Principal Investigator

Nelson J.
Chao
Awardee Organization

Duke University
United States

Fiscal Year
2020
Activity Code
R01
Project End Date

Patient-centered home-based hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HCT) has the potential to cure people with cancer and other life- threatening diseases. However, patients risk prolonged vulnerability to infections and other complications as well as substantial treatment-related mortality. Consequently, HCT typically occurs in the hospital, with stays lasting three months or more. Yet hospitalization is not without problems, including nosocomial infections, disrupted homeostasis, and increased resource utilization and costs. Patient-centered home transplant (PCHT) is a novel alternative that may improve patient safety, clinical efficacy, and value for HCT patients. PCHT begins with a comprehensive assessment of each patient's needs. This includes meetings with patients, caregivers, social workers, nutritionists, nurses, and physicians. Following an individualized care plan, clinicians visit patients in their homes every morning to perform assessments and draw labs. Labs are analyzed at the hospital, and nurses return to patient homes to deliver needed medical interventions (e.g. antibiotics, blood transfusions). Leveraging the power of our electronic health record, clinician laptops allow remote access to all of a patient's health information, potential drug interactions, and other important details. In addition, patients are provided with iPads to videoconference daily with physicians to report complications or concerns. We have successfully piloted this approach with HCT patients, demonstrating feasibility. By allowing patients to stay at home, PCHT may reduce exposure to hospital pathogens, decreasing nosocomial infections. PCHT may also reduce graft-versus-host disease (GVHD), which affects 40-60% of HCT patients and is a leading cause of morbidity and mortality. GVHD is driven by inflammation, which may be triggered by changes in the bacteria living in the gut. This "gut microbiota" is affected by changes in the environment (e.g. hospitalization); however, if patients stay in their normal environment (home), they may preserve their normal gut microbiota, decreasing inflammation and GVHD. Staying at home also may promote independence and improve quality of life (QOL) by allowing greater access to nutrition, exercise, and social support. While more intensive staffing may be needed, these advantages may combine to lower overall costs. This proposal describes a randomized phase 2 study to compare PCHT vs. standard care. The first aim is to compare clinical outcomes, include GVHD (primary endpoint), infections, survival, quality of life, and symptoms. Potential mediators of these outcomes (e.g. nutrition, exercise, social support, self -efficacy) will also be evaluated. The second aim is to evaluate the safety of this approach, assessing treatment-related mortality and adverse events. The third aim is to conduct an economic evaluation of the direct medical costs, health resources utilization, and indirect costs (e.g., patient time) with PCHT vs. standard care. The long-term objectives are to improve patient safety and longevity by preventing complications such as GVHD and infections, promote QOL, and lower costs while improving quality of care.

Publications

  • Schluter J, Peled JU, Taylor BP, Markey KA, Smith M, Taur Y, Niehus R, Staffas A, Dai A, Fontana E, Amoretti LA, Wright RJ, Morjaria S, Fenelus M, Pessin MS, Chao NJ, Lew M, Bohannon L, Bush A, Sung AD, Hohl TM, Perales MA, van den Brink MRM, Xavier JB. The gut microbiota is associated with immune cell dynamics in humans. Nature. 2020 Dec;588(7837):303-307. Epub 2020 Nov 25. PMID: 33239790
  • Sung AD, Giri VK, Tang H, Nichols KR, Lew MV, Bohannon L, Ren Y, Jung SH, Dalton T, Bush A, Van Opstal J, Artica A, Messina J, Shelby R, Frith J, Lassiter M, Burleson J, Leonard K, Potter AS, Choi T, Gasparetto CJ, Horwitz ME, Long GD, Lopez RD, Sarantopoulos S, Chao NJ. Home-Based Hematopoietic Cell Transplantation in the United States. Transplantation and cellular therapy. 2022 Apr;28(4):207.e1-207.e8. Epub 2022 Jan 20. PMID: 35066211
  • Sung AD, Nichols KR, Chao NJ. House calls for stem cell transplant patients during the COVID-19 pandemic. Blood. 2020 Jul 16;136(3):370-371. PMID: 32488235
  • Nguyen CL, Markey KA, Miltiadous O, Dai A, Waters N, Sadeghi K, Fei T, Shouval R, Taylor BP, Liao C, Slingerland JB, Slingerland AE, Clurman AG, Maloy MA, Bohannon L, Giardina PA, Brereton DG, Armijo GK, Fontana E, Gradissimo A, Gyurkocza B, Sung AD, Chao NJ, Devlin SM, Taur Y, Giralt SA, Perales MA, Xavier JB, Pamer EG, Peled JU, Gomes ALC, van den Brink MRM. High-resolution analyses of associations between medications, microbiome, and mortality in cancer patients. Cell. 2023 Jun 8;186(12):2705-2718.e17. Epub 2023 Jun 8. PMID: 37295406
  • Stein-Thoeringer CK, Nichols KB, Lazrak A, Docampo MD, Slingerland AE, Slingerland JB, Clurman AG, Armijo G, Gomes ALC, Shono Y, Staffas A, Burgos da Silva M, Devlin SM, Markey KA, Bajic D, Pinedo R, Tsakmaklis A, Littmann ER, Pastore A, Taur Y, Monette S, Arcila ME, Pickard AJ, Maloy M, Wright RJ, Amoretti LA, Fontana E, Pham D, Jamal MA, Weber D, Sung AD, Hashimoto D, Scheid C, Xavier JB, Messina JA, Romero K, Lew M, Bush A, Bohannon L, Hayasaka K, Hasegawa Y, Vehreschild MJGT, Cross JR, Ponce DM, Perales MA, Giralt SA, Jenq RR, Teshima T, Holler E, Chao NJ, Pamer EG, Peled JU, van den Brink MRM. Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science (New York, N.Y.). 2019 Nov 29;366(6469):1143-1149. PMID: 31780560
  • Thompson JC, Ren Y, Romero K, Lew M, Bush AT, Messina JA, Jung SH, Siamakpour-Reihani S, Miller J, Jenq RR, Peled JU, van den Brink MRM, Chao NJ, Shrime MG, Sung AD. Financial incentives to increase stool collection rates for microbiome studies in adult bone marrow transplant patients. PloS one. 2022 May 4;17(5):e0267974. doi: 10.1371/journal.pone.0267974. eCollection 2022. PMID: 35507633
  • Racioppi A, Dalton T, Ramalingam S, Romero K, Ren Y, Bohannon L, Arellano C, Jonassaint J, Miller H, Barak I, Fish LJ, Choi T, Gasparetto C, Long GD, Lopez RD, Rizzieri DA, Sarantopoulos S, Horwitz ME, Chao NJ, Shah NR, Sung AD. Assessing the Feasibility of a Novel mHealth App in Hematopoietic Stem Cell Transplant Patients. Transplantation and cellular therapy. 2021 Feb;27(2):181.e1-181.e9. Epub 2020 Dec 13. PMID: 33830035
  • Guo H, Chou WC, Lai Y, Liang K, Tam JW, Brickey WJ, Chen L, Montgomery ND, Li X, Bohannon LM, Sung AD, Chao NJ, Peled JU, Gomes ALC, van den Brink MRM, French MJ, Macintyre AN, Sempowski GD, Tan X, Sartor RB, Lu K, Ting JPY. Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites. Science (New York, N.Y.). 2020 Oct 30;370. (6516). PMID: 33122357
  • Khan N, Lindner S, Gomes ALC, Devlin SM, Shah GL, Sung AD, Sauter CS, Landau HJ, Dahi PB, Perales MA, Chung DJ, Lesokhin AM, Dai A, Clurman A, Slingerland JB, Slingerland AE, Brereton DG, Giardina PA, Maloy M, Armijo GK, Rondon-Clavo C, Fontana E, Bohannon L, Ramalingam S, Bush AT, Lew MV, Messina JA, Littmann E, Taur Y, Jenq RR, Chao NJ, Giralt S, Markey KA, Pamer EG, van den Brink MRM, Peled JU. Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study. Blood. 2021 Mar 18;137(11):1527-1537. PMID: 33512409
  • Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, Weber D, Hashimoto D, Slingerland AE, Slingerland JB, Maloy M, Clurman AG, Stein-Thoeringer CK, Markey KA, Docampo MD, Burgos da Silva M, Khan N, Gessner A, Messina JA, Romero K, Lew MV, Bush A, Bohannon L, Brereton DG, Fontana E, Amoretti LA, Wright RJ, Armijo GK, Shono Y, Sanchez-Escamilla M, Castillo Flores N, Alarcon Tomas A, Lin RJ, Yáñez San Segundo L, Shah GL, Cho C, Scordo M, Politikos I, Hayasaka K, Hasegawa Y, Gyurkocza B, Ponce DM, Barker JN, Perales MA, Giralt SA, Jenq RR, Teshima T, Chao NJ, Holler E, Xavier JB, Pamer EG, van den Brink MRM. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. The New England journal of medicine. 2020 Feb 27;382(9):822-834. PMID: 32101664
  • Markey KA, Schluter J, Gomes ALC, Littmann ER, Pickard AJ, Taylor BP, Giardina PA, Weber D, Dai A, Docampo MD, Armijo GK, Slingerland AE, Slingerland JB, Nichols KB, Brereton DG, Clurman AG, Ramos RJ, Rao A, Bush A, Bohannon L, Covington M, Lew MV, Rizzieri DA, Chao N, Maloy M, Cho C, Politikos I, Giralt S, Taur Y, Pamer EG, Holler E, Perales MA, Ponce DM, Devlin SM, Xavier J, Sung AD, Peled JU, Cross JR, van den Brink MRM. The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD. Blood. 2020 Jul 2;136(1):130-136. PMID: 32430495

Clinical Trials

Study Name Clinical Trial ID
Medical Home Care for Hematopoietic Stem Cell Transplantation Phase 2 NCT02218151