Takahiro Karasuno

Vidarabine therapy for virus-associated cystitis after allogeneic bone marrow transplantation

We describe a method of diagnosing virus-associated cystitis after allogeneic bone marrow transplantation (BMT) and treatment with vidarabine therapy. At 7–10 days post-BMT when cystitis was suspected, we observed urinary sediments by the Papanicolaou stain to detect virus inclusion bodies. When positive, we examined urinary sediments by transmission electron microscope and measured the diameter of viral particles to determine the families. This process needed only 4 days. Among 16 consecutive cases, adenovirus and polyomavirus were each detected in three. Adenovirus caused hemorrhagic cystitis in two cases and cystitis without macroscopic hematuria in one case. Polyomavirus caused cystitis without macroscopic hematuria in one case. Polyomavirus was also detected in two cases without any symptoms. Vidarabine (10 mg/kg/day i.v.) was administered for 5 days as one course. Soon after one course of vidarabine, most symptoms subsided and virus inclusion bodies disappeared in all cases except for one with severe hemorrhagic cystitis. From these experiences, vidarabine reduces excretion of adenovirus and polyomavirus in the urine of BMT recipients and improves clinical symptoms in some cases of cystitis associated with these viruses.

Acute abdomen without cutaneous signs of varicella zoster virus infection as a late complication of allogeneic bone marrow transplantation: importance of empiric therapy with acyclovir

Two patients complained of severe abdominal pain as the first sign of varicella zoster virus infection about 1 year after allogeneic BMT. In case 1, eruptions, found on the face and chest on admission, became vesicular and dispersed on the third hospital day. Though acyclovir (ACV) was immediately started, he died on the fourth day. In case 2, skin rash was never observed during the clinical course. Laparotomy on the third hospital day revealed many hemorrhagic spots on the liver surface and mucous membrane of the upper GI tract, indicating disseminated visceral disease. Empiric therapy with ACV was successful. Bone Marrow Transplantation (2000) 25, 1003–1005.

Allogeneic myeloablative transplantation for patients aged 50 years and over

Summary:Allogeneic hematopoietic stem cell transplantation (HSCT) has been performed mainly for young patients due to concern about the high incidence of treatment-related mortality (TRM). Recent advances to reduce TRM by using peripheral blood stem cells or nonmyeloablative conditioning regimens have increased the age limit for this procedure, and correctly identifying the indication for transplant is essential for older patients. In this study, we analyzed data from 398 patients aged 50 or over selected from 5147 patients, who received conventional allogeneic HSCT (c-HSCT). Patients aged 50 or older showed inferior outcomes for TRM and overall survival (OS). Mulitivariate analyses confirmed that an age of 50 or over was an independent risk factor for TRM (P<0.0001) and OS (P<0.0001). Among patients aged 50 or older, increasing age remained an adverse factor for OS (P=0.0213). Regimens including total-body irradiation (TBI) correlated with a higher risk of TRM and a lower OS for older patients (P=0.0095 and 0.0303, respectively). These findings indicate that allogeneic c-HSCT should be offered to patients over 50 years only if the increased risk of TRM is acceptable, and that a non-TBI regimen is preferable when the transplant is performed.

Impact of cytogenetics on outcome of stem cell transplantation for acute myeloid leukemia in first remission: A large-scale retrospective analysis of data from the Japan Society for Hematopoietic Cell Transplantation

On the basis of transplantation data from the Japan Society for Hematopoietic Cell Transplantation, we retrospectively analyzed the impact of cytogenetics at diagnosis on the outcome of transplantation in 628 patients with acute myeloid leukemia who underwent autologous (n = 200), allogeneic related (n = 363), or allogenic unrelated (n = 65) stem cell transplantation (SCT) at first complete remission. For autologous SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .017) and a significantly higher event-free survival (EFS) (P = .013) compared with those at intermediate risk. For allogeneic SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .019) and insignificantly higher EFS (P = .093) than those at poor risk. For unrelated SCT, there was no significant difference in relapse rate or EFS between patients at good risk and those at intermediate risk. Comparison of the 3 transplantation modalities revealed that autologous SCT patients had a significantly higher incidence of relapse compared with related or unrelated SCT patients in the intermediate-risk group but not in the good-risk group. However, there were no significant differences in EFS among the 3 transplant modalities in either of these 2 risk groups. In multivariate analysis, cytogenetics was found to be an independent predictor of relapse as well as of treatment failure.

Late onset cyclosporine-induced cerebral blindness with abnormal SPECT imagings in a patient undergoing unrelated bone marrow transplantation.

A 23-year-old woman underwent HLA-matched unrelated BMT for CML. She developed cerebral blindness on day 81. Brain magnetic resonance imaging revealed hyperintensity on a T2-weighted image in the white and gray matter of the right frontal and both occipital lobes. Single-photon emission computed tomography (SPECT) was consistent with a decrease in radionuclide uptake in these areas, suggesting a vasoconstrictive mechanism. A diagnosis of CsA-induced encephalopathy was made and CsA was discontinued. Her vision recovered completely after 24 h and abnormal imaging resolved within 2 weeks. This case demonstrates late onset CsA-induced cerebral blindness with the previously unreported abnormalities on SPECT. Bone Marrow Transplantation (2000) 26, 105–108.

Induction of autologous graft-versus-host disease after autologous peripheral blood stem cell transplantation

BACKGROUND Autologous graft-versus-host disease has been reported after the administration of cyclosporine in patients who have received autologous bone marrow transplantation. OBJECTIVE The purpose of this study was to determine whether autologous graft-versus-host disease could be induced in recipients of autologous peripheral blood stem cell transplantation and whether tacrolimus induced the disease instead of cyclosporine. METHODS Twelve patients with acute leukemia and 5 patients with malignant lymphoma received either cyclosporine (1 mg/kg/day) or tacrolimus (0. 05 mg/kg/day) orally after autologous bone marrow or peripheral blood stem cell transplantation. RESULTS Autologous graft-versus-host disease of the skin, confirmed by histopathologic criteria, occurred in 40% of the patients at 8 to 25 days after transplantation and lasted 3 to 15 days. The frequency of autologous graft-versus-host disease was approximately the same (40%) irrespective of the source of the graft (bone marrow cells or peripheral blood stem cells) and the drug used for induction (cyclosporine or tacrolimus). CONCLUSIONS This pilot study suggests that autologous graft-versus-host disease can be induced in recipients of autologous peripheral blood stem cell transplantation by cyclosporine or tacrolimus.

Phase II study of dose-modified busulfan by real-time targeting in allogeneic hematopoietic stem cell transplantation for myeloid malignancy.

We aimed to evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation with targeted oral busulfan (BU) and cyclophosphamide (CY) in a phase II study. Busulfan (1.0 mg/kg) was given initially in six doses. Based on the estimated concentration at steady state after the first dose of BU, subsequent (7th–16th) doses were adjusted to obtain a targeted overall concentration at steady state of 700–900 ng/mL. The primary endpoint was 1‐year overall survival (OS). Fifty patients were registered and 46 (median age, 53 years; range, 18–62 years) received planned transplant, including 24 with AML, 16 with myelodysplastic syndrome, and six with CML. Fourteen patients were categorized as standard risk. Nineteen patients received transplant from human leukocyte antigen‐identical siblings, 27 from unrelated donors. The BU dose required reduction in 32 patients and escalation in six patients. One‐year OS was 65% (95% confidence interval, 50–77%). Cumulative incidence of hepatic sinusoidal obstruction syndrome was 11%. One‐year transplant‐related mortality was 18%. Both OS and transplant‐related mortality were favorable in this study, including patients of older age and with high risk diseases. Individual dose adjustment based on BU pharmacokinetics was feasible and effective in the current phase II study. This trial is registered in the University Hospital Medical Information Network Clinical Trial Registry System (UMIN‐CTR, ID:C000000156).

Simple diagnosis of graft-versus-host disease

BACKGROUND Among patients undergoing allogeneic bone marrow transplantation, we previously detected an increase of CD8+S6F1+ and CD8+CD57- cells with the onset of acute graft-versus-host disease. OBJECTIVE This study was an attempt to develop a simple laboratory test for graft-versus-host disease. METHODS We analyzed the percentage of the two lymphocyte subsets in the peripheral blood mononuclear cells of healthy volunteers, patients with posttransfusion graft-versus-host disease, and recipients of allogeneic bone marrow transplants. RESULTS Two patients with posttransfusion graft-versus-host disease showed a high percentage of both subsets. When the graft-versus-host disease pattern was defined as 45% or more CD8+S6F1+ cells and 35% or more CD8+CD57- cells, it was found in none of 17 recipients without acute graft-versus-host disease, 9 of 16 recipients with grade I disease, and 8 of 9 recipients with grade II or worse disease had this pattern. CONCLUSIONS Our test may be useful for the laboratory diagnosis of acute graft-versus-host disease.