Citations

In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients.

Objectives To quantify associations between inflammatory biomarkers and hippocampal volume ( HV ) and to examine effect modification according to sex, race, and age. Design Cross‐sectional analyses using generalized estimating equations to account for familial clustering; standardized β ‐coefficients adjusted for age, sex, race, and education. Setting Community cohorts in Jackson, Mississippi and Rochester, Minnesota. Participants The Genetic Epidemiology Network of Arteriopathy study. Measurements C‐reactive protein ( CRP ), interleukin‐6 ( IL ‐6), and soluble tumor necrosis factor receptors 1 ( sTNFR ‐1) and 2 ( sTNFR ‐2) from peripheral blood were measured in a sample of 773 non‐Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. Results In the full sample, higher sTNFR ‐1 and sTNFR ‐2 were associated with smaller HV . Each standard deviation ( SD ) increase in sTNFR ‐1 was associated with 59.1 mm 3 (95% confidence interval ( CI ) = −101.4 to −16.7 mm 3 ) smaller HV and each SD increase in sTNFR ‐2 associated with 48.8 mm 3 (95% CI = −92.2 to −5.3 mm 3 ) smaller HV . Relationships were stronger for sTNFR ‐2 in men ( HV = −116.6 mm 3 for each SD increase, 95% CI = −201.0 to −32.1) than women ( HV = −26.0 per SD increase, 95% CI = −72.4–20.5) and sTNFR ‐1 in non‐Hispanic whites ( HV = −84.7 mm 3 per SD increase, 95% CI = −142.2 to −27.1) than African Americans ( HV = −14.1 mm 3 per SD increase, 95% CI = −78.3–50.1). Associations between IL ‐6 or CRP and HV were not supported. Conclusion Higher levels of sTNFR s were associated cross‐sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late‐life cognitive impairment.

Resident participation in international health electives (IHEs) has been shown to be beneficial, yet not all residents have the opportunity to participate. We sought to determine whether participating in simulated global health cases, via the standardized Simulation Use for Global Away Rotations (SUGAR) curriculum, was useful for all pediatric residents, not merely those planning to go on an IHE. Pediatric residents in our program took part in 2 SUGAR cases and provided feedback via an online survey. Thirty-six of 40 residents participated (90%); 72% responded to the survey. Three of 10 residents not previously planning to work in resource-limited settings indicated participation in SUGAR made them more likely to do so. Nearly all residents (88%) felt SUGAR should be part of the residency curriculum. All felt better prepared for working cross-culturally. While designed to prepare trainees for work in resource-limited settings, SUGAR may be beneficial for all residents.

Context: Factors that regulate physiological feedback by pulses of glucocorticoids on the hypothalamic-pituitary unit are sparsely defined in humans in relation to gluco- or mineralocorticoid receptor pathways, gender, age, and the sex steroid milieu. Objective: The objective of the study was to test (the clinical hypothesis) that glucocorticoid (GR) and mineralocorticoid (MR) receptor-selective mechanisms differentially govern pulsatile cortisol-dependent negative feedback on ACTH output (by the hypothalamo-pituitary unit) in men and women studied under experimentally defined T and estradiol depletion and repletion, respectively. Setting: The study was conducted at the Mayo Center for Translational Science Activities. Subjects: Healthy middle-aged men (n = 16) and women (n = 25) participated in the study. Interventions: This was a randomized, prospective, double-blind, placebo- and saline-controlled study of pulsatile cortisol infusions in low cortisol-clamped volunteers with and without eplerenone (MR blocker) and mifepristone (GR blocker) administration under a low and normal T and estradiol clamp. During frequent sampling, a bolus of CRH-arginine vasopressin was infused to assess corticotrope responsiveness. Analytical Methods and Outcomes: Deconvolution and approximate entropy of ACTH profiles were measured. Results: Infusion of cortisol (but not saline) pulses diminished ACTH secretion. The GR antagonist, mifepristone, interfered with negative feedback on both ACTH burst mass and secretion regularity. Eplerenone, an MR antagonist, exerted no detectable effect on the same parameters. Despite feedback imposition, CRH-arginine vasopressin-stimulated ACTH secretion was also increased by mifepristone and not by eplerenone. Withdrawal vs addback of sex steroids had no effect on ACTH secretion parameters. Nonetheless, ACTH secretion was greater (P = .006) and more regular (P = .004) in men than women. Conclusion: Pulsatile cortisol feedback on ACTH secretion in this paradigm is mediated by the glucocorticoid receptor, in part acting at the level of the pituitary, and influenced by sex.

Abstract Background Uncertainty exists whether patients with spinal cord compression (SCC) from a highly radiosensitive tumor require decompressive spinal surgery in addition to radiotherapy (RT). This study addressed the question by evaluating patients receiving RT alone for SCC from myeloma. Patients and methods Data of 238 patients were retrospectively analyzed for response to RT and local control of SCC. In addition, the effect of RT on motor function (improvement, no further progression, deterioration) was evaluated. Overall response was defined as improvement or no further progression of motor dysfunction. Prior to RT, patients were presented to a neurosurgeon for evaluation whether upfront decompressive surgery was indicated (e.g. vertebral fracture or unstable spine). Results In the entire cohort, the overall response rate was 97% (53% improvement plus 44% no further progression). Following RT, 88% of the patients were able to walk. Of the 69 non-ambulatory patients 44 patients (64%) regained the ability to walk. Local control rates at 1, 2 and 3 years were 93%, 82% and 82%, respectively. A trend towards better local control was observed for patients who were ambulatory before starting RT (p = 0.08) and those with a more favorable performance status (p = 0.07). Conclusions RT alone provided excellent response rates, functional outcomes and local control in patients with SCC from myeloma. These results should be confirmed in a prospective randomized trial.

Recent literature has demonstrated concern over the risk of Pneumocystis jirovecii pneumonia (PJP) when administering rituximab with combination chemotherapy such as in R‐CHOP; however, the exact risk and potential need for prophylaxis is unknown. We sought to determine the incidence of PJP infection following R‐CHOP administration in patients with B‐cell lymphoma. Consecutive patients diagnosed with B‐cell lymphoma receiving R‐CHOP were evaluated from chemotherapy initiation until 180 days after the last administration. The primary outcome was cumulative incidence of PJP infection. Secondary endpoints included the association of rituximab, prednisone and subsequent chemotherapy with PJP infection risk. A total of 689 patients (53% male, median age 66 years) were included. Seventy‐three percent of patients completed at least 6 cycles of R‐CHOP treatment. Median rituximab and prednisone cumulative doses were 3950 mg and 5325 mg, respectively. Median daily prednisone dose through end of treatment was 45 mg (range 7.6 mg to 119 mg). The cumulative incidence of PJP was 1.51% (95% CI 0.57–2.43, at maximum follow‐up of 330 days), below 3.5%, the conventional threshold for prophylaxis. Univariate analysis did not detect a statistically significant association between PJP and rituximab, steroids, or receipt of additional chemotherapy in this patient population. Our results demonstrate a low occurrence of Pneumocystis pneumonia during R‐CHOP treatment of B‐cell lymphoma and argue against universal anti‐Pneumocystis prophylaxis in this setting. Further investigations should focus on targeted anti‐Pneumocystis prophylaxis for patients presenting with high‐risk baseline characteristics or when receiving rituximab‐inclusive intensive combination chemotherapy regimens as treatment for other aggressive lymphoma subtypes. Am. J. Hematol. 91:1113–1117, 2016. © 2016 Wiley Periodicals, Inc.