia vera.

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