Akinori Mori

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.

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.

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.

Maintenance with Pamidronate Following First-line MP or VAD Therapy in Multiple Myeloma

We investigated the anti-tumor effect of pamidronate after obtaining a decrease of serum monoclonal immunoglobulin (Ig) level by conventional chemotherapy in patients with multiple myeloma (MM) in order to evaluate whether the drug is useful as maintenance therapy for MM. Eight patients with MM received 60 mg/d pamidronate every third week for 6-18 months without chemotherapeutic agents or corticosteroids after the treatment with melphalan and prednisolone, or vincristine, adriamycin and prednisolone. Serum Ig and β 2-microglobulin (b2MG) levels were maintained at the levels obtained after the termination of chemotherapy in six and four out of eight patients, respectively. Hemoglobin levels were maintained at, or increased to more than, the levels observed at the end of chemotherapy in six patients. Decreased plasma cells in the bone marrow after the chemotherapy were evident in five patients. Two patients were categorized as non-responders, because Ig and b2MG increased and anemia progressed after treatment with the drug. Despite the very small numbers, the results suggest that pamidronate may have anti-tumor activity and be useful for treatment after the conventional chemotherapy in some cases of MM.

Effects of rituximab on a patient with Waldenström's macroglobulinaemia with deletion 13q14

Abstract: The haematological and serological responses of Waldenströms macroglobulinaemia (WM) to rituximab have been recently reported, but there have been few reports examining the genetic responses of the drug in the treatment of WM. We report here a case of WM associated with deletion 13q14 and JH gene rearrangement that was successfully treated with rituximab alone. Three months after the therapy, the patient achieved haematological remission with the disappearance of constitutional symptoms and chromosomal abnormalities; however, the remission was partial, because the serum monoclonal immunoglobulin M and JH gene rearrangement persisted. Our case demonstrates that first‐line therapy with rituximab is clinically and cytogenetically beneficial for WM.

Remission Induction of Refractory Anaemia with Excess Blasts in Transformation by Sole Treatment with Granulocyte Colony-Stimulating Factor with Persistent Chromosomal Abnormality

We report a patient with myelodysplastic syndrome (MDS), refractory anaemia with excess blasts in transformation, in whom complete remission (CR) was achieved with the administration of granulocyte colony-stimulating factor (G-CSF). The 76-year-old patient was admitted to our hospital with a fever and a productive cough; a diagnosis of pneumonia was thus made. Following treatment with antibiotics, the patient’s condition improved, and MDS was diagnosed from peripheral blood and bone marrow examinations after the patient recovered from the infection. The patient achieved a sustained haematological CR that was confirmed by morphological and flow cytometric examination after treatment with G-CSF alone, although chromosomal abnormalities persisted. According to the literature, in almost all patients with acute myeloid leukaemia or MDS who were reported to achieve CR by G-CSF, the course was associated with infection, although our case did not have this complication during the course of G-CSF therapy. We suggest that patients with G-CSF alone without infection can achieve CR and that this may be related to a differentiation effect of G-CSF based on persistent chromosomal abnormality in this case.

CASE REPORT: Acute Pancreatitis Induced by Diffuse Pancreatic Invasion of Adult T-cell Leukemia/Lymphoma Cells

Adult T-cell leukemia/lymphoma (ATLL) is a Tlymphocytic hematological malignancy and is caused by human T-lymphotropic virus type I (HTLV-I) infection. HTLV-I is endemic to the Caribbean, southwestern Japan, Central and South Africa, and South America (1). This virus belongs to the complex type C retrovirus and can immortalize human CD4-positive T-lymphocytes (1, 2). HTLV-I is mainly transmitted from mother to child through breast-feeding, and ATLL can occur 40 to 60 years after the infection. ATLL has been classified into four types, ie, smoldering, chronic, lymphoma, and acute types. The clinical course of acute-type ATLL progresses rapidly, and the patients often die (1). Cases of acute pancreatitis associated with ATLL have been reported (3–5). In these cases, the cause of acute pancreatitis was often considered to be hypercalcemia, and an ATLL invasion into the pancreas was not confirmed. Here, we report that the acute pancreatitis is associated with a diffuse pancreatic invasion of ATLL, which was detected using fine needle biopsy (FNB) specimens. Furthermore, this pancreatitis was improved by chemotherapy for ATLL.