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Adenovirus (AdV) infections constitute a significant cause of morbidity and mortality during haematopoietic stem cell transplantation. Recent guidelines recommend repeated screening for AdV in whole blood (WB), with quantitative PCR (qPCR) as the reference standard. Despite pre-emptive antiviral treatment based on qPCR in WB, the mortality rate after disseminated AdV infection remains very high. The aim of our study was to advance early screening for AdV, using a standardized method, so as to enable the earlier initiation of antiviral treatment or adoptive immunotherapy. The diagnostic value of AdV DNA quantification in stool samples was investigated retrospectively and compared with antigen detection and cell culture in 21 patients with AdV infection, from 182 patients followed in the Transplant Unit of Nancy University Hospital Centre, including 18 patients with systemic infection. In 16/18 patients with positive AdV viraemia, AdV DNA was present in stool samples earlier than in WB (median, 42 days; range, 3-199 days), whereas both antigen detection and cell culture were still negative for 11/18 patients with systemic AdV infection. The course of AdV viral loads in stool samples was predictive of adenoviraemia (sensitivity, 89%). Very late and lethal AdV infections were observed in cord blood transplant recipients, and would have been detected much earlier with the use of qPCR on stool samples. This study confirmed that quantification of AdV in stool samples by qPCR is beneficial for the management of transplant recipients, with or without antigen detection.

transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts.Patients and methods: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts.Results: Median overall survival was 7.9 months [61.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (61.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE).Conclusions: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.

We report two cases of invasive infections due to Geosmithia argillacea, an emerging mold, in patients with chronic granulomatous disease receiving prolonged azole antifungal prophylaxis. One patient died despite receiving a combination of four antifungals, and the other developed cerebral and medullary lesions under a combination of caspofungin, posaconazole, terbinafine, and gamma interferon. CASE REPORTSPatient 1. A 14-year-old girl with chronic granulomatous disease (CGD; autosomal recessive form implying the CYBA gene encoding subunit p22 phox ) was admitted to Nancy University Hospital (Nancy-F) for allogeneic peripheral blood stem cell transplantation using a matched unrelated donor. Her medical history included a prior undocumented granulomatous pulmonary mass requiring lobectomy in 2006. She received a primary antifungal prophylaxis, with 200 mg voriconazole twice a day (b.i.d.) from the day of grafting. On day 43 postgraft, she developed acute grade II graft-versus-host disease, requiring methylprednisolone. On day 60, galactomannan was detected in serum, and a computed tomography (CT) scan revealed a T1 spondylodiscitis with a paravertebral abscess. Liposomal amphotericin B (3 mg/kg of body weight per day), combined with caspofungin (70-mg loading dose, followed by 50 mg daily), was initiated. A biopsy of the paravertebral abscess was performed. Microscopic examination of histological sections stained with periodic acid-Schiff stain, hematoxylin-eosin, and Gomori methenamine silver revealed branching, septate hyphae, and many vesicular swellings of different sizes (Fig. 1A). Cultures of the biopsy specimen (isolate 1) rapidly grew brownish colonies on Sabouraud agar at 30°C. The microscopic morphology, with penicillate conidiophores attached to hyaline septate hyphae, resembled that of a Penicillium species. On day 143, she had a persistent cough with dyspnea and fever and received empirical antibiotics. On day 198 postgraft, she experienced a seizure, and cerebral magnetic resonance imaging (MRI) revealed disseminated cerebellar and cerebral abscesses. A cerebral biopsy was not performed. She subsequently received terbinafine (250 mg b.i.d.) and then flucytosine (6 g/day) in addition to liposomal amphotericin B and caspofungin but died on day 258 postgraft.Patient 2. A 30-year-old patient with X-linked recessive CGD was admitted in March 2010 at the Centre d'Infectiologie Necker-Pasteur (Paris-F) with bilateral pulmonary infiltrates (Ն4 cm) and a thoracic subcutaneous abscess with local rib lysis.He previously experienced relapsing otitis media and Mycobacterium bovis adenitis. He also had developed 3 prior episodes of invasive aspergillosis, the latest being in May 2009 and related to Aspergillus nidulans, for which he received voriconazole. Subsequently, he was transiently colonized by Penicillium chermesinum and Scopulariopsis brevicaulis (both confirmed by internal transcribed spacer [ITS] sequencing). Bronchoalveolar lavage fluid culture and biopsy of the subcutaneous lesion revealed septate hyp...

Summary In a phase II study, daclizumab was given as single second‐line agent to 62 patients with steroid‐refractory acute graft‐versus‐host disease (aGVHD). Complete resolution of aGVHD was achieved in 68·8% of patients. This response rate was significantly associated with a lower number of involved organs and smaller extent of skin involvement. The 4‐year event‐free survival (EFS) was 54·6%. Grade ≥III aGVHD, ≥2 involved organs at baseline and patient age >18 years were independently associated with lower EFS. Daclizumab could be a suitable alternative treatment for aGVHD, particularly when limited to the skin or gastrointestinal tract.

Background:Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported.Methods:We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months.Results:Three-year OS was 20% (s.e.±8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s.e.±10%) and 11% (s.e.±6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR.Conclusion:The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.

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BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB).MethodsFourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment.ResultsOne patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease.ConclusionsAdoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0469-0) contains supplementary material, which is available to authorized users.