Yuya Koda

Automorphisms of the 3-sphere that preserve spatial graphs and handlebody-knots

We consider the group of isotopy classes of automorphisms of the 3-sphere that preserve a spatial graph or a handlebody-knot embedded in it. We prove that the group is finitely presented for an arbitrary spatial graph or a reducible handlebody-knot of genus two. We also prove that the groups for “most” irreducible genus two handlebody-knots are finite.

Essential surfaces of non-negative Euler characteristic in genus two handlebody exteriors

We provide a classification of the essential surfaces of non-negative Euler characteristic in the exteriors of genus two handlebodies embedded in the 3-sphere.

Strongly-cyclic branched coverings and the Alexander polynomial of knots in rational homology spheres

Let K be a knot in a rational homology sphere M . In this paper we correlate the Alexander polynomial of K with a g -word cyclic presentation for the fundamental group of the strongly-cyclic covering of M branched over K . We also give a formula for the order of the first homology group of the strongly-cyclic branched covering.

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.

Persistent parvovirus B19 infection resulting in red cell aplasia after allogeneic hematopoietic stem cell transplantation

Persistent parvovirus B19 (PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patients family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic.

Successful treatment with bendamustine and rituximab for paraneoplastic pemphigus

Dear Editor, Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with neoplasms, particularly lymphoid malignancies [1, 2]. PNP is characterized by painful stomatitis, polymorphous skin eruption, and the presence of antibodies against desmogleins (Dsg) 1 and 3, envoplakin, and periplakin [1, 2]. Various treatments have been applied to PNP, including corticosteroid, cyclophosphamide, plasmapheresis, and rituximab, but their efficacy has been limited and an optimal treatment remains to be established. We herein report a case of follicular lymphoma developing PNP that was successfully treated with bendamustine and rituximab. A 74-year-old woman noticed rapidly progressing left axillary lymphadenopathy. She had a 23-year history of follicular lymphoma (histological grade 2) and had been receiving a series of treatments including CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomicin), rituximab alone, and local radiation therapy. The adenopathy was histologically diagnosed as a recurrence of follicular lymphoma. The lesion was treated with local radiation therapy (total 36 Gy) delivered against the lesion. Two months after the initiation of radiation therapy, blisters developed at the radiation site (from the left shoulder to the back) along with eruptions and blisters at the oral, vaginal, and anal mucosa (Fig. 1a, b). Prednisolone (0.5 mg/kg/ day) was initiated but the lesions remained unchanged. The patient was referred to our hospital’s dermatology service. The histopathological studies of the skin and oral mucosa lesions showed suprabasal blister, acantholysis, and basal cell layer degeneration. Immunoblot analysis of the serum revealed the presence of antibodies against envoplakin, periplakin, Dsg1, and Dsg3. The anti-Dsg3 antibody value was 47.5 U/mL (normal range, less than 20.0 U/mL). On the basis of these findings, a diagnosis of PNP was made. Prednisolone was increased to 1.0 mg/kg/day, but there was no improvement. Bendamustine (90 mg/m on days 1, 2) in combination with rituximab (375 mg/m on day 1), BR, was initiated. After 2 weeks, the skin lesions and oral eruption had begun to improve and were almost resolved at 4 weeks (Fig. 1c, d). During the treatment, cytomegalovirus reactivation and neutropenia developed and were successfully treated with an antiviral agent and granulocyte colony-stimulating factor. After two courses of BR, anti-Dsg3 antibodywas undetectable. At 1 year after the initiation of BR treatment, prednisolone administration was successfully tapered to 6 mg/day without recurrence of PNP or follicular lymphoma. Although corticosteroid has been used for the treatment of PNP, it has not been effective for mucosal lesions of PNP [1–5]. Recently, the efficacy of rituximab against PNP associated with malignant lymphoma has been reported [6]. Bendamustine has been used as both a firstand second-line therapy for follicular lymphoma [7, 8]. Although there was a case of PNP developing after BR chemotherapy for follicular lymphoma [9], we observed that BR dramatically improved PNP lesions. The inconsistency between these findings suggests that the pathogenesis and clinical features of PNP associated with malignant lymphoma are diverse. * Taku Kikuchi taku_k_1123@mac.com

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.

Post-transplant lymphoproliferative disorder of the adrenal gland after allogeneic hematopoietic stem cell transplantation: Report of two cases and literature review

Post‐transplant lymphoproliferative disorder (PTLD) is one of the life‐threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein–Barr virus (EBV). We herein report 2 cases of EBV‐associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced‐stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV‐associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.