A Japanese family with X-linked sideroblastic anemia affecting females and manifesting as macrocytic anemia.

X-linked sideroblastic anemia (XLSA) is a rare hereditary disorder that typically manifests in males as microcytic anemia. Here, we report a family with XLSA that affects females and manifests as macrocytic anemia. The proband was a Japanese woman harboring a heterozygous mutation c.679C>T in the ALAS2 gene. This mutation causes the amino acid substitution R227C, which disrupts the enzymatic activity of erythroid-specific δ-aminolevulinic acid synthase. The mutation was not detected in the ALAS2 complementary DNA from peripheral blood red blood cells of the proband, indicating that the cells were mostly derived from erythroblasts expressing wild-type ALAS2. The proband's mother, who had been diagnosed with myelodysplastic syndrome, also had XLSA with the same mutation. Clinicians should be aware that XLSA can occur not only in males but also in females, in whom it manifests as macrocytic anemia.

Co-occurrence of monoclonal gammopathy and myelodysplasia: a retrospective study of fourteen cases.

We report a series of 14 patients with myelodysplastic syndrome (MDS) accompanied by a monoclonal gammopathy unrelated to therapy. Twelve of these had monoclonal gammopathy of undermined significance (MGUS) and two had smoldering multiple myeloma. These cases represent 10.2 % of all MDS cases seen at our institution over a 14-year period (January 2000 to December 2013). The incidence of MGUS was determined to be significantly higher in MDS than in age-matched concurrent controls by χ(2) test. Absence of prior chemotherapy and simultaneous presentation of MDS and MGUS in most cases suggest true co-occurrence of the two disorders. MGUS was found in all WHO subtypes of MDS with a wide range of risk factors. However, 11 out of the 12 MDS cases accompanied with MGUS had relatively low karyotypic risks. In addition, serum M protein levels remained largely unchanged in 4 cases of MGUS for which serial determinations were performed. These findings indicate that MGUS may not affect the prognosis of MDS.

Absent or extremely low neutrophil alkaline phosphatase activity levels in patients with myelodysplastic syndromes.

Three patients with myelodysplastic syndrome (MDS) had absent or extremely low levels of neutrophil alkaline phosphatase (NAP) activity (arbitrarily defined as an NAP score <10). All patients showed varying degrees of hypogranulation in neutrophil morphology. The NAP activity levels transiently normalized following the administration of granulocyte colony-stimulating factor (G-CSF) in two cases. No patients experienced any severe infectious episodes. These results suggest that NAP activity is not central to the neutrophil function.

Morphologic analysis in myelodysplastic syndromes with del(5q) treated with lenalidomide. A Japanese multiinstitutional study.

Lenalidomide is known to be effective in myelodysplastic syndromes (MDS) with del(5q) in improving anemia and suppressing del(5q) cells. MDS with del(5q) shows increase of nonlobulated megakaryocytes. However, histopathology of MDS with del(5q) treated with lenalidomide has not been fully studied. We investigated the morphologic changes in lenalidomide treated low- or intermediate-1-risk MDS with del(5q). All of evaluable patients showed high proportion of nonlobulated megakaryocytes. The nonlobulated megakaryocytes were markedly decreased in 6 patients during therapy in parallel with suppression of del(5q) cells. Our analysis suggests that single allele deletion of common deleted region inhibits nuclear lobulation of megakaryocytes.

Immune pancytopenia associated with a leukemic B-cell tumor carrying t(14;18)(q32;q21) translocation.

We report a 75-year-old man who was initially suggested to have acute leukemia. The hemoglobin level was 3.8 g/dL, white cell count was 7,700/µL with an absence of mature neutrophils and 69.0% leukemic cells, and platelet was 0.4 × 10(4)/µL. Coombs' antiglobulin test was positive. Leukemic cells were CD5(-), CD10(+), CD20(+), CD23(-), and IgG/λ(dim+). The bone marrow consisted of normal hematopoietic precursors, whereas fluorescence in situ hybridization detected the BCL2/IgH fusion gene. He was treated with rituximab-containing chemotherapy, resulting in the resolution of pancytopenia. The underlying disease was a leukemic B-cell tumor with t(14;18)(q32;q21), and the pancytopenia was mainly caused by autoimmune mechanisms.

The duration of functioning of a subcutaneous implantable port for the treatment of hematological tumors: a single institution-based study.

BACKGROUND: Although subcutaneous implantable ports have been indicated as venous access for chemotherapy, these devices have not been used routinely for hematological tumors. METHODS: Between May 2006 and April 2009, 39 ports were implanted in 37 patients with hematological tumors and 16 ports were implanted in 14 patients with nonhematological tumors. The patients were treated with standard/first-line and/or salvage/second-line or greater chemotherapy, and were prospectively followed until port removal, death, or the end of the study. RESULTS: Thirty-five (96%) patients with hematological tumors developed grade 4 hematological toxicity, while 1 (7%) patient with nonhematological tumors showed grade 4 neutropenia. The actual duration of the port in situ ranged from 14 to 719 days (mean, 271.4 days) in the hematology group, and from 50 to 955 days (mean, 419.5 days) in the nonhematology group (P = 0.039). The Kaplan-Meier-estimated median duration of port in situ in the hematology group was 364 days, which was significantly shorter than that in the nonhematology group (P = 0.009). When patient death and port removal for the end of treatment were censored, the rate of port functioning at 1 year was estimated to be 83% in the hematology group. Bloodstream infection (BSI) occurred in 7 patients with hematological tumors and in 1 patient with metastatic colorectal cancer; however, microbiological confirmation that the implantable port was the source of the BSI was inconclusive. CONCLUSION: The duration of port functioning in patients with hematological tumors was comparable to that in patients with nonhematological tumors. The higher rate of BSI in the hematology group was primarily attributable to profound neutropenia.

Lenalidomide is active in Japanese patients with symptomatic anemia in low- or intermediate-1 risk myelodysplastic syndromes with a deletion 5q abnormality.

Lenalidomide is an immunomodulatory agent recently reported to be effective in the treatment of transfusion-dependent anemia due to low- or intermediate-1 risk myelodysplastic syndromes (MDS) associated with a deletion 5q (del 5q) cytogenetic abnormality. We conducted a multicenter, single-arm clinical trial to evaluate the safety and efficacy of lenalidomide in Japanese patients with anemia in low- or intermediate-1 risk MDS associated with the del 5q cytogenetic abnormality. Eleven patients (5 with transfusion-dependent anemia; 6 with transfusion-independent symptomatic anemia) received once daily oral administrations of 10 mg of lenalidomide for 21 consecutive days in a 28-day treatment cycle. The efficacy was assessed by the IWG criteria. At an interim analysis after > or =24 weeks of therapy, hemoglobin increase was noted in all 11 patients, with a median increase of 6.0 g/dL (range, 0.9-10.9) from the baseline. All transfusion-dependent patients achieved transfusion independence. Histopathologic and cytogenetic improvement was also noted. Neutropenia and thrombocytopenia were the most common adverse events related to lenalidomide. The adverse events were manageable, and no patients experienced serious adverse events or adverse events requiring treatment discontinuation. The results indicate that lenalidomide can be a useful agent for treating Japanese patients with anemia associated with low- or intermediate-1 risk MDS with the del 5q cytogenetic abnormality.

John Auer and Auer rods; controversies revisited.

John Auer first described needle or rod-shaped intracytoplasmic inclusion bodies in leukemia cells in 1906. Auer rods can be seen in myeloid neoplasms ranging from acute myeloid leukemias (AML) to myelodysplasia, but not in normal or non-neoplastic reactive states. This article briefly describes John Auer's experience and discusses debates on Auer rods, and criticizes their place in the definition of refractory anemia with excess of blasts-2 (RAEB-2) in the WHO classification of the myelodysplastic syndromes (MDS).

Historical review. The light and shadow of Paul Kaznelson: his life and contribution to hematology.

Paul Kaznelson is credited with describing the first case of pure red cell aplasia. He was also known for his contribution to the discovery of the therapeutic role of splenectomy in idiopathic thrombocytopenic purpura. Most of his academic works appeared in 1910s and 1920s, when he used to work in Karl-Ferdinand University in Prague. Trail of his rather tragic postwar life is briefly added.

DNA ploidy and cell cycle analyses in the bone marrow cells of patients with megaloblastic anemia using laser scanning cytometry.

BACKGROUND: Megaloblastic anemias are characterized by several hematopoietic cells with dysplastic nuclear morphology. The analyses of DNA ploidy and cell cycle of these cells are important to understand the property of such diseases. METHODS: As laser scanning cytometry (LSC) is a useful tool to evaluate the morphology of the cells fixed on the slide glass together with the quantitative analysis of the fluorescence information of each cell by rapid scanning of the specimens, the authors examined the DNA ploidy and cell cycle of six cases with megaloblastic anemia using LSC. RESULTS: Giant neutrophilic series such as giant metamyelocytes and giant band cells were found to have extraordinarily higher DNA ploidy, while hypersegmented neutrophils represented the normal diploid pattern like normal neutrophils. As to megaloblasts, cell cycle analysis showed that the proportion of the cells in S phase was increased as compared with the case of normal erythroblasts. CONCLUSIONS: The present study clearly demonstrates the abnormal aspects of the hematopoietic cells with megaloblastic anemia from the viewpoint of the DNA ploidy and cell cycle analyzed by the use of LSC.

Evolving new treatment for myelodysplastic syndromes.

Over the last several years, there has been substantial progress in the definition, diagnosis, and management of myelodysplastic syndromes (MDSs). This progress includes the new World Health Organization classification and the revised standardized response criteria to be applicable to most new compounds, which, taken together with the International Prognostic Scoring System, provide a uniform basis for the management of individual patients. The recent introduction of certain new agents, as well as an apparent increase in the use of stem cell transplantation with a variety of so-called reduced-intensity settings, has indeed raised the hope that we are entering a new era of MDS treatment.

A prospective study of cyclosporine A treatment of patients with low-risk myelodysplastic syndrome: presence of CD55(-)CD59(-) blood cells predicts platelet response.

Although immunosuppressive therapy using antithymocyte globulin or cyclosporine A (CSA) is effective in selected patients with low-risk myelodysplastic syndrome, the response rates reported so far are inconsistent, and the indication of immunosuppressive therapy for myelodysplastic syndrome has not been clearly defined. We treated 20 myelodysplastic syndrome patients (17 refractory anemia cases [RA], 2 RA with excess blasts, and one RA with ringed sideroblasts) with 4 mg/kg per day of CSA for 24 weeks. Among the 19 patients evaluated, 10 showed hematologic improvement; 8 patients showed an erythroid response, 6 showed a platelet response, and one showed a neutrophil response. Most patients with hematologic improvement continued CSA thereafter, and the progressive response was observed until the latest follow-up (median, 30 months). Most toxicities associated with CSA usage were manageable, and no patient had developed acute leukemia up to this point. Short duration of illness, refractory anemia with minimal dysplasia determined by bone marrow morphology, and the presence of paroxysmal nocturnal hemoglobinuria-type cells were significantly associated with the platelet response. A minority of RA patients who did not possess such predictive variables achieved an isolated erythroid response. In conclusion, CSA may be a therapeutic option for patients with RA who do not have adverse prognostic factors.

Angioimmunoblastic T-cell lymphoma initially presenting with replacement of bone marrow and peripheral plasmacytosis.

A 73-year-old man presented with lymphadenopathy, hepatosplenomegaly, and a variety of hematological and immunological abnormalities. The bone marrow was replaced by polymorphic cellular infiltrates containing aggregates of CD10(+) T-cells. Circulating lymphoplasmacytic/immunoblastic cells showed an early plasma cell immunophenotype on flow cytometric analysis. Combination of these observations indicated that the underlying disorder of this patient was angioimmunoblastic T-cell lymphoma (AITL); postmortem pathology was consistent with progression of peripheral T-cell lymphoma. Even in the absence of definitive lymph node biopsy, the appearance of the bone marrow and the peripheral blood can lead to the diagnosis of AITL.

Interferon-alfa treatment of essential thrombocythemia during pregnancy.

We report on 2 successful pregnancies in a young woman who has essential thrombocythemia. The platelet count remained well controlled with interferon-alfa administration together with acetylsalicylic acid in each pregnancy. The present case and the published series suggest that close monitoring of the platelet count is crucial and that interferon may be the preferred therapeutic option in the management of pregnancy in patients with essential thrombocythemia.