scholarly journals Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome with Ring Sideroblasts and Multilineage Dysplasia

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Jacob D. Kjelland ◽  
Denis M. Dwyre ◽  
Brian A. Jonas
Keyword(s):  
Bone Marrow ◽  
Chest Pain ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Biopsy ◽  
Myelodysplastic Syndromes ◽  
Rare Case ◽  
Elderly Male ◽  
Multilineage Dysplasia ◽  
Ring Sideroblasts

Acquired elliptocytosis is a known but rarely described abnormality in the myelodysplastic syndromes (MDS). Here we report the case of an elderly male who was admitted to the hospital with chest pain, dyspnea, and fatigue and was found to be anemic with an elliptocytosis that had only recently been noted on peripheral smears of his blood. After bone marrow biopsy he was diagnosed with MDS with ring sideroblasts and multilineage dysplasia and acquired elliptocytosis. Here we report a rare case of acquired elliptocytosis cooccurring with MDS with ring sideroblasts and multilineage dysplasia.

Histopathological and immunohistochemical evaluation of bone marrow biopsy in myelodysplastic syndromes

2013 ◽  
Vol 2 (3) ◽  
pp. 219-228
Author(s):  
Emanuela Boveri ◽  
Giorgio Croci ◽  
Umberto Gianelli ◽  
Marcello Gambacorta ◽  
Giuseppe Isimbaldi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Myelodysplastic Syndromes

Bone Marrow Biopsy in RAEB and RAEB-t Myelodysplastic Syndromes

1992 ◽  
pp. 67-73 ◽  
Author(s):  
G. Lambertenghi-Deliliers ◽  
D. Soligo ◽  
C. Annaloro ◽  
E. Pozzoli ◽  
A. Riva
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Myelodysplastic Syndromes

scholarly journals A man with recurrent fever, arthritis, and rashes-brucellosis? A case report

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wen Wang ◽  
Xu Lu ◽  
Chengbo Li ◽  
Myong Jun Ri ◽  
Wei Cui
Keyword(s):  
Infectious Disease ◽  
Bone Marrow ◽  
Case Report ◽  
Myelodysplastic Syndrome ◽  
Skin Biopsy ◽  
Rare Case ◽  
Glucocorticoid Therapy ◽  
Recurrent Fever ◽  
Neutrophilic Dermatosis ◽  
Case Presentation

Abstract Background We report a rare case of chronic brucellosis accompanied with myelodysplastic syndrome and neutrophilic dermatosis, which to the best of our knowledge, has never been reported. Case presentation A young man was admitted to our hospital complaining of recurrent fever, arthritis, rashes and anemia. He had been diagnosed with brucellosis 6 years prior and treated with multiple courses of antibiotics. He was diagnosed with myelodysplastic syndrome and neutrophilic dermatosis following bone marrow puncture and skin biopsy. After anti-brucellosis treatment and glucocorticoid therapy, the symptoms improved. Conclusions Clinicians should consider noninfectious diseases when a patient who has been diagnosed with an infectious disease exhibits changing symptoms.

scholarly journals Treatments targeting MDS genetics: a fool’s errand?

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 277-285 ◽  
Author(s):  
Amy E. DeZern
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Patient Outcomes ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Failure ◽  
Targeted Agents ◽  
Clonal Hematopoiesis ◽  
Myeloid Neoplasms ◽  
Improve Patient

Abstract The myelodysplastic syndromes are collectively the most common myeloid neoplasms. Clonal hematopoiesis present in these diseases results in bone marrow failure characteristically seen in patients. The heterogeneity of myelodysplastic syndrome pathobiology has historically posed a challenge to the development of newer therapies. Recent advances in molecular characterization of myelodysplastic syndromes are improving diagnostic accuracy, providing insights into pathogenesis, and refining therapeutic options for patients. With the advent of these developments, appropriately chosen therapeutics or even targeted agents may be able to improve patient outcomes in the future.

scholarly journals Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors

Blood ◽  
2006 ◽  
Vol 108 (13) ◽  
pp. 4170-4177 ◽  
Author(s):  
Tony A. Navas ◽  
Mani Mohindru ◽  
Myka Estes ◽  
Jing Ying Ma ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
P38 Mapk ◽  
Myelodysplastic Syndromes ◽  
Clinical Investigation ◽  
P38 Map Kinase ◽  
Hematopoietic Progenitors ◽  
Molecule Inhibitor ◽  
Pharmacologic Inhibition

Abstract The myelodysplastic syndromes (MDSs) are collections of heterogeneous hematologic diseases characterized by refractory cytopenias as a result of ineffective hematopoiesis. Development of effective treatments has been impeded by limited insights into any unifying pathogenic pathways. We provide evidence that the p38 MAP kinase is constitutively activated or phosphorylated in MDS bone marrows. Such activation is uniformly observed in varied morphologic subtypes of low-risk MDS and correlates with enhanced apoptosis observed in MDS hematopoietic progenitors. Most importantly, pharmacologic inhibition of p38α by a novel small molecule inhibitor, SCIO-469, decreases apoptosis in MDS CD34+ progenitors and leads to dose-dependant increases in erythroid and myeloid colony formation. Down-regulation of the dominant p38α isoform by siRNA also leads to enhancement of hematopoiesis in MDS bone marrow progenitors in vitro. These data implicate p38 MAPK in the pathobiology of ineffective hematopoiesis in lowrisk MDS and provide a strong rationale for clinical investigation of SCIO-469 in MDS.

Clinical Relevance of Bone Marrow Fibrosis and CD34-Positive Cell Clusters in Primary Myelodysplastic Syndromes

2009 ◽  
Vol 27 (5) ◽  
pp. 754-762 ◽  
Author(s):  
Matteo Giovanni Della Porta ◽  
Luca Malcovati ◽  
Emanuela Boveri ◽  
Erica Travaglino ◽  
Daniela Pietra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Transfusion Requirement ◽  
Free Survival ◽  
Cell Clusters ◽  
Multilineage Dysplasia ◽  
Poor Risk ◽  
Marrow Fibrosis

Purpose We studied bone marrow (BM) histologic abnormalities in myelodysplastic syndromes (MDS) classified according to WHO criteria to determine their clinical correlates and prognostic value. Patients and Methods Three hundred one consecutive patients were retrospectively evaluated for BM fibrosis and CD34 immunoreactivity. Marrow fibrosis was assessed following the European consensus guidelines. Results Moderate to severe BM fibrosis was detected in 17% of cases and was associated with multilineage dysplasia (P = .001), high transfusion requirement (P < .001), and poor-risk cytogenetics (P = .007). CD34+ cell clusters were found in 23% of patients and were associated with WHO categories with excess of blasts (P < .001) and poor-risk cytogenetics (P = .001). In multivariable analysis, BM fibrosis and presence of CD34+ cell clusters had independent negative impact on overall survival (P < .001 and P = .019, respectively) and leukemia-free survival (P < .001 and P = .004, respectively). A hierarchical clustering analysis identified three subsets of patients with distinct clinical features. One cluster consisted mainly of patients with BM fibrosis, multilineage dysplasia, and high transfusion requirement; these individuals had lower overall survival and leukemia-free survival (P = .001 and P < .001, respectively). Within patients stratified according to International Prognostic Scoring System and WHO classification–based Prognostic Scoring System categories, BM fibrosis involved a shift to a one-step more advanced risk group. Conclusion BM fibrosis identifies a distinct subgroup of MDS with multilineage dysplasia, high transfusion requirement, and poor prognosis and represents an independent prognostic factor that may be useful in clinical decision making. Furthermore, the presence of CD34+ cell clusters is an independent risk factor for progression to acute leukemia.

Clinical Utility of Multiparameter Flow Cytometry in the Diagnosis of 1013 Patients with Suspected Myelodysplastic Syndrome: Correlation to Cytomorphology, Cytogenetic, and Clinical Data.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 595-595
Author(s):  
Wolfgang Kern ◽  
Claudia Haferlach ◽  
Susanne Schnittger ◽  
Torsten Haferlach
Keyword(s):  
Flow Cytometry ◽  
Myelodysplastic Syndrome ◽  
Expression Pattern ◽  
Antigen Expression ◽  
Refractory Anemia ◽  
Multiparameter Flow Cytometry ◽  
Multilineage Dysplasia ◽  
Cytogenetic Aberrations ◽  
Ring Sideroblasts ◽  
Equity Ownership

Abstract Abstract 595 Diagnosis and classification of myelodysplastic syndromes (MDS) is based on cytomorpholgy (CM) and cytogenetics (CG). By the identification of MDS-related aberrant antigen expression multiparameter flow cytometry (MFC) may add important diagnostic information. Examples include an aberrant expression pattern of CD13 and CD16 in granulocytes, an aberrante expression pattern of HLA-DR and CD11b in monocytes and the expression of lymphoid markers on myeloid blasts (Haematologica 2009:94:1124). To evaluate the potential role of MFC in the diagnostic setting of MDS we analyzed 1013 cases with suspected MDS by CM, CG, and MFC in parallel. Cases were classified by CM as refractory anemia (RA, n=31, 3.1%), refractory anemia with ring sideroblasts (RARS, n=27, 2.7%), refractory cytopenia with multilineage dysplasia (RCMD, n=64, 6.3%), refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS, n=49, 4.8%), refractory anemia with excess of blasts 1 (RAEB-1, n=133, 13.1%), RAEB-2 (n=81, 8.0%), 5q- syndrome (n=24, 2.4%), chronic myelomonocytic leukemia (CMML, n=65, 6.4%), myelodysplastic syndrome unspecified (MDS-u, n=15, 1.5%), MDS borderline to acute myeloid leukemia (MDS/AML, n=6, 0.6%), MDS/myeloproliferative neplasia overlap (MDS/MPN, n=16, 1.6%), suspected MDS (n=225, 22.2%), reactive condition (n=266, 26.3%), and normal findings (n=11, 1.1%). Cytogenetic findings were normal karyotype (n=768, 75.8%), isolated deletion of long arm of chromosome 5 (del(5q), n=43, 4.2%), isolated aberrations of chromosome 7 (n=14, 1.4%), isolated trisomy 8 (n=30, 3.0%), isolated deletion of long arm of chromosome 20 (del(20q), n=21, 2.1%), complex karyotype (n=23, 2.3%), loss of Y-chromosome (n=43, 4.2%), other aberrations (n=71, 7.0%). Concordance between CM and MFC was 82.0% for diagnostic results in 788 cases with unequivocal CM. 277 of these 788 cases were classified by CM as not having MDS, 13 (4.7%) of which showed MDS-typical features by MFC. Additional 225 cases showed only minor dysplastic features by CM, 51 (22.7%) of which showed clear evidence of MDS by MFC. To further analyze the significance of MDS-related findings by MFC we then focused on cytogenetically aberrant cases without unequivocal MDS by CM. In 6/12 (50.0%) cases with no indication of MDS by CM and MDS-typical cytogenetic aberrations MFC revealed MDS characteristics. In another 11/23 (47.8%) cases with minor dysplastic features by CM and MDS-typical cytogenetic aberrations MFC revealed MDS characteristics. Furthermore, we compared blast counts as determined by CM and MFC and found a strong correlation (p<0.001) although the mean±SD percentage was higher as determined by CM as compared to MFC (4.67±4.18 vs. 3.78±2.97). Frequencies of aberrantly expressed antigens significantly differed between cases rated by CM as MDS (median number of aberrantly expressed antigens: 3), suspected MDS (1), and no MDS (0, p<0.001). In various cases MFC identified MDS-typical aberrant antigen expression in cell compartments not rated dysplastic by CM. Spearman rank correlation confirmed a highly significant relation between the number of aberrantly expressed antigens and IPSS (r=0.409, p<0.001). In 257 cases with data on overall survival (OS) the presence of MDS-related findings (≥3 aberrantly expressed antigens or a blast count >5% in MFC or a reduced side-scatter signal) resulted in significantly inferior 6-year-OS (68% vs. 100% p=0.008). The present analysis clearly demonstrates a diagnostic yield of MFC in addition to cytomorphology and cytogenetics in cases with suspected MDS. Disclosures: Kern: MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

scholarly journals Towards CD177 As a Predictive Biomarker for Hypomethylating Agent Response in Myelodysplastic Syndrome

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4665-4665
Author(s):  
James Ignatz-Hoover ◽  
Pingfu Fu ◽  
Shufen Cao ◽  
Benjamin Tomlinson ◽  
Howard Meyerson
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
High Risk ◽  
Risk Stratification ◽  
Myelodysplastic Syndrome ◽  
Treatment Response ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Biopsies ◽  
Wide Range ◽  
Very High

Abstract Background Myelodysplastic syndrome (MDS) represents a heterogenous spectrum of pre-leukemic conditions with a wide range of outcomes. Higher risk MDS as classified by the revised international prognostic scoring system (IPSS-R) score is associated with poor overall survival and up to 30% of patients progressing to acute myeloid leukemia. Hypomethylating agents (HMA) such as azacitadine can improve cytopenias and delay progression to leukemia in about 30% of patients, but these agents may take months to promote response and initially exacerbate cytopenias. Thus treatment related biomarkers that help predict eventual hematologic response are of interest. CD177 is expressed in neutrophils and plays a role in cellular adhesion. In healthy cells, it exhibits bimodal expression by flow cytometry that is stable over time within an individual. The percentage of CD177 positive neutrophils is often decreased in hematopoietic malignancies and myelodysplastic syndromes. Our group has demonstrated that CD177 has diagnostic utility in the identification of myelodysplastic syndromes. As transcription of CD177 is regulated by CpG methylation of its promotor, we hypothesized that treatment with HMAs may improve CD177 expression in clinical responders and potentially guide continuation of HMA therapy. Methods To interrogate the above, we performed a retrospective review of patients with a diagnosed with MDS or MDS/MPN overlap syndromes who received disease modifying therapy with HMA at our institution from 2015 to 2018. Inclusion criteria required documentation of serial bone marrow biopsies with aspirate flow cytometry analysis. CD177 positivity was determined by increase in mean florescence intensity compared to isotype controls. Data was analyzed with using cox multivariate and univariate analysis correlating to treatment response. Results Of the 237 patients, 27 patients met the above criteria. Their average age was 62 (21 to 77) at time of diagnosis with 20 men and 7 women. They exhibited a range of R-IPSS risk stratification with four very high risk, eight high risk, six intermediate risk, and four low risk. Five cases were MDS/MPN overlap. Patients received on average 10 months of HMA treatment with a wide range from 1 month to 42 months of treatment. Median baseline CD177 positivity was 16, 31, 28.5, and 72 percent respectively amongst R-IPSS groups. Of the 27 patients analyzed with repeat bone marrow biopsies, eight patients exhibited 20% or greater increase in CD177(+) neutrophils, ten exhibited a decrease in CD177(+) neutrophils of 20% or greater, and nine exhibited less than a 20% change in CD177(+) neutrophils. with similar distribution of R-IPSS risk stratification amongst groups. (CD177-decreased: 1 very high, 3 high, 1 intermediate, 2 low risk, CD177-stable 1 very high, 2 high, 2 intermediate, and 1 low, Improved-CD177 1 very high, 4 high, 2 intermediate and 1 low). Cox proportional hazard analysis suggests that patients exhibiting a decrease or stable CD177 were less likely to exhibit a treatment response with results trending to significance (OR= 0.13 p=0.099). Conclusion Our initial data suggests that change in CD177 may help predict HMA treatment response. More uniform prospective analysis is indicated to compared CD177 changes over initial treatment. Furthermore, CD177 in peripheral blood and bone marrow samples correlate excellently (R 2=0.95). Prospective studies are underway to correlate CD177 change and initial treatment response utilizing flow analysis of pre-treatment CBCs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome with Isolated Del(5q) with Lenalidomide, Bortezomib, and Dexamethasone

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Nyomi Washington ◽  
Eugen A Shippey ◽  
Michael B Osswald
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Partial Response ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Biopsy ◽  
Induction Therapy ◽  
Successful Treatment ◽  
Light Chain ◽  
Plasma Cells ◽  
Bone Marrow Blasts

Lenalidomide is known to be an effective therapy for multiple myeloma (MM) and for myelodysplastic syndrome with isolated del(5q). However, there have been very few reports of treatment of both conditions using lenalidomide when they are diagnosed concurrently. A review of the literature revealed two reports of MM and del(5q) MDS treated with lenalidomide. We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide. The patient is a 74 year old female who was referred to hematology for worsening chronic macrocytic anemia with a hemoglobin of 9.4 g/dL. A serum protein electrophoresis (SPEP) was obtained during her workup and demonstrated an IgG kappa monoclonal spike of 4.7 g/dL. Free light chain analysis demonstrated a kappa/lambda ratio of 36.7. The patient was mildly hypercalcemic at 10.6 g/dL but had no renal insufficiency. Platelet and white blood cell counts were normal. There were no osteolytic lesions on skeletal survey and a whole body PET scan identified no bony disease or plasmacytomas. A β-2 microglobulin level was 3.7 mg/L and albumin was 3.3 g/dL. Bone marrow biopsy revealed 60% plasma cells in a 70% cellular marrow. Granulocytic and megakaryocytic dysplasia was identified. Fluorescence in situ hybridization returned showing a 4:14 translocation in 72% of analyzed nuclei and monosomy 13 in 61% of nuclei analyzed consistent with an unfavorable risk profile. Chromosome analysis also revealed a 5q deletion in 15 of 20 analyzed cells. Bone marrow blasts were measured at 1%. Therefore, the patient concurrently met diagnostic criteria for stage II IgG kappa multiple myeloma per the International Staging System and low risk myelodysplastic syndrome with isolated del(5q) per the 2016 WHO classification of MDS with a Revised International Prognostic Scoring System Score (IPSS-R) of 2. She was started on lenalidomide 25 mg daily, bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 and dexamethasone 20 mg on days 1, 8, and 15 of a 21 day cycle. After 3 cycles of therapy, serum immunofixation electrophoresis showed an unquantifiably low IgG kappa monoclonal spike and the patient's kappa/gamma light chain ratio had normalized to 1.1. Hemoglobin and calcium returned to normal. On repeat bone marrow biopsy, there was normocellular marrow with 4% polytypic plasma cells by kappa/lambda immunohistochemistry. No dysplasia was identified and bone marrow blasts were 1.5%. Therefore, the patient achieved a very good partial response (VGPR) to therapy for multiple myeloma according to International Myeloma Working Group criteria within 3 months. She met National Comprehensive Cancer Network criteria for response of her MDS to lenalidomide by normalization of hemoglobin. The patient's case demonstrates successful treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) using lenalidomide. Among the two other similar cases we discovered in the literature, one patient was treated with low-dose lenalidomide and dexamethasone [Nolte, et al. Eur J Haematol. 2017 Mar;98(3):302-310.], and the other patient was treated with high-dose lenalidomide and dexamethasone, achieving a partial response [Ortega, et al. Leuk Res. 2013 Oct;37(10):1248-50.]. Neither patient received a proteasome inhibitor. In our case, the patient was treated with higher intensity induction therapy for multiple myeloma and achieved a VGPR. She did not have worsening cytopenias during therapy, and in fact experienced normalization of her blood counts. Therefore, it is reasonable to treat patients simultaneously diagnosed with MM and MDS with isolated del(5q) with standard three-drug induction therapy for multiple myeloma. While our approach makes sense in the abstract, hematology/oncologists should be aware that it works in practice. Disclosures No relevant conflicts of interest to declare.

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