Hypertension and Diabetes Mellitus in Adult and Pediatric Survivors of Allogeneic Hematopoietic Cell Transplantation

Abstract

Hypertension and diabetes are frequent early complications of allogeneic hematopoietic cell transplantation (HCT); however, their long-term outcomes are not well known. We conducted a retrospective cohort study to describe the risk factors and natural history of post-HCT hypertension and diabetes in 180 consecutive adult (n = 106) and pediatric (n = 74) allogeneic HCT recipients from 2003-2005 who had survived for 1 year post-HCT. The pediatric patients were less likely than the adult patients to have pre-HCT hypertension and diabetes, smoking history, or high-risk disease and more likely to receive myeloablative (MA) conditioning. All patients were followed until at least 2 years post-HCT; of these 1-year survivors, 156 (87%) were alive at 2 years. Acute or chronic graft-versus-host disease (aGVHD, cGVHD) occurred in 118 (66%) patients; of these, 24% received cyclosporine (CsA) for >12 months and 47% received prednisone for >12 months. Within 2 years post-HCT, 126 (70%) had hypertension and 54 (30%) had diabetes. Rates were similar for the adult recipients (hypertension, 68%; diabetes, 30%) and the pediatric recipients (hypertension, 73%; diabetes, 30%). At 2 years post-HCT, in the patients with hypertension, hypertension had not resolved in 34%, and among patients with diabetes, diabetes had not resolved in 32%. On multivariate analyses, exposure to CsA increased the risk of developing hypertension post-HCT (relative risk, 1.6; 95% confidence interval [CI], 1.1-2.5; P = .03), but did not affect its persistence at 2 years. Exposure to high-dose corticosteroids (cumulative prednisone dose of > 0.25 mg/kg/day) increased the likelihood of developing diabetes (relative risk, 3.6; 95% CI, 1.7-7.5; P < .01) and for having persistent diabetes at 2 years post-HCT (relative risk, 4.1; 95% CI, 1.0-18.2; P = .05). Hypertension and diabetes are frequent early complications of allogeneic HCT, but subsequently resolve in a large proportion of recipients in the first 2 years after transplantation. Continued monitoring and treatment of hypertension and diabetes is necessary in allogeneic HCT survivors, especially in those exposed to high doses of corticosteroids.

Cardiovascular risk factors in hematopoietic cell transplantation survivors: role in development of subsequent cardiovascular disease

“…Previous studies, conducted largely in allogeneic HCT recipients, have reported wide-ranging estimates for prevalence of hypertension (15%-70%), 9,12,13,16 diabetes (7%-30%), 12,16 and dyslipidemia (16%-56%), 10,14,16 due, in part, to a variety of definitions used for CVRFs and varying lengths of follow-up of the study cohorts. In the current study, we used a conservative approach to defining CVRFs, therefore a condition had to be present for Ͼ 6 months and persist for Ͼ 1 year after HCT, highlighting the magnitude of disease burden that persists long after the immediate post-HCT period.…”

“…Although recurrence of primary disease remains the leading cause of mortality after HCT, 3,28,29 nonmalignant late effects such as CVD contribute increasingly with longer follow-up, 4-6 a problem that can be compounded by the high prevalence of CVRFs in HCT survivors, as demonstrated in the current study. Studies to date have been limited by relatively short follow-up after HCT, 12-14 reliance on questionnaire-based self-reported outcomes, 9 lack of comparison with the general population, 11,12,14 and lack of information regarding the contribution of CVRFs in the development of CVD in patients previously exposed to cardiotoxic agents such as anthracyclines and chest radiation. [15][16][17] The current study overcomes these limitations by comprehensively evaluating the risk of CVRFs and their modifying effect on subsequent development of CVD in a large cohort of HCT survivors with 11 700 person-years of followup.…”

“…8 HCT recipients may be at increased risk of developing these cardiovascular risk factors (CVRFs) because of pre-HCT and conditioning-related therapeutic exposures, as well as graft versus host disease (GVHD) and its management. [9][10][11] Previous studies evaluating CVRFs in HCT survivors have been limited by small sample sizes, 10-13 relatively short follow-up after HCT, [12][13][14] lack of evaluation among autologous HCT recipients, 10,14 lack of comparison with age-and sex-matched general population, 11,12,14 and reliance on self-reported outcomes. 9 Previous studies have also been limited by the lack of contribution of CVRFs and pre-HCT therapeutic cardiotoxic therapeutic exposure in the development of CVD.…”

How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT

“…In a study of 180 allo-HSCT recipients, Majhail et al 12 reported 30% prevalence of DM within the first 2 years post transplantation and was similar in children and adults; DM had not resolved in 32% of these patients by 2 years. Exposure to high-dose corticosteroids (cumulative dose of 40.25 mg/kg/day) increased the likelihood of developing PTDM and its persistence at 2 years.…”

Predicting posttransplantation diabetes mellitus by regulatory T-cell phenotype: implications for metabolic intervention to modulate alloreactivity

“…[1][2][3] Insulin resistance is a prominent characteristic of the metabolic syndrome. This pro-inflammatory disorder is highly prevalent in survivors of HSCT and is associated with increased risk for cardiovascular mortality.…”