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Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
Although the diagnosis of chronic myelomonocytic leukaemia (CMML) is based upon laboratory, morphological and clinical parameters, the utility of genetic testing is now well recognized, with the presence of at least one somatic mutation noted in over 90% and clonal cytogenetic abnormalities in over 30% of patients. The genetic landscape reveals mutations in TET2 (50–60%), SRSF2 (40–50%), ASXL1 (35–40%) and RUNX1 (15%). Concurrent mutations in TET2 and SRSF2 appear to be highly specific for CMML. Other mutations include those affecting cytosine methylation (DNMT3A, IDH2, IDH1), RNA splicing (SF3B1, U2AF35, ZRSR2), chromatin remodelling (UTX, EZH2) and signalling pathways (NRAS, KRAS, CBL, JAK2, FLT3 CSF3R).
Case 37
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
Chronic myelomonocytic leukemia is a slowly progressive condition which is usually treated with oral chemotherapy (e.g. hydroxyurea or etoposide). Splenectomy is helpful if patients become transfusion-dependent or if there are symptoms due to an enlarged organ. Transformation to acute leukemia occurs with a median interval of 18–24 months, but intensive chemotherapy is rarely successful. Younger patients should be considered for intensive therapy, possibly followed by bone marrow transplantation; however, this particular patient did not have a suitable donor 5 azacitidine is often helpful. Recent publications have indicated a role for eltrombopag as an orally active agent.
Diagnostic Utility of Bone Marrow Pathology in Chronic Myeloproliferative Disorders
Published in Richard T. Silver, Ayalew Tefferi, Myeloproliferative Disorders, 2007
Juergen Thiele, Attilio Orazi, Hans Michael Kvasnicka
Following the recent discovery of an activating JAK2V617F mutation in patients with Philadelphia chromosome–negative (Ph1-) chronic myeloproliferative disorders or neoplasms (MPNs—according to the forthcoming WHO nomenclature), currently a conflict of opinion exists on whether and to which extent conventional methods of diagnosis and classification, such as bone marrow (BM) morphology, are still needed (1). In this context, it is important to note that the mutation has been reported to occur at a strikingly different incidence (2–4) among the various types of clinicopathologically defined conditions. Detection of the JAK2V617F mutation has been described in up to 95% of polycythemia vera (PV) cases and in 30–50% cases of essential thrombocythemia (ET) and primary myelofibrosis (PMF; chronic idiopathic myelofibrosis). The mutation has also been found, although at a much lower frequency, in a minority (5–10%) of cases of chronic myelomonocytic leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and acute myeloid leukemia, as well as in other atypical myeloproliferative disorders (3–6).
Tagraxofusp as treatment for patients with blastic plasmacytoid dendritic cell neoplasm
Published in Expert Review of Anticancer Therapy, 2020
Sophia S. Lee, Deborah McCue, Naveen Pemmaraju
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy [1,2]. The incidence of BPDCN has not been systematically studied, owing to the multiple name changes and rarity of this disease, but studies have reported an extremely low incidence of 0.44% in all hematologic malignancies and 0.7% of cutaneous lymphomas [3,4]. BPDCN predominantly affects men, with a male to female ratio of 3:1, up to 5:1 in some series. The median age at diagnosis is in the seventh decade of life [3–5]. There are no well-established environmental or hereditary risk factors, although, approximately 10–20% of patients have a prior or concomitant (PCHM) myeloid hematologic malignancy including myelodysplastic syndrome (MDS), myeloproliferative neoplasm, chronic myelomonocytic leukemia (CMML), and/or acute myeloid leukemia (AML) [6,7].
Leukocytapheresis for patients with acute myeloid leukemia presenting with hyperleukocytosis and leukostasis: a contemporary appraisal of outcomes and benefits
Published in Expert Review of Hematology, 2020
Rory M. Shallis, Maximilian Stahl, Jan Philipp Bewersdorf, Jeanne E. Hendrickson, Amer M. Zeidan
AML is not the only hematologic malignancy associated with hyperleukocytosis and leukostasis, though the likelihood of leukostasis appears to be more strongly tied to the peripheral blood myeloblast burden. Patients with acute lymphoblastic leukemia (ALL) present with hyperleukocytosis in 10–20% of cases, respectively [13]. However, in comparison to AML, leukostasis in ALL is an uncommon event and typically observed only with extreme hyperleukocytosis (WBC >400,000 × 109 cells/L); this has been attributed to the smaller size of lymphoblasts in comparison to myeloblasts [13,34]. Leukemia characterized by mature peripheral leukocytosis, like chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and chronic myelomonocytic leukemia (CMML), though frequently presenting with hyperleukocytosis, rarely manifest with leukostasis [13,35–37]. Mature lymphocytes, neutrophils, monocytes, metamyelocytes, and monocytes are not only smaller than blasts but are hypothesized to be more pliable when confronted with insufficient vascular space resulting from an increased leukocrit and/or smaller vasculature. However, patients with CLL and leukostasis have been reported in the literature, mostly with a WBC >500,000–1,000,000 × 109 cells/L [36,37]. Leukostasis with CML is rare in chronic phase and almost always observed in either accelerated phase or blast crisis; this is likely influenced by the availability of effective tyrosine kinase inhibitor therapy [38]. The presence of leukostasis irrespective of culprit cell lineage should always be regarded as an emergency.
Immunosuppressive therapy in myelodysplastic syndromes: a borrowed therapy in search of the right place
Published in Expert Review of Hematology, 2018
Rory M. Shallis, Nora Chokr, Maximilian Stahl, Alexander B. Pine, Amer M. Zeidan
Increasing evidence also supports the role of immune dysregulation in the pathogenesis of MDS [7]. Clinical observation has long noted a correlation with disordered immune homeostasis and MDS, and recent retrospective and registry studies have recognized a clear association of MDS and chronic myelomonocytic leukemia (CMML) with the presence of autoimmune disease [8–13]. No dedicated prospective study with serial marrow evaluations has been performed to date to determine whether confirmed autoimmune disease precedes or induces the expansion of myelodysplastic clones and the subsequent development of MDS or whether the converse is true. In a large study of 1408 MDS patients, 28% of patients had an autoimmune disease; a more recent study noted a nearly 50% incidence of such with hypothyroidism being the most common disease with an attributed autoimmune pathogenesis. The prognostic impact of the presence of autoimmune disease in MDS remains controversial with these studies reporting discordant results [8,10]. Investigation into the immune microenvironment as it relates to innate and adaptive immunity has further reinforced the assertion that immune pathways are critical to development of impaired hematopoiesis and ultimately MDS.