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Pearson syndrome
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Refractory anemia requires repeated transfusion of blood. Erythropoietin is generally ineffective. Thrombocytopenia may require platelet transfusion. Pancreatic extract is useful in the management of the pancreatic insufficiency. It may also improve diarrhea and lead to weight gain [37].
Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Frédéric Baron, Frederick R. Appelbaum, Brenda M. Sandmaier
Ho et al. analyzed data from 62 patients with myelodysplastic syndrome given allografts from related (n = 24) or unrelated (n = 38) donors after reduced-intensity conditioning with fludarabine (150 mg/m2), oral busulfan (8 mg/kg), and alemtuzumab (100 mg total dose) (46). Postgrafting immunosuppression consisted of CSP alone. Median patient age at HCT was 56 years for patients given grafts from siblings and 52 years for patients given grafts from unrelated donors. Sixteen patients had refractory anemia, 19 refractory anemia with blast excess, 23 refractory anemia with blast excess in transformation, and 4 chronic myelomonocytic leukemia. The one-year probabilities of nonrelapse mortality, overall survival, and progression-free survival were 5%, 73%, and 61%, respectively, for patients given grafts from related donors versus 21%, 71%, and 59%, respectively, for patients given grafts from unrelated donors.
Different Types of Leukemias, Lymphomas, and Myelomas
Published in Tariq I Mughal, John M Goldman, Sabena T Mughal, Understanding Leukemias, Lymphomas, and Myelomas, 2017
Tariq I Mughal, John M Goldman, Sabena T Mughal
The FAB classification of MDS proposed in 1982 was intended for diagnostic and prognostic purposes. The classification had several important limitations. First, the term “refractory anemia” was imprecise and could not be identified morphologically. Second, CMML is perhaps more closely related to the myeloproliferative disorders than to the other subtypes of MDS. Third, the use of an arbitrary criterion, for example, the percentage of marrow blasts, to distinguish between an advanced MDS and a frank AML, was often misleading. This classification also had other severe limitations, in particular since there is little concordance for the clinical, molecular, and biological features of the proposed sub-categories. The present WHO classification has attempted to rectify this. Table 4.8 shows the FAB and WHO classifications of MDS.
VEXAS: is it time to reshape the nosology of clonal hematopoiesis?
Published in Expert Review of Hematology, 2023
Pierre Sujobert, Laetitia Largeaud, Yvan Jamilloux, Maël Heiblig, Olivier Kosmider
What we now call MDS was historically recognized with the functional description of refractory anemia, i.e. an anemia that was not corrected by iron or vitamin supplementation. These conditions have been recognized as pre-leukemic states, with equivocal wordings such as preleukaemia, smoldering leukemia, subacute leukemia, or atypical leukemia [12]. In a seminal paper published in 1982, the French-American-British group provided a comprehensive definition of the morphological features defining dysmyelopoiesis, thus enabling the recognition of myelodysplastic syndromes as morphologically defined entities [13]. At the same time, the clonal nature of this disease was highlighted by the demonstration of acquired and recurrent cytogenetic abnormalities in about half of the patients [14]. Hence, at the early 1980s, the conceptual framework of MDS that we still use was established based on the three criteria of clonality of hematopoiesis, myeloid dysplasia, and ineffective myelopoiesis [15].
Myelodysplastic syndromes: a review of therapeutic progress over the past 10 years
Published in Expert Review of Anticancer Therapy, 2020
Jonathan Feld, Abigail Belasen, Shyamala C Navada
Anemia continues to be the predominant pathology for patients with MDS-LR. Erythrocyte stimulating agents (ESAs), and if no initial response, in combination with granulocyte-colony stimulating factor (G-CSF) and intermittent red blood cell transfusions remain the frontline treatment for non-del5q MDS-LR. A phase II study evaluated this combination for elderly patients and showed improvements in quality in life [18]. An additional single-arm phase II trial showed erythroid responses (ERs) of greater than 70% for this combination for patients with serum erythropoietin (EPO) level less than 500 milliunits per milliliter (mU/ml), hemoglobin less than 10 grams per deciliter (g/dL), and low-transfusion burden (LTB) [19]. In a large retrospective study, ESA treatment appeared to improve overall survival (OS) in patients with hemoglobin levels between eight to 10 g/dL, as well in those with WHO classification refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), and del5q MDS [20]. Further retrospective studies showed patients with hematologic response to ESAs have improved OS [21]. Moreover, earlier ESA initiation within six months of diagnosis was associated with a longer duration of transfusion independence (TI) [22]. While the paradigm defining studies for ESAs were completed before this decade, the first phase III trials were only recently published, comparing both epoetin-alpha [23] and darbepoetin-alfa [24] to placebo to evaluate response over a 24-week period. Both trials involved MDS-LR patients, with hemoglobin less than 10 g/dL, and LTB. The darbepoetin study required serum EPO less than 500 mU/ml. Epoetin-alpha showed a 45.9% ER rate compared to 4.4% for placebo. Darbepoetin led to a 14.7% response versus a 0% response in the placebo arm. These studies led to the approval of ESAs by the European Medicines Agency (EMA). Although these agents have not been approved by the FDA for use in MDS, they are used widely as first line treatment in MDS-LR. More recent evidence supporting their use comes from meta-analyses of ESA monotherapy which demonstrate consistent efficacy [25]. Studies combining ESA with G-CSF demonstrated that the addition of G-CSF to low/standard-dose ESA is more effective than ESA alone [26], though there are only a few true randomized trials testing this drug combination.
Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy
Published in Expert Review of Hematology, 2018
Jamile M. Shammo, Rami S. Komrokji
The clinical consequences of iron overload in patients with MDS have been largely studied retrospectively, and in many studies the effectiveness of ICT in reducing iron overload-associated complications has been investigated. At present, however, there are little prospective interventional data available to support the use of ICT in patients with MDS. In a retrospective, case-control study examining a large US health insurance claims database between 1997 and 2004, patients with MDS or other hematopoietic disorders were identified (n = 511 cases and controls) [19]. In this study, the receipt of at least one transfusion was associated with a significantly increased risk of potential complications of iron overload (odds ratio [OR] = 2.90; P = 0.0008), whereas the risk of cardiomyopathy or heart failure was not significant (OR = 1.62; P = 0.2955). However, the risk of conduction/rhythm disorders (OR = 4.18; P = 0.0005), diabetes (OR = 5.06; P = 0.0025), and liver disease (OR = 3.31; P = 0.0008) were all significantly increased in this study, and having four or more transfusion episodes was associated with a greater than five-fold increased risk of any iron overload-related complication (OR = 5.59; P = 0.0049) [19]. These results are consistent with another study of US Medicare beneficiaries (N = 2253 patients with MDS) that showed a higher incidence of cardiac disease, diabetes, dyspnea, hepatic disease, and infectious diseases (e.g. sepsis, fungal infection, pneumonia) among patients with MDS receiving transfusions (n = 205) compared with those who were not (n = 307); these findings were significant in the case of cardiac disease (82.4% vs. 67.1%; P < 0.001), dyspnea (62.9% vs. 40.4%, P < 0.001), and infectious disease (81.0% vs. 55.7%; P < 0.001) [20]. Another more recent retrospective study examined clinical outcomes in patients who had transfusion-associated iron overload and chronic refractory anemia (N = 13, >2 units/month for >1 year) [21]. In this study, SF levels increased to 1830–5740 ng/mL overall, with nine patients having levels >3500 ng/mL, and 10 of 13 patients having liver dysfunction, mainly elevations in alanine transaminase and glutamic oxaloacetic transaminase. A total of eight patients, all with a 3- to 5-year transfusion dependence and SF levels exceeding 3500 ng/mL, died during the follow-up; causes of death included heart and liver dysfunction, as well as severe infection [21].