Goal 2: Reduce Human Disease

Intervening on Metabolic Derangements Induced by Allogeneic Hematopoietic Stem Cell Transplantation

Can standardized screening, pharmacological/behavioral prevention, and optimized treatment of metabolic complications after allogeneic hematopoietic stem cell transplantation improve outcomes and decrease transplant-related morbidity and mortality?

Tags (Keywords associated with the idea)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

The development of type 2 diabetes mellitus (DM) is a significant complication for long-term cancer survivors including patients treated with allogeneic hematopoietic stem cell transplantation (HCT). New onset, post-transplant DM (PTDM) occurs in up to 60% of HCT recipients, often precedes the development of acute GVHD, and negatively impacts survival. Type 2 DM is a complex disorder characterized by hyperglycemia, insulin resistance, and relative insulin insufficiency. The transition from insulin resistance to diabetes is associated with an inflammatory milieu characterized by the accumulation of IFN-γ secreting T cells (Th1 cells) and depletion of immunosuppressive Foxp3+ regulatory T cells in visceral organs and adipose tissue. Similarities exist between the immunology of insulin resistance and GVHD. However, the initiating events and mechanisms that culminate in PTDM development remain understudied, and formal recommendations for screening and treatment are lacking. All pregnant women undergo screening for diabetes, which complicates 2-10% of pregnancies in the United States. About 30% of renal transplant patients develop diabetes (NODAT), and current recommendations include weekly fasting blood glucose measurements. No such recommendations exist for HCT recipients, of whom up to 60% will develop de novo PTDM. Through clinical investigation, effective strategies for screening, preventing, and optimally treating PTDM can be developed and HCT outcomes improved.

Feasibility and challenges of addressing this CQ or CC :

It is time to make up for lost (scientific) ground. It will require the efforts of a large network like the BMT-CTN to quickly address problems, answer important scientific questions, and raise awareness for a frequent but understudied complication following HCT.

Name of idea submitter and other team members who worked on this idea : Brian Engelhardt and Madan Jagasia, Vanderbilt University

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Idea No. 807