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Adenovirus is an infrequent but challenging viral complication of transplantation that is rarely reported after autologous stem cell transplant. We present a case of disseminated adenovirus infection in a woman who received an autologous stem cell transplant for treatment of multiple sclerosis. After presenting with post‐transplant episodic diarrhea and viremia, endoscopic biopsies and immunohistochemical staining confirmed the diagnosis of disseminated adenovirus infection. Her symptoms and viremia resolved after treatment with cidofovir. This case demonstrates that a high index of suspicion, a systematic clinical approach, and immunohistochemical tissue staining are necessary to diagnose disseminated adenovirus infection in an unexpected host. [ABSTRACT FROM AUTHOR]

Introduction: High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is an effective treatment modality for immunoglobulin light-chain (AL) amyloidosis; however, its application remains restricted to patients with good performance status and limited organ involvement. In recent years, the paradigm for AL amyloidosis has changed with the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). We hypothesized that use of novel agent induction regimens has improved outcomes for patients with AL amyloidosis undergoing HDM/SCT at our center. Methods: All patients with AL amyloidosis, age ≥18 years who underwent HDM/SCT between 2001 and 2014 at the Fred Hutchinson Cancer Research Center and University of Washington Medical Center were included in this study. Any regimen administered within 6 months prior to HDM/SCT including an IMiD or a PI was considered a novel induction regimen. Use of induction regimen was evaluated in a Cox proportional hazard model for association with progression-free survival (PFS) and overall survival (OS). Results: Forty-five patients with AL amyloidosis underwent HDM/SCT. The median age was 57.2 years (range 39–74.4), 15 (33.3%) were women. The median number of organs involved was 2 (range 1–5), with 20 patients having only 1 (44.4%), 10 patients having 2 (22.2%), and 15 patients (33.3%) having ≥ 3 organs involved. Novel agent induction regimens were used prior to HDM/SCT in 21 patients (46.7%); these comprised PI in 13/21 (57.1%), IMiD alone in 6/21 (28.6%), PI and cyclophosphamide (CyBorD) in 3/21 (14.3%), and IMiD and PI in 3/21 (14.3%). Use of a novel agent induction regimen was associated with improved, but not OS. The 3-year PFS for patients who received a novel agent induction was 79%, while for those who did not was 53% (hazard ratio [HR] = 0.317,p = 0.048). The 3-year OS for patients who received novel agent induction regimens was 95%, while for those who did not was 71% (HR = 0.454,p = 0.247). Discussion: Our data suggest that use of a novel agent induction regimen including an IMiD or PI prior to HDM/SCT for patients with AL amyloidosis could improve outcomes, with improvement in PFS. Although these results are limited by sample size and lack of randomization, these results support possible further investigation of novel agent induction regimens in the context of a prospective clinical trial. [ABSTRACT FROM AUTHOR]

In mice and humans, there are two known members of the Huntingtin interacting protein 1 (HIP1) family, HIP1 and HIP1-related (HIP1r). Based on structural and functional data, these proteins participate in the clathrin trafficking network. The inactivation of Hip1 in mice leads to spinal, hematopoietic, and testicular defects. To investigate the biological function of HIP1r, we generated a Hip1r mutant allele in mice. Hip1r homozygous mutant mice are viable and fertile without obvious morphological abnormalities. In addition, embryonic fibroblasts derived from these mice do not have gross abnormalities in survival, proliferation, or clathrin trafficking pathways. Altogether, this demonstrates that HIP1r is not necessary for normal development of the embryo or for normal adulthood and suggests that HIP1 or other functionally related members of the clathrin trafficking network can compensate for HIP1r absence. To test the latter, we generated mice deficient in both HIP1 and HIP1r. These mice have accelerated development of abnormalities seen in Hip1 -deficient mice, including kypholordosis and growth defects. The severity of the Hip1r/Hip1 double-knockout phenotype compared to the Hip1 knockout indicates that HIP1r partially compensates for HIP1 function in the absence of HIP1 expression, providing strong evidence that HIP1 and HIP1r have overlapping roles in vivo. [ABSTRACT FROM AUTHOR]

Huntingtin-interacting protein 1-related (HIP1r) is the only known mammalian relative of huntingtin-interacting protein 1 (HIP1), a protein that transforms fibroblasts via undefined mechanisms. Here we demonstrate that both HIP1r and HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains. In contrast to other ENTH domain-containing proteins, lipid binding is preferential to the 3-phosphate-containing inositol lipids, phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,5-bisphosphate. Furthermore, the HIP1r ENTH domain, like that of HIP1, is necessary for lipid binding, and expression of an ENTH domaindeletion mutant, HIP1r/ΔE, induces apoptosis. Consistent with the ability of HIP1r and HIP1 to affect cell survival, full-length HIP1 and HIP1r stabilize pools of growth factor receptors by prolonging their half-life following ligand-induced endocytosis. Although HIP1r and HIP1 display only a partially overlapping pattern of protein interactions, these data suggest that both proteins share a functional homology by binding 3-phosphorylated inositol lipids and stabilizing receptor tyrosine kinases in a fashion that may contribute to their ability to alter cell growth and survival. [ABSTRACT FROM AUTHOR]

Presents a study that reported that Huntingtin-interacting protein 1 (HIP1) is expressed in prostate and colon tumor cells, but not in corresponding benign epithelia. Relationship between HIP1 expression in primary prostate cancer and clinical outcomes; Association of HIP1 expression with prostate cancer progression and metastasis; Absence of progress in primary prostate cancers lacking HIP1 expression after radical prostatectomy.

Circulating plasma cells (CPCs) have been detected in patients with multiple myeloma (MM) at various stages of disease and associated with worse outcomes. Little data exist regarding the impact of CPCs at the time of autologous peripheral blood stem cell (PBSC) collection on outcomes, and the impact of maintenance therapy after autologous stem cell transplantation (ASCT) on prognosis in patients with CPC-containing collections. All patients with MM who underwent first ASCT at Fred Hutchinson Cancer Research Center from 2012 to 2015 and had evaluation for CPCs at the time of PBSC collection were included in our analysis. Seven-color flow cytometry was used to detect the presence of CPCs. Kaplan-Meier estimates were used to generate overall survival (OS) and progression-free survival (PFS) rates from the time of ASCT. A multivariate analysis, including receipt of maintenance therapy post-ASCT, high-risk cytogenetics, and international staging system (ISS) stage, was included in a Cox proportional hazards regression model for associations with OS and PFS. We identified 227 patients with MM who underwent ASCT; of these, 144 (63.4%) patients had routine assessment of CPCs at the time of PBSC collection. One hundred seventeen (81.3%) patients did not have CPCs and 27 (18.8%) did have CPCs. The presence of CPCs was highly associated with poorer PFS ( P  = .031 by log-rank analysis), but did not affect OS. The median PFS for those patients without CPCs was 39.4 months (95% confidence interval [CI], 31.1 to not reached), while the median PFS for those patients with CPCs was 16.5 months (95% CI, 13.7 to not reached). A subgroup analysis of patients achieving very good partial response (VGPR) or better at time of collection, showed the median PFS for patients without CPCs was 38.3 months (95% CI, 29 to not reached), as compared with those patients with CPCs, where it was only 16.5 months (95% CI, 12 months to not reached; P  = .02). There was no statistically significant difference in PFS or OS among those patients achieving partial response at the time of collection. In a Cox proportional hazards model, adjusting for post-ASCT maintenance therapy, high-risk cytogenetics, and ISS stage at time of initial diagnosis, there was a 43% higher risk of progression or death among the patients with CPCs ( P  = .04). The presence of CPCs at the time of autologous PBSC collection is a negative prognostic factor for risk of early relapse or death despite the advent of novel agents and maintenance strategies. The impact of CPCs was most significant among patients achieving a VGPR or better at time of collection. The presence of CPCs denotes a unique group of high-risk MM patients for whom alternative treatment strategies are needed to overcome resistance to current standard therapies. [ABSTRACT FROM AUTHOR]