A B S T R A C TWe analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for 2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and 55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.
Patients with primary immunodeficiencies undergoing allogeneic hematopoietic cell transplantation (HCT) for difficult-to-control infections can experience immune reconstitution inflammatory syndrome (IRIS) following engraftment. In 3 patients with post-HCT IRIS related to mycobacterial infection, in vitro data demonstrate the emergence of pathogen-specific immune responses and a concomitant rise in plasma inflammatory markers.
We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales. CASE REPORTA 41-year-old Indian female living in Barbados was diagnosed with stage IV nodular sclerosing Hodgkin's lymphoma in July 2007. She was initially treated with 6 cycles of Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, with only a partial response. Therefore, she required second-line treatment with 2 cycles of ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by autologous stem cell transplantation (ASCT). She relapsed 5 months following ASCT (August 2008) and received salvage chemotherapy with gemcitabine, vinorelbine, and liposomal doxorubicin followed by radiation to a residual supraclavicular node (in India), attaining a complete response. Lacking a sibling or HLA-matched unrelated donor, she was referred to the National Institutes of Health in August 2009 for double umbilical cord blood transplantation (UCBT).The patient received reduced-intensity conditioning with fludarabine (120 mg/m 2 ) and cyclophosphamide (4,800 mg/m 2 ) over 4 days followed by double UCBT on 19 November 2009. Graft-versus-host disease prophylaxis consisted of tacrolimus and sirolimus. Prophylactic antimicrobials included ceftazidime, micafungin, and acyclovir. The patient's pretransplant course was complicated by angioedema, requiring the discontinuation of sirolimus, treatment with high-dose dexamethasone, and admission to the intensive care unit for airway protection. Her immediate posttransplant course was complicated by acute renal failure and pulmonary edema, necessitating continued intubation with mechanical ventilation.On 24 November 2009, the patient developed distributive/ cardiogenic shock. Blood cultures revealed extended-spectrum -lactamase (ESBL)-producing Escherichia coli. Fluid resuscitation, vasopressors, and broad-spectrum antibiotics were administered with good response. By 28 November, the patient was off vasopressors but was found to have no purposeful response to stimuli. On 1 December, computed axial tomography (CT) scans of the head and chest were obtained. The head CT was normal. The chest CT revealed a cavitary lung infarction distal to the pulmonary artery catheter. The pulmonary artery catheter tip grew E. coli. Bronchoscopy with bronchoalveolar lavage (BAL) was nondiagnostic, but voriconazole was empirically added. Brain magnetic resonance imaging (MRI) on 7 December showed diffuse fluid-attenuated inversion recovery (FLAIR) hyperintensity due to the patient's 100% oxygen requirement but was otherwise unremarkable. A cerebrospinal fluid sample had no white blood cells, and glucose and protein were within normal limits; all microbiological studies were negative. Neutropenia persisted due ...
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