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. Dr. Sorror, and a collaborator, Dr. R. Diaconescu, have published the first reports describing the importance of comorbidities in predicting HCT outcomes. Dr. Sorror went on to develop a new and more sensitive tool to assess comorbidities specific for recipients of allogeneic HCT. The HCT-specific-comorbidity index (HCT-CI) has created unique opportunities to better understand the impact of comorbidities on HCT outcomes and it forms the basis for this proposal. The 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, the reliability and validity of the HCT-CI will be retrospectively tested among patients transplanted at multiple centers. In addition, scores weighting the impact of age intervals on HCT outcomes will be developed to form composite scores with the HCT-CI. Results of these studies will guide Dr. Sorror to proceed into the Independent Phase, which will address two parallel major aims. First, the biological impact of comorbidities on causes of death, particularly those associated with acute graft-versus-host disease and organ failures, and quality of life after HCT will be assessed comparing scores from the ? HCT-CI to those from the comorbidity-aging composite index. 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.
The second aim will prospectively investigate three different methods aimed at 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. ? ? Relevance: The goal of the proposal is to improve pretransplant prognostic assessment of survival and quality of life in patients with malignant and non-malignant blood disorders who are treated with allogeneic HCT and eventually establish a universally applicable comorbidity index, which will facilitate comparing results of clinical trials conducted at different academic centers. (End of Abstract) ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Career Transition Award (K99)
Project #
1K99HL088021-01
Application #
7245516
Study Section
Special Emphasis Panel (ZHL1-CSR-M (F1))
Program Officer
Mondoro, Traci
Project Start
2006-12-01
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
1
Fiscal Year
2007
Total Cost
$89,346
Indirect Cost
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
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
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
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
Sorror, Mohamed L (2015) Defining vulnerability in allogeneic transplants is more complicated than the two numerical digits of age. Leuk Lymphoma 56:2235-6
Vaughn, Jennifer E; Storer, Barry E; Armand, Philippe et al. (2015) Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation. Biol Blood Marrow Transplant 21:1418-24
Vaughn, Jennifer E; Gooley, Ted; Maziarz, Richard T et al. (2015) Pre-transplant comorbidity burden and post-transplant chronic graft-versus-host disease. Br J Haematol 171:411-6

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