Pericardial graft vs. host disease in a patient with myelodysplastic syndrome following peripheral blood stem cell transplantation.

A patient with myelodysplastic syndrome developed pericardial effusion 20 month after allogenic peripheral blood stem cell transplantation. Sclerotic and erythematous skin lesions were observed over the face and extremities, and a diagnosis of chronic graft vs. host disease (GVHD) was made based on skin biopsy findings. Pericardial fluid contained numerous CD8+/HLA-DR+ lymphocytes, but no leukaemic cells. Tumour necrosis factor alpha (TNFalpha) and soluble Fas (sFas) levels were highly elevated in both the effusion and serum. The patient was treated with methylprednisolone and tacrolimus. Skin GVHD improved rapidly associated with resolution of pericardial effusion and reductions in cytokine levels. We concluded that pericardial effusion was due to pericarditis and was a manifestation of chronic GVHD in this patient, and that cytotoxic lymphocytes and specific cytokines played significant roles.

Aplastic anemia associated with initiation of nizatidine therapy in a hemodialysis patient.

We report on a hemodialysis (HD) patient in whom fatal aplastic anemia developed after the administration of nizatidine, a histamine 2 (H2)-receptor antagonist. The patient was a 55-year old Japanese woman and had been on HD for 2 years due to endstage diabetic nephropathy. The patient had a hemorrhagic duodenal ulcer and had been treated with lansoprazole, a proton pump inhibitor, for 2 months. After improvement, lansoprozole was discontinued and she was subsequently treated with nizatidine. Twelve days after initiation of nizatidine treatment, the patient developed a high-grade fever with symptoms suggestive of upper respiratory infection. Hematological tests showed severe pancytopenia, and drug-induced aplastic anemia was diagnosed. Nizatidine was suggested as the causal drug. Despite intensive therapies, the patient died on the 23rd hospital day from generalized fungal infections. Although hematological adverse events have been reported in HD patients receiving H2-receptor antagonists, few studies of fatal aplastic anemia associated with these drugs have been reported. This case emphasized that careful observation is required after the initiation of H2-receptor antagonist treatment in HD patients.

[Treatment outcome of myelodysplastic syndrome patients younger than 60 years old].

We evaluated the clinical outcome of 92 patients younger than 60 years who were treated between January 1987 and May 2003. Low, Int-1, Int-2 and High risk groups categorized by IPSS consisted of 7, 34, 24 and 27 patients, respectively. There was no significant difference in the overall survival between 30 patients who received allogeneic stem cell transplantation and 62 patients who did not. Allogeneic stem cell transplantation provided significantly better outcomes in the Int-2 and the High risk groups. Risk factors for overall survival were age and disease status at transplantation. Acute and chronic GVHD did not influence the relapse free survival rate. Allogeneic stem cell transplantation is a curative therapy for MDS. It is necessary to reduce transplantation related death and to perform stem cell transplantation as soon as possible for patients with Int-2 or High risk of IPSS.

TCR Vbeta repertoire analysis in CD56+ CD16(dim/-) T-cell large granular lymphocyte leukaemia: association with CD4 single and CD4/CD8 double positive phenotypes.

We report 10 patients with T-cell large granular lymphocyte (LGL) leukaemia: four patients had CD16+ CD56- LGL lymphocytes (typical for LGL leukaemia), and six patients had CD56+ CD16(dim/-) LGL lymphocytes (atypical). Among the CD56+ CD(dim/-) patients, LGL lymphocytes were CD4+ CD8- in one patient, CD4/CD8 double positive (DP) in three, and CD4- CD8+ in two. The CD4+ CD8dim DP cells expressed a CD8alphaalpha homodimer. T-cell receptor (TCR) Vbeta complementarity-determining region 3 (CDR3) size distribution analysis and direct sequencing identified at least 1 in-frame clonal TCR Vbeta transcript in each patient; three patients had two or three different clonal sequences. To determine whether these transcripts were translated into cell surface TCR, we performed flow cytometric analysis using Vbeta monoclonal antibodies (mAbs). A single Vbeta protein was identified in patients, even those with multiple in-frame transcripts. Previous and present results suggest that CD56+ CD16(dim/-) LGL leukaemia is more common than previously thought, and is associated with unusual phenotypes. When assessed using only molecular techniques, the monoclonal status of this disease may be misinterpreted as oligoclonal; thus, flow cytometric analysis using Vbeta mAb is quite useful. Because mAbs do not cover the entire Vbeta repertoire, assessing clonality using a combination of molecular methods and mAbs is preferable.

High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by increased platelet clearance because of antiplatelet antibodies. It was recently reported that the balance of T helper 1 (Th1) and T helper 2 (Th2) subsets has been implicated in the regulation of many immune responses. In this study, the intracellular interleukin-4 and interferon-gamma production in CD4+ T-lymphocytes activated by phorbol 12-myristate 13-acetate and ionomycin was assessed via flow cytometry in order to determine the clinical significance of the Th1/Th2 ratio in 42 patients with ITP. The study cohort included 28 untreated patients, seven postprednisolone therapy patients and seven postsplenectomy patients. The mean level of the Th1/Th2 ratio in the untreated group was 36.9 (95% CI 25.8-47.9), and significantly higher than in the control group (mean 12.8, 95% CI 9.5-16.1). The mean levels of the Th1/Th2 ratio in the postprednisolone therapy and postsplenectomy groups were 20.5 (95% CI 8.4-32.6) and 16.4 (95% CI 3.1-29.7), respectively, but were no significant differences as compared with control subjects. When untreated patients were divided into two subgroups by Th1/Th2 ratio, the mean level of platelet associated IgG in the high Th1/Th2 subgroup (higher than upper limit of control group) tended to be higher than in the normal Th1/Th2 subgroup. In conclusion, the high Th1/Th2 ratio was closely related to the etiology and disease status of chronic ITP.