Yusuke Yamane

New-onset food allergy following cord blood transplantation in adult patients.

New-onset food allergy has been recognized as one of the complications after liver transplantation, especially in pediatric patients, which was closely associated with tacrolimus administration in several studies. One prospective study reported that 21% of pediatric patients receiving liver transplantation developed new-onset food allergy. In contrast to the extensive investigation of food allergy after liver transplantation, food allergy after hematopoietic stem cell transplantation has not been fully evaluated. In bone marrow or peripheral blood stem cell transplantation, allergic disease can be transferred from donors. However, cord blood donors are considered free from allergic disease, and the development of food allergy in cord blood transplantation (CBT) recipients is probably due to the dysregulated immune reconstitution. Recently, sporadic cases of newonset food allergy after CBT have been reported, including five pediatric and two adult patients. To elucidate its incidence and clinical features, we retrospectively evaluated patients who developed new-onset food allergy after CBT. This is a single-institutional retrospective study using the institutional database and medical records of adult patients who underwent CBT for hematological disorders between October 2001 and June 2014 at Keio University Hospital (Tokyo, Japan). This retrospective study was approved by the Ethical Committee of Keio University School of Medicine. After excluding three cases of graft rejection, one case of autologous bone marrow recovery and three cases of insufficient data, 51 patients (male, 31; female, 20) who achieved donor cell myeloid engraftment and survived longer than 30 days after CBT were selected and enrolled into the analysis. Median age of the patients at transplantation was 49 years (range, 18–64), and median follow-up time was 16.9 months (range, 1.4–149.7). Underlying diseases were hematological malignancies, except in one patient with aplastic anemia. The GvHD prophylaxis was cyclosporine A (CsA)-based in 25 patients and tacrolimus-based in 26. Raw foods were avoided during the neutropenic period after transplantation, and grapefruit was avoided until calcineurin inhibitors were discontinued. A diagnosis of food allergy was made on the basis of the clinical presentations repeatedly observed after the oral intake of a specific food, and on the basis of the positive results of the oral food challenge and/or radioallergosorbent tests for specific IgE against the allergens. The probability of food allergy was estimated on the basis of cumulative incidence curves to accommodate deaths due to any causes and the second hematopoietic stem cell transplantation as the competing event. Analyses were performed with EZR, a graphical user interface for R. Of the 51 patients, 3 patients developed food allergy at 5, 6 and 10 months after CBT, respectively. The medical histories of the three patients were not remarkable for any food allergies. The cumulative incidence of food allergy was estimated to be 6.6% (95% confidence interval, 1.7–16.4%) at 1 year after transplantation (Figure 1). The clinical characteristics of the three patients who developed food allergy are shown in Table 1. The patients were aged 19, 55 and 57 years at transplantation, and all developed food allergy within 1 year after CBT. All patients had repeated episodes of the same symptoms shortly after taking specific foods, which prompted the physicians to suspect food allergy. Together with such clinical presentations, the diagnosis of food allergy and incriminated allergens was confirmed by 0 50 100 150 0.0 0.2 0.4 0.6 0.8 1.0

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.

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

Recurrent bacterial pneumonia due to immunoglobulin G2 subclass deficiency after allogeneic hematopoietic stem cell transplantation: Efficacy of immunoglobulin replacement

Immunoglobulin (Ig) G2 subclass deficiency is known to be associated with recurrent bacterial respiratory infections caused by capsulated bacteria. We encountered a case of recurrent pneumonia due to Streptococcus pneumoniae after allogeneic hematopoietic stem cell transplantation (HSCT). IgG2 subclass level was specifically low, and prophylactic Ig replacement successfully prevented subsequent infections. However, the cessation of Ig replacement resulted in subsequent pneumonia. These findings suggested that IgG2 deficiency could be a cause of recurrent pneumococcal infection after allogeneic HSCT.

Invasive hepatic mucormycosis: A case report and review of the literature

Mucormycosis generally develops under immunocompromised conditions, including hematological malignancies and solid organ or hematopoietic stem cell transplantation. Although mucormycosis usually affects the lungs and paranasal sinuses, sporadic cases of invasive mucormycosis of the liver have been reported. We hereby report a patient with myelofibrosis who developed hepatic mucormycosis diagnosed by post-mortem examination. An extensive literature review identified 13 reported cases of hepatic mucormycosis, including ours, without lung involvement. Most of the underlying diseases or conditions were hematological malignancies and solid organ transplantation. Three cases had splenic lesions and four had gastrointestinal lesions, suggesting the possibility of translocation to the liver and/or spleen from the gastrointestinal tracts. Hepatic mucormycosis should be recognized as one of the presentations of invasive mucormycosis, especially when hepatic nodules are found in immunocompromised patients such as those with hematological malignancy or recipients of solid organ transplantation.

Very Late Relapse of Acute Promyelocytic Leukemia 17 Years after Continuous Remission

The prognosis of acute promyelocytic leukemia (APL) has been improved by the combination of all-trans retinoic acid (ATRA) with chemotherapy. Nonetheless, relapse occurs in a certain proportion of patients, mostly within three to four years after treatment. We herein report a patient treated with ATRA and chemotherapy achieving remission who relapsed approximately 17 years after the treatment. A literature review identified 5 additional reported cases of APL relapse after more than 10 years. None of them presented with generally established risk factors for relapse, such as a high leukocyte count. The potential for late relapse of APL occurring more than 10 years after treatment should be recognized.

Cellulitis due to Achromobacter xylosoxidans during bortezomib therapy for multiple myeloma

Achromobacter xylosoxidans (A. xylosoxidans) is a non-fermentative gram-negative rod. This organism is reportedly a causative pathogen of bacteremia mainly in patients with hematological disorders. However, only one case of cellulitis due to A. xylosoxidans associated with hematological malignancy has been reported. An 80-year-old man developed cellulitis and subsequent bacteremia due to A. xylosoxidans during bortezomib therapy for multiple myeloma. Although his condition was serious enough to require intensive care, he fully recovered with appropriate antimicrobial agents and supportive care. The isolate was broadly resistant to antimicrobial agents, including cefepime, amikacin, and ciprofloxacin. Therefore, the identification and selection of appropriate antimicrobial agents were considered to have contributed to the successful outcome in this case. Physicians should recognize A. xylosoxidans as a possible pathogen causing cellulitis and secondary bacteremia, as well as being aware of its broad resistance to antimicrobial agents.