Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for various hematological diseases. However, many patients who could potentially benefit from HCT have been ineligible for the procedure due to comorbidities and age. With the development of reduced-intensity regimens and improvements in supportive care after myeloablative HCT, increasing numbers of elderly patients and those with comorbidities have been offered allogeneic HCT. I have published the first report describing the importance of comorbidities in predicting HCT outcomes. I then went on to develop a more sensitive new tool to assess comorbidities specific for recipients of allogeneic HCT. The HCT-specific-comorbidity index (HCTCI) served to better understand the impact of comorbidities on HCT outcomes and it forms the basis for this proposal. This proposal is focused on further evaluating and developing the prognostic value of comorbidities for outcomes in HCT recipients with the eventual aim of creating a universally applicable comorbidity index. During the Mentored Phase, I have collected data from 3331 patients transplanted at five institutions and confirmed the multi-center validity of the HCT-CI. I also demonstrated lack of impact of age on nonmyeloablatlve HCT outcomes but higher risks for mortality among patients of >50 years given myeloablative regimens. Scores weighting the impact of age intervals on HCT outcomes were added to the HCT-CI to form composite scores. Results of these studies have guided me to proceed into the Independent Phase, which will address three parallel major aims. First, I will test homogeneity of outcome prediction per the HCT-CI across institutions and validation ofthe predictive impacts ofthe HCT-CI/age scores of outcomes in a large dataset (n=15,000) of patients from the Center of International Blood and Marrow Transplantation Research (CIBMTR). Second, I will assess the biological impact of comorbidities on causes of death, particularly those associated with acute graft-versus-host-disease and organ failures, and on quality of life after HCT using the HCT-CI/age scores as well as individual comorbidity burden. This will involve both retrospective reviews of medical records of previously transplanted patients and analyses of prospective clinical trials to include larger number of patients and to ensure prospective reproducibility of the impacts of comorbidities. Third, I will prospectively investigate three different methods for simplifying collection of comorbidity data and develop an educational program for evaluation of comorbidities by data registrars and, thereby, facilitate the more wide-spread incorporation of comorbidity assessment at HCT centers.

Public Health Relevance

A universally-applicable reproducible health assessment measure would improve decision-making for patients with malignant and non-malignant blood disorders who are treated with allogeneic HCT, which will eventually improve their survival and quality of life. Our improved understanding of comorbidity impact will facilitate comparing results of clinical trials conducted at different academic centers and aid in the generation of future clinical trials.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Mondoro, Traci
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Fred Hutchinson Cancer Research Center
United States
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Walter, R B; Gyurkocza, B; Storer, B E et al. (2015) Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia 29:137-44
Walter, Roland B; Sandmaier, Brenda M; Storer, Barry E et al. (2015) Number of courses of induction therapy independently predicts outcome after allogeneic transplantation for acute myeloid leukemia in first morphological remission. Biol Blood Marrow Transplant 21:373-8
Jaklic, Alenka; Collins, Carol J; Mrhar, Ales et al. (2013) High prevalence of potential drug interactions affecting mycophenolic acid pharmacokinetics in nonmyeloablative hematopoietic stem cell transplant recipients. Int J Clin Pharmacol Ther 51:711-7
Sorror, Mohamed L; Appelbaum, Frederick R (2013) Risk assessment before allogeneic hematopoietic cell transplantation for older adults with acute myeloid leukemia. Expert Rev Hematol 6:547-62
Danner-Koptik, K E; Majhail, N S; Brazauskas, R et al. (2013) Second malignancies after autologous hematopoietic cell transplantation in children. Bone Marrow Transplant 48:363-8
Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E et al. (2011) Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. JAMA 306:1874-83
Sorror, Mohamed L (2011) Comorbidities and outcomes: advancing the field comes at a price. Biol Blood Marrow Transplant 17:1721-3
Loren, Alison W; Chow, Eric; Jacobsohn, David A et al. (2011) Pregnancy after hematopoietic cell transplantation: a report from the late effects working committee of the Center for International Blood and Marrow Transplant Research (CIBMTR). Biol Blood Marrow Transplant 17:157-66
Walter, Roland B; Gooley, Ted A; Wood, Brent L et al. (2011) Impact of pretransplantation minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol 29:1190-7
Nemecek, Eneida R; Guthrie, Katherine A; Sorror, Mohamed L et al. (2011) Conditioning with treosulfan and fludarabine followed by allogeneic hematopoietic cell transplantation for high-risk hematologic malignancies. Biol Blood Marrow Transplant 17:341-50

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