“Many patients who receive allogeneic stem cell transplants, even those without a pre-transplant diagnosis of diabetes, have elevated blood glucose levels after transplant,” says Dr. Marco Mielcarek, Medical Director of the Adult Blood and Marrow Transplant Program at Fred Hutch Cancer Center. In a recent study published in Transplantation and Cellular Therapy, Dr. Mielcarek and his team analyzed the associations between blood glucose levels and non-relapse mortality in stem cell transplant patients with or without pre-existing diabetes. Although, it is not always clear what causes elevated blood glucose levels following the transplant, medications and changes in nutrition are frequently responsible. Many patients receive prednisone, an immune-suppressive drug, and feeding via a gastric tube or intravenously following the transplant, which may disrupt control of blood glucose levels. The stem cell transplant group previously performed a study analyzing the contribution of malglycemia – defined as elevated or reduced blood glucose levels or increased glycemic variability – to mortality after stem cell transplant at Fred Hutch more than a decade ago. According to this study, malglycemia, is associated with increased mortality after transplant. “Thus, our dogma has been that keeping blood sugar levels as close to “normal” as possible after transplant should lead to better transplant outcomes. We therefore collaborate with the Glycemic Control Consult service at University of Washington to help us with blood glucose management of complicated patients.” Given the passage of time since their previous work, Dr Mielcarek’s team decided to reassess patient outcomes relative to blood glucose management after transplant, and by considering pre-existing diagnoses of diabetes.
In the new study, the team conducted a retrospective analysis of more than 1,000 Fred Hutch transplant patients, including nearly 60,000 measurements of early post-transplant blood glucose levels collected over a 5-year period. As previously reported, higher blood glucose levels measured within 100 days after transplant were associated with increased non-relapse mortality. Surprisingly, the association was more pronounced among patients without pre-existing diabetes. Thus, patients with diabetes appeared to be relatively protected from the negative effects of post-transplant hyperglycemia. “The main finding from our analysis was that patients with a pre-transplant diagnosis of diabetes don’t seem to benefit as much from tightly controlled blood sugar levels after transplant compared to those who don’t have diabetes. We hypothesize that in patients with diabetes that is not well controlled, abruptly reducing blood sugar levels into the normal range (referred to as “relative hypoglycemia”) triggers a stress response that is counter-productive and leads to increased mortality.It is therefore conceivable that avoidance of relative hypoglycemia may improve clinical outcomes in critically ill diabetic patients, including transplant patients,” says Dr. Mielcarek. “Our data suggest that a one-size-fits-all approach to glycemic management may not be appropriate as too aggressive blood glucose lowering may lead to relative hypoglycemia in transplant patients who have diabetes.” So while the study confirms that reducing blood sugar levels in patients without pre-existing diabetes appears to be beneficial, patients with pre-existing diabetes may respond less favorably. Looking to the future, Dr. Mielcarek says “prospective studies are needed to define a more nuanced and risk-appropriate approach to malglycemia management after blood stem cell transplantation.”
The spotlighted research was funded by the National Institutes of Health and the National Heart, Lung, and Blood Institute.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Marco Mielcarek, Michael Boeckh and Ted Gooley contributed to this work.
Citation: Rashid N, Gooley T, Boeckh M, Oshima MU, Chao JH, Hirsch IB, Mielcarek M. 2024. Differential association between blood glucose levels and nonrelapse mortality after allogeneic hematopoietic cell transplantation based on presence or absence of preexisting diabetes. Transplantation and Cellular Therapy S2666-6367(24)00159-3.