Aspergillus calidoustus and Talaromyces columbinus infections in chronic graft-versus-host disease.

Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids. However, azole prophylaxis may cause resistant Aspergillus species like A. calidoustus, which are difficult to treat. We report a case from our institution where a patient developed a dual infection with Aspergillus calidoustus and Talaromyces columbinus after alloHSCT and posaconazole prophylaxis. While A. calidoustus is known to cause IFIs in HSCT recipients, T. columbinus represents a previously unreported occurrence in medical literature. This case underscores the importance of a multifaceted diagnostic strategy, integrating BAL diagnosis, mycological cultures, direct microscopy, fungal speciation, susceptibility testing, and biomarkers. These comprehensive approaches are indispensable for accurate pathogen identification and effective management of IFIs with appropriate antifungal agents.

Disseminated Mucormycosis and T-Cell-Depleted Allogeneic Stem Cell Transplantation: An Unusual Case Study.

INTRODUCTION: Invasive fungal infections are a primary cause of morbidity and mortality in patients with haematological malignancies. CASE PRESENTATION: We describe an unusual clinical and radiological presentation of invasive mucormycosis (IM) in a 69-year-old patient with relapsed acute myeloid leukaemia. The patient was diagnosed with disseminated IM with involvement of the central nervous system in an atypical location, lung, spleen, muscle, bone, and heart, after having completed induction and bridging chemotherapy to allogeneic haematopoietic stem cell transplant (HSCT). Her clinical presentation was atypical with mild neurological symptoms slowly progressing over 2 months and without appropriate signs of systemic inflammation. Mucorales was eventually confirmed from bronchoalveolar lavage and subdural collection. CONCLUSION: This report highlights the difficult challenges of managing disseminated IM in an immunocompromised patient, where close multidisciplinary specialist care enabled successful treatment, followed by T-cell-depleted allogeneic HSCT for a high-risk haematological malignancy.

A rapidly expanding cutaneous tumour in the context of a Janus kinase inhibitor agent following allogeneic stem cell transplant.

Ruxolitinib is a selective, Janus kinase (JAK)1 and JAK2 inhibitor, which is effective in management of chronic graft-versus-host disease (cGvHD). However, the ensuing immunosuppressive effects can give rise to aggressive cutaneous tumours, including Merkel cell carcinoma. We present this case to highlight the development of cutaneous tumours with ruxolitinib, an increasingly used therapy, and the challenge of managing such tumours in the context of refractory cGvHD. Click here for the corresponding questions to this CME article.

Early and late-onset veno-occlusive disease/sinusoidal syndrome post allogeneic stem cell transplantation - a real-world UK experience.

Classical veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication post allogeneic hematopoietic stem cell transplantation (HSCT). Before the recently revised EBMT criteria, the Baltimore and modified Seattle criteria failed to recognize the syndrome of late-onset VOD. We present real-world experience from a large UK transplant center reporting on VOD/SOS in consecutive HSCT adult patients (n = 530), transplanted for hematological cancers. We identified 27 patients treated with Defibrotide for VOD/SOS diagnosis, where detailed data were available for final analysis. Using standard definitions including EBMT criteria, around 30% (n = 8/27) of cases classified as late-onset VOD presenting at median of 46 (22-93) days but with D100 survival (63% vs 58%, Log-rank; P = 0.81) comparable to classical VOD. Hazard ratio for D100 mortality was 2.82 (95% CI: 1.74-4.56, P < .001, Gray test) with all VOD/SOS events. Twenty percent (n = 2/8) of late-onset VOD patients were anicteric and 42% (n = 8) classical VOD patients presented with refractory thrombocytopenia, while less than half met EBMT criteria for classical VOD in adults, highlighting gaps in real-world diagnostic limitations using EBMT criteria. However, challenges remain about underrecognition and difficulties related to early defibrotide access for treatment of late-onset VOD in current treatment guidelines. Our report strongly supports early Defibrotide for the treatment of severe VOD/SOS in adults regardless of time of onset.

Epstein-Barr Virus and Monoclonal Gammopathy of Clinical Significance in Autologous Stem Cell Transplantation for Multiple Sclerosis.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) with anti-thymocyte globulin (ATG) conditioning as treatment of active multiple sclerosis (MS) is rapidly increasing across Europe (EBMT registry data 2017). Clinically significant Epstein-Barr virus reactivation (EBV-R) following AHSCT with ATG for severe autoimmune conditions is an underrecognized complication relative to T-cell deplete transplants performed for hematological diseases. This retrospective study reports EBV-R associated significant clinical sequelae in MS patients undergoing AHSCT with rabbit ATG. METHODS: Retrospective data were analyzed for 36 consecutive MS-AHSCT patients at Kings College Hospital, London. All patients routinely underwent weekly EBV DNA polymerase chain reaction monitoring and serum electrophoresis for monoclonal gammopathy (MG or M-protein). EBV-R with rising Epstein-Barr viral load, M-protein, and associated clinical sequelae were captured from clinical records. RESULTS: All patients had evidence of rising EBV DNA-emia, including 7 who were lost to long-term follow-up, with a number of them developing high EBV viral load and associated lymphoproliferative disorder (LPD). Nearly 72% (n = 18/29) developed de novo MG, some with significant neurological consequences with high M-protein and EBV-R. Six patients required anti-CD20 therapy (rituximab) with complete resolution of EBV related symptoms. Receiver operating characteristics estimated a peak EBV viremia of >500 000 DNA copies/mL correlated with high sensitivity (85.5%) and specificity (82.5%) (area under the curve: 0.87; P = .004) in predicting EBV-R related significant clinical events. CONCLUSION: Symptomatic EBV reactivation increases risk of neurological sequelae and LPD in MS-AHSCT. We recommend regular monitoring for EBV and serum electrophoresis for MG in MS patients in the first 3 months post-AHSCT.

Mesenchymal stromal cells for acute graft-versus-host disease: response at 1 week predicts probability of survival.

Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid-resistant graft-versus-host-disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients' overall survival. In our cohort, cell dose, patients' age and type of organ involvement are crucial factors associated with clinical responses.