Citations

AbstractBackgroundMycobacterium tuberculosis (TB) is common worldwide, but is rarely reported after hematopoietic transplantation (HSCT). We reviewed all TB cases among HSCT since 2010 to provide an update on its epidemiology, clinical presentation, management and outcome.MethodsSeveral databases were reviewed from January 1, 2010 to June 30, 2018 using key words tuberculosis and hematopoietic transplantation.ResultsThe 47 cases of TB were reported during the study period. The highest TB frequency was reported from India (2.9%), with a median frequency of 2% (range, 0.18%‐2.9%). The majority were recipients of allogeneic transplants (45/47, 95.7%). Pulmonary TB was the most common clinical presentation (20/47, 42.6%). The median time to clinical presentation was 4.6 (range, 3‐12.9) and 2.4 (range, 0.6‐5) months, based on cohort data and case reports, respectively. Fever was reported in 87.5% (14/16) of patients. First‐line quadruple drug therapy was frequently used (29/35, 82.9%), with a median length of 12 and 9 months for cohorts and case reports, respectively. All‐cause and attributable mortality was 27.6% (13/47), and 8.5% (4/47), respectively.ConclusionsMycobacterium tuberculosis presents early after HSCT, most commonly as fever. A high index of suspicion is needed for early diagnosis and treatment, to prevent TB‐attributable mortality.

AbstractThis study of 64 solid organ and hematopoietic stem cell transplant recipients found that peripheral blood absolute lymphocyte count of <610 and <830/µL, respectively, correlated with cytomegalovirus infection. In an era when sophisticated measures of CMV-specific T cells are emerging, we emphasize the utility of the inexpensive and readily-available absolute lymphocyte count.

AbstractBackgroundTacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non‐systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described.MethodsTo assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole.ResultsThe median percent tacrolimus dose change was an increase of 66.7% (IQR28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was −42.5% (IQR−52.3%, −30.9%). Five cases of allograft rejection were observed.ConclusionIn conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single‐center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.

Abstract Despite advances in preventive strategies, cytomegalovirus (CMV) infection remains a major complication in solid organ and hematopoietic cell transplant recipients. CMV infection may fail to respond to commercially available antiviral therapies, with or without demonstrating genotypic mutation(s) known to be associated with resistance to these therapies. This lack of response has been termed “resistant/refractory CMV” and is a key focus of clinical trials of some investigational antiviral agents. To provide consistent criteria for future clinical trials and outcomes research, the CMV Resistance Working Group of the CMV Drug Development Forum (consisting of scientists, clinicians, regulatory officials, and industry representatives from the United States, Canada, and Europe) has undertaken establishing standardized consensus definitions of “resistant” and “refractory” CMV. These definitions have emerged from the Working Group’s review of the available virologic and clinical literature and will be subject to reassessment and modification based on results of future studies.

Background. Control of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) requires a functional immune system. We assessed the association between quantitation and function of CMV-specific CD8+ T cells and CMV infection in SOT recipients. Methods. During a 10-year period, selected kidney, heart, lung, pancreas, liver, and composite tissue recipients were tested for CMV-specific CD8+ T cells immune competence (CMV-CD8+), as measured by enumeration, interferon-gamma production, and CD107a/b degranulation. Quantitative and functional data were used to assemble T-cell immune competence (TIC) score. CMV infection was diagnosed by polymerase chain reaction in blood and other samples or histopathology. Results. Of 130 patients tested, 59 had CMV infection or disease. The median onset to CMV infection was 10.5 months (interquartile range [IQR], 5.5–18.7). Gastrointestinal disease (28.8%), pneumonia (20.3%), and CMV syndrome (17%) were most common presentation. An impaired nonspecific or CMV-CD8+ TIC score was associated with tissue-invasive disease (hazard risk, 2.84, 95% confidence interval, 1.03–11.81; P = 0.04). Patients with impaired CMV-CD8+ TIC score had longer viremia duration (42.4 days vs 18.8 d; P < 0.001). Patients with impaired nonspecific or CMV-CD8+ TIC score had higher risk of relapse (68.8% vs 27.9%; hazard risk, 2.56; 95% confidence interval, 1.09–5.89; P = 0.03). Patients with CMV infection or disease had lower median absolute lymphocyte count (380 [IQR, 240–540] vs 940 [IQR, 551–1210] cells/mm 3 ; P < 0.0001) and CD4+ T cell count (29 cells/mm 3 [IQR, 1.3–116.0] vs 325.5 cells/mm 3 [IQR, 151.5–589.8]; P < 0.0001). Conclusions. Nonspecific and CMV-specific CD8+ T-cell function correlated with the course of CMV after SOT, and measuring these has the potential to assist in its clinical management.

AbstractBackgroundMycobacterium tuberculosis may be transmitted via the allograft to cause a morbid and potentially fatal infection after solid organ transplantation (SOT). We reviewed all reported cases of donor‐derived tuberculosis (DDTB) to provide an update on its epidemiology, clinical course, and outcome after SOT.MethodsMEDLINE, OVID, and EMBASE were reviewed from its inception until December 31, 2016 using key words donor‐derived infection, tuberculosis and solid organ transplant or transplantation.ResultsWe retrieved 36 cases of proven (n = 17), probable (n = 8), and possible (n = 11) DDTB among 16 lung, 13 kidney, 6 liver, and 1 heart recipients. Most patients were male (21/35, 60%) with median age of 48 (range 23‐68) years. Median time to clinical presentation or diagnosis was 2.7 months (range 0.2‐29). The most common donor risk factor was residence in a TB‐endemic area (13/28, 46.4%). Fever was the most frequent presenting symptom (20/36, 56.5%). Diagnosis of tuberculosis was mostly made via AFB smear or mycobacterial culture (30/36, 83.3%). Allograft involvement was expectedly common; there were almost equal proportions of pulmonary (36%), extra‐pulmonary (28%) and disseminated (36%) cases. All cases of pulmonary TB were identified only among lung transplant recipients. The median duration of TB treatment was 10.5 (range 3‐24) months. Graft loss occurred in four (4/22, 18.2%) patients. All‐cause mortality was 25% (9/36); four of nine deaths were attributed to TB.ConclusionsDonor‐derived TB presents early after SOT, most commonly as fever, and carries a high mortality risk. Donors should be screened, with particular attention to TB risk factors. Fever during the early post‐operative period should prompt a thorough evaluation for DDTB in endemic regions and among patients with “at‐risk” donors.