Distinct subgroups of paroxysmal nocturnal hemoglobinuria (PNH) with cytopenia: results from South Korean National PNH Registry.

We retrospectively assessed the clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria (PNH) according to severity of cytopenia. A total of 282 patients with hematological parameters assessed at the time of diagnosis of PNH were included. There were 24 patients with PNH/severe aplastic anemia (SAA) (at least two of the three criteria; hemoglobin ≤8 g/dL; absolute neutrophil count (ANC) <0.5 × 10(9)/L; platelet count <20 × 10(9)/L), 96 patients with PNH/aplastic anemia (AA) (at least two of the three criteria; hemoglobin ≤10 g/dL; ANC 0.5-1.5 × 10(9)/L; platelet count 20-100 × 10(9)/L), and 162 classic PNH patients. Compared with the classic PNH subgroup, the PNH/SAA subgroup had a significantly lower median granulocyte PNH clone size (26.7 vs. 51.0 %, P = 0.021) and lower incidence of lactate dehydrogenase ≥1.5 times the upper limit of normal (52.9 vs. 80.0 %, P = 0.049). The incidence of thromboembolism was similar in both subgroups. Overall survival was significantly lower in the PNH/SAA subgroup than in the classic PNH subgroup (P = 0.033). Our findings suggest that identification of patients with PNH/SAA at the time of diagnosis is important because of different clinical manifestations and poorer outcome compared with patients with classic PNH (clinicaltrials.gov identifier: #NCT01224483).

The shadowlands of MDS: idiopathic cytopenias of undetermined significance (ICUS) and clonal hematopoiesis of indeterminate potential (CHIP).

The WHO classification provides the best diagnostic approach to myelodysplastic syndromes (MDS). However, biologic and analytic limitations have emerged in the criteria currently adopted to establish the diagnosis and to classify MDS. The provisional category of idiopathic cytopenia of undetermined significance (ICUS) has been proposed to describe patients in whom MDS is possible but not proven. To formulate a diagnosis of ICUS, a thorough diagnostic work-up is required and repeated tests should be performed to reach a conclusive diagnosis. Recent studies provided consistent evidence of age-related hematopoietic clones (clonal hematopoiesis of indeterminate potential; CHIP), driven by mutations of genes that are recurrently mutated in myeloid neoplasms and associated with increase in the risk of hematologic cancer. A subset of mutated genes, mainly involved in epigenetic regulation, are likely initiating lesions driving the expansion of a premalignant clone. However, in a fraction of subjects the detected clone may be a small malignant clone expanding under the drive of the detected and additional undetected mutations. In addition, several experimental evidences suggest the potential relevance of an abnormal bone marrow environment in the selection and evolution of hematopoietic clones in MDS. The spreading of massively parallel sequencing techniques is offering translational opportunities in the clinical approach to myeloid neoplasms. Although several issues remain to be clarified, targeted gene sequencing may be of potential value in the dissection between clonal myelodysplasia, nonclonal cytopenia, and clonal hematopoiesis arising upon aging or in the context of acquired marrow failure.

Spectrum of hematological malignancies and peripheral cytopenias.

BACKGROUND: Peripheral cytopenias such as anemia, thrombocytopenia, bicytopenia and pancytopenia are common peripheral blood findings in hematological malignances for which bone marrow evaluation is often required. The study was conducted to identify the spectrum of hematological malignancies in association with peripheral cytopenia. METHODS: One year retrospective study was conducted in Tribhuvan University Teaching Hospital. Data of bone marrow examination were retrieved from the archives of the hematology department and analyzed. RESULTS: Total number of hematological malignancies out of 400 cases of bone marrow examination was 86 (21.5%). Median age was 13 years. 48 (55.81 %) were children. Male: female ratio was 1.26:1. Frequency of bicytopenia, pancytopenia, anemia and thrombocytopenia were 34.88%, 23.25%, 23.25% and 9.3% respectively. Commonest hematological malignancy was acute leukemia (70.73%) followed by chronic myeloid leukemia (6.97%), plasma cell neoplasm (8.13%), myelodysplastic syndrome (4.65%), Non-Hodgkin lymphoma (2.32%) and hypereosinophilic syndrome (1.16%). In cases of acute leukemia 27 presented with bicytopenia, 15 each with pancytopenia and anemia; and seven with thrombocytopenia. Number cases presenting with bicytopenia and pancytopenia in multiple myeloma was one each and with anemia two. Thrombocytopenia was seen in monoclonal gammopathy of undetermined significance. Bicytopenia and pancytopenia were seen in two cases each of myelodysplastic syndrome. Chronic myeloid leukemia and non-Hodgkin lymphoma showed anemia and pancytopenia respectively. CONCLUSIONS: More than 90% of hematological malignancies presented with cytopenia. Bicytopenia and pancytopenia together constituted 58%. 97% of acute leukemia presented with cytopenia and majority of them had pancytopenia or bicytopenia.

Resumen de Datos Clínicos / Abstract clinical datun

Niño de 2 meses de vida eutrófico que fue derivado a este hospital en regular estado general, con fiebre de dos días de evolución, nistagmus, petequias en miembros superior derecho, reticulado marmóreo, hepatoesplenomegalia, y pancitopenia. Ante la sospecha de Sepsis había recibido tratamiento con Ceftriaxona durante dos días y Amikacina durante un día