Risa Hashida

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

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.

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

Optic nerve involvement of Waldenström’s macroglobulinemia: with autopsy findings

Abstract Waldenström’s macroglobulinemia (WM) is an indolent chronic lymphoproliferative disorder within the spectrum of lymphoplasmacytic lymphoma (LPL), characterized by a proliferation of plasmacytoid lymphocytes and the production of monoclonal IgM. Although, peripheral neurologic complications commonly occurs due to hyperviscosity in WM, central nervous system (CNS) involvement is very rare. Herein, we present the case of a 67-year-old man who initially presented with progressive visual loss and was diagnosed as WM/LPL with a very aggressive clinical course. He underwent chemotherapy with high dose methotrexate (MTX) plus cytarabine (Ara-C). However, he died and findings of a subsequent autopsy revealed the presence of lymphoplasmacytoid cells in the optic nerve.

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.

[Isolated central nervous system relapse in type II enteropathy-associated T cell lymphoma].

A 75-year-old male presented with progressive lower abdominal discomfort. CT scan demonstrated hypertrophy of the intestinal wall, small bowel dilatation, and masses in the descending colon. Biopsy specimens of the jejunum and descending colon revealed widespread distribution of medium-sized atypical lymphocytes with an immunophenotype, positivity for CD3, CD8, CD56, TAI-1, granzyme B and TCRβ, but negativity for CD4, CD5, CD20, CD30 and EBER-ISH. Type II enteropathy-associated T cell lymphoma (EATL; Lugano, stage IIE) was diagnosed. Subsequently, he received 6 cycles of chemotherapy with 2/3 dose CHOP and obtained complete remission. However, 18 months after the initial presentation, he presented with rapidly progressive mental deterioration. Gadolinium enhanced T1-weighted brain MR images showed multiple masses with mild heterogeneous enhancement. Brain biopsy revealed necrotic tumors composed of medium-sized atypical lymphocytes, positive for CD3, CD8, CD56, TIA-1, granzyme B and TCRβ, but negative for CD4, CD20, and EBER-ISH. CT scan disclosed no evidence of systemic lymphoma relapse, indicating central nervous system relapse of EATL. Despite immediate high-dose chemotherapy with methotrexate, he died of disease progression. EATL is a rare disease with a very poor outcome, for which a validated standard treatment is still lacking. Further studies are needed to identify innovative therapies for treating EATL.