Masaki Yamaguchi

Preemptive therapy of human herpesvirus-6 encephalitis with foscarnet sodium for high-risk patients after hematopoietic SCT.

Human herpesvirus-6 (HHV-6) is a major cause of limbic encephalitis with a dismal prognosis after allogeneic hematopoietic SCT (HSCT). A prospective, multicenter study was conducted to assess the safety and efficacy of preemptive therapy with foscarnet sodium (PFA) for the prevention of HHV-6 encephalitis. Plasma HHV-6 DNA was measured thrice weekly from day 7 until day 36 after umbilical cord blood transplantation (UCBT) or HSCT from HLA-haploidentical relatives. PFA, 90 mg/kg/day, was started when HHV-6 DNA exceeded 5 × 102 copies/mL. Mild and transient adverse events were associated with PFA in 7 of 8 patients. Twelve of 15 UCBT recipients became positive for HHV-6 DNAemia, defined by greater than 1 × 102 copies/mL of HHV-6 DNA in plasma. The virus exceeded 5 × 102 copies/mL in seven patients, whereas none of the five HLA-haploidentical HSCT recipients became positive. One patient developed mild limbic encephalitis just after initial PFA administration. Preemptive PFA therapy is safe, but as HHV-6 DNAemia can abruptly develop before neutrophil engraftment in UCBT recipients, prophylactic PFA administration from day 7 or earlier after UCBT may be needed.

Treatment of pure red cell aplasia after major ABO-incompatible peripheral blood stem cell transplantation by induction of chronic graft-versus-host disease

This report concerns a case of long-lasting pure red cell aplasia (PRCA) with a duration of 178 days after major ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). The patient needed red blood cell transfusion every week from day 54 following PBSCT. He showed no evidence of GVHD and the dose of cyclosporin A (CsA) was reduced rapidly from day 123, followed by the development of chronic GVHD around day 145. The patient no longer needed transfusions from day 167, the reticulocyte count began to increase on day 179, and antidonor isohemagglutinin titers became undetectable. Chronic GVHD induced by tapering of CsA thus appeared to be related to improvement in PRCA.

Graft rejection and hyperacute graft-versus-host disease in stem cell transplantation from non-inherited maternal antigen complementary HLA-mismatched siblings

Human leukocyte antigen (HLA)‐mismatched stem cell transplantation from non‐inherited maternal antigen (NIMA)‐complementary donors is known to produce stable engraftment without inducing severe graft‐versus‐host disease (GVHD). We treated two patients with acute myeloid leukemia (AML) and one patient with severe aplastic anemia (SAA) with HLA‐mismatched stem cell transplantation (SCT) from NIMA‐complementary donors (NIMA‐mismatched SCT). The presence of donor and recipient‐derived blood cells in the peripheral blood of recipient (donor microchimerism) and donor was documented respectively by amplifying NIMA‐derived DNA in two of the three patients. Graft rejection occurred in the SAA patient who was conditioned with a fludarabine‐based regimen. Grade III and grade IV acute GVHD developed in patients with AML on day 8 and day 11 respectively, and became a direct cause of death in one patient. The findings suggest that intensive conditioning and immunosuppression after stem cell transplantation are needed in NIMA‐mismatched SCT even if donor and recipient microchimerisms is detectable in the donor and recipient before SCT.

Polyclonal B cell chronic lymphoproliferative disease with hairy cell morphology: A case report and clonal studies

We describe a patient who has a chronic polyclonal B lymphocyte proliferation with a hairy‐cell appearance. A 48‐year‐old Japanese woman with marked splenomegaly, systemic lymphadenopathy, and leukocytosis was referred to our hospital. Laboratory examination revealed marked polyclonal IgG hypergammaglobulinemia. Morphologic examination of the patients peripheral blood, including May‐Glemsa staining and scanning electron microscopy, showed a monotonous proliferation of hairy‐appearing mature lymphocytes. An immunophenotypic study revealed an expansion of cells with mature B cell antigens positive for CD11c; however, light‐chain restriction was not seen. The lack of both immunoglobulin heavy‐chain and T cell receptor gene rearrangements by Southern blot analysis indicated the polyclonal nature of the proliferating B cells. This was confirmed further by a clonal analysis of the patients lymphocytes using an X‐chromosome‐linked restriction fragment polymorphism within the X‐linked phosphoglycerate kinase (PGK) gene. Since chronic B cell lymphoproliferation with a hairy cell appearance has not been described previously, this case might be extremely rare, and has important implications for the pathogenesis of mature B cell lymphoproliferative diseases, including hairy cell leukemia.

Successful treatment of refractory peripheral T-cell lymphoma with a combination of fludarabine and cyclophosphamide.

We report a case of refractory peripheral T-cell lymphoma (PTCL) successfully treated with a combination of fludarabine and cyclophosphamide (FLU/CY). A 68-year-old man with concurrent PTCL and diffuse large B-cell lymphoma was treated effectively with 3-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy, but PTCL relapse occurred and was resistant to ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) therapy. FLU/CY therapy led to complete remission, which was maintained for almost 14 months after a single course. We concluded that a FLU/CY regimen may be useful for attaining long-term remission in patients with refractory relapsed PTCL and should therefore be considered a valuable treatment choice.

Relative erythroid hyperplasia in the bone marrow at diagnosis of aplastic anaemia: a predictive marker for a favourable response to cyclosporine therapy

Predicting the treatment response of aplastic anaemia (AA) is essential when considering cyclosporine (CyA) therapy among several treatment options, because it requires at least 2 months to determine whether the therapy is beneficial to a patient with AA. To identify the characteristics of patients with AA who are likely to respond to CyA therapy we retrospectively reviewed the clinical records and bone marrow smears of patients treated with CyA. Among 30 patients who received the therapy for at least 3 months within 1 year after diagnosis of AA, and who had not been exposed to antilymphocyte or antithymocyte globulin, 16 (53%) responded with disease remission. CyA‐responsive patients had a significantly higher ratio of erythroblasts to granulocytes (E/G ratio) in the bone marrow at the time of diagnosis as compared with patients refractory to therapy (P = 0.004). Multivariate analysis revealed that a high E/G ratio (>0.6) was significantly associated with a good response to CyA (P = 0.03): 15 (83%) of the 18 patients with an E/G ratio >0.6 responded, but only one (8%) of the 12 with an E/G ratio ≥0.6 did. Although the presence of subclinical paroxysmal nocturnal haemoglobinuria was suspected from the relative erythroblastosis observed in the bone marrow of these patients, flow cytometric analysis of neutrophils in the peripheral blood failed to reveal neutrophils deficient for glycosyl‐phosphatidylinositol (GPI) anchored membrane proteins in all but one case. Identification of the presence of relative erythroid hyperplasia in the bone marrow when AA is diagnosed may help to predict a favourable response to CyA therapy, and therefore facilitate the selection of optimal therapy for AA.

Trilineage response to rhG-CSF with subsequent clonal hematopoiesis in a patient with severe bone marrow aplasia.

We treated a patient with severe aplastic anemia with long-term administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF). When a trilineage response of hematopoiesis was obtained after the first treatment, a chromosomal change [45XX, -7] was observed in 20 of the 20 metaphases examined. Later, we were able to show a monoclonal X inactivation pattern in the phosphoglycerate kinase (PGK) gene in the peripheral blood polymorphonuclear leukocytes and mononuclear cells, indicating the presence of clonal hematopoiesis regardless of the disappearance of the karyotype abnormality. We suggest that it is important to pay close attention to the appearance of clonal hematopoiesis during the administration of G-CSF to patients with idiopathic severe bone marrow aplasia.

Human herpesvirus-8-unrelated primary effusion lymphoma of the elderly not associated with an increased serum lactate dehydrogenase level: A benign sub-group of effusion lymphoma without chemotherapy

Abstract Human herpesvirus-8-unrelated primary effusion lymphoma characterized by lymphomatous effusion without nodal lesions occasionally exhibits spontaneous remission. To elucidate the factors associated with a good prognosis, this study analyzed the clinical parameters of four patients treated in the department and 109 patients reported in case reports. The median age was 71 years and the median overall survival was 20 months. Patients possessing two independent favorable factors, an elderly status (≥ 70 years) and low serum lactate dehydrogenase (< 500 IU/L) showed a markedly higher 1-year survival than patients lacking either of the two factors in the absence of chemotherapy (94% vs 20%, p = 3 × 10−5), which was similarly observed in the chemotherapy group (94% vs 51%, p = 0.002). The use of rituximab was also a strong predictor of survival (89% vs 49%, p = 7 × 10−6). Elderly patients not exhibiting an increased lactate dehydrogenase may represent a benign sub-group of effusion lymphoma, which do not require chemotherapy to achieve remission.

Safety of marrow harvesting procedure. A study of complications from 66 marrow donors.

The experience at Kanazawa bone marrow transplantation team in harvesting marrow for allogeneic BMT from 66 normal donors is presented in detail. Six donors were less than 10 years old and three donors were older than 50 years old. No special difficulties were encountered with these donors. Median volume of harvesting marrow was 750ml, median duration of the anesthesia and the operation were two hours and 35 minutes and one hour and a half respectively. Fifty-nine % of the donors was associated with transient fever and 4.7% of the donors needed medication for pain of aspiration site. The median duration of hospitalisation after the operation was 4 days. Three donors needed further hospitalisation than 8 days after the operation for treatment of goat, bronchial asthma and lung tuberculosis. No major complications occurred in any of the donors.