Citations

SummaryGraft‐versus‐host disease (GVHD) is the major complication of hematopoietic stem cell transplantation and is associated with high mortality in severe cases. The skin is one of the major organs affected in both acute and chronic GVHD. This review aims to elucidate the basic characteristics of GVHD, and the role and contribution of dermatologists in the care of patients with this condition.

AbstractBackgroundScreening for vancomycin‐resistant Enterococcus (VRE) is performed at many transplant centers, but data on the impact of VRE colonization and bloodstream infection (BSI) on hematopoietic cell transplantation (HCT) outcomes remain conflicting.MethodsConsecutive adults with acute myeloid leukemia who underwent allogeneic HCT between 2004 and 2014 were retrospectively reviewed. Patients were screened by perirectal PCR swabs targeting vanA and vanB twice weekly while inpatient.ResultsOf a total of 203 patients (median age 54 years), 73 (36%) were VRE colonized prior to HCT, 23 (11%) became colonized within the first 100 days, and 107 (53%) remained non‐colonized through day 100 post HCT. A landmark analysis on HCT day 0 revealed no significant difference in overall survival according to pre‐transplant colonization status (P=.20). However, patients with subsequent VRE colonization within the first 100 days of HCT had a significantly worse survival on both univariable (P=.04) and multivariable (P=.03) analyses. During the first 30 days post HCT, 11 (5% of total and 11% of the VRE colonized) patients developed VRE BSI. Ten (91%) of these had screened positive for VRE colonization before the bacteremia. Age ≥60 years, HCT‐comorbidity index ≥3, and VRE colonization were independent risk factors for VRE BSI on multivariable analysis (P=.04, .03, .003, respectively). Only 1 (9%) patient with VRE BSI died within the first 100 days post HCT.ConclusionVRE colonization is a surrogate marker and not an independent predictor of worse outcomes post HCT. VRE BSI is associated with increased morbidity, but does not impact post‐HCT survival.

AbstractMyelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by abnormal cellular differentiation and maturation with variable progression to acute leukemia. Over the last decade, scientific discoveries have unraveled specific pathways involved in the complex pathophysiology of MDS. Prominent examples include aberrations in cytokines and their signaling pathways (such as tumor necrosis factor‐alpha, interferon‐gamma, SMAD proteins), mutations in genes encoding the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, and U2AF1 genes), mutations in genes disrupting the epigenetic machinery (TET2, DNMT3A, DNMT3B, EZH2, ASXL1). In addition, abnormalities in regulatory T‐cell dynamics and atypical interactions between the bone marrow microenvironment, stroma and progenitor cells, and abnormal maintenance of telomeres are also notable contributors to the complex pathogenesis of MDS. These pathways represent potential targets for novel therapies. Specific therapies include drugs targeting aberrant DNA methylation and chromatin remodeling, modulating/activating the immune system to enhance tumor‐specific cellular immune responses and reduce anomalous cytokine signaling, and blocking abnormal interaction between hematopoietic progenitors and stromal cells.

AbstractCentral nervous system (CNS) involvement with diffuse large B‐cell lymphoma (DLBCL) is a relatively uncommon manifestation; with most cases of CNS involvement occuring during relapse after primary therapy. CNS dissemination typically occurs early in the disease course and is most likely present subclinically at the time of diagnosis in many patients who later relapse in the CNS. CNS relapse in these patients is associated with poor outcomes. Based on a CNS relapse rate of 5% in DLBCL and weighing the benefits against the toxicities, universal application of CNS prophylaxis is not justified. The introduction of rituximab has significantly reduced the incidence of CNS relapse in DLBCL. Different studies have employed other agents for CNS prophylaxis, such as intrathecal chemotherapy and high‐dose systemic agents with sufficient CNS penetration. If CNS prophylaxis is to be given, it should be preferably administered during primary chemotherapy. However, there is no strong evidence that supports any single approach for CNS prophylaxis. In this review, we outline different strategies of administering CNS prophylaxis in DLBCL patients reported in literature and discuss their advantages and drawbacks.

AbstractBackgroundRespiratory syncytial virus (RSV) infection causes significant morbidity and mortality in allogeneic stem cell transplant (allo‐SCT) recipients. Although ribavirin and immunoglobulins are common components of therapy, the role of adjunct corticosteroids is not established.ObjectivesWe sought to evaluate corticosteroid utilization in the setting of post‐allo‐SCT RSV infection in our center and assess post‐transplant outcomes including pulmonary function decline.MethodsPatients with a history of RSV infection from 2008 to 2014 seen at our institution were identified. Treatment and outcome data were retrospectively collected. Forced expiratory volume at 1 s (FEV1) and carbon monoxide diffusion capacity (DLCO) were collected pre‐ and post‐RSV infection.ResultsDuring the observation period, RSV was isolated in 53 of 552 patients undergoing allo‐SCT (10%) and 45 had evaluable therapy data. RSV‐related mortality in this cohort was 4/45 (9%). Twenty‐one (47%) were on corticosteroids prior to RSV diagnosis, of whom 11 (24%) had a dose increase post symptom onset. Eight (18%) patients were started on corticosteroids at the time of RSV infection. Corticosteroid therapy at symptom onset was associated with a higher rate of upper respiratory infection (URTI) to lower respiratory infection (LRTI) progression risk ratio (RR) 2.49 (1.21–5.13; P = 0.016), hospital admission RR 2.05 (1.24–3.37; P = 0.005), or intensive care unit admission RR 2.91 (1.89–5.01; P = 0.002). No significant difference was seen with FEV1 and DLCO decline (P = 0.3 and 0.24, respectively) or mortality (P = 0.26).ConclusionAdjunct corticosteroid use in the setting of RSV infection did not improve RSV‐related outcomes including long‐term pulmonary function. Our results do not support the routine use of corticosteroids; however, this finding does need to be verified in a larger cohort of patients.

BACKGROUNDABO incompatibility is not a contraindication to hematopoietic cell transplantation (HCT), but it has been associated with additional risks including delayed engraftment, pure red cell aplasia (PRCA), and higher transfusion needs. Data on these events and on patient survival after reduced‐intensity conditioning (RIC) HCT are limited.STUDY DESIGN AND METHODSA total of 127 consecutive patients, 86 with acute myeloid leukemia and 41 with myelodysplastic syndromes, who underwent HLA‐matched peripheral blood RIC allogenic HCT between 2005 and 2014 were retrospectively analyzed.RESULTSEighty ABO‐compatible, 26 major/bidirectional, and 21 minor‐ABO‐mismatch HCT were identified. Compared to the ABO‐compatible group, major/bidirectional mismatches had increased red blood cell (RBC) transfusion requirement during the first 100 days (p = 0.009), delayed RBC and PLT engraftment (p = 0.0011 and p = 0.005, respectively), and higher incidence of grade II to IV acute graft‐versus‐host disease (aGVHD; p = 0.037). In multivariable analysis, major/bidirectional mismatches had significantly higher non‐relapse mortality (NRM) and inferior disease‐free survival (DFS) and overall survival (OS) compared with ABO‐compatible patients (p = 0.01, p = 0.04, and p = 0.035, respectively). Minor ABO mismatch had no impact on survival (p = 0.99). Four (15%) of 26 major/bidirectional mismatches developed PRCA. There was a significant association between fludarabine plus busulfan conditioning and PRCA (p = 0.0046).CONCLUSIONMajor/bidirectional ABO mismatch is associated with higher NRM and shortened DFS and OS in the setting of RIC HCT. Increased transfusion need, delayed RBC and platelet engraftment, PRCA, and increased severity of aGVHD are additional complications contributing to the morbidity.

Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long‐term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft‐versus‐host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT. Cancer 2015;121:4124–4131. © 2015 American Cancer Society.

The widespread use of complementary and alternative medicine (CAM) in cancer survivors is well known despite a paucity of scientific evidence to support its use. The number of survivors of hematopoietic stem cell transplant (HCT) is growing rapidly and HCT clinicians are aware that many of their patients use CAM therapies consistently. However, due to a paucity of data regarding the benefits and harms of CAM therapies in these survivors, clinicians are reluctant to provide specific recommendations for or against particular CAM therapies. A systematic literature review was conducted with a search using PubMed, the Cochrane Database of Systematic Reviews, and Ovid online for each CAM therapy as defined by the National Center of Complementary and Alternative Medicine. The search generated 462 references, of which 26 articles were deemed to be relevant for the review. Due to extensive heterogeneity in data and limited randomized trials, a meta‐analysis could not be performed but a comprehensive systematic review was conducted with specified outcomes for each CAM therapy. In randomized controlled trials, certain mind and body interventions such as relaxation were observed to be effective in alleviating psychological symptoms in patients undergoing HCT, whereas the majority of the other CAM treatments were found to have mixed results. CAM use is an understudied area in HCT survivorship and clinicians should convey the benefits and uncertainties concerning the role of CAM therapies to their patients. Cancer 2015;121:2303–2313. © 2015 American Cancer Society.

AbstractBackgroundVoriconazole is a commonly used antifungal medication in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) patients. In solid organ transplantation, voriconazole use has been associated with the development of cutaneous squamous cell carcinoma (SCC). We sought to determine if voriconazole use was associated with SCC in patients undergoing allo‐HSCT.MethodsWe retrospectively reviewed consecutive adult patients who underwent allo‐HSCT at Mayo Clinic from January 2007 through July 2012. Multivariable Cox models were created to assess the relationship of SCC with two time‐dependent voriconazole exposure variables: (i) history of voriconazole exposure (yes/no), and (ii) cumulative days of voriconazole use.ResultsIn our cohort of 381 allo‐HSCT patients, SCC developed in 26 of 312 patients exposed to voriconazole (25 post‐voriconazole) and in 1 of 69 patients who received alternative antifungal agent(s). Cumulative incidence of SCC was estimated to be 19% at 5 years post allo‐transplant. Cumulative days of voriconazole use was found to be a risk factor for SCC, and this relationship persisted in a multivariable model using previously identified risk factors as covariates (hazard ratio 1.859 for each 180 days of use, P < 0.001).ConclusionThis is the first study, to our knowledge, to identify cumulative days of voriconazole use as a risk factor for SCC development following allo‐HSCT, and may help guide appropriate antifungal use in this patient population.

BackgroundComplications from graft‐vs.‐host disease (GVHD), a major contributor to morbidity and mortality following hematopoietic cell transplantation, may be mitigated by early diagnosis and intervention. However, differentiation between acute cutaneous GVHD and other common skin eruptions that develop in the post‐transplantation period, such as drug hypersensitivity reaction, can be challenging clinically and microscopically. Because recent evidence indicates that CD123, a marker of plasmacytoid dendritic cells, can help to distinguish gastrointestinal GVHD from the clinicopathologic mimic cytomegalovirus colitis, we aimed to determine whether CD123 could aid in the diagnosis of acute cutaneous GVHD.MethodsWe studied 12 skin specimens of patients with grades I–II cutaneous GVHD and 12 from patients who had drug hypersensitivity reaction with vacuolar interface changes on biopsy.ResultsNo differences were seen between the two groups with regards to density or distribution of CD123 expression. Specimens representing GVHD showed significantly less spongiosis (P < 0.001) and fewer dermal eosinophils (P = 0.03) compared to those representing drug hypersensitivity reaction.ConclusionsWe conclude that CD123 does not appear to be a useful ancillary test in the diagnosis of acute cutaneous GVHD. Careful correlation between clinical findings and features with microscopy remains the cornerstone of accurate diagnosis of acute cutaneous GVHD.