Heckman, Michael G.

Introduction Atrial fibrillation/flutter (Afib) contributes independently to the hematopoietic cell transplant comorbidity index (HCTCI) and is a known complication of allogeneic hematopoietic transplantation (AlloHCT) which has been linked to inferior outcomes, particularly in older patients. An electrocardiogram (ECG)-based artificial intelligence (AI) algorithm to predict Afib and cardiac contractile dysfunction risk has been validated (Lancet 394:861, 2019). We hypothesized that assessment of pre-transplant Afib risk using the AI algorithm may predict future development of Afib and help identify patients at higher risk for this complication. Methods 191 consecutive MDS patients undergoing AlloHCT with curative intent using myeloablative (28.3%) or reduced intensity conditioning (62.3%) in the Mayo Clinic Comprehensive Cancer Center (Rochester, Jacksonville, Phoenix) between November 2015 and January 2022 were included in this retrospective analysis. Primary outcome was Afib within 100 days and 365 days of transplantation, and we also assessed the outcomes of Death and Relapse. Revised IPSS (IPSS-R) and HCTCI scores were included for all patients. Elevated Afib risk score using the AI algorithm was calculated from pre-transplant ECG, performed during vital organ testing at AlloHCT clearance. In addition to left ventricular (LV) ejection fraction (EF) we evaluated detailed echocardiographic (Echo) parameters including LV volume and mass indices, left atrial volume index (LAVI), maximum trans mitral flow velocities during LV filling (E velocity) and during the diastolic phase due to atrial contraction (A velocity), the velocity of the annulus away from the apex during the protodiastolic phase (e' velocity), E/A and E/e' ratios, the presence of valvular disease, and right ventricular systolic pressure (RVSP). We performed an analysis using a Cox proportional hazards regression models (adjusting for age and sex) to evaluate associations with Afib risk, Relapse, and Overall Survival. Results The median age was 64 years (18-75), 58.6% were male, 6.9% non-white race, and 3.7% Hispanic/Latino ethnicity. Most patients had an HCTCI score of 0-3 (76.3%). GVHD prophylaxis was predominantly with calcineurin inhibitor-based regimes plus/minus methotrexate or mycophenolate mofetil (83.8%). 5.2% of patients had a history of Afib before transplant. Non-relapse mortality was 7.9% at 100 days, and 18.3% at 365 days. N=25 patients (13.1%) developed Afib within 100 days, and n=28 (14.7%) within 1-year after AlloHCT. On multivariable analysis, Age [Hazard Ratio (HR) 2.83, 95% Confidence Interval (CI) 1.36-5.89, p=0.0055] and Echo parameters [including LAVI (HR 2.10, CI 1.23-3.58, p=0.0067), E velocity (HR 3.28, CI 1.29-8.80, p=0.013), E/A ratio (HR 3.74, CI 1.75-7.97, p=0.0006), E/e ' ratio (HR 1.81, CI 1.07-3.07, p=0.026) and RVSP (HR 1.68, CI 1.04-2.70, p=0.032)] were significantly associated with Afib risk; elevated AI risk score was significant in the univariate model (HR 2.74, CI 1.15-6.53, p=0.023) but was borderline in the multivariate model (HR 2.34, CI 0.98-5.60, p=0.056) ( Table 1). Based on previous observations we evaluated the association of AI and Echo parameters with Relapse and Death after AlloHCT ( Table 1). Age (HR 1.32, CI 1.01-1.71, p=0.041) and IPSS-R (HR 1.20, CI 1.08-1.33, p=0.0009) were significantly associated with Death after AlloHCT, while HCTCI (HR 1.10, CI 1.00-1.22, p=0.052) and higher LV EF (HR 0.63, CI 0.38-1.06, p=0.084) were borderline. For Relapse, only IPSS-R (HR 1.52, CI 1.31-1.75, p=1.22E-08) was significant, while increase Echo E velocity was of borderline significance (HR 0.45, CI 0.20-1.02, p=0.057). Conclusions Afib is a common post-AlloHCT complication and is more frequent with increasing Age. Echo parameters (specifically E/A ratio) predict significantly higher Afib risk, while the baseline ECG AI algorithm was of borderline significance. The selection of patients with lower HCTCI scores, and the low background prevalence of Afib in this cohort (i.e., selection of patients with lower baseline cardiac morbidity) are possible explanations for non-significance of the AI algorithm. As anticipated Age and IPSS-R are the greatest predictors of Death after AlloHCT, although the suggestion of an association with baseline Echo parameters highlights the importance of identifying those who may benefit from preemptive Cardiology intervention.

Background: The presence of various growth factors in platelets makes platelet-rich plasma (PRP) a powerful tool in the stimulation of collagen regeneration in aging skin. The main objective of this study was to determine efficacy and safety of PRP compared with saline solution in women with aging skin of the hands. Methods: In this prospective, randomized clinical trial, 18 women with hand aging received PRP injections every 4 weeks into the unilateral dorsal hand for 12 weeks total; with saline injections into the contralateral hand in a randomized, controlled, single-blind fashion. Physician assessment, photographs, and quality-of-life questionnaires were used for assessment at baseline and at 12-week and 24-week follow-up. Results: The majority of patients reported pain and discomfort along with a burning/stinging sensation in both PRP- and saline-treated hands, with no significant differences noted in any patient outcome measures between the 2 treatments (all P ≥ 0.25). No differences were reliably detected between the treatment hands by a blinded investigator comparing before-and-after clinical photographs of the hands. Conclusions: Three injections of PRP spaced 4 weeks apart did not appear to be effective for treatment of aging skin of the hands in women, with no noted difference as compared with baseline, or saline injection. Although age older than 45 years may be a factor accounting for nonresponse (ie, subtle skin changes are difficult to appreciate, and possible limited platelet regenerative capacity in advanced age), it appears that PRP is not a reliable cosmetic option for management of hand aging. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Abstract Purpose Loneliness may compromise health-related quality of life (HRQOL) outcomes and the immunological impacts of loneliness via neuroendocrinological mechanisms likely have consequences for patients who have undergone a hematopoietic stem cell transplantation (HSCT). Research Approach and Measures: Loneliness (pre-transplant), immunological recovery (Day 30, Day 100, 1-year post-transplant), and HRQOL (Day 100, 1 year) were measured in a sample of 205 patients completing a HSCT (127 autologous, 78 allogenic). Results Greater levels of pre-transplant loneliness predicted poorer HRQOL at Day 100 and 1-year follow-up. Loneliness also was associated with higher absolute neutrophil to absolute lymphocyte (ANC/ALC) ratios in the entire sample at Day 30, which in turn predicted Day 100 HRQOL. Conclusions Findings demonstrate that pretransplant loneliness predicts HRQOL outcomes and inflammatory immunological recovery patterns in HSCT patients. The balance of innate neutrophils to adaptive lymphocytes at Day 30 present a distinct profile in lonely individuals, with this immunity recovery profile predicting reduced HRQOL 100 days after the transplant. Addressing perceptions of loneliness before HSCT may be an important factor in improving immunological recovery and HRQOL outcomes.

Context.— Unlike B-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL), there have been few therapeutic advances in T-cell ALL (T-ALL)/LBL, an aggressive ALL/LBL subtype. Objective.— To perform a focused tissue array study to elucidate tumor markers of therapeutic potential in T-ALL/LBL. Design.— Using immunohistochemistry, we evaluated expression of leukemic antigens of interest, specifically CC-chemokine receptor 4 (CCR4), among others, on available remnant diagnostic material, including tumor tissue slides obtained from formalin-fixed, paraffin-embedded preserved tissues. Results.— Our analysis identified, for the first time, expression of CCR4 in T-ALL/LBL in 11 of 27 cases (40.7%) and confirmed common expression of BCL2, CD38, and CD47, as reported previously. We also identified the expression of CD123 in 4 of 26 cases (15.4%), whereas BCL6 and PDL1 were expressed in a small number of T-ALL/LBL cases. The potential novel target CCR4 was significantly more common in the Pre/Pro-T immunophenotypic subtype, 6 of 9 (66.7%, P = .01). No additional differences in clinical and epidemiologic variables were noted among positive or negative CCR4 cases. Conclusions.— These findings support preclinical and clinical testing of therapies targeting CCR4, CD47, BCL2, CD38, and CD123 in T-ALL/LBL, and may help guide the development of targeted clinical trials in T-ALL/LBL, a rare disease in urgent need of novel therapies.