Research Spotlight

Chen, Y. B., T. Wang, M. T. Hemmer, C. Brady, D. R. Couriel, A. Alousi, J. Pidala, A. Urbano-Ispizua, S. W. Choi, T. Nishihori, T. Teshima, Y. Inamoto, B. Wirk, D. I. Marks, H. Abdel-Azim, L. Lehmann, L. Yu, M. Bitan, M. S. Cairo, M. Qayed, R. Salit, R. P. Gale, R. Martino, S. Jaglowski, A. Bajel, B. Savani, H. Frangoul, I. D. Lewis, J. Storek, M. Askar, M. A. Kharfan-Dabaja, M. Aljurf, O. Ringden, R. Reshef, R. F. Olsson, S. Hashmi, S. Seo, T. R. Spitzer, M. L. MacMillan, A. Lazaryan, S. R. Spellman, M. Arora and C. S. Cutler (2016). “Gvhd after umbilical cord blood transplantation for acute leukemia: An analysis of risk factors and effect on outcomes.” Bone Marrow Transplant: 2016 Dec [Epub ahead of print].

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Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.

Cortazar, F. B., W. F. Pendergraft, 3rd, J. Wenger, C. T. Owens, K. Laliberte and J. L. Niles (2016). “The effect of continuous b cell depletion with rituximab on pathogenic autoantibodies and total igg levels in anca vasculitis.” Arthritis Rheumatol: 2016 Dec [Epub ahead of print].

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OBJECTIVE: To evaluate the effect of rituximab on pathogenic autoantibodies and total immunoglobulin levels, and to identify serious adverse events, in patients with ANCA vasculitis treated with continuous B cell depletion. METHODS: We conducted a retrospective analysis of 239 patients with ANCA vasculitis treated with rituximab-induced continuous B cell depletion. Two treatment cohorts were analyzed: an induction group (n= 53) and a maintenance group (n=237). The change in ANCA titers and total immunoglobulin levels over time were evaluated using mixed-effects models. Risk factors for serious infections during maintenance were evaluated with Poisson regression. RESULTS: During induction, IgG levels fell at a rate of 6% per month (95% CI, 4 to 8%), while ANCA levels declined at 47% per month (95% CI, 42 to 52%) and 48% per month (95% CI, 42 to 54%) for anti-MPO and anti-PR3 titers, respectively. During maintenance treatment, with a median duration of 2.4 (IQR, 1.5- 4.0) years, IgG levels declined at 0.6% per year (95% CI, -0.2 to 1.4%). New significant hypogammaglobulinemia (IgG < 400 mg/dL) during maintenance occurred in 4.6% of patients, all of whom were in the lowest baseline IgG quartile. Serious infections during maintenance occurred at a rate of 0.85 [95% CI, 0.66 to 1.1] per 10 patient years and were independently associated with an IgG level < 400mg/dL. CONCLUSION: B cell targeted therapy causes a preferential decline in ANCA titers relative to total IgG levels. Despite prolonged maintenance therapy with rituximab, IgG levels remain essentially constant. Serious infections were rare.

Daubert, M. A., N. J. Weissman, R. T. Hahn, P. Pibarot, R. Parvataneni, M. J. Mack, L. G. Svensson, D. Gopal, S. Kapadia, R. J. Siegel, S. K. Kodali, W. Y. Szeto, R. Makkar, M. B. Leon and P. S. Douglas (2016). “Long-term valve performance of tavr and savr: A report from the partner i trial.” JACC Cardiovasc Imaging: 2016 Dec [Epub ahead of print].

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OBJECTIVES: The aim of this study was to evaluate the long-term performance of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) through longitudinal echocardiographic analysis. BACKGROUND: The long-term performance of the SAPIEN TAVR is not well-described. Therefore, we examined the hemodynamic and valvular profile of the SAPIEN TAVR over 5 years. METHODS: All patients receiving TAVR or SAVR with first post-implant (FPI) and 5-year echoes were analyzed for aortic valve (AV) peak velocity, AV mean gradient, AV area, peak left ventricular (LV) outflow tract and in-stent velocities, Doppler velocity index, aortic regurgitation (AR), LV mass index, stroke volume index, and cardiac index. The FPI and 5-year data were compared using a paired t test or McNemar’s analyses. RESULTS: There were 86 TAVR and 48 SAVR patients with paired FPI and 5-year echocardiograms. Baseline characteristics were similar between groups. The AV area did not change significantly 5 years after TAVR (p = 0.35). The AV mean gradient also remained stable: 11.5 +/- 5.4 mm Hg at FPI to 11.0 +/- 6.3 mm Hg at 5 years (p = 0.41). In contrast, the peak AV and LV outflow tract velocities decreased (p = 0.03 and p = 0.008, respectively), as did in-stent velocity (p = 0.015). Correspondingly, the TAVR Doppler velocity index was unchanged (p = 0.07). Among TAVR patients, there was no change in total AR (p = 0.40), transvalvular AR (p = 0.37), or paravalvular AR (p = 0.26). Stroke volume index and cardiac index remained stable (p = 0.16 and p = 0.25, respectively). However, there was a significant regression of LV mass index (p < 0.0001). The longitudinal evaluation among SAVR patients revealed similar trends. There was a low rate of adverse events among TAVR and SAVR patients alive at 5 years. CONCLUSIONS: Longitudinal assessment of the PARTNER I trial (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial) demonstrates that valve performance and cardiac hemodynamics are stable after implantation in both SAPIEN TAVR and SAVR in patients alive at 5 years.

Dess, R. T., W. C. Jackson, S. Suy, P. D. Soni, J. Y. Lee, A. E. Abugharib, Z. S. Zumsteg, F. Y. Feng, D. A. Hamstra, S. P. Collins and D. E. Spratt (2016). “Predictors of multidomain decline in health-related quality of life after stereotactic body radiation therapy (sbrt) for prostate cancer.” Cancer: 2016 Dec [Epub ahead of print].

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BACKGROUND: Stereotactic body radiation therapy (SBRT) for localized prostate cancer involves high-dose-per-fraction radiation treatments. Its use is increasing, but concerns remain about treatment-related toxicity. The authors assessed the incidence and predictors of a global decline in health-related quality of life (HRQOL) after prostate SBRT. METHODS: From 2008 to 2014, 713 consecutive men with localized prostate cancer received treatment with SBRT according to a prospective institutional protocol. Expanded Prostate Cancer Index Composite (EPIC-26) HRQOL data were collected at baseline and longitudinally for 5 years. EPIC-26 is comprised of 5 domains. The primary endpoint was defined as a decline exceeding the clinically detectable threshold in >/=4 EPIC-26 domains, termed multidomain decline. RESULTS: The median age was 69 years, 46% of patients had unfavorable intermediate-risk or high-risk disease, and 20% received androgen-deprivation therapy. During 1 to 3 months and 6 to 60 months after SBRT, 8% to 15% and 10% to 11% of patients had multidomain declines, respectively. On multivariable analysis, lower baseline bowel HRQOL (odds ratio, 1.8; 95% confidence interval, 1.2-2.7; P < .01) and baseline depression (odds ratio, 5.7; 95% confidence interval, 1.3-24.3; P = .02) independently predicted for multidomain decline. Only 3% to 4% of patients had long-term multidomain declines exceeding twice the clinical threshold, and 30% of such declines appeared to be related to prostate cancer treatment or progression of disease. CONCLUSIONS: Prostate SBRT has minimal long-term impact on multidomain decline, and the majority of more significant multidomain declines appear to be unrelated to treatment. This emphasizes the importance of focusing not only on the side effects of prostate cancer treatment but also on other comorbid illnesses that contribute to overall HRQOL.

Gotha, H. E. and J. R. Zide (2017). “Current controversies in management of calcaneus fractures.” Orthop Clin North Am 48(1): 91-103.

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Displaced intraarticular fractures of the calcaneus represent a technically challenging injury. Although there is conflicting evidence regarding advantages and disadvantages of operative versus nonoperative treatment, a growing body of literature suggests operative management with near-anatomic reduction of the posterior facet and restoration of overall calcaneal morphology offers greater potential for superior short- and long-term outcomes. A thorough understanding of calcaneal anatomy, fracture pattern, and associated injuries, along with careful selection of surgical approach and timing to surgery are critical to minimize the risk of complication and maximize potential for optimal outcomes.