A Novel Automated Image Analysis System Using Deep Convolutional Neural Networks to Diagnose MDS

Myelodysplastic syndrome: An inability to appropriately respond to damaged DNA?

Leukemia Lineage-Specific Chimerism Analysis and Molecular Monitoring Improve Outcome of Donor Lymphocyte Infusions

Response to Hypomethylating Agents Plus Venetoclax in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome: Real World Data from a Developing Country

Relationship Between Myelodysplastic Syndrome and Paroxysmal Nocturnal Hemoglobinuria: Spanish Erythropathology Group and Spanish Paroxysmal Nocturnal Hemoglobinuria Working Group Experience

This review highlights the main changes in the revised 2016 WHO Classification of Myeloid Neoplasms (published in 2017) that impact the diagnosis and management of patients with myelodysplastic syndrome (MDS). The revision was based on data accumulated since the 2008 WHO classification of MDS, much of which relates to new molecular genetic information about these neoplasms. The new information has led to some reorganization of the MDS disease categories, including a broadening of the subset of cases classified as MDS with ring sideroblasts, many of which have mutations in the spliceosome gene SF3B1. Other revisions have refined the definitions of some disease categories to improve disease risk stratification. The revised categories in the new classification ensure that MDS patients receive risk-adapted therapies based on the most recently available data.

Transfusion Requirements in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria with or without a History of Bone Marrow Disorder Receiving Ravulizumab and Eculizumab: Results from a Phase 3 Non-Inferiority Study Extension

GATA1 mutations in acute leukemia in children with Down syndrome

Transcriptional down-regulation of the Wnt antagonist SFRP1 in haematopoietic cells of patients with different risk types of MDS

Overview The existence of a hematopoietic disorder characterized by anemia and dyspoiesis preceding the onset of acute myelocytic leukemia (AML) has been recognized since the early part of the twentieth century. Initially designated as preleukemia, the syndrome was ill defined and could only be established with certainty retrospectively. Moreover, the terminology itself conveyed an unwarranted confidence in predicting the outcome that often belied the facts. The more accurately descriptive and appropriate designation as a myelodysplastic syndrome (MDS) was adopted in 1976 by the French–American–British (FAB) study group. The FAB classification permitted the prospective identification of patients within this heterogeneous clonal disorder. MDS, derived from a multipotent hematopoietic stem cell, is characterized clinically by a hyperproliferative bone marrow, reflective of ineffective hematopoiesis, and is accompanied by one or more peripheral blood cytopenias. Bone marrow failure results, leading to death from bleeding and infection in the majority, while transformation to acute leukemia occurs in up to 40% of patients. The evolution of the disease proceeds in accordance with the multistep pathogenesis theory of carcinogenesis and can thus serve as an important model in furthering our understanding of the processes involved in neoplastic transformation. This constellation of findings raises the question of whether MDS represents a frank neoplastic state or is merely a preneoplastic condition in transition. The syndrome appears to represent a spectrum where the initial lesion in the genome, though clinically undetectable, subsequently evolves, with the acquisition of additional genetic and epigenetic lesions, to a state of frank neoplasia. The designation of this disorder as an MDS, rather than preleukemia, permits its distinction from other abnormalities that are known to be associated with the development of acute leukemia. These latter include the classic myeloproliferative syndromes (polycythemia vera, chronic myelocytic leukemia, agnogenic myeloid metaplasia, essential thrombocythemia), aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), as well as Fanconi, Bloom, and Down syndromes. These particular “preleukemic states” are beyond the scope of this chapter. MDS can be further divided into primary and secondary syndromes. The former arise de novo and are of indeterminate etiology, while the latter are induced by identifiable environmental, occupational, or iatrogenic causes. Estimates of the incidence of MDS range from a frequency equal to that of AML or approximately 14,000 new cases per year in the United States to almost twice that of AML. The SEER database now tracks the disease; thus more accurate data will be available in the future. An estimate based on medical insurance claims indicated a total of 107,000 cases in the observation period from 2009 through 2011. The consensus is that the incidence is increasing owing to a number of factors, including greater awareness, greater diagnostic precision, and the aging of the population.

Acute Leukemias Following a Diagnosis of Colorectal Cancer: Are They Therapy-Related?

Blood and bone marrow smears from 49 dogs and cats, believed to have myeloproliferative disorders (MPD), were examined by a panel of 10 clinical pathologists to develop proposals for classification of acute myeloid leukemia (AML) in these species. French-American-British (FAB) group and National Cancer Institute (NCI) workshop definitions and criteria developed for classification of AML in humans were adapted. Major modifications entailed revision of definitions of blast cells as applied to the dog and cat, broadening the scope of leukemia classification, and making provisions for differentiating erythremic myelosis and undifferentiated MPD. A consensus cytomorphologic diagnosis was reached in 39 (79.6%) cases comprising 26 of AML, 10 of myelodysplastic syndrome (MDS), and 3 of acute lymphoblastic leukemia (ALL). Diagnostic concordance for these diseases varied from 60 to 81% (mean 73.3 +/- 7.1%) and interobserver agreement ranged from 51.3 to 84.6% (mean 73.1 +/- 9.3%). Various subtypes of AML identified included Ml, M2, M4, M5a, M5b, and M6. Acute undifferentiated leukemia (AUL) was recognized as a specific entity. M3 was not encountered, but this subclass was retained as a diagnostic possibility. The designations M6Er and MDS-Er were introduced where the suffix "Er" indicated preponderance of erythroid component. Chief hematologic abnormalities included circulating blast cells in 98% of the cases, with 36.7% cases having >30% blast cells, and thrombocytopenia and anemia in approximately 86 to 88% of the cases. Bone marrow examination revealed panmyeloid dysplastic changes, particularly variable numbers of megaloblastoid rubriblasts and rubricytes in all AML subtypes and increased numbers of eosinophils in MDS. Cytochemical patterns of neutrophilic markers were evident in most cases of Ml and M2, while monocytic markers were primarily seen in M5a and M5b cases. It is proposed that well-prepared, Romanowsky-stained blood and bone marrow smears should be examined to determine blast cell types and percentages for cytomorphologic diagnosis of AML. Carefully selected areas of stained films presenting adequate cellular details should be used to count a minimum of 200 cells. In cases with borderline diagnosis, at least 500 cells should be counted. The identity of blast cells should be ascertained using appropriate cytochemical markers of neutrophilic, monocytic, and megakaryocytic differentiation. A blast cell count of > 30% in blood and/or bone marrow indicates AML or AUL, while a count of < 30% blasts in bone marrow suggests MDS, chronic myeloid leukemias, or even a leukemoid reaction. Myeloblasts, monoblasts, and megakaryoblasts comprise the blast cell count. The FAB approach with additional criteria should be used to distinguish AUL and various subtypes of AML (Ml to M7 and M6Er) and to differentiate MDS, MDS-ER, chronic myeloid leukemias, and leukemoid reaction. Bone marrow core biopsy and electron microscopy may be required to confirm the specific diagnosis. Immunophenotyping with lineage specific antibodies is in its infancy in veterinary medicine. Development of this technique is encouraged to establish an undisputed identity of blast cells. Validity of the proposed criteria needs to be substantiated in large prospective and retrospective studies. Similarly, clinical relevance of cytomorphologic, cytochemical, and immunophenotypic characterizations of AML in dogs and cats remains to be determined.

Role of Platelet Indices and Thrombopoietin (TPO) Serum Levels in the Differential Diagnosis of Thrombocytopenia

Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in chronic lymphocytic leukemia (CLL). We retrospectively identified 95 patients with CLL, also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2 (0-9) and 1 (0-8), respectively; the most common regimen was purine analog combined with alkylating agent±CD20 monoclonal antibody. Twelve cases had no prior CLL treatment. Among 38 cases with AL, 33 had acute myelogenous leukemia (AML), 3 had acute lymphoid leukemia (ALL; 1 Philadelphia chromosome positive), 1 had biphenotypic and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, and intermediate risk in 7 patients. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all International Prognostic Scoring System (IPSS) were represented; karyotype was unfavorable in 36, intermediate in 6 and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher risk IPSS, poor-risk karyotype and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were very poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed.

MDR-1 and GST Polymorphisms Are Involved in Myelodysplasia Progression,

Background & objective:Pancytopenia is the reduction in the number of all 3 major cellular elements of blood and leads to anemia, leukopenia, and thrombocytopenia. A wide variety of etiologies result in pancytopenia including leukemia, aplastic anemia, and megaloblastic anemia. The current study identified the different etiologies of pancytopenia based on bone marrow examination in Iranian patients with pancytopenia.Methods:A total of 683 cases of pancytopenia with various etiologies were selected for this retrospective study. Bone marrow biopsy was performed with the standard technique using Jamshidi needle. The inclusion criteria for patients with pancytopenia were hemoglobin (Hb) <10 g/dL, total leukocyte count (TLC) <4 x 109/L, and platelet count <140 x 109/L.Results:In the present study acute leukemia was the first most common etiology detected in 235 (35.4%) patients in which acute myeloid leukemia (AML) comprised the majority of cases 142 (21.4%), followed by myelodysplastic syndrome (MDS) 100 (15%). In patients less than 20 years old, acute leukemia was also the commonest cause identified in 56 (57.7%) cases in which acute lymphoblastic leukemia (ALL) with 38.7% was the most common etiology; however in adults (>45 year old), AML accounted for the majority of cases 76 (53.5%).Conclusion:Since acute leukemia was the commonest etiology in both young and adults in which AML accounted for the majority of cases with pancytopenia in Iranian population, there was an urgent need to identify the underlying molecular or genetic mechanism of this malignancy for better further medical management and patients` survival.