Research Spotlight

Kim, H. T., K. W. Ahn, Z. H. Hu, M. S. Davids, V. O. Volpe, J. H. Antin, M. L. Sorror, M. Shadman, O. Press, J. Pidala, W. Hogan, R. Negrin, S. Devine, J. Uberti, E. Agura . . . and J. R. Brown (2019). “Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report.” Clin Cancer Res 25(16): 5143-5155.

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PURPOSE: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). EXPERIMENTAL DESIGN: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. RESULTS: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >/=5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). CONCLUSIONS: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.

Kaneko, T., V. H. Thourani, G. Ailawadi, M. B. Leon, M. J. Mack and G. H. L. Tang (2019). “Transseptal Access-Gateway to Transcatheter Mitral Interventions.” Ann Thorac Surg 108(3): 654-656.

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Over the past 8 years, we have witnessed a significant growth of transcatheter aortic valve replacement (TAVR) replacing 1 of our most commonly performed surgeries, the surgical aortic valve replacement for severe aortic stenosis. In 2017, for the first time, the number of TAVRs performed exceeded surgical aortic valve replacements with or without coronary revascularization. Recently, 2 randomized studies comparing surgical aortic valve replacement with TAVR in low-risk patients with severe aortic stenosis revealed superiority on mortality and disabling stroke with a balloon-expandable valve, and non-inferiority with a self-expanding valve will most definitely favor an increase in transcatheter aortic valve procedures. With the success in TAVR, industry is searching for the next frontier. In 2015, Edwards Lifesciences (Irvine, CA) bought a start-up company, CardiAQ for $200 million, and Medtronic (Minneapolis, MN) bought another start-up company, Twelve, for $458 million. These start-up companies have one thing in common—they both created new technology for transcatheter mitral valve replacement. Investment in these start-up companies clearly shows the direction of the next chapter in the treatment of structural heart disease. (Excerpt from text, p. 654; no abstract available.)

Jones, B. P., S. Saso, A. L’Heveder, T. Bracewell-Milnes, M. Y. Thum, C. Diaz-Garcia, D. A. MacIntyre, I. Quiroga, S. Ghaem-Maghami, G. Testa, L. Johannesson, P. R. Bennett, J. Yazbek and J. R. Smith (2019). “The vaginal microbiome in uterine transplantation.” BJOG Aug 8. [Epub ahead of print].

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Women with congenital absolute uterine factor infertility (AUFI) often need vaginal restoration to optimise sexual function. Given their lack of procreative ability, little consideration has previously been given to the resultant vaginal microbiome (VM). Uterine transplantation (UTx) now offers the opportunity to restore these women’s reproductive potential. The structure of the VM is associated with clinical and reproductive implications that are intricately intertwined with the process of UTx. Consideration of how vaginal restoration methods impact VM is now warranted and assessment of the VM in future UTx procedures is essential to understand the interrelation of the VM and clinical and reproductive outcomes. TWEETABLE ABSTRACT: The vaginal microbiome has numerous implications for clinical and reproductive outcomes in the context of uterine transplantation.

Jones, B. P., S. Saso, T. Bracewell-Milnes, M. Y. Thum, J. Nicopoullos, C. Diaz-Garcia, P. Friend, S. Ghaem-Maghami, G. Testa, L. Johannesson, I. Quiroga, J. Yazbek and J. R. Smith (2019). “Human uterine transplantation: a review of outcomes from the first 45 cases.” BJOG 126(11): 1310-1319.

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Uterine transplantation restores reproductive anatomy in women with absolute uterine factor infertility and allows the opportunity to conceive, experience gestation, and acquire motherhood. The number of cases being performed is increasing exponentially, with detailed outcomes from 45 cases, including nine live births, now available. In light of the data presented herein, including detailed surgical, immunosuppressive and obstetric outcomes, the feasibility of uterine transplantation is now difficult to refute. However, it is associated with significant risk with more than one-quarter of grafts removed because of complications, and one in ten donors suffering complications requiring surgical repair. TWEETABLE ABSTRACT: Uterine transplantation is feasible in women with uterine factor infertility, but is associated with significant risk of complication.

Johnson, C. M., C. D. Linzay and T. Dassopoulos (2019). “Maneuvering Clinical Pathways for Ulcerative Colitis.” Curr Gastroenterol Rep 21(10): 52.

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PURPOSE OF REVIEW: Recent years have brought about several advances in the treatment of patients with ulcerative colitis (UC). Here, we discuss salient recommendations of recent treatment guidelines; review the efficacy, safety, and real-world data of vedolizumab and tofacitinib; appraise their place vis-a-vis established agents; and consider the newly proposed approaches of risk-stratified and treat-to-target therapy. RECENT FINDINGS: Once daily oral mesalamine dosing is equivalent to split dosing in mild-moderate UC. Real-world data are accumulating on the effectiveness and safety of vedolizumab for moderate to severe UC, while there are few such data on the most recently approved agent, tofacitinib. High-dose infliximab is being investigated for severe UC. New approaches are challenging the established paradigm of selecting therapy based on current disease activity. The risk-stratified approach incorporates long-term risk as well as the current burden of inflammation. The treat-to-target approach aims at improved long-term outcomes by adjusting therapy to resolve intestinal inflammation. The therapeutic options for UC are continually expanding. Risk-stratified therapy and the treat-to-target approach represent paradigm shifts in UC management. Optimal disease control requires an individualized approach that takes into consideration current inflammatory burden, long-term risk, patient preferences, and ongoing assessment of response to treatment.