Takaaki Toyama

Nephrotoxicity of concomitant use of tacrolimus and teicoplanin in allogeneic hematopoietic stem cell transplant recipients

Both tacrolimus and glycopeptide antibiotics are known to be nephrotoxic, and are often concomitantly given after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. The aim of this study is to evaluate the nephrotoxicity of concomitant use of tacrolimus and glycopeptide antibiotics in HSCT recipients. We retrospectively evaluated 67 patients who received intravenous tacrolimus and teicoplanin concomitantly for >4 days after allogeneic HSCT for hematologic diseases. Therapeutic drug monitoring (TDM) was performed in all patients for both tacrolimus and teicoplanin. The median age of the patients was 48 years (range: 16–62), and the median duration of the co‐administration of tacrolimus and teicoplanin was 11 days (range: 4–40). The mean serum creatinine (sCr) level tended to be elevated after the co‐administration (from 0.69 ± 0.26 to 0.75 ± 0.30 mg/dL; P = 0.08); however, a 2‐fold or greater increase in sCr was observed only in 2 (3.0%) patients. Increased sCr was reversible, and no patient required hemodialysis. These results suggest that the incidence of clinically significant nephrotoxicity can be minimized if the TDM of each drug is properly applied.

Successful treatment of tafro syndrome with tocilizumab, prednisone, and cyclophosphamide

TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, pleural effusion, fever, renal dysfunction, reticulin fibrosis of the bone marrow, and organomegaly. The clinical course varies significantly among patients. However, the prognosis is usually dismal in patients with severe TAFRO syndrome, and no optimal treatment has yet been established. We herein describe the first case of TAFRO syndrome, which was successfully treated with combination therapy consisting of tocilizumab, prednisone, and cyclophosphamide.

Sinusitis caused by Exserohilum rostratum after cord blood transplantation for myelodysplastic syndrome: A case report and literature review

Invasive fungal disease is a serious infectious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Exserohilum rostratum is a species causing phaeohyphomycosis, which rarely causes invasive disease in humans. We treated a case of sinusitis caused by E. rostratum after cord blood transplantation (CBT). A 60‐year‐old man with myelodysplastic syndrome, who had a medical history of an operation to correct deviation of the nasal septum, developed sinusitis caused by E. rostratum under prolonged profound neutropenia after a second CBT because of the graft rejection of the first transplantation. Liposomal amphotericin B improved the sinusitis. A literature review revealed nine reported cases of sinusitis caused by E. rostratum, including our case. Although five cases had severe neutropenia at onset (HSCT recipients, n = 2; aplastic anemia, n = 3), the remaining four had no preexisting immunosuppressive conditions. However, three of the four patients had preexisting nasal diseases with or without a history of surgery, as in our case. Excluding our case, the outcome was fatal in five neutropenic patients, whereas the four patients without neutropenia recovered. Although sinusitis caused by E. rostratum is rare, E. rostratum should be recognized as a possible pathogen causing sinusitis in highly immunosuppressed patients such as HSCT recipients. Preexisting nasal disease and/or nasal surgery could be risks for this infection.

False-positive serum (1, 3)-β-D-glucan elevation due to intake of seaweed in a hematopoietic stem cell transplant recipient

The (1, 3)-β-D-glucan (β-D-glucan) is one of the polysaccharides composing the fungal cell wall, and assays to detect serum β-D-glucan through specific enzyme activity have been widely used as a tool for the diagnosis and monitoring of invasive fungal infection.1 However, the usefulness of this assay is partly limited by its poor specificity owing to various factors.1,2 We experienced a patient showing a marked elevation of serum β-D-glucan after allogeneic hematopoietic stem cell transplantation, which was found to be caused by daily oral intake of kelp, a widely consumed seaweed. This article is protected by copyright. All rights reserved.

Nosocomial BK Polyomavirus Infection Causing Hemorrhagic Cystitis Among Patients With Hematological Malignancies After Hematopoietic Stem Cell Transplantation

BK polyomavirus (BKPyV) is recognized as a pathogen that causes diseases such as hemorrhagic cystitis and nephritis after allogeneic hematopoietic stem cell transplantation (HSCT) or renal transplantation. BKPyV‐associated disease is thought to occur through reactivation under immunosuppression. However, the possibility of its nosocomial transmission and the clinical significance of such transmission have not been elucidated. During a 6‐month period, nine adult patients (median age: 47 years) who had hematological disorders and who were treated with HSCT (n = 7) or chemotherapy (n = 2) in a single hematology department developed hemorrhagic cystitis due to BKPyV infection. The polymerase chain reaction products of BKPyV DNA obtained from each patient were sequenced. Of the nine patients, six had subtype I, 2 had subtype IV, and 1 had subtype II or III. In the alignment of sequences, four and two of the six subtype I strains were completely homologous (100%). These results strongly suggest that BKPyV has the potential to cause nosocomial infection within a medical facility, especially among recipients of HSCT. Further studies are clearly warranted to elucidate the route(s) of BKPyV transmission in order to establish optimal infection control.

Reduced-dose cyclophosphamide in combination with fludarabine and anti-thymocyte globulin as a conditioning regimen for allogeneic hematopoietic stem cell transplantation for aplastic anemia

patients received grafts from HLA-matched (high-resolution) unrelated donors. Patient and donor characteristics are shown in Table 1. The conditioning regimen was given following that described in a previous report by Okuda et al. [8] with a modification in the dosage of ATG. The regimen consisted of fludarabine (30 mg/kg) and CY (25 mg/ kg) each on days −6 to −3, and ATG (Thymoglobulin; 1.25 mg/kg) on days −4 and −3. Except in the case of one patient (No. 6) who had received a limited number of blood transfusions before transplantation, total body irradiation (TBI; 2 Gy) was delivered at a single fraction on day −2 or −1. TBI was delivered with ovarian shielding in three young female patients (Cases 1–3) to spare ovarian function [8]. Tacrolimus or cyclosporine A (CSA) and shortterm methotrexate were given as graft-versus-host disease (GVHD) prophylaxis. The administration of lenograstim at a dose of 5 μg/kg was started one day after the bone marrow infusion and continued until neutrophil recovery was achieved. Cytomegalovirus (CMV) reactivation was monitored by CMV antigenemia assay, which triggered the preemptive therapy with ganciclovir or foscarnet [9]. The day of myeloid engraftment was defined as the first day of three consecutive days when the absolute neutrophil count exceeded 0.5 × 10/L. Regimen-related toxicities of grades 2–3 were diarrhea (n = 5), nausea (n = 5), oral mucositis (n = 2), and liver dysfunction (n = 2); grade 4 toxicities were not observed. Bacteremia was documented in three patients, and was successfully treated with antimicrobial treatment. CMV reactivation was observed in four patients, and was successfully managed with preemptive therapy. None of the cases developed lymphoproliferative disorder. Other transplant outcomes as well as clinical courses are listed in Table 1. One patient (Case 1) developed acute GVHD of the skin (Grade 2) during the tapering of CSA, but the other patients To the Editor: We read with great interest the recent report by Ashizawa et al. showing a favorable outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia by use of a conditioning regimen consisting of reduced-dose cyclophosphamide (CY: total 100 mg/kg), fludarabine, and anti-thymocyte globulin (ATG) [1]. Although the outcome seems favorable, some issues remain to be solved with this regimen, including mixed chimerism and late-onset cytopenia. In addition, the small number of cases has limited the impact of their conclusion. Although there have been attempts to reduce the dose of CY in the conditioning regimen for aplastic anemia, the optimal dose of CY has yet to be established [2–7]. Based on a previous study by the same institute, we also applied the same conditioning regimen for patients with aplastic anemia undergoing allogeneic HSCT [8]. In the present report, we present several of these cases, which we believe further support and reinforce the conclusions of Ashizawa et al. We would also like to present our data on the recovery of ovarian function after transplantation in young female patients as another potential advantage of this regimen. Between November 2010 and October 2011, six patients with aplastic anemia underwent allogeneic bone marrow transplantation (BMT) at Keio University Hospital (Tokyo, Japan) after being conditioned with the regimen described below. Three patients received grafts from human leukocyte antigen (HLA)-identical siblings and the remaining three