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Background: Clinical decision-making for patients with myelodysplastic syndromes (MDS) is challenging, and both disease and treatment effects heavily impact health-related quality of life (HRQoL) of these patients. Therefore, disease-specific HRQoL measures can be critical to harness the patient voice in MDS research., Methods: We report a prospective international validation study of the Quality of Life in Myelodysplasia Scale (QUALMS) with a main focus on providing information on the psychometric characteristics of its three subscales: physical burden (QUALMS-P), emotional burden (QUALMS-E), and benefit finding (QUALMS-BF). The analysis is based on patients enrolled from three European countries and Israel, participating to the MDS-RIGHT Project. The scale structure and psychometric properties of the QUALMS were assessed., Results: Overall, 270 patients with a median age of 74 years were analyzed and the majority of them (60.3%) had a low MDS-Comorbidity Index score. Results of the confirmatory factor analysis supported the underlying scale structure of the QUALMS, which, in addition to a total score, includes three subscales: QUALMS-P, QUALMS-E, and the QUALMS-BF. The QUALMS-P exhibited the highest Cronbach's alpha coefficients. Discriminant validity analysis indicated good results with the QUALMS-P and QUALMS-E distinguishing between patients with different performance status, comorbidity, anemia, and transfusion dependency status. No floor and ceiling effects were observed. Responsiveness to change analysis supported the validity of the measure. Patients with a hemoglobin (Hb) level of <11 g/dL at study entry, who subsequently showed an improvement in their Hb levels, also reported a mean score change of 9 and 8 points (scales ranging between 0 and 100) in the expected direction of the QUALMS-E and QUALMS-P, respectively., Conclusions: Our study provides additional validation data on the QUALMS from the international MDS-RIGHT Project. The use of this disease-specific HRQoL measure may contribute to raise quality standards of patient-centered outcomes research in MDS., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Multiple myeloma (MM) is an incurable clonal neoplasm that usually requires long-term treatment, which may result in secondary cytopenia(s) and myeloid neoplasms. We investigated the landscape of mutations detected by NextGen sequencing (NGS) in myeloma patients with cytopenia., Methods and Materials: MM patients (n = 196) with cytopenia(s) and NGS results were identified and divided into 4 groups: 1) patients with myeloma only and no myeloid neoplasms; 2) patients with myeloid neoplasms but no myeloma; 3) patients with concurrent myeloma and myeloid neoplasms; and 4) patients with no myeloma or myelodysplasia., Results: The most frequently mutated genes were TP53, DNMT3A, TET2, ASXL1, and KRAS. TP53 mutations were predominantly found among patients with myeloid neoplasms with or without concomitant MM. SF3B1 and TET, the genes most commonly mutated in myelodysplastic syndromes, were less frequently identified among MM patients. ASXL1 mutations were more commonly associated with myeloid neoplasms, whereas KRAS and DNMT3A mutations were more closely associated with MM than myeloid neoplasms. RUNX1 mutations showed closer association with myeloid neoplasms. Fifty-eight patients harbored clonal myeloid gene mutations but no overt morphologic or cytogenetic abnormalities, of which 7 patients had myelodysplastic syndromes that was missed by the original pathologists. Thrombocytopenia appeared to be a more reliable marker than anemia or neutropenia to trigger work-up for myeloid neoplasms., Conclusion: NGS could greatly help with diagnosing myeloid neoplasms in MM patients with cytopenia(s). The depicted gene landscape may facilitate our daily interpretation of NextGen sequencing (NGS)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 5-year-old female cat with nonregenerative anemia and thrombocytopenia was diagnosed with myelodysplastic syndromes (MDS), since peripheral blood and bone marrow (BM) examination revealed various dysplasias and a blast ratio of 19%. Chemotherapy with azacytidine (AZA; 70-35 mg/m 2 , 3-5 days, three cycles) and treatment with prednisolone, antibiotics, and vitamin K2, and blood transfusion were performed. On day 106, blast cells and dysplasia had decreased in the BM, and the cat remained alive for at least 1,474 days. This report is the first on feline MDS treated with AZA, suggesting appropriate drug dosage, interval and effective combination should be investigated and the pharmacological and cell biological mechanisms needs to be elucidated in the future.

Copper deficiency can produce changes mimicking myelodysplasia, but its prevalence among haematology patients is unknown. This study evaluates the prevalence of deficiency in a population of patients with unexplained cytopenia(s) and dysplasia. Of 17 patients recruited, only one was found to have a low copper level. This is the first study evaluating hypocupremia in patients with isolated haematological manifestations. Our results suggest that copper deficiency is uncommon in this population, and the routine measurement of copper seems unlikely to be cost-effective. We recommend a risk-assessed approach to testing based on the identification of risk factors and of signs suggestive of deficiency.

Copper deficiency is a known cause of anemia and neutropenia that is easily remedied with copper supplementation. Copper is primarily absorbed in the stomach and proximal duodenum, so patients receiving enteral nutrition via methods that bypass this critical region may be at increased risk for copper deficiency. In pediatrics, postpyloric enteral feeding is increasingly utilized to overcome problems related to aspiration, severe reflux, poor gastric motility, and gastric outlet obstruction. However, little is known about the prevalence of copper deficiency in this population. We describe three pediatric patients receiving exclusive jejunal feeds who developed cytopenias secondary to copper deficiency., (© 2017 Wiley Periodicals, Inc.)

Anemia is a key survival prognostic factor in lower-risk myelodysplastic syndromes (MDS). Lenalidomide (LEN) can correct anemia in 25% of MDS patients without deletion 5q (del5q). As this therapy will inevitably fail, understanding the outcome of these patients will facilitate development of subsequent treatment strategies. To answer this question, an international retrospective study focused on LEN-treated lower-risk, non-del5q, MDS patients was performed. We analyzed the overall survival after LEN failure, its prognostic factors and the impact of post LEN treatment options. We included a total of 384 patients. The median overall survival after failure of LEN was 43 months. In multivariate analysis, adverse cytogenetics, excess of blasts at the initiation of LEN, and the type of failure (classified as stable disease, relapse, intolerance, or progression) were the main determinants of outcome. Subsequent therapy with hypomethylating agents was associated with a prolonged survival compared to BSC (median OS= 51m vs. 36m, p=0.01). In conclusion, the survival for non-del5q MDS patients after failure of LEN remains relatively prolonged, though with a wide range. Clinical trial participation remains the recommendation for these patients even if options such as hypomethylating agents may be considered.

Aplastic anaemia is a rare, previously fatal condition with a significantly improved survival rate owing to advances in understanding of the pathophysiology and improved treatment strategies including haematopoietic stem cell transplantation. Although a rare condition, aplastic anaemia continues to present a high burden for affected patients, their families and the health system due to the prolonged course of disease often associated with high morbidity and the uncertainty regarding clinical outcome. Modern molecular and genetic techniques including next-generation sequencing have contributed to a better understanding of this heterogeneous group of conditions, albeit at a cost of increased complexity of clinical decision-making regarding prognosis and choice of treatment for individual patients. Here we present a concise and comprehensive review of aplastic anaemia and closely related conditions based on extensive literature review and long-standing clinical experience. The review takes the reader across the complex pathophysiology consisting of three main causative mechanisms of bone marrow destruction resulting in aplastic anaemia: direct injury, immune mediated and bone marrow failure related including inherited and clonal disorders. A comprehensive diagnostic algorithm is presented and an up-to-date therapeutic approach to acquired immune aplastic anaemia, the most represented type of aplastic anaemia, is described. Overall, the aim of the review is to provide paediatricians with an update of this rare, heterogeneous and continuously evolving condition. [ABSTRACT FROM AUTHOR]

Objectives: To determine the diagnostic importance of bone marrow aspiration and biopsy in work up of cases presenting with anemias of unknown etiology. Study Design: Cross sectional descriptive study. Setting: Pathology Department, Khyber Teaching Hospital, Peshawar. Period: July 2015 to July 2017 (two year). Material & Methods: All patients presenting with anemia (Hemoglobin less than 12gm/dL for females and 13 gm/d L for males), whose cause cannot be established on clinical history, examination and blood counts, and were thus referred for bone marrow examination for further workup were included in the study. Patients having malignancies, chemotherapy or radiotherapy associated marrow suppression, and those with diluted marrow unfit for comments were excluded from the study. Bone marrow aspiration and biopsy was done, slides were examined, and diagnoses was made and recorded. The results were drawn accordingly. Results: A total of 199 patients were referred for bone marrow aspiration, presenting with unexplained anemia, during the study period. About 12 patients had blast cells on peripheral blood film, giving diagnosis of leukemia. So they were excluded from the study. Remaining 187 cases were included in the study. The age of the study sample ranged 3 years to 63 years (mean age 42 years ±8.1 SD). There were 96 (51%) males and 91 (49%) females. Male to female ratio was 1.05:1. Out of 187 cases presenting with unexplained anemias, about 44(23.5%) cases were of iron deficiency anemia, 39(20.7%) cases were of anemia of chronic disorder, 16 (8.7%) cases as hemolytic anemia, about 19 (10.3%) cases as aplastic anemia, and 52 (27.8%) cases of megaloblastic anemia on bone marrow examination. Conclusion: Bone marrow aspiration and biopsy successfully gives the final diagnosis in cases of anemia where cause cannot be found by routine lab investigations. It helps physician decide further management plan of the patients. So, it should be done in all cases with unexplained anemia. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes are a group of clonal diseases of hematopoietic stem cells and are characterized by multilineage dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, genetic instability and a risk of transformation to acute myeloid leukemia. Some patients with non-Hodgkin lymphomas (NHLs) may have developed secondary myelodysplasia before therapy. Bone marrow (BM) hematopoiesis is regulated by a spectrum of epigenetic factors, among which microRNAs (miRNAs) are special. The aim of this work is to profile miRNA expression in BM cells in untreated NHL patients with secondary myelodysplasia. A comparative analysis of miRNA expression levels between the NHL and non-cancer blood disorders samples revealed that let-7a-5p was upregulated, and miR-26a-5p, miR-199b-5p, miR-145-5p and miR-150-5p were downregulated in NHL with myelodysplasia (p < 0.05). We for the first time developed a profile of miRNA expression in BM samples in untreated NHL patients with secondary myelodysplasia. It can be assumed that the differential diagnosis for blood cancers and secondary BM conditions based on miRNA expression profiles will improve the accuracy and relevance of the early diagnosis of cancerous and precancerous lesions in BM.

The diagnosis of ecthyma gangrenosum should be evoked in front of maculopapular lesions rapidly evolving to necroting ulcers, particularly in the presence of prolonged neutropaenia or other hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: Bone marrow changes are common throughout the course of HIV infection. There is scanty data addressing this issue in Indian subcontinent. The present study was aimed at characterizing the bone marrow changes in the antiretroviral naive HIV-infected Indian patients with anemia. Materials and Methods: This was a nonrandomized cross-sectional observational study undertaken over a period of 2 years. Forty-six randomly selected patients with documented anemia served as the study population. None of them was on any antiretroviral therapy or suffering from any known causes of anemia. All the patients underwent thorough evaluation, including bone marrow examination. Results: Majority of the patients had normocytic-normochromic anemia (63%), in tune with the available data. In most of the cases bone marrow was hypercellular (63.04%), although in a significant proportion it was found to be hypocellular (19.57%). Erythropoiesis was suppressed in 36.96% of patients. Dysplastic changes involving isolated cell lines ranged from 13.04% to 45.65%, dysmegakaryopoiesis being the most common, followed by dyserythropoiesis. Marrow plasmacytosis was detected in 23.91% of patients. No statistically significant correlation was detected in between immunological status (CD4 count) and marrow cellularity, myelodysplastic changes or marrow plasmacytosis. In a fair number of cases bone marrow examination aided in the diagnosis of opportunistic infections. Conclusions: Bone marrow changes are common in Indian HIV-infected anemic population, particularly in the advanced stages of the disease. HIV infection should be considered in the differential diagnosis of patients with secondary myelodysplasia or unexplained bone marrow changes.

Anemia and transfusion need constitute major problems for patients with myelodysplastic syndromes (MDS) and are associated with reduced quality of life, poorer survival and an increased risk for transformation to AML. Treatment with erythropoiesis-stimulating agents (ESAs) is first-line treatment for the anemia of most patients with MDS. Erythropoietin acts synergistically with G-CSF to inhibit erythroid apoptosis and promote erythrocyte production. The median duration of response is 2–3 years, with patients responding for more than a decade. Onset of a permanent transfusion need is delayed if treatment is introduced early after the onset of symptomatic anemia. A positive effect on long-term outcome has been suggested by several large epidemiological studies, with no difference in the rate of leukemic transformation between treated and untreated patients. Moreover, responding patients show improvement of quality of life and exercise capacity. Response to treatment can be predicted by combining serum erythropoietin, transfusion rate, and flow cytometry profiling. [Copyright &y& Elsevier]

This commentary discusses the current use of arbitrary boundaries to distinguish the continuum of incipient (clonal cytopenias), oligoblastic (subacute), and polyblastic (acute) myelogenous leukemia. The historical path that led to the application of these boundaries is discussed, and simplification of the current diagnostic classification is proposed. [ABSTRACT FROM AUTHOR]

Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L. Methods: Thirty-six elderly patients with low- and intermediate-1 risk MDS received darbepoetin (DA) 300 μg/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA ± G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb >120 g/L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cardiac complications secondary to iron overload remain a significant matter in patients with transfusion dependent anemias. Patients and methods: To evaluate cardiac siderosis, Magnetic resonance imaging T2* (MRI T2*) was performed in 3 cohorts of transfusion dependent patients: 99 with thalassemia major (TM), 20 with thalassemia intermedia (TI), and 10 with acquired anemias (AA). Serum ferritin was measured and all patients underwent echocardiographic evaluation. Results: In TM patients cardiac T2* pathologic values (below 20ms) were found in 37 patients. Serum ferritin was negatively associated with age (r=−0.32, p=0.001) and weakly with T2* values (r=−0.19, p=0.057). A positive correlation was found between T2* and LVEF (r=0.27, p=0.006). Out of 37 patients with T2*<20ms, 18 (48%) had serum ferritin values<1000ng/ml. In TI cohort, 3 patients had cardiac T2* pathologic values. In AA cohort, pathologic T2* values were found in 2 patients, who received 234 and 199 PRBC units, respectively, and were both on chelation therapy (in one patient ferritin value was 399ng/ml). T2* values were negatively associated, but not significantly, with the number of PRBC transfused (r=−0.53, p=0.07). Conclusion: In our experience, 37% of TM patients had a myocardial iron overload assessed by MRI T2*; this value is higher than in TI patients. Serum ferritin measurement was a poor predictor of myocardial siderosis. In patients with AA, more than 200 PRBC units transfused were required to induce cardiac hemosiderosis, in spite of chelation therapy and, in one patient, of normal ferritin values. [ABSTRACT FROM AUTHOR]

This study highlights the iron profile of myelodysplastic patients in the era of hepcidin and its pro-hormone, pro-hepcidin. Previous studies have focused on the anemia of chronic renal failure, thalassemia, and hemochromatosis. We determined if pro-hepcidin played a role in iron overload in patients with myelodysplasia (MDS). Thirty adult patients with MDS and 20 healthy adults (controls) were selected. Our results revealed a statistically significant difference in pro-hepcidin levels between the two tested groups (Z = 2.9, p = 0.003). There was a weak positive correlation between pro-hepcidin and hematocrit (HCT; r = 0.49, p = 0.02) in the healthy group only. Neither age, subtypes of MDS, gender, soluble transferrin receptor (sTFR) or ferritin affected the pro-hepcidin level in patients with MDS. The role of ineffective erythropoiesis in the regulation of pro-hepcidin is superior to the role of chronic blood transfusion therapy. [ABSTRACT FROM AUTHOR]

Abstract: Peripheral blood cytopenia such as anemia, leukopenia with neutropenia and thrombocytopenia is frequently observed in cats infected with feline immunodeficiency virus (FIV). Although previous studies report that cytopenia has been observed in FIV-infected symptomatic cats, yet the asymptomatic cats also present cytopenia occasionally. In the present study, hematological and virological analyses in FIV-infected asymptomatic cats were carried out to understand the prevalence and pathogenesis of peripheral blood cytopenia in FIV infection. Hematological abnormalities were detected in 24 of 50 FIV-infected asymptomatic cats (48%) in which no other cause of cytopenia than FIV infection was observed. Anemia only, neutropenia only, thrombocytopenia only, bicytopenia and pancytopenia were observed in 10%, 10%, 6%, 14% and 8%, respectively. Bone marrow (BM) examination was performed in 8 FIV-infected asymptomatic cats with peripheral blood cytopenia. Myeloid dysplasia was observed in 4 cats with neutropenia of which 2 cats with concurrent thrombocytopenia presented morphological abnormalities of megakaryocytes. FIV-infected BM cells in the 8 cats were analyzed by PCR and immunocytochemistry. Lobulated mononuclear cells in BM were infected with FIV in 5 cats with neutropenia of which 2 cats with concurrent thrombocytopenia showed FIV-infected megakaryocytes. Parts of isolated stromal cells from BM were infected with FIV in all the 8 cats. Present results suggest that FIV infection of BM cells can cause peripheral blood cytopenia and myelodysplasia even if the cat is asymptomatic. Such FIV-related hematological abnormalities are supposed to be diagnosed as FIV-myelopathy. [Copyright &y& Elsevier]

An 11-year-old female Dachshund was presented with depression, diarrhea, weight loss, and radiographic evidence of masses involving the liver, spleen, and cranial lobe of the right lung. Results of a CBC included severe nonregenerative anemia (HCT 14.2%, hemoglobin, 4.3 g/dL, reticulocytes 66,000/μL) with marked metarubricytosis (nucleated RBCs 6.39 × 103/μL). Examination of the peripheral blood smear revealed marked erythroid dysplasia, including marked anisocytosis with a prevalence of macrocytes, Howell–Jolly bodies, diffuse basophilic stippling, and multinucleated and atypical nucleated RBCs. Neutrophil hypersegmentation and giant forms were also noted. Numerous erythrocytes, particularly polychromatophilic cells, contained inclusions consistent with Cabot rings, which appeared as delicate red–purple ellipsoid or figure 8 structures. Rarely, Cabot rings were observed extracellularly. The dog was treated symptomatically with blood transfusions, prednisone, erythropoietin, and vitamin supplementation, but the anemia progressively worsened. The dog was euthanized 2 months after presentation. Bone marrow aspirate and core biopsy specimens obtained at the time of euthanasia revealed marked dysplastic changes in all cell lines, especially dyserythropoiesis, along with infiltrating carcinoma cells. A necropsy was performed, and histologic examination revealed poorly differentiated adenocarcinoma of the lung with multiple metastases to the marrow, spleen, and liver. The final diagnosis was marked myelodysplasia secondary to metastatic adenocarcinoma. Cabot rings are found rarely in humans with myelodysplasia, but have not been described previously in dogs. Based on the findings in this case, Cabot rings may occur rarely in dogs with severe dyserythropoiesis. [ABSTRACT FROM AUTHOR]

Summary: Treatment of myelodysplastic syndromes (MDS) has evolved to encompass a broad spectrum of therapies aiming to inhibit apoptosis, promote hemopoiesis, and reduce proliferation of clonal immature cells. A small but expanding cohort of patients with MDS may be cured, but for the majority the aim of treatment is to prolong survival and to improve quality of life. Patients with low-risk MDS mainly suffer from the effects of severe anemia and an important therapeutic goal is to maintain acceptable hemoglobin levels by optimal transfusion regimens or by erythropoietin±granulocyte-colony-stimulating factor, which normalizes hemoglobin levels or abolish transfusion need in around 40% of patients. Lenalidomide has emerged as a drug of choice for patients with low-risk MDS and a 5q deletion, leading to complete erythroid response and cytogenetic remission in 2/3 of patients. A small cohort of younger patients may show excellent responses to anti-thymocyte globulin. Patients with more advanced disease may respond to treatment with the hypomethylating agents azacytidine and decitabine, who both have been shown to prolong time to leukemic transformation / death in MDS. In addition, there are several new agents under clinical investigation targeted to potential mechanisms of disease and progression in MDS. New therapeutic drug include inhibitors of angiogenesis, histone deacetylation, tyrosine kinases and farnesylation, as well as drugs interacting with apoptotic mechanisms. The role of these, alone and in combination with more established therapies will be discussed. [Copyright &y& Elsevier]

Objective. The objective was to assess the efficacy and safety of erythropoiesis-stimulating proteins (ESPs) in anemia of myelodysplastic syndrome (MDS). Method. A systematic review and meta-analysis was conducted covering English-language studies published from 1980 to December 2005. Results. Fifty-nine studies qualified: five controlled trials (n = 354), all epoetin versus control (EvC); 51 epoetin single-arm studies (n = 1,650); and three darbepoetin single-arm studies (n = 102). In the EvC studies, epoetin patients demonstrated a significant advantage over controls in terms of hemoglobin (Hb) response (odds ratio, 5.2; 95% confidence interval, 2.5-10.8). Hb response was 48.1% in single-arm darbepoetin studies, 32.1% in epoetin single-arm studies, and 27.3% in EvC studies. Major Hb response averaged 38.8% in darbepoetin studies, 24.5% in epoetin single-arm studies, and 11.4% in EvC studies. Stratified analyses suggest that lower baseline erythropoietin levels, longer treatment durations, and concurrent iron may be associated with greater Hb response to ESPs. None of the analyzable predictors of Hb response (gender, baseline Hb, ESP type, and ESP duration) were significant in meta-regression analyses. In the few studies with quality-of-life measures, ESP groups attained a pre--post change (Functional Assessment of Cancer Therapy -- Fatigue) that exceeded minimum clinically important differences. Selected adverse event rates did not differ between the epoetin and darbepoetin groups. Conclusion. Published studies suggest that ESPs are efficacious in anemia of MDS. Hb response appears higher in darbepoetin patients than in epoetin patients, and safety appears comparable, but darbepoetin data are sparse, and there are as yet no direct comparison studies. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen G (HLA-G) molecules corresponding to nonclassic class I genes of the major histocompatibility complex exhibit immunomodulatory properties. They are either membrane-bound or solubly expressed during certain tumoral malignancies. Soluble human leukocyte antigen G (sHLA-G) molecules seem more frequently expressed than membrane-bound isoforms during hematologic malignancies, such as lymphoproliferative disorders. Assay of these molecules by enzyme-linked immunosorbent assay in patients suffering from another hematologic disorder (acute leukemia) highlights increased sHLA-G secretion. This increased secretion seems more marked in acute leukemia subtypes affecting monocytic and lymphoid lineages such as FABM4 and FABM5, as well as both B and T acute lymphoblastic leukemia (ALL). Moreover, this study uses in vitro cytokine stimulations and reveals the respective potential roles of granulocyte--macrophage colony-stimulating factor and interferon-γ in increasing this secretion in FABM4 and ALL. Correlations between sHLA-G plasma level and clinical biologic features suggest a link between elevated sHLA-G level and 1) the absence of anterior myelodysplasia and 2) high-level leukocytosis. All these findings suggest that sHLA-G molecules could be a factor in tumoral escape from immune survey during acute leukemia. [ABSTRACT FROM AUTHOR]

An 8-year retrospective study of bone marrow reports was conducted to evaluate the incidence and classification of feline bone marrow disorders. Bone marrow reports from 203 cats were reviewed. Blood smears, bone marrow aspiration smears, bone marrow core biopsy specimens, and case records were reviewed for all cats with the exception of those bone marrows reported to be nondiagnostic or cytologically normal. Bone marrows with nonneoplastic/nonmyelodysplastic pathologic changes ( n=96) were subclassified into 16 categories. Frequently observed disorders included erythroid hyperplasia, nonregenerative immune-mediated anemia, pure red cell aplasia, aplastic anemia, bone marrow necrosis, myelofibrosis, and lymphocytosis. Dysmyelopoiesis ( n=27) was subcategorized into myelodysplastic syndromes ( n=20) and secondary ( n=7) dysmyelopoiesis. Thirty-four cases of acute leukemia, 3 cases of chronic lymphocytic leukemia, and 14 cases of other neoplasia were identified. These results indicate that a relatively small group of disorders account for the majority of the feline bone marrow disorders. Routine evaluation of blood and bone marrow aspiration smears and core biopsy specimens is needed for proper classification of bone marrow disorders. Ancillary testing, including flow cytometry and immunophenotyping, are useful in some circumstances. [ABSTRACT FROM AUTHOR]

Summary: Myelodysplastic syndromes (MDS) are a set of oligoclonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis that manifest clinically as anemia, neutropenia, and/or thrombocytopenia of variable severity. The result often is transfusion-dependent anemia, an increased risk of infection or hemorrhage, and a potential to progress to acute myelogenous leukemia (AML). Although progression to acute leukemia can lead to death in patients with MDS, many deaths are consequences of cytopenias and marrow failure in the absence of transformation. Approximately 2/3 of patients succumb to the disease within 3–4 years after presentation, and individuals with high-risk MDS generally survive about 1 year. Given that the disease is more prevalent in the elderly who often have comorbid conditions, the current treatment of MDS consists mainly of supportive care. Curative treatments are restricted to younger, healthy individuals with histocompatible (HLA)-matched donors for allogenic transplant or those able to undergo intensive chemotherapeutic regimens. However, understanding of the pathophysiology of MDS and identification of potential cellular and molecular targets in recent years has led to novel therapeutic approaches. Encouraging results using these heterogeneous therapeutic approaches alone or in combination in Phase I and II trials, have, in turn, called into question previous classification systems and have confirmed the need for an all-encompassing molecular, diagnostic and prognostic staging system. [Copyright &y& Elsevier]

Prior to the introduction of effective therapies, the high mortality rates of severe aplastic anemia (AA) precluded recognition of late complications of this disease. Once the survival of AA improved, observation of clonal evolution raised questions as to whether the development of secondary myelodysplastic syndrome (MDS) is a part of the extended natural history of the disease or is related to the therapies applied. Clinical features of myelodysplasia and AA can overlap, and typical MDS may evolve as a complication of AA. Common pathophysiologic elements operate in these diseases and are subject to many studies and theories as to what mechanisms in AA may lead to the late evolution of MDS. Similarly, AA has been hypothesized to be a reflection of an over-reactive immune response triggered by the appearance of genetically altered and/or phenotypically abnormal dysplastic clones. Hypocellular variants of myelodysplasia and responsiveness of certain forms of MDS to immunosuppressive regimens serve as the most appealing examples of the intricate and close pathophysiologic relationship of this disease with AA. The diagnosis of clonal evolution in the course of AA can be obvious if secondary cytopenia involves hypercellularity and a high percentage of blasts. In addition, the occurrence of a new karyotypic defect objectively heralds the progression of disease to MDS. However, the diagnostic imprecision of dysplasia recognition in the context of marrow hypocellularity, inability to obtain informative cytogenetics, and a high proportion of MDS cases with normal karyoptype have hampered studies designed to determine the frequency and timing of MDS evolution in AA. In addition, the diagnostic criteria and definitions used are not unified. While some centers recognize that the abnormal karyotype does not preclude the diagnosis of AA; in others, the diagnosis of AA includes the presence of normal karyoptype. Many typical features of dysplastic evolution in AA have been clarified. For example, karyotypes most frequently encountered in MDS secondary to AA involve chromosomes 6, 7 and 8. The evolution rates seem to be in the range of 10 - 15% in 10 years, but there are no predictive clues as to which patients are at greatest risk for this complication. Study of the mechanisms of clonal evolution in AA may help understand the pathophysiology of other forms of MDS and leukemia and also the mechanisms of antileukemic surveillance. Clinically, identification of patients at increased risk for clonal complications may influence the choice of therapies applied. [ABSTRACT FROM AUTHOR]

Summary The aim of this study was to test the clinical utility of reticulocyte maturation parameters in the differential diagnosis of macrocytic anemias. Using an automated reticulocyte counter, we analyzed immature reticulocyte fraction (IRF), mean reticulocyte volume (MRV) and mean fluorescence index (MFI) in peripheral blood samples from healthy donors (n = 30), patients diagnosed with myelodysplastic syndromes (MDS, n = 35), with megaloblastic anemia (MA, n = 10) and with non-megaloblastic macrocytic anemias (NMMA, n = 30). Macrocytic anemias due to ineffective erythropoiesis (MA and MDS) showed reticulocytes skewed to a more immature fraction. Therefore, they have a larger volume and a greater RNA content than healthy controls. Interestingly, reticulocytes in both low and high risk MDS are significantly larger (127.3 vs . 118.3 fl, P < 0.01) and have a greater RNA content (MFI 20.5 vs . 12.9, P < 0.01 and IRF 22.5 vs . 9.1%, P < 0.01) than NMMA patients. We conclude that measurement of reticulocyte maturation parameters may be a very useful tool in the differential diagnosis of macrocytic anemia. The presence of extremely high values of IRF (>16%), MFI (>18) and MRV (>129 fl), makes the diagnosis of NMMA very unlikely. An underlying MDS should, therefore, be sought. [ABSTRACT FROM AUTHOR]

Thiamine-responsive megaloblastic anaemia (TRMA) syndrome with diabetes and deafness was found in two patients from a Tunisian kindred. The proband was homozygous for a novel mutation, 287delG, in the high-affinity thiamine transporter gene, SLC19A2. We demonstrated that fibroblasts from this patient exhibited defective thiamine transport. These data confirm that the SLC19A2 gene is the high-affinity thiamine carrier and that this novel mutation is responsible for TRMA syndrome. [ABSTRACT FROM AUTHOR]

No abstract available [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes are a group of clonal diseases of hematopoietic stem cells and are characterized by multilineage dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, genetic instability and a risk of transformation to acute myeloid leukemia. Some patients with non-Hodgkin lymphomas (NHLs) may have developed secondary myelodysplasia before therapy. Bone marrow (BM) hematopoiesis is regulated by a spectrum of epigenetic factors, among which microRNAs (miRNAs) are special. The aim of this work is to profile miRNA expression in BM cells in untreated NHL patients with secondary myelodysplasia. A comparative analysis of miRNA expression levels between the NHL and non-cancer blood disorders samples revealed that let-7a-5p was upregulated, and miR-26a-5p, miR-199b-5p, miR-145-5p and miR-150-5p were downregulated in NHL with myelodysplasia (p < 0.05). We for the first time developed a profile of miRNA expression in BM samples in untreated NHL patients with secondary myelodysplasia. It can be assumed that the differential diagnosis for blood cancers and secondary BM conditions based on miRNA expression profiles will improve the accuracy and relevance of the early diagnosis of cancerous and precancerous lesions in BM. [ABSTRACT FROM AUTHOR]

Clonal abnormalities are identified by standard cytogenetic analysis of bone marrow cells in 40-50% of individuals with acquired idiopathic sideroblastic anemia/refractory anemia with ringed sideroblasts, a distinctive hematologic illness which is also classified as a form of myelodysplasia. Certain recurring chromosomal abnormalities, including 5q-, 7q-, 20q-, and trisomy 8, are the most frequent examples. Isolated trisomy 19 as a sole clonal aberration in this disorder is a rare event. The case presented here, and which demonstrated 30% involvement of bone marrow cells with trisomy 19, as quantified by fluorescent in situ hybridization studies, appears to represent only the fifth reported instance of such association. An atypical feature in this case was the unique histological appearance of the excessive cytoplasmic mitochondrial-associated iron deposition present in 30% of the bone marrow erythroid precursors as large chunks of Prussian blue-staining material rather than the individual, punctuate, multiple iron granules typically evident in refractory sideroblastic anemias. [ABSTRACT FROM AUTHOR]

Good syndrome (GS) is a rare adult-onset immunodeficiency disease characterised by hypogammaglobulinaemia and thymoma. Here we describe a 72-yearold male patient who was diagnosed with GS when he was 62, after a two-year history of recurrent respiratory infections. A chest CT scan showed a mediastinal mass which was surgically removed; its histology revealed a thymoma. The patient was hypogammaglobulinaemic and his clinical condition dramatically improved after starting an appropriate dosage of IVIG. Two years ago he developed a normochromic normocytic anaemia requiring several transfusions. A bone marrow biopsy revealed a myelodysplastic syndrome. The patient started cyclosporine and the anaemia gradually improved, achieving transfusion independence. [ABSTRACT FROM AUTHOR]

The article presents a study on patients with myelodysplastic syndrome (MDS) and mylofibrosis. It is stated that multiple blood transfusions with consequent iron overload is required in many patients with MDS that develops to severe anaemia. However, future studies will clarify the mechanisms of iron overload in the subtype of MDS with transfusion requirement and hepcidin levels.

The triad of thiamine-responsive anaemia, diabetes mellitus and deafness has been reported in 15 patients with macrocytic anaemia, sometimes associated with moderate thrombocytopenia. The bone marrow aspirate usually shows megaloblastic changes and ringed sideroblasts. However, tri-lineage myelodysplasia has never been reported. We describe two patients who presented with diabetes, deafness and thiamine-responsive pancytopenia. Bone marrow aspirate and biopsy were typical of tri-lineage myelodysplasia. These findings suggest that thiamine may have a role in the regulation of haemopoiesis at the stem cell level. We propose the term ‘thiamine-responsive myelodysplasia’ rather than that of thiamine-responsive anaemia. [ABSTRACT FROM AUTHOR]