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.

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.

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.

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.

Polyclonal proliferation of plasma cells associated with marked hypergammaglobulinemia in an elderly patient.

We describe an 89-year-old woman who presented with prominent plasmacytosis mimicking plasma cell leukemia. The apparent serum M-protein level of > 7 g/dL of gamma mobility was revealed to be a polyclonal increase of immunoglobulins. The plasma cells in the peripheral blood expressed polyclonal surface/cytoplasmic immunoglobulins as well as CD19, CD30, CD38, and CD138 antigens but lacked CD10, CD20, CD25, and CD56. The bone marrow plasma cells showed the CD45+, CD19+, CD56-, MPC-1(-/+), and CD49e- immunophenotype, which was in clear contrast with the immunophenotypes of the neoplastic myeloma cells. Abdominal lymphadenopathy, splenomegaly, and a high level of soluble interleukin 2 receptor may have been reflections of an underlying lymphoproliferative disorder, potentially leading to the polyclonal proliferation of plasma cells.

Clinical implications of blast immunophenotypes in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are malignant disorders of hematopoietic cells. For many neoplasms, immunophenotype data of the neoplastic cells provide valuable information in clinical practice. However, the clinical values of immunophenotype data have not yet been firmly established for MDS. Since MDS blasts are not predominant in the bone marrow and peripheral blood, which makes reliable immunophenotyping of blasts difficult, we used a newly developed density-centrifugation reagent to generate blast-enriched MDS samples for phenotyping. The key findings of our study, which phenotyped blasts from 116 patients with MDS or acute leukemia transformed from MDS, were the following. (1) MDS blasts were usually CD34( + )CD38( + )HLA-DR( + )CD13( + )CD33( + )CD2(-)CD3(-)CD5(-)CD8(-)CD19(-)CD20(-) in flow cytometric analysis and often lacked myeloperoxidase in cytochemistry, regardless of the MDS subtype. (2) MDS blasts showed asynchronous expression of antigens (expression of both stem cell antigens and antigens of mature myeloid cells). (3) During disease progression of MDS, phenotypic clonal evolution (transition from blasts with a relatively mature phenotype to blasts with a more immature phenotype) occurred in at least some cases. (4) CD7-positivity was an independent variable associated with a short survival in MDS. Further studies of blast immunophenotypes will deepen our understanding of MDS and hopefully improve the clinical approach to these intractable disorders.

Association between phenotypic features of blasts and the blast percentage in bone marrow of patients with myelodysplastic syndromes.

Although the blast percentage in the bone marrow (BM) is a key parameter for the classification of myelodysplastic syndromes (MDS), the current blast percentages used to define MDS subtypes have not been shown to have strong biological relevance. We determined the blast phenotypes and examined their relationship with the BM blast percentage in 90 MDS cases. When the BM blast percentage increased, cases whose blasts expressed CD7, CD56 and CD117 increased whereas cases whose blasts expressed CD10, CD11b and CD15 decreased. The BM blast percentages where the blast immunophenotype changed were 5, 10, 20 and 25%. Blast immunophenotypes have the potential to provide a biological basis for and refine the present MDS classifications.

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.

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).