A Ishida’s research while affiliated with Tachikawa Hospital and other places

To evaluate the efficacy and safety of a combined regimen of bendamustine (B) and rituximab (R) in Japanese patients with relapsed/refractory (r/r) indolent B-cell non-Hodgkin lymphomas (B-NHLs) and mantle cell lymphoma (MCL). Patients aged 20-79 years with pathologically confirmed B-NHLs or MCL, which were r/r after 1-2 R-containing regimens, were included in this study. The BR regimen consisted of B (90 mg/m(2)) for two consecutive days and R (375 mg/m(2)) on day 1, 2, or 3. The course was repeated every 4 weeks for up to four cycles. Fifty-three patients were enrolled in this study and analyzed. The diagnosis included follicular lymphoma (FL) (77 %), mucosa-associated lymphoid tissue lymphoma (13 %) and others (10 %). Forty-seven (90 %) patients completed four cycles of treatment as per schedule. Best overall response rate (ORR) and complete response rate (CRR) was 94 and 71 %, respectively (for FL, ORR 95 % and CRR 80 %). The treatment was well tolerated and the primary toxicity was myelosuppression; the incidence of grade 3/4 leukopenia and neutropenia were 42 and 40 %, respectively. There were no grade 5 toxicities. The BR regimen is safe in Japanese patients with r/r indolent B-NHLs and MCL, and is effective for those with r/r indolent B-NHLs. For the evaluation of late toxicity, especially infection, longer follow-up of this cohort is needed.

A 41-year-old man with hairy cell leukemia developed erythroid crisis after the transfusion of red cell concentrate. He was diagnosed with Parvovirus B19 infection based upon the presence of B19-specific IgM antibody and viral DNA in the sera. The repository sample from the corresponding red cell concentrate was negative for B19 antigen by red cell hemo-agglutination method, but was found to contain B19 virus DNA. Furthermore, a genomic PCR direct sequencing showed that B19 in both patient's sera and repository sample were identical. This is the first report directly demonstrating the transmission of B19 through B19 antigen-negative red cell concentrate transfusion. Further accumulation of the cases is warranted to estimate its incidence and to reconsider the screening methods of blood products.

Pemphigus is an autoimmune bullous disease caused by circulating IgG autoantibodies against cell-cell adhesion molecules between keratinocytes: desmoglein (Dsg) 3 and Dsg1. Plasmapheresis is often used to treat severe cases of pemphigus. Enzyme-linked immunosorbent assays (ELISAs) against recombinant Dsg3 and Dsg1 have recently become available, allowing us to quantify IgG autoantibodies against Dsg3 and Dsg1. Using ELISA against recombinant Dsg3 and Dsg1, to evaluate the efficacy of plasmapheresis in pemphigus. Sera obtained from 10 patients with pemphigus vulgaris and one with pemphigus foliaceus following a total of 16 cycles of centrifugal plasmapheresis and 12 effluents from the plasmapheresis were subjected to ELISA against Dsgs. The percentage of IgG autoantibodies removed was calculated using two different formulae: one used serum titres before and immediately after plasmapheresis and the other used the absolute amounts of IgG autoantibodies in the effluents. The percentage fall of anti-Dsg antibody level was also calculated using the serum titres 1 day after plasmapheresis. Using serum titres immediately after plasmapheresis, there was a mean fall per treatment in anti-Dsg 3 antibody level of 43.0% (n = 12) and in anti-Dsg1 antibody level of 48.4% (n = 7). By contrast, calculated from the effluents, on average one treatment removed only 14.6% of anti-Dsg3 antibodies (n = 12) and 16.4% of anti-Dsg1 antibodies (n = 7). This should reflect the correct percentage as it is based on the absolute amounts of IgG autoantibodies removed. Using serum titres 1 day after plasmapheresis, there was a mean fall per treatment in anti-Dsg 3 antibody level of 12.9% (n = 2) and in anti-Dsg1 antibody level of 8.4% (n = 4). The percentage of IgG autoantibodies removed 1 day after plasmapheresis was lower than that found to be removed immediately after plasmapheresis (n = 6). One centrifugal plasmapheresis procedure eliminates about 15% of the IgG autoantibodies from the whole body. The percentage fall of anti-Dsg IgG antibody level differed depending on when the serum samples were obtained after plasmapheresis. The change in the percentage fall of anti-Dsg antibody level within 1 day after plasmapheresis is thought to be attributable to the passive diffusion of the IgG autoantibodies from the extravascular space to the intravascular space. Therefore, removal of IgG autoantibodies calculated using serum titres only should be evaluated carefully considering the equilibration of the IgG autoantibodies between the different body spaces.

Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.

Massive transfusion is defined as transfusion of more than total blood volume within 24 hours. There are several adverse effects associated with massive transfusion, and dilutional thrombocytopenia is known as one of the major adverse effects. Dilutional thrombocytopenia is caused by platelet loss out of the body and platelet dilution with replaced red cells and crystalloids. Volume of blood loss or replaced volume is a good indicator of dilutional thrombocytopenia, and previous reports suggest that severe thrombocytopenia doesn't occur before replaced volume surpasses over one hundred and fifty percent of total blood volume. Recently, an automated blood cell counter has spread and platelet count is available in a short time, even at night. To treat the patient with dilutional thrombocytopenia, platelet count is very helpful to decide when to start platelet transfusion. When platelet count decreases as low as 50,000/mm3, platelet transfusion should be considered. Nowadays, dilutional thrombocytopenia is less frequent complications of massive transfusion than before, because platelet transfusion tends to be performed before platelet count fall to the critical point. Thus, exceeded platelet transfusion might become another problem after massive transfusion.

Bacterial meningoencephalitis occurring in the pre-engraftment period after bone marrow transplantation (BMT) is a rare complication, and the feasibility of granulocyte transfusion (GTX) in such cases remains to be elucidated. A 37-year-old man developed enterococcal meningoencephalitis during a severely granulocytopenic pre-engraftment period after BMT. Despite therapy with appropriate antibiotics, cultures of blood and cerebro-spinal fluid (CSF) continued to grow Enterococcus faecalis, and he developed rapid mental deterioration and seizure. Granulocytes were collected from his HLA-mismatched, ABO-matched sibling with subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) and oral dexamethazone. Transfusion of 4.4 x 10(10) granulocytes resulted in a 12-h post-transfusion granulocyte increment of 2.0 x 10(9)/l, and maintained peripheral blood granulocyte counts above 0.5 x 10(9)/l for 3 days. A rapid increase of granulocytes in CSF was also observed, and cultures of blood and CSF became negative after GTX. A transient worsening of seizure was observed as a potential side effect of GTX. The patient subsequently developed septic shock because of Pseudomonas aeruginosa and died. Further studies are warranted to evaluate the clinical efficacy of GTX for the treatment of uncontrolled infections in granulocytopenic stem cell transplant recipients.

Although allogeneic transplantation is a curative therapy for chronic myelogenous leukemia (CML), treatment-related mortality is still a major cause of death after transplantation, especially in older patients. We investigated the safety and efficacy of reduced-intensity conditioning consisting of low-dose (600 cGy) total body irradiation and cytosine arabinoside (1 g/m2) together with a continuous infusion of granulocyte colony-stimulating factor and cyclophosphamide (120 mg/kg) in patients with CML in the chronic phase. Fractionated splenic irradiation (5 Gy) was also administered as part of the conditioning treatment. Eight patients older than 40 years underwent allogeneic bone marrow transplantation from an HLA-matched sibling following this conditioning. Regimen-related toxicities (equal to or greater than grade III) were not observed. Rapid restoration of 100% donor chimerism was confirmed by fluorescence in situ hybridization methods in 5 sex-mismatched transplant recipients. One patient died from severe acute graft-versus-host disease and another from Pneumocystis carinii pneumonia early in the course of transplantation. A sustained engraftment was achieved in 5 long-term survivors; in 1 case, the graft was rejected but the Philadelphia chromosome and BCR/ABL-negative autologous hemopoiesis were restored. After a minimum follow-up period of 60 months, 6 patients, including the patient with restored autologous hemopoiesis, were still alive and in remission with 100% donor chimerism. Six years after the transplantation, 1 patient experienced a cytogenetic relapse, which was successfully treated with donor lymphocyte infusions. In summary, this reduced-intensity conditioning resulted in a cure with markedly reduced regimen-related toxicities in this relatively older cohort of patients with CML.

We prospectively evaluated a risk-adapted pre-emptive treatment with ganciclovir for CMV diseases in patients undergoing allogeneic bone marrow transplantation (BMT). High-level CMV antigenemia (10 or more positive cells on two slides) or CMV antigenemia at any level in patients with grade II-IV acute graft-versus-host disease (aGVHD) were chosen as risk factors. We also retrospectively evaluated virus reactivation in plasma using quantitative real-time polymerase chain reaction (PCR). Fifty patients were evaluable. None of the 27 patients with or without grade I aGVHD developed high-level CMV antigenemia or CMV disease. Among the 23 patients with grade II-IV aGVHD, 12 patients (52%) developed CMV antigenemia and were treated pre-emptively, of whom two developed CMV gastroenteritis or retinitis in spite of therapy. Six of the remaining 11 patients developed CMV gastroenteritis before CMV antigenemia was detectable. All of the eight patients with CMV diseases were successfully treated with ganciclovir and no deaths directly related to CMV disease occurred. In four of the seven evaluable patients with CMV gastroenteritis, real-time PCR was able to detect virus reactivation earlier than CMV antigenemia. Although our risk-adapted pre-emptive therapy effectively reduced CMV-related mortality, further refinements of this approach, particularly in the prevention of CMV gastroenteritis, may be achieved by incorporating real-time PCR.