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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Transition Award (R00)
Project #
5R00HL088021-05
Application #
8438405
Study Section
Special Emphasis Panel (NSS)
Program Officer
Mondoro, Traci
Project Start
2011-03-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2013
Total Cost
$237,049
Indirect Cost
$102,362
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Sorror, Mohamed L; Gooley, Ted A; Maclean, Kirsteen H et al. (2018) Pre-transplant expressions of microRNAs, comorbidities, and post-transplant mortality. Bone Marrow Transplant :
Hill, Joshua A; Mayer, Bryan T; Xie, Hu et al. (2017) The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality. Blood 129:2316-2325
Green, Margaret L; Leisenring, Wendy; Xie, Hu et al. (2016) Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol 3:e119-27
Graf, Solomon A; Vaughn, Jennifer E; Chauncey, Thomas R et al. (2016) Comorbidities, Alcohol Use Disorder, and Age Predict Outcomes after Autologous Hematopoietic Cell Transplantation for Lymphoma. Biol Blood Marrow Transplant 22:1582-1587
Cassaday, Ryan D; Alan Potts Jr, D; Stevenson, Philip A et al. (2016) Evaluation of allogeneic transplantation in first or later minimal residual disease - negative remission following adult-inspired therapy for acute lymphoblastic leukemia. Leuk Lymphoma 57:2109-18
Festuccia, Moreno; Deeg, H Joachim; Gooley, Theodore A et al. (2016) Minimal Identifiable Disease and the Role of Conditioning Intensity in Hematopoietic Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Evolving from Myelodysplastic Syndrome. Biol Blood Marrow Transplant 22:1227-1233
Vaughn, Jennifer E; Sorror, Mohamed L; Storer, Barry E et al. (2015) Long-term sustained disease control in patients with mantle cell lymphoma with or without active disease after treatment with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Cancer 121:3709-16
ElSawy, Mahmoud; Storer, Barry E; Pulsipher, Michael A et al. (2015) Multi-centre validation of the prognostic value of the haematopoietic cell transplantation- specific comorbidity index among recipient of allogeneic haematopoietic cell transplantation. Br J Haematol 170:574-83
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
Sorror, Mohamed L (2015) Defining vulnerability in allogeneic transplants is more complicated than the two numerical digits of age. Leuk Lymphoma 56:2235-6

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