Impact Of Myelofibrosis (MF) In MDS Treated With Azacitidine (AZA). A Single Center Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1539-1539
Author(s):  
Clemence Legoupil ◽  
Marie Sebert ◽  
Thorsten Braun ◽  
Claude Gardin ◽  
Antoine Martin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Fish Analysis ◽  
Trisomy 8 ◽  
Bone Marrow Fibrosis ◽  
Monosomy 7 ◽  
Poor Prognostic Factor ◽  
Bone Marrow Trephine Biopsy ◽  
The Impact ◽  
Marrow Fibrosis

Abstract Background Bone marrow fibrosis is observed in 10-20% of MD, and is a poor prognostic factor, both in lower and higher risk MDS (Della Porta, JCO 2009). AZA, the current reference treatment for higher risk MDS, approved in EU for patients with up to 30% bone marrow blasts not candidates to intensive chemotherapy (IC) or allogeneic SCT, gives 50-60% responses and improves OS in higher-risk MDS but its role in MDS with myelofibrosis remains unknown. Methods Between 2004 and 2012, we treated at our center 172 consecutive MDS patients (pts) including FAB RAEB-T / WHO AML with 20-30% blasts, with AZA (75 mg/m2/d x7 d every 4 weeks, for a median of 6 cycles). We assessed in those patients the impact of myelofibrosis (MF), evaluated on bone marrow trephine biopsy and graded according to the European consensus on grading bone marrow fibrosis. Results Median age of the 172 pts was 73 years and 67% were males. According to WHO classification, 1 had del(5q) syndrome, 4 RARS/RCMD-RS, 24 RCMD, 37 RAEB-1, 54 RAEB-2, 29 AML (20-30% blasts), 17 CMML and 6 MDS unclassified. Median Hb level, WBC, platelet count and marrow blast count were 9.4 g/dl (range 3.5-15), 1.6 G/L (0-58), 75G/l (8-1080) and 12%(1-29), respectively. IPSS was low, Int-1, Int-2, High and a failure in 1(>1%), 29(17%), 65 (38%), 59 (34%) and 18 (11%) patients, respectively. Twenty-three pts (13%) had grade 2-3 myelofibrosis (MF). Patients with MF were younger (median 68 vs. 74 years, p= 0.04), but had similar hematological characteristics: hemoglobin (median 9 vs. 9.45g/dl, p= 0.69); WBC (2.2 vs. 1.6 G/l, p= 0.48) Platelet (47 vs 77 G/l,p= 0.43) and bone marrow blast (10 vs. 12%, p=0.67). IPSS was int 1, int 2, high and a failure in 4, 7, 6 and 6 patients respectively without difference compared to patients without fibrosis. Cytogenetics was complex in 8, del(20q) +/- 1 additional abn in 5 patients, normal in 4 patients, failed in 6 patients (but with trisomy 8 and monosomy 7, resp, detected in 2 patients by FISH analysis). Overall, 73 (42%) patients achieved a response according to IWG2006 criteria, including 31 (18%) CR. The response rate and CR rate were 52% and 17% respectively in pts with MF, compared to 44% and 20% in pts without MF (p= 0.507 and p=1.00, respectively). With a median follow-up of 6.5 yr, median OS was 12 months in pts with MF, compared to 16 months in pts without MF (p=0.45). Conclusion In this MDS series, presence of MF was not associated with specific features (but blasts were often counted on marrow aspirates, with a possible underestimate in case of MF). Response to AZA and survival after AZA onset did not significantly differ based on the presence of MF. 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.

Splenectomy In Patients with MDS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1879-1879
Author(s):  
Alina V Kokhno ◽  
Elena A Mikhailova ◽  
Elena N Parovichnikova ◽  
Karen I Ntanisian ◽  
Suren R Karagulyan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Treatment Algorithm ◽  
Cytotoxic Chemotherapy ◽  
Spleen Weight ◽  
Bone Marrow Blast ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Blast Count

Abstract Abstract 1879 Splenectomy in patients with MDS is a treatment option that is beeing applied very rare [Steensma D., et al, Leuk Res.,2003; Bourgeosis E., et al, Leukemia, 2001]. There are anecdotal reports with very few patients demonstrating its efficacy. In most cases splenectomy was indicated for MDS patients with immune related thrombocytopenia. Here we would like to report the results of 33 splenectomies in patients with MDS who have been treated in our Center during 1994–2010. Within this period of follow-up totally 155 patients were diagnosed with different forms of MDS, 35% of them presenting with hypoplasia. The MDS treatment algorithm in our Center incorporates splenectomy as one of the options for pts with hypoplastic forms of MDS with bone marrow blast count less than 10%, refractory to initial cyclosporin A treatment or refractory to transfusions. Among patients who were splenectomised there were 20 females, 13 males with a median age of 40 years (range 18–74). Median time from diagnosis to splenectomy was 12 months (range 4–107). By WHO-classification there were 2 patients with RA, 22 – with RCMD, 2 – with MDS and del (5q), 6 - with RAEB, 1 - with AML after MDS. Cytogenetic analysis was available in 32 cases, and karyotype was normal in 15 patients (47%).The most common abnormalities were: del (5q) - 3, del (20q) - 2, trisomy 8 - 2, tetrasomy 8 - 1, monosomy 7 - 2, complex karyotype - 4. Bone marrow biopsy revealed hypoplasia in 25 patients (75%), myelofibrosis – in 7 (21%). The median WBC count was 2,6*109/L (range 0,6-8,7), hemoglobin 6,9 g/dL (47-119) and platelets 26*109/L (6-170). 27 pts (82%) were RBC transfusion dependent, 22 (67%) - platelets transfusion dependent. 13 pts had received immunosuppression therapy (ATG, cyclosporine A) before splenectomy, 2 - cytotoxic chemotherapy, 3 - decitabine. The majority of splenectomies were done by laparoscopic method - 26 (79%), in one case the convertion was done. In all cases we performed liver biopsy. Postoperative complications (hemorrhage) occurred in 1 patient but there were no deaths due to operation. One death occurred in 7 days after splenectomy due to fulminant progression to AML. Median spleen weight was 180 gms (range 70–930). Median intraoperative blood loss was 250 ml (range 50–9350). Histology was available in 30 patients. Extramedullary hematopoesis was revealed in 3 cases (10%), blast infiltration - in 2 (7%), massive lymphoid infiltration was detected in 5 cases and in one patient in was proved to be clonal (marginal zone lymphoma, MZL). Hemosiderin depositions in the macrophages were seen in half of the cases -16 (53%). One case was characterized by granulomatosis in spleen and liver with negative immunohistohemical staining to Mycobacteria tuberculosis. Splenectomy lead to sustained improvement of cytopenias in 16 cases (48%): decreased transfusion dependence in 14 (42%) and transfusion independence in 2 (6%). After splenectomy 5 patients were followed by “wait and see” approach, 17 continued with immunosuppressive therapy (ATG,CyA), 3 patients were treated with cytotoxic chemotherapy, 1 – with decytabine, 2 received EPO, 1- danazol, 2 - iron chelation therapy, 2 – only transfusions therapy. We did not noticed the infections rate augmentation after splenectomy. Transformation to AML was registered 6 (18%) at median 6 months (0,3 -9). 13 splenectomized patients (39%) died at a median 12 months (range 0,3-84) and the main death reasons were: AML progression, aplasia deterioration followed by infections and hemorrhage. 20 patients are alive with a median follow-up after splenectomy 33 months (2-108). Analysis of our 15-years study data give us a confidence to conclude that splenectomy still may be an adequate option for distinct forms of MDS (hypoplastic forms with bone marrow blast count less than 10%, refractory to initial immunosupressive treatment or refractory to transfusions), producing cytopenia improvement in half of the patients with decreasing transfusion dependance also in half of the patients, sometimes bringing a clear diagnosis (MZL). The mechanism of action is not very clear but we can speculate that splenectomy removes the “cell-destroying” organ, deminishes immune pathways of cytopenias due to large lymphoid compartment deletion, provides the resustainment of sensitivity to immunosupressive agents. Disclosures: No relevant conflicts of interest to declare.

Do Leukemic Cells and Mesenchymal Stem Cells (MSCs) From AML Patients Share The Same Chromosomal Defect? A Cytogenetics, FISH and aCGH/Snpa Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2602-2602
Author(s):  
Paolo Bernasconi ◽  
Irene Dambruoso ◽  
Manuel Gotti ◽  
Marina Boni ◽  
Rita Zappatore ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Gradient Centrifugation ◽  
Leukemic Cells ◽  
Hematopoietic Tissue ◽  
Trisomy 8 ◽  
Commercial Fish ◽  
Monosomy 7 ◽  
Microarray Scanner

Abstract Recent evidence suggests that leukemia is not solely a cancer autonomous process, but rather a disease in which the bone marrow microenvironment, the niche, plays a crucial role too (Raaijmakers, 2011). MSCs are key component of the niche. Thus, several studies have tested whether these cells from haematological patients contain chromosomal defects identical or different from those present in leukemic cells. Based on these findings the principal aim of the present study was to evaluate whether leukemic and MSC from six AML patients shared the same cytogenetic defects after examination with three different technologies, conventional cytogenetics (CC), FISH and aCGH/SNPa. At the onset of the disease and after informed consent all the six patients were submitted to bone marrow (BM) aspiration. BM cells were submitted to CC and FISH analyses. In addition, MSC were isolated from BM cell suspension (10-15 ml) as previously described. Briefly, mononucleated cells were isolated from BM by density gradient centrifugation using Lympholyte®-H and seeded in 75 cm2 cell culture flasks at a cell density of 106 cells/cm2. Cells were cultured at 37°C, 5% CO2 in MEM-alpha medium containing 1% Penicillin/Streptomycin, 1% L-Glutamine and 10% fetal bovine serum. After 48-h adhesion, non-adherent cells were removed and culture medium replaced (Achille et al, 2011). Growth medium was changed every three days. MSCs were examined after the first passage and their phenotype was evaluated by flow cytometry. Cells were detached from culture using Tripsin-EDTA, washed twice with PBS and stained for ten minutes with the following fluorochrome-conjugated antibodies: anti-CD90-FITC, anti-CD105-PE, anti-CD14-FITC, anti-CD73-PE, anti-CD34-FITC, anti-CD80-PE, anti-CD133-APC, anti-CD31-PE and anti-CD45-APC-Alexa750. Stained cells were acquired with a Beckman Coulter Navios instrument and data analyzed with Kalooza software. The commercial FISH probes used were LSI D7S486/CEP7, LSI AMLETO from Abbot Molecular Inc. (Chicago, Il, USA) and ON c-Myc/SE8, SE10(D10Z1) from Kreatech (Amsterdam, NL). These probes were applied according to manufactures guidelines and cut-off values determined by applying a one-sided 95% confidence interval using a binomial distribution. aCGH/SNPa was carried out with the SureScan Microarray Scanner G4900DA (Agilent Technologies Inc. Santa Clara, CA). CC revealed a monosomy 7 in two patients, a del(7)(q31) in one, a trisomy 8 and a trisomy 10 in one patient each, a t(8;21)(q24,q22) translocation in the last patient. All these defects were confirmed by FISH. In order to establish whether leukemic cells and MSCs shared these same abnormalities, MSCs cultures were tested with FISH. MSC purity assessed by flow-cytometry was 50-87%. FISH revealed a normal pattern in all the cultures examined. In contrast, aCGH/SNPa revealed neither gains/losses nor LOH in four patients, a trisomy 5 in one and the LOH of a 3.8 Mb sized region located on 13q31.1 in one patient. This study, the first one that applied aCGH/SNPa to investigate the MSC chromosomal pattern, suggests that i) MSCs from chromosomally abnormal AML patients may show a normal FISH pattern, but may be either normal or contain chromosomal aberrations different from those present in leukemic cells on aCGH/SNPa analysis; ii) these defects are uncommonly seen in AML; iii) MSCs defects may flag that the leukemogenic event targets not only the hematopoietic tissue but also the stromal cell compartment, i.e. the niche; iii) aCGH/SNPa provides an in-depth view of MSC chromosomal pattern allowing the identification of potential clonal markers. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Splenectomy in a Child of X-Linked Thrombocytopenia with Thalassemia and Bone Marrow Fibrosis : Hemoglobin and Platelet Count Were Improved

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1367-1367
Author(s):  
Yang Wan ◽  
Xiaofan Zhu ◽  
Xiaojuan Chen ◽  
Wenbin An ◽  
Peihong Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Bone Marrow Biopsy ◽  
Peripheral Blood ◽  
Clinical Characteristics ◽  
Blood Count ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Bone Marrow Fibrosis ◽  
Marrow Fibrosis

Abstract X-linked thrombocytopenia with thalass emia (XLTT)(OMIM 314050)was first described by Thompson in 1977(Thompson et al. J Blood 1977 50(2):303-16). This rare inherent disorder was caused by a nucleotide change G>A at position 647, which leads to an amino acid substitution of arginine to glutamine (R216Q) in the gene of GATA-1 on the band p11-12 ohuman X chromosome(Raskind et al. Blood 2000, 95(7):2262-8 ;Yu et al.J Blood 2002,100(6): 2040-2045). GATA-1, belonging to the GATA family of transcription factors plays a crucial role in the development of several hematopoietic cell lines ( Ferreira et al. J Mol Cell Biol 2005,25(4): 1215-1227) . The missense mutation(R216Q) in XLTT affects GATA-1 binding to palindromic DNA sites (Yu et al.J Blood 2002,100(6): 2040-2045). The clinical characteristics of XLTT are mild thrombocytopenia, splenomegaly, reticulocytosis, hemolytic anemia and unbalanced hemoglobin (Hb) chain synthesis resembling ¦Â-thalassemia (Raskind et al. Blood 2000, 95(7):2262-8 ; Balduini et al. J Thromb Haemost 2004, Jan;91(1):129-40). About 7 families of XLTT were reported before (Millikan et al.J Semin Thromb Hemost 2011,37(6): 682-689; Danielsson et al. J Lakartidningen 2012 ,109(34-35): 1474-1477).Bone marrow fibrosis is described only in tow Swedish families ( Danielsson et al. J Lakartidningen 2012 ,109(34-35): 1474-1477).But there is limited data about the treament and prognosis of the diesase. Here we describe the full clinical characteristics of a boy of XLTT who was treated by splenectomy. The patient was first admitted at the age of 1year and 8 months in 2011.The chief complain was skin petechia and pale for more than one month. The boy had lower weight but no visible malformation. Feeding difficult and lag of language development were also complained.His Liver was 2.3cm below the right ribs and spleen was 3.2cm below the left. Peripheral blood count showed hemoglobin 8 g/dL, MCV76.7fl, MCH21.8 pg,MCHC284 g/L and reticulocyte count 0.1764¡Á1012/L. Peripheral blood smear demonstrated marked anisopoikilocytosis, polychromasia and nucleated RBCs.Platelet count was 64¡Á109/L with normal morphology.Wight blood cell was normal in number and morphology.elevated to 0.226(normal range 0-0.025) while HBA2 and hemoglobin electrophoresis was normal. Bone marrow biopsy and aspirate smear revealed a hypercellular marrow with dysplasia of erythrocyte series and megakaryoblasts (Figure 1 A). Polynuclear erythroblast ,micromegakaryocytes and hypolobated megakaryocytes could be easily seen (Figure 1 B). Fibrosis proliferation was obvious (Figure 1 A). Genetic analysis discovered a mutantion of GATA-1(R216Q)and excluded mutations of hemoglobin gnens and JAK-2. Patient was treated with dexamethasone and thalidomide which got little effect. The baseline hemoglobin was 6-8 g/dL.Platelet count ranged from 30 to 70¡Á109/L. Splenectomy was done at the age of 5years and 4 months because of constantly RBC transfusion and splenomegaly. Fibrosis proliferation and extramedullary hematopoiesis in spleen were proved by biopsy (Figure 1 C,D).The boy's complete blood count was recovered 4 months after splenectomy. Hemoglobin rose to11.6 g/dL and platelet count was 337¡Á109/L. HBF was still high at 0.226. Multifocal fibrosis proliferation still existed in bone marrow biopsy but with no myelodysplasia (Figure 1 E,F). Hepatomegaly didn't progress. He has good quality of life,and normal growth and intelligence development. Splenectomy can be a therapeutic strategy of X-linked thrombocytopenia with thalassemia. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Primary Myelofibrosis In Children

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3079-3079
Author(s):  
Melissa R. DeLario ◽  
Andrea Sheehan ◽  
Ramona Ataya ◽  
Alison A. Bertuch ◽  
Carlos Vega ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Case Series ◽  
Primary Myelofibrosis ◽  
Jak2v617f Mutation ◽  
World Health ◽  
Bone Marrow Fibrosis ◽  
Hematopoietic Stem ◽  
Molecular Features ◽  
Marrow Fibrosis

Abstract Abstract 3079 Primary myelofibrosis is a chronic myeloproliferative disorder characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. It is a serious medical condition in adults, often requiring major interventions such as hematopoietic stem cell transplantation (HSCT) for cure. In comparison to adults, children are rarely affected by this entity; the largest case series reports on four such patients. Most of these reports suggest that the majority of affected children have spontaneous resolution of their myelofibrosis with no long term complications. To better describe the clinical characteristics and outcomes of pediatric primary myelofibrosis, we performed a retrospective chart review of children diagnosed with myelofibrosis by bone marrow pathology at our institution from 1996 to 2009. Eighteen patients with primary myelofibrosis were identified. At presentation, all patients had one or more cytopenias and only one had leukoerythroblastosis. Three of 11 patients tested (27%) had cytogenetic abnormalities, as opposed to up to two-thirds of adults with primary myelofibrosis. Eleven of 18 patients (61%) demonstrated erythroid hypoplasia in the bone marrow, which is uncommon in adults. Based on recent molecular studies of myeloproliferative disorders in adults, the World Health Organization now includes the presence of a clonal marker such as JAK2V617F as a major criterion for diagnosis of myelofibrosis in adults. In contrast to approximately half of adults (43-63%) with primary myelofibrosis, JAK2V617F mutation in the bone marrow has not been reported in children. JAK2V617F mutation analysis was negative on 16 of 18 bone marrow specimens tested. In this series, only 5 of the 18 children (27.8%) had spontaneous recovery. No child developed malignant transformation. Eight children underwent HSCT, four of whom were cured of their myelofibrosis; the remaining four children died from infections acquired during transplantation. Four children died prior to transplantation, or were identified as having myelofibrosis at autopsy. One child transferred care to another facility and thus outcome data was not available. In all children, infection was the most common cause of death. Notably, the degree of bone marrow fibrosis did not correlate with outcome. Our series demonstrates that children with primary myelofibrosis have hematologic, bone marrow and molecular features that differ from adults. In contrast to what is found in the literature, our series of pediatric patients with primary myelofibrosis, the largest reported thus far, indicates a poor outcome for the majority of these patients. Disclosures: No relevant conflicts of interest to declare.

Bone Marrow Fibrosis In Patients With Multiple Myeloma: A New Prognostic Factor For Survival?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1946-1946 ◽  
Author(s):  
Tinna Hallgrimsdottir ◽  
Anna Porwit ◽  
Magnus Björkholm ◽  
Eva Rossmann ◽  
Hlif Steingrimsdottir ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
University Hospital ◽  
Bone Marrow Fibrosis ◽  
Significant Difference ◽  
The Difference ◽  
Marrow Fibrosis

Abstract Introduction Multiple myeloma (MM) is characterized by the proliferation of plasma cells in the bone marrow and a secretion of monoclonal immunoglobulins. Survival in MM is very variable and multiple factors are known to influence prognosis such as age, ISS stage, and genetic abnormalities. Fibrosis can be found in the bone marrow of MM patients but the literature reporting the incidence of fibrosis and its effect on prognosis is very limited. The purpose of this study was to estimate the incidence of bone marrow fibrosis in MM patients and its effect on survival. Materials and methods Data was collected at the Karolinska University Hospital in Solna, Sweden and information obtained from the hospital's records. We gathered information on all patients diagnosed with MM between 2003 and 2011. All bone marrow reports were reviewed and the presence of bone marrow fibrosis (evaluated using reticulin staining) at diagnosis was recorded. Fibrosis was graded as 1 (mild), 2 (significant) and 3 (advanced), in accordance with WHO 2008 criteria. Patients with fibrosis were paired with patients without fibrosis (matched by sex, birth year, and year of diagnosis). Survival comparing MM patients with and without fibrosis was evaluated using Kaplan-Meier estimate and Cox regression model. Results A total of 586 individuals, 327 males and 259 females, were diagnosed with MM at the Karolinska University Hospital, Solna during 2003 – 2011. Evidence of bone marrow fibrosis was noted in 223 (38%) patients at diagnosis, and 175 had fibrosis grade 1, 33 grade 2, and 15 grade 3. No significant difference was observed between males (N = 135) and females (N = 88) (p = 0.085). Mean age at diagnosis was significantly lower for patients with fibrosis (67.1 years) than in patients without fibrosis (69.7 years) (p = 0.013). Compared with paired patients without fibrosis (N = 217), patients with fibrosis had significantly worse survival (Figure), being 5.0 years vs. 4.4 years, respectively (relative risk (RR)=1.3, 95% confidence interval (CI) 1.00-1.70; p= 0.049). The difference was greatest in male patients and patients younger than 65 years at diagnosis. Survival was worse in patients with advanced fibrosis, 4.5 (95% CI 3.6-6.4) years for grade 1 fibrosis, and 3.0 (95% CI 1.6-NA) years for higher degree of fibrosis. Conclusion In this study, based on almost 600 patients with MM we show that bone marrow fibrosis is common at diagnosis (38%). Importantly, our findings show that the presence of fibrosis was associated with inferior survival. More studies are needed regarding the underlying causes for these findings, including treatment response, treatment-related complications and relation to other known prognostic factors. Disclosures: No relevant conflicts of interest to declare.

Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 381-383 ◽  
Author(s):  
Christine Beham-Schmid ◽  
Ute Apfelbeck ◽  
Heinz Sill ◽  
Oleksiy Tsybrovsky ◽  
Gerald Höfler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Bone Marrow Fibrosis ◽  
Bone Marrow Trephine Biopsy ◽  
Significant Regression ◽  
Marrow Fibrosis

Morphologic bone marrow changes in patients with BCR-ABL–positive chronic myelogenous leukemia (CML) were investigated during treatment with the tyrosine kinase inhibitor STI571. Bone marrow trephine biopsy specimens from 23 pretreated patients with CML were examined morphologically and by morphometry before and 6 weeks and 3 months after the initiation of STI571 therapy (Glivec, Novartis, Basel, Switzerland). Bone marrow changes during treatment showed a quantitative normalization of erythropoiesis, a marked reduction of granulopoiesis, and a significant decrease in megakaryocytes with the reappearance of normal-sized forms. Furthermore, a significant regression of bone marrow fibrosis was observed in patients with initial fibrosis (P < .000 000 001). These results may expand the profile of STI571 and may offer novel therapeutic possibilities in diseases with bone marrow fibrosis.

Bone Marrow Fibrosis in Patients with Inherited Bone Marrow Failure Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3192-3192
Author(s):  
Neelam Giri ◽  
Irina Maric ◽  
Robert Wesley ◽  
Diane C. Arthur ◽  
Pierre Noel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Bone Marrow Failure ◽  
Prognostic Significance ◽  
P Value ◽  
Fisher Exact Test ◽  
Bone Marrow Fibrosis ◽  
Bone Marrow Biopsies ◽  
Bone Marrow Failure Syndromes ◽  
Marrow Fibrosis

Abstract Abstract 3192 Poster Board III-129 Introduction Bone marrow fibrosis has been reported in many benign and malignant disorders, and it may be associated with a poor prognosis in patients with chronic idiopathic myelofibrosis and adult myelodysplastic syndrome (MDS). There are no data on the incidence or significance of bone marrow fibrosis in patients with the inherited bone marrow failure syndromes (IBMFS), genetic disorders characterized by cytopenias, distinctive clinical features, varied molecular pathways and high risks of MDS and acute myeloid leukemia. We have now studied marrow fibrosis in the four most common IBMFS: Fanconi anemia (FA), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DC), and Shwachman-Diamond syndrome (SDS). Patients and Methods Blinded bone marrow biopsies were analyzed from 42 patients: 12 FA, 13 DBA, 13 DC, and 4 SDS. Reticulin fibrosis was graded on a scale of 1-4 according to the quantity and pattern of distribution of reticulin. The frequencies of abnormalities in marrow fibrosis, cellularity, MDS, cytogenetic clones, blood counts, erythropoietin levels and treatment were compared between the disorders. Fisher exact test was used to compare frequencies and two-sided Wilcoxon rank sum test was used to compare continuous variables. P value of less than 0.05 was considered statistically significant for all tests. Results See Table. Patients with FA, DBA and DC were older than those with SDS; there was an excess of females with FA and males with DC and DBA. Patients with FA, DC and SDS had multilineage cytopenias, while most patients with DBA had only anemia. All patients with FA and DC had bone marrow hypocellularity; it was less frequent in those with DBA or SDS (P<0.001). A significantly higher proportion of patients with FA or DC (75%) had increased reticulin fibrosis (grade 2 or 3) compared with DBA or SDS (P=0.002). Most patients had grade 2 fibrosis; only 2 patients with FA had grade 3 fibrosis, and none had grade 4 fibrosis. In a multivariate analysis, bone marrow fibrosis correlated significantly with the presence of thrombocytopenia (P=0.01) and neutropenia (P=0.01), but not with anemia (P=0.8). The presence of fibrosis correlated significantly with the presence of high erythropoietin levels (P=0.006) and the presence of hypocellularity (P=0.003); contrary to expectations, even very hypocellular marrow biopsies had increased reticulin. Fibrosis did not correlate with the need for treatment, morphologic MDS (P=0.7) or cytogenetic abnormalities (P=0.2). Conclusion This is the first report of bone marrow fibrosis in patients with an IBMFS. The frequency of grade 2 or 3 bone marrow fibrosis was as high as 75% in FA and DC. There was a direct correlation between the presence of marrow hypoplasia and fibrosis in patients with FA and DC. Longitudinal studies are required to determine the prognostic significance of increased marrow fibrosis in patients with an IBMFS. Disclosures No relevant conflicts of interest to declare.

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.

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