Haruki Kondo

Beneficial effects of rituximab on primary cold agglutinin disease refractory to conventional therapy.

Abstract: A case is reported of lymphoplasmacytoid lymphoma (LPL) associated with a monoclonal immunoglobulin (Ig) M and cold agglutinin disease (CAD) that was successfully treated with rituximab. A 52‐yr‐old male was admitted with a direct antiglobulin test positive haemolytic anaemia and thrombocytopenia associated with monoclonal IgM. Bone marrow examinations disclosed the marked infiltration of medium‐sized lymphoma cells with plasmacytoid differentiation that indicated non‐Hodgkins lymphoma of B‐cell origin (LPL). Prednisolone and combination chemotherapy were temporarily effective for both anaemia and thrombocytopenia, although these strategies became refractory and bone marrow lymphoplasmacytosis persisted. CAD ameliorated, and the serum level of IgM decreased in association with the disappearance of lymphoma cells and clonal rearrangement of the Ig heavy chains in the bone marrow after treatment with rituximab. Rituximab played a significant role in the treatment of refractory CAD associated with LPL.

Haematological Effects of Oral Cobalamin Preparations on Patients with Megaloblastic Anaemia

We investigated the haematological effects of a massive dose of oral cobalamin (vitamin B12) on patients with cobalamin deficiency anaemia who had severe anaemia with a few neurological impairments and found that oral treatment was almost as effective as conventional injection therapy. The recovery of haematological indices with oral cobalamin preparations was slightly slower than with parenteral preparations, although the subjective symptoms disappeared soon after the start of therapy. The results of this study indicate that oral treatment keeps the cobalamin body stores satisfactorily filled and might be useful for older patients in whom injecting might be difficult.

Autoimmune haemolytic anaemia, Sjögren's syndrome and idiopathic thrombocytopenic purpura in a patient with sarcoidosis.

A unique occurrence of sarcoidosis autoimmune haemolytic anaemia (AIHA), Sjögrens syndrome and idiopathic thrombocytopenic purpura (ITP) in the same patient is reported. Although the occurrence of autoimmune disease with sarcoidosis is well known, a case in which several of these diseases coexist with sarcoidosis is rare. We present a man with longstanding sarcoidosis who developed AIHA. Sjögrens syndrome and ITP. This case report seems to be the first case in which three autoimmune diseases were accompanied by sarcoidosis in 1 patient.

T-Large Granular Lymphocyte Leukemia Accompanied by an Increase of Natural Killer Cells (CD3-) and Associated with Ulcerative Colitis and Autoimmune Hepatitis

Clonal expansion of large granular lymphocyte(LGL) have been classified into T-LGL and NK-LGL leukemia. T-LGL leukemia cells have a CD3+ phenotype and show clonal T-cell receptor(TCR) gene rearrangement. NK-LGL leukemia cells have a CD3-phenotype and no TCR gene rearrangement. We report a case of T-LGL leukemia accompanied by NK LGL expansions in a 65-year-old man who was observed 3 years earlier to have a LGL lymphocytosis in association with ulcerative colitis(UC) and autoimmune hepatitis (AIH). Phenotypic analysis of peripheral blood by flow cytometry disclosed an increase of both T-LGL(CD3+,CD56-,CD57+,and TCRαβ+) and NK-LGL (CD3-,CD16+,CD56+, and CD57+). Clonal rearrangement of the TCR β gene was detected. A diagnosis of UC and AIH was made on the basis of the X-ray and mucosal biopsy findings of the large intestine, and on the scoring system for diagnosis of AIH, respectively. The disease was nonprogressive, and mesalazine and prednisolone were successful for treatment of UC and AIH. Previously reported cases of T-LGL, NK-LGL leukemia, or NK cell lymphocytosis had no association with UC or AIH, and there have been no reports having both T-LGL leukemia with T-cell receptor gene rearrangement and chronic NK cell lymphocytosis co-existing in a single patient.

Anti-tumor Activity of Pamidronate in Human Multiple Myeloma

We report a patient with multiple myeloma who was treated with pamidronate disodium every 3 weeks for 18 months without any other chemotherapeutic agents. Pamidronate therapy resulted in a marked reduction of marrow plasmacytosis and serum paraprotein levels, and recovery from anemia together with an increase in bone mineral density (BMD). To our knowledge, this is only the third report in which bisphosphonates showed anti-myeloma effects in humans and the result suggests that the compound has a clinically useful anti-tumor effect.

Pure Red Cell Aplasia Associated with Parvovirus B19 Infection in T-large Granular Lymphocyte Leukemia

There have been few reports of large granular lymphocyte (LGL) leukemia with neutropenia complicated with pure red cell aplasia (PRCA) that developed after human parvovirus (HPV) B19 infection. We report here the case of a 35-year-old female who developed HPV B19-associated PRCA with T-LGL leukemia. LGL count of peripheral blood was lower than 2 × 109 1-1, although phenotypic analysis of LGL showed CD3+, CD16-, CD56-, CD57+ with double positive for CD3 and CD57, and genetic study showed the clonal rearrangement of T-cell receptor gene. Microscopically, the patients bone marrow showed characteristic giant proerythroblasts. A serologic study of HPV B19 was positive for IgM, but negative for IgG, with a positive result on Dot-blot hybridization assay for HPV B19 DNA. Severe anemia and reticulocytopenia ameliorated without treatment 10 days after the initial examination, but slight anemia, neutropenia, a moderate increase of LGL counts with rearrangement of TCR gene, and positive result of HPV B19 DNA has persisted 7 months after the initial examination. We suggest that this viral infection may play an etiologic role in some patients with LGL leukemia who develop PRCA.

CD3+, CD4–, CD8–, TCRαβ–, TCRγδ+ Granular Lymphocyte Proliferative Disorder without Lymphocytosis and Clinical Symptoms

Granular lymphocyte-proliferative disorder is characterized by a proliferation of large granular lymphocytes (LGLs). It is often associated with neutropenia, rheumatoid arthritis (RA), and pure red cell aplasia (PRCA). Phenotypic analysis has demonstrated that in most cases, the LGLs show a clonal rearrangement of the TCRαβ rearrangement. We are reporting a patient with TCRγδ LGL proliferation without clinical findings and lymphocytosis. The patient showed an expansion of the CD3+, CD16+, CD56+, and CD57+ LGL populations which involved coexpression of TCRγδ with TCR Jγ and Jδ1 gene rearrangement. Autoimmune manifestations, including RA and PRCA, have not appeared and the results of laboratory examinations have not changed for 1 year after the diagnosis.

IgM myeloma: different features from multiple myeloma and macroglobulinaemia.

To the Editor: A lack of osteolytic lesions is usually used as a criterion for differentiating Waldenstrom’s macroglobulinaemia (WM) from multiple myeloma (MM). The association of increased monoclonal IgM molecule production with diffuse osteolytic lesions is a rare clinical form, and it has been estimated that the incidence of a such a combination is 2% of patients with WM (1-3) with most of these cases being interpreted as WM accompanying bone lesions (4-6). Although the existence of IgM myeloma is argumentative, some of the reports have shown that IgM myeloma should be considered a clinical entity of MM (7-9). However, recently immunologic analysis of the malignant cell suggested that IgM myeloma phenotypically is an intermediate form between MM and WM (10). We present here a case with macroglobulinaemia and bone lesions of which the clinical features and laboratory findings were different from those of WM and MM, and discuss the distinction between WM, MM, and IgM myeloma.

Autologous stem cell transplantations for recurrent adult T cell leukaemia/lymphoma using highly purified CD34+ cells derived from cryopreserved peripheral blood stem cells.

We performed double autologous PBSCT in one fulminantly relapsed ATL patient. Cryopreserved PBSCs containing tumour cells were thawed, and CD34+ cells were selected for by immunomagnetic beads, with the aim of decreasing the number of re-infused tumour cells. The patient received 0.72 × 106 and 0.90 × 106 CD34+ cells/kg. The graft contained less than 0.1% T cells. The patient had a very good recovery, and maintained a good quality of life, until she died on Day 339 after her first PBSCT in third relapse. We conclude that autologous PBSCT for ATL patient has benefit in some instances, and cryopreserved PBSCs can be used for CD34+ selection.

Direct-Antiglobulin-Test-Negative Immune Haemolytic Anaemia and Thrombocytopenia in a Patient with Hodgkin’s Disease

A case of direct-antiglobulin-test (DAT)-negative auto-immune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) associated with Hodgkin’s disease (HD) is reported. A 52-year-old male was admitted with anaemia, thrombocytopenia, and lymphadenopathy. The patient was DAT negative, although he exhibited the clinical features of warm-type AIHA and elevated levels of red-blood-cell-associated IgG (RBC-IgG). The serum level of platelet-associated IgG (PA-IgG) was markedly increased. A biopsy specimen of the inguinal lymph nodes showed HD of mixed cellularity. Marked improvement of subjective symptoms, normalization of haematological values and a decrease in the level of both RBC- and PA-IgG were observed after the start of combination chemotherapy for HD. Although the association of HD, ITP, and/or AIHA has been infrequently reported, the measurement of RBC-IgG is recommended in cases of HD with anaemia even though DAT is negative, since HD is known to be associated with various protean immunological abnormalities.