Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients.

To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC).

The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.

The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05).

The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.

Obesity and diabetes can modulate immune responses, which may impact allogeneic HCT outcomes and GvHD. From the EBMT registry, we included 36,539 adult patients who underwent allogeneic HCT for a hematological malignancy between 2016 and 2020. Of these, 5228 (14%) had obesity (BMI ≥ 30 kg/m2), 1415 (4%) had diabetes (requiring treatment with insulin or oral hypoglycemics), and 688 (2%) had obesity + diabetes pre-transplantation. Compared with patients without diabetes or obesity, the hazard ratio (HR) of grade II-IV acute GvHD was 1.00 (95% confidence interval [CI] 0.94-1.06, p = 0.89) for patients with obesity, 0.95 (CI 0.85-1.07, p = 0.43) for patients with diabetes, and 0.96 (CI 0.82-1.13, p = 0.63) for patients with obesity + diabetes. Non-relapse mortality was higher in patients with obesity (HR 1.08, CI 1.00-1.17, p = 0.047), diabetes (HR 1.40, CI 1.24-1.57, p < 0.001), and obesity + diabetes (HR 1.38, CI 1.16-1.64, p < 0.001). Overall survival after grade II-IV acute GvHD was lower in patients with diabetes (HR 1.46, CI 1.25-1.70, p < 0.001). Pre-transplantation diabetes and obesity did not influence the risk of developing acute GvHD, but pre-transplantation diabetes was associated with poorer survival after acute GvHD.

Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.

Diabetes negatively impacts cancer prognosis. The objective of this work was to evaluate a tripartite oncologist-pharmacist-diabetologist collaboration in the management of patients with diabetes starting chemotherapy.

The prospective ONCODIAB study (NCT04315857) included 102 adults with diabetes starting chemotherapy by whom a continuous glucose monitoring device was worn for fourteen days from the first day of the first and second chemotherapy cycles. The primary outcome was to assess pharmacist and diabetologist interventions. The secondary outcome was to evaluate the impact of the ONCODIAB follow-up on individualized patient glycemic targets at 6 months.

A total of 191 (2 per patient) were made either by clinical pharmacists (n = 95) or diabetologists (n = 96) during the first two chemotherapy cycles. The anatomic therapeutic chemical drug classes most frequently involved in pharmacist interventions were cardiovascular system (23%), alimentary tract and metabolism (22%), and anti-infectives for systemic use (14%). Diabetologists modified the antidiabetic treatment in 58 (62%) of patients: dose reduction (34%), drug discontinuation (28%), drug addition (24%), and dose increase (15%). Glycated hemoglobin decreased from 7.6 ± 1.7% at baseline to 7.1 ± 1.1% at 6 months (p = 0.02). Compared to individualized targets, HbA1c was higher, in the interval, or lower in 29%, 44%, and 27% of patients at baseline vs. in 8%, 70%, and 22% of patients at 6 months, respectively (p < 10-3).

In our study, a close collaboration between oncologists, pharmacists, and diabetologists helped by continuous glucose monitoring led to overall medication optimization and better glycemic control in patients with diabetes starting chemotherapy.

Allogeneic Hematopoietic stem cell transplantation (HSCT) offers a potential cure for patients with hematologic malignancies. Unfortunately, graft-versus-host disease (GVHD) remains a major obstacle to the greater success of this treatment. Despite intensive research efforts over the past several decades, GVHD is still a major cause of morbidity and mortality in patients receiving allogeneic HSCT. The genetic disparity between donor and recipient is the primary factor that dictates the extent of alloimmune response and the severity of acute GVHD (aGVHD). However, some nongenetic factors are also actively involved in GVHD pathogenesis. Thus, identifying host factors that can be readily modified to reduce GVHD risk is of important clinical significance. We are particularly interested in the potential role of nutrition, as a nongenetic factor, in the etiology and management of aGVHD. In this article, we summarize recent findings regarding how different routes of nutritional support and various dietary factors affect aGVHD. Since diet is one of the most important factors that shape gut microbiota, we also provide evidence for a potential link between certain nutrients and gut microbiota in recipients of allogeneic HSCT. We propose a shifting role of nutrition from support to therapy in GVHD by targeting gut microbiota.

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-hsct) can require intensive care unit (ICU) admission in the post-transplant period. Whereas outcomes of ICU admission are poor, little is known about the pre-transplant risk factors leading to them. We conducted a retrospective analysis to investigate the impact of pre-transplant individual comorbidities on acute inpatient complications, focusing on ICU admission, ventilator support and multi-system organ failure, following allo-hsct. During the initial hospitalization, 33 (11%) patients required ICU admission, 29 (10%) required ventilator support and 33 (11%) developed multi-system organ failure. Risk factors for ICU admission and ventilator support included pre-transplant infection, pre-transplant diabetes, time to neutrophil engraftment, donor type and older transplant decade (2008-2010). Risk factors for multi-system organ failure included pre-transplant diabetes, time to neutrophil engraftment and older transplant decade (2008-2010). For ICU patients, the 60-day and 6-month mortality was 58% and 67%, respectively and the median overall survival was 1.4 months. Patients with diabetes and infection at the time of HSCT and longer time to neutrophil engraftment during transplant are at an increased risk for ICU admission, ventilator support and multi-system organ failure. Patients admitted to the ICU are also at a high risk for mortality leading to poor survival.

Background: Malglycemia in pediatric, adolescent and young adult (AYA) patients who undergo hematopoietic stem cell transplant (HSCT) is associated with increased infection and mortality rate. Continuous glucose monitoring (CGM) has been safely used in pediatric/AYA HSCT recipients, but there is a need for a composite metric that can easily be used in clinical settings to assess the glycemic control and identify high-risk patients who needs therapeutic intervention. Composite metrics derived from CGM have not been studied in pediatric/AYA HSCT patients. Methods: Patients aged 2-30 years old who are admitted inpatient while undergoing HSCT at Children's Hospital Colorado underwent CGM using the Abbot Freestyle Libre Pro device from up to 7 days before and 60 days after HSCT. A composite metric Q-score, comprising five primary factors of CGM profiles (central tendency, hyperglycemia, hypoglycemia, intradaily variations, and interdaily variations), was calculated for each patient for the duration of CGM wear. Results: Twenty-nine patients received CGM for an average of 25 days per participant. The median Q-score was 10.2 (interquartile range [IQR]: 8.3, 14.3). Sixty-nine percent of patients had Q-scores that would be categorized into the Fair or Poor category. There was no difference in the Q-score by sources of stem cell, types of primary disease, types of preparative regimen, need for PICU admission, presence of documented infections, and total parenteral nutrition use in the peri-HSCT period. Conclusions: Most pediatric/AYA HSCT recipients have Q-scores indicating suboptimal glycemic control in the peri-HSCT period. Future study should focus on developing screening and treatment strategies to improve malglycemia and its associated adverse clinical outcomes. This study was registered at clinicaltrials.gov (NCT03482154).

Glucocorticoids are a central part of cancer treatment protocols. Their use in patients receiving chemotherapy increases patient risk of hyperglycemia and associated adverse outcomes. Despite this, there have been few published protocols that guide the management of this patient group. In this narrative review, we use the quadruple aim as a framework to evaluate the current literature, including interventions, on glucocorticoid-induced hyperglycemia in patients receiving oncologic treatment, with a focus on the outpatient setting. Findings were drawn from published review articles, observational studies, qualitative reports and costing data. Results were synthesized using the framework's 4 dimensions of care: population health, provider experience, patient experience and cost. Prospective studies proposing an intervention on oncologic patients receiving glucocorticoids were identified as intervention studies. Management of glucocorticoid-induced hyperglycemia in oncologic patients is a complex problem with no published interventions addressing all components of the quadruple aim. Most evidence on this population is based on retrospective studies. Six prospective intervention studies were identified and highlighted in this review, and only 2 were exclusively in the outpatient context. Challenges included lack of standardization in screening strategies and a paucity of interventions that have examined impact on patient and provider experience. There is limited evaluation of the impact of interventions targeting glycemic management on clinical outcomes and cost of care delivery, especially in the outpatient context. We propose a conceptual framework for evaluation of quality improvement programs. Management of glucocorticoid-induced hyperglycemia in the outpatient setting is complex and requires well-designed intervention studies evaluated across the quadruple aim.

Diabetes mellitus (DM) has attained the status of a global pandemic. Cardiovascular disease (CV) was the leading cause of morbidity in people with type 2 DM, however, a transition from CV to cancer as the leading contributor to DM related death has been observed lately. Multiple myeloma (MM) is the second most common haematological malignancy. Obesity is a common risk factor for both DM and MM. Although data are limited, studies have shown that DM might be associated with increased risk for the development of MM. The presence of DM might affect the course of patients with MM, since hyperglycemia may have an impact on both the efficacy and the adverse effects of antimyeloma therapy. In parallel, DM and MM share common clinical presentations, such as nephropathy, neuropathy, and CV. In terms of antidiabetic medications, metformin might present a synergistic effect with antimyeloma drugs and also prevent some of the adverse effects of these drugs; pioglitazone might have favourable effects when given as add on treatment in people with relapsed or refractory MM. No clinically important interactions have been observed between antidiabetic agents and the most commonly used antimyeloma drugs. Further data are needed to examine the effect of all classes of antidiabetic medication on MM and its complications. A baseline assessment of risk factors for glucose intolerance and close monitoring of glucose levels during therapy is strongly suggested for patients with MM.

Among pediatric hematopoietic stem cell transplant (HSCT) recipients, abnormal glycemic control is shown to be associated with increased risk of transplant-related mortality, death from any cause, risk of infection, increased hospitalized, and intensive care days. Independent effects of higher glycemic variability, a component of glycemic control, have not been described. This study aimed to characterize risk factors for, and consequences of, higher glycemic variability in HSCT patients.

Medical records for a cohort of 344 patients, age 0-30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose coefficients of variation (CV) were analyzed for HSCT days -14 to 0 and 0-30, and patients were assessed for potential risk factors and outcomes.

Roughly one-third of patients had pre-HSCT and day 0-30 glucose CV above the reported healthy adult range. Independent of HSCT type, doubling of pre-HSCT glucose CV was associated with a 4.91-fold (95% confidence interval [CI], 1.40-17.24) increased hazard of infection, as well as increased risk for intensive care hospitalization for allogenic HSCT patients. Multivariable analysis demonstrated that allogeneic HSCT patients had a 1.40- and 1.38-fold (95% CI, 0.98-1.99 and 1.00-1.91) increased hazard of death for every doubling of pre-HSCT and day 0-30 glucose CV, respectively.

Just as with higher mean glucose, higher glycemic variability in the pediatric HSCT population is independently associated with significantly increased morbidity. Additional research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes.

Nutrition support is often required during hematopoietic cell transplant (HCT) given the gastrointestinal toxicity that frequently precludes adequate protein-calorie intake. This article reviews the latest evidence for enteral versus parenteral nutrition in the adult and pediatric HCT population and addresses key considerations as well as barriers to implement this in practice. Registered Dietitian Nutritionists are key members of the interdisciplinary team to proactively manage enteral nutrition support to provide timely, adequate protein and calories to help prevent malnutrition, loss of lean body mass, and functional decline as well as provide evidence-based diet recommendations. This article also reviews emerging research supporting the role of luminal nutrients to maintain microbiotal diversity.

Background: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) may be at risk for malglycemia and adverse outcomes, including infection, prolonged hospital stays, organ dysfunction, graft-versus-host-disease, delayed hematopoietic recovery, and increased mortality. Continuous glucose monitoring (CGM) may aid in describing and treating malglycemia in this population. However, no studies have demonstrated safety, tolerability, or accuracy of CGM in this uniquely immunocompromised population. Materials and Methods: A prospective observational study was conducted, using the Abbott Freestyle Libre Pro, in patients aged 2-30 undergoing HSCT at Children's Hospital Colorado to evaluate continuous glycemia in this population. CGM occurred up to 7 days before and 60 days after HSCT, during hospitalization only. In a secondary analysis of this data, blood glucoses collected during routine HSCT care were compared with CGM values to evaluate accuracy. Adverse events and patient refusal to wear CGM device were monitored to assess safety and tolerability. Results: Participants (n = 29; median age 13.1 years, [interquartile range] [4.7, 16.6] years) wore 84 sensors for an average of 25 [21.5, 30.0] days per participant. Paired serum-sensor values (n = 893) demonstrated a mean absolute relative difference of 20% ± 14% with Clarke Error Grid analysis showing 99% of pairs in the clinically acceptable Zones (A+B). There were four episodes of self-limited bleeding (4.8% of sensors); no other adverse events occurred. Six patients (20.7%) refused subsequent CGM placements. Conclusions: CGM use appears safe and feasible although with suboptimal accuracy in the hospitalized pediatric HSCT population. Few adverse events occurred, all of which were low grade.

The relationship between body mass index and overall survival has been controversial in patients who suffered from hematological malignancies and underwent hematopoietic stem cell transplantation.

We collected the data of 686 acute leukemia patients who received only one allogeneic hematopoietic stem cell transplantation in our center from 2008 to 2017. Patients were divided into four groups (underweight, normal weight, overweight and obesity) according to their body mass index pre-hematopoietic stem cell transplantation.

56.4% of patients had normal body mass indices, 17.3% were underweight, 20.4% were overweight and 5.8% were with obesity. Concerning long-term follow-up, the probability of overall survival was significantly lower in overweight (P = 0.010) and patients with obesity (P = 0.065) as compared with normal weight patients, and no statistically significant difference between underweight and normal weight individuals (P = 0.810). The results demonstrated that higher body mass index was associated with poorer overall survival (hazard ratio: 1.79; 95% confidence interval: 1.33-2.40, P < 0.001) and shorter leukemia-free survival (hazard ratio: 1.78; 95% confidence interval: 1.35-2.34, P < 0.001). Additionally, patients exhibiting a higher body mass index were more likely to face the problem of relapse (30.6 vs 20.9%, P < 0.001). Furthermore, non-relapse mortality of patients with obesity was statistically higher than normal weight patients (22.5 vs 9.6%, P = 0.027). Besides, individuals with a higher abdominal girth had shorter survival (hazard ratio: 1.73; 95% confidence interval: 1.29-2.31, P < 0.001) and higher relapse rate (hazard ratio: 1.78; 95% confidence interval: 1.29-2.45, P = 0.001) as compared with those with a lower abdominal girth.

Our results indicate that obesity at pre-hematopoietic stem cell transplantation stage, whether characterized by higher body mass index or abdominal girth, is correlated with poorer outcome.

Glycemic variability is associated with risks for adverse events in patients with cancer. Several studies have evaluated the presence and impact of hyperglycemia and/or hypoglycemia in patients with cancer; however, few studies have evaluated glycemic variability. The purpose of this integrative review of studies in patients with gastrointestinal cancers was to investigate the presence and methods of reporting glycemic variability during and following treatments.

A comprehensive review of the literature was conducted. PubMed, CINAHL, EMBASE, and Cochrane databases were searched for publications between 1/1/1969 and 7/24/2019. Studies of patients with gastrointestinal cancer following surgery, during treatment, and <5 years following treatment were included and evaluated by cancer type and method of glucose and glycemic variability measurement.

Among 1526 patients with gastrointestinal cancer across 19 studies, gastric and pancreatic cancers were most prevalent. Timing of glucose testing and methods of analyzing glycemic variability varied. Most analyses used the standard deviation or interquartile range. Glycemic variability was more prevalent among patients with Type 2 Diabetes and among those with pancreatic cancer. In some patients glycemic variability remained notable > one year following surgery despite improvements in glycemic control.

Patients with gastrointestinal cancer experience glycemic variability during and up to one year following treatment. There was heterogeneity in methods related to timing of testing and reporting glycemic variability among the 19 studies in this review. Future investigations need to identify the presence and define the methods of measuring glycemic variability in patients with gastrointestinal cancer.

Malglycemia (hypoglycemia, hyperglycemia, and/or glycemic variability) in adult hematopoietic stem cell transplant (HSCT) recipients is associated with increased infection, graft-versus-host disease, organ dysfunction, delayed engraftment, and mortality. Malglycemia has not been studied in pediatric HSCT recipients. This study aimed to characterize the incidence and consequences of malglycemia in this population. Medical records for a cohort of 344 patients, age 0 to 30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose data were analyzed in intervals and assessed for potential risk factors and associated outcomes. Malglycemia occurred in 43.9% of patients. Patients with a day 0 to 100 mean glucose of 100 to 124 mg/dL had a 1.76-fold (95% confidence interval [CI], 1.10-2.82; P = .02) increased risk of death and patients with a day 0 to 100 mean glucose ≥ 125 mg/dL had a 7.06-fold (95% CI, 3.84-12.99; P < .0001) increased risk of death compared with patients with a day 0 to 100 mean glucose < 100 mg/dL. For each 10 mg/dL increase in pre-HSCT glucose, there was a 1.11-fold (95% CI, 1.04-1.18; P = .0013) increased risk of post-HSCT infection. These adverse impacts of malglycemia occurred independent of transplant type, graft-versus-host disease, and steroid therapy. Malglycemia in the pediatric HSCT population is independently associated with significantly increased risk of morbidity and mortality. Further research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03482154.

Background/aim: To determine insulin sensitivity before chemotherapy and during febrile neutropenia in patients with acute leukemia and to assess its effect on the number of documented infections, the severity of infection and the outcome of the first hospitalization. To compare insulin sensitivity in the study group to a group of patient with obesity. Materials and methods: The study group consisted of 30 (37% of the total number) patients with newly diagnosed acute leukemia. Testing of insulin sensitivity was done before chemotherapy and during febrile neutropenia. Parameters were compared to a group of 30 age, and sex matched patients with obesity. Results: Insulin sensitivity was normal before chemotherapy. Obese patients were characterized by insulin resistance. Febrile neutropenia led to the development of insulin resistance (t = -2.43, p = 0.021). The level of insulin resistance was in positive correlation with fibrinogen (r = 0.59, p < 0.05). Patients with a documented site of infection had higher fasting insulin and an insulin resistance before chemotherapy (t = -2.38, p = 0.024). Insulin sensitivity did not influence outcome of the first hospitalization. Conclusion: Patients with acute leukemia in febrile neutropenia developed changes in insulin sensitivity similar to those seen in obesity. Insulin resistance was present in patients with a documented site of infection, and it worsened with the extent of inflammation. The outcome of the first hospitalization was not affected.

New-onset post-transplant diabetes mellitus (PTDM) occurs frequently after allogeneic hematopoietic cell transplant (HCT). Although calcineurin inhibitors and corticosteroids are assumed to be the cause for hyperglycemia, patients developing PTDM have elevated fasting C-peptide levels before HCT and before immunosuppressive medications. To determine if PTDM results from established insulin resistance present before transplant, we performed oral glucose tolerance tests (OGTTs) and measured whole body, peripheral, and hepatic insulin sensitivity with euglycemic hyperinsulinemic clamps before and 90 days after HLA-identical sibling donor HCT in 20 patients without pretransplant diabetes. HCT recipients were prospectively followed for the development of new-onset PTDM defined as a weekly fasting blood glucose ≥ 126 mg/dL or random blood glucose ≥ 200 mg/dL. During the first 100 days all patients received calcineurin inhibitors, and 11 individuals (55%) were prospectively diagnosed with new-onset PTDM. PTDM diagnosis preceded corticosteroid treatment. During the pretransplant OGTT, elevated fasting (87 mg/dL versus 101 mg/dL; P = .005) but not 2-hour postprandial glucose levels predicted PTDM diagnosis (P = .648). In response to insulin infusion during the euglycemic hyperinsulinemic clamp, patients developing PTDM had lower whole body glucose utilization (P = .047) and decreased peripheral/skeletal muscle uptake (P = .031) before and after transplant, respectively, when compared with non-PTDM patients. Hepatic insulin sensitivity did not differ. Survival was decreased in PTDM patients (2-year estimate, 55% versus 100%; P = .039). Insulin resistance before HCT is a risk factor for PTDM independent of immunosuppression. Fasting pretransplant glucose levels identified PTDM susceptibility, and peripheral insulin resistance could be targeted for prevention and treatment of PTDM after HCT.

Advances in the field of omics have led to a significant expansion in biomarkers identified for complications after hematopoietic stem cell transplantation (HSCT). Biomarkers can offer an effective method for early identification of a specific disease and can be used to guide therapies. Ongoing investigations to discover biomarkers for acute graft-versus-host disease as well as other post-HSCT complications may improve early diagnosis, prognosis, and the development of new therapeutic targets. The authors review the most recent and validated diagnostic, prognostic, predictive, and response to treatment biomarkers for early complications following HSCT consistent with 2014 NIH consensus on biomarker criteria.

Patients who receive autologous hematopoietic cell transplantation (HCT) for the treatment of hematologic malignancies are at risk of serious adverse outcomes including infections and death. Hyperglycemia following the HCT is associated with increased risk of these adverse outcomes. However, limited information is available on demographic and clinical characteristics that contribute to changes in blood glucose levels following HCT.

The objective of this study was to determine the trajectories of fasting blood glucose (FBG) levels as well as the demographic and clinical characteristics that predicted interindividual differences in these FBG trajectories.

A sample of adult patients with hematologic malignancies who were scheduled to receive autologous HCT (n = 53) was enrolled in the study. Patients with preexisting diabetes were excluded. Demographic and clinical characteristics were abstracted from electronic medical records. Morning fasting laboratory tests (ie, FBG and absolute neutrophil counts) were obtained. Data were analyzed using hierarchical linear modeling from the day of HCT (day 0) through 14 days post-HCT.

Among 8 characteristics evaluated, pre-HCT FBG was associated with variability in both the initial levels and the trajectories of FBG. Body mass index was only associated with initial levels of FBG.

The large amount of interindividual variability in the trajectories of FBG levels following autologous HCT suggests that glucose control in these patients warrants ongoing assessments and preemptive tailoring.

Fasting blood glucose monitoring is warranted. Additional research with larger samples is warranted to identify additional modifiable and nonmodifiable characteristics associated with interindividual variability in FBG levels.

Poor health outcomes have been associated with hyperglycemia in patients with and without diabetes. However, the impact of hyperglycemia on the health-related outcomes of patients with cancer has shown conflicting results. The purpose of this review was to explore definitions and measurement issues related to the assessment of hyperglycemia and the subsequent impact on the findings of health-related outcomes in adults with cancer.
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Four electronic databases were searched.

A total of 30 articles were reviewed. Quantitative articles were synthesized using integrative review strategies. 
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Three key gaps were identified in the literature.

This review highlights the inconsistencies in measuring or assessing hyperglycemia and the lack of standardized guidelines in treating hyperglycemia. Failure to have a standard approach to the measurement and management of hyperglycemia impedes the ability of healthcare providers to determine the significance of its impact on health outcomes. Further research is needed to establish appropriate measurement guidelines to address hyperglycemia in people with cancer.
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Evidence-based measurement and treatment guidelines are needed to inform and assist healthcare providers with clinical decision making for people with cancer who experience hyperglycemia.

To examine the prevalence and impact of hyperglycemia on health outcomes (number of neutropenic days, infection, and hospital length of stay) in patients hospitalized for acute myeloid leukemia (AML) receiving initial induction therapy.
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Retrospective, descriptive study.
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A large urban hospital in Indianapolis, Indiana.
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103 patients with AML and a subset of 41 patients aged 65 years or older. 
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Demographics and medical information were extracted from electronic health records. Serum-fasting blood glucose was used to assess glycemic status. The association of hyperglycemia with the health outcomes was analyzed. A subset of patients aged 65 years or older was also analyzed.
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Hyperglycemia, age, and health outcomes in patients with AML.
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Forty patients experienced hyperglycemia during initial induction for AML. In the larger sample, no associations were noted between hyperglycemia and health outcomes. A significant relationship (p = 0.022) was noted between hyperglycemia and infection in patients aged 65 years or older. Patients aged 65 years or older had 5.6 times the risk of developing infection as those aged younger than 65 years. Although not statistically significant, patients aged 65 years or older with hyperglycemia had 2.5 more days of neutropenia and 1.5 days longer hospital length of stay. 
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This study provides preliminary evidence that hyperglycemia is prevalent during initial induction for AML and may have harmful consequences, particularly for patients aged 65 years or older. More research is needed to determine clinically significant levels of hyperglycemia and their impact on health outcomes.
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Oncology nurses can assess and proactively collaborate with members of the healthcare team to implement strategies to prevent or mitigate the harmful consequences of hyperglycemia.

Although parenteral nutrition (PN) is often used after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there is controversy regarding PN management, for instance in the use of fat emulsion and glucose control (GC). To clarify these issues, we conducted a multi-center prospective study with intensive GC, randomizing the use of fat emulsion after allo-HSCT using a myeloablative conditioning regimen.

The primary endpoint was the cumulative incidence of documented infectious disease, namely bacterial and fungal infection, at day 100 after allo-HSCT. Between August 2007 and March 2012, we enrolled 81 patients at 5 centers. Excluding 5 ineligible patients, 76 patients received the protocol treatment. The target fasting glucose level was 80-110 mg/dL.

The median follow-up of surviving patients was 1796 days. The cumulative incidences of documented infectious disease at day 100 were 16% (95% confidence interval [CI] 6-29%) in the no-fat group and 19% (95% CI 8-32%) in the fat group, indicating no significant difference. The mean glucose level at 28 days after allo-HSCT was 107 mg/dL in the no-fat group and 111 mg/dL in the fat group. Grade 3 hyperglycemia (>250 mg/dL) and grade 3 hypoglycemia (<40 mg/dL) occurred in 4 patients each (5.3%). Overall survival and non-relapse mortality rates at 4 years were 75% and 11% in the no-fat group and 69% and 8% in the fat group, respectively.

Irrespective of the use of fat emulsion, the long-term clinical outcomes of the enrolled patients were favorable under intensive GC. To further clarify the benefits of GC after allo-HSCT, a prospective study randomizing the level of GC is warranted.

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications in organ and bone marrow transplantation, leading to much morbidity and mortality. Obesity has been associated with increased risk of development of various inflammatory diseases. Here, we investigated the in vitro and in vivo effects of obese donor splenocytes on the development of acute graft-versus-host disease (aGVHD). In this study, mixed lymphocyte reactions (MLR) in vitro showed that obese donor mouse CD4+ T cell promoted the production of interleukin-2 (IL-2), interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Meanwhile, the inducible Tregs population decreased greatly in obese donor mouse CD4+ T cells' induction group, compared with normal group. Then in the murine aGVHD model, we found that obese donor splenocytes dramatically increased the severity of aGVHD through down-regulating immune tolerance while enhancing systemic and local immunity. Moreover, we showed that aGVHD induced by obese donors resulted in massive expansion of donor CD3+ T cells, release of Th1-related cytokines, interleukin-17 (IL-17) and chemokines, significant increase of Th17 cells and inhibition of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and impaired suppressive ability of donor Tregs. Expression of sphingosine-1-phosphate receptor 1 (S1PR1), phosphorylated Akt, mammalian target of rapamycin (mTOR) and Raptor increased, while the phosphorylation level of SMAD3 was decreased in the skin, intestine, lung and liver from obese donor splenocytes-treated aGVHD mice. Furthermore, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of obese donor splenocytes to migrate into target organs, such as IL-2, IL-17, IFN-γ, TNF-α, CXCR3, CXCL9, CXCL10, CXCL11 and CCL3. Therefore, these results imply that obese donor cells may be related to the risk of aGVHD and helping obese donor individuals lose weight represent a compulsory clinical strategy before implementing transplantation to control aGVHD of recipients.

Hematopoietic stem cell transplantation is an established treatment option for various hematological diseases. This therapy involves complex procedures and is associated with several systemic complications. Due to the toxic effects of the conditioning regimen used in allogeneic transplantations, patients frequently suffer from severe gastrointestinal complications and are unable to feed themselves properly. This complex clinical scenario often requires specialized nutritional support, and despite the increasing number of studies available, many questions remain regarding the best way to feed these patients. Parenteral nutrition has been traditionally indicated when the effects on gastrointestinal mucosa are significant; however, the true benefits of this type of nutrition in reducing clinical complications have been questioned. Hyperglycemia is a common consequence of parenteral nutrition that seems to be correlated to poor transplantation outcomes and a higher risk of infections. Additionally, nutrition-related pre-transplantation risk factors are being studied, such as impaired nutritional status, poorly controlled diabetes mellitus and obesity. This review aims to discuss some of these recent issues. A real case of allogeneic transplant was used to illustrate the scenario and to highlight the most important topics that motivated this literature review.

To determine prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies METHODS: We performed retrospective analysis of patients who were hospitalized on any of the four hematology services or bone marrow transplant service and who received systemic steroids during a 2-month period. Mean glucoses for days 1-4 and maximum glucose were calculated and the total daily steroid dose was converted to equivalent dose of dexamethasone. Hyperglycemia was defined as any glucose >9.917 mmol/l during days 1-4. We examined associations between variables using Spearman's correlations and multivariable linear regression RESULTS: 168 patients were included in the analysis. Mean age was 57.1 ± 14.4 years with 59% males and 90% Caucasians. The prevalence of hyperglycemia was 39%. Eight patients received intravenous insulin. In patients without diabetes, steroid dose equivalent to >12 mg dexamethasone and longer acting steroids caused greater degree of hyperglycemia compared to a dose <12 mg. Maximum glucose was a predictor of hospital length of stay among patients without diabetes (but not those with diabetes), and with acute leukemia or stem cell transplant (but not other hematologic malignancies). There were no significant differences in in mortality or other outcomes between the groups with and without hyperglycemia CONCLUSIONS: Hyperglycemia is common in patients with hematologic malignancies, which require frequent corticosteroids. Higher steroid dose and long-acting steroids caused a greater degree of hyperglycemia. Maximum glucose was a predictor of length of stay but this was only significant for patients without diabetes, those with acute hematologic malignancy or stem cell transplant.

In order to clarify the association between hyperglycemia during the early period after allogeneic stem cell transplantation (allo-SCT) and adverse outcomes, we retrospectively analyzed 563 consecutive patients who underwent allo-SCT at our institute between 2008 and 2015. Patients were categorized into three groups according to mean fasting blood glucose levels on days 0-7 (normoglycemia group<110 mg/dL, n=347; mild hyperglycemia group 110-149 mg/dL, n=192 and moderate/severe hyperglycemia group≥150 mg/dL, n=24). The median follow-up was 2.7 years. Patients in the moderate/severe hyperglycemia group had significantly worse characteristics. The cumulative incidences of 2-year non-relapse mortality (NRM) and the probabilities of 2-year overall survival (OS) in the normoglycemia, mild hyperglycemia and moderate/severe hyperglycemia groups were 7.5%, 19% and 29%, respectively (P<0.01), and 69%, 53% and 33%, respectively (P<0.01). In multivariate analyses, hyperglycemia was an independent predictor of high NRM (vs normoglycemia; mild hyperglycemia, hazard ratio (HR) 2.56, 95% confidence interval (CI) 1.56-4.18; moderate/severe hyperglycemia, HR 4.46, 95% CI 1.92-10.3) and poor OS (vs normoglycemia; mild hyperglycemia, HR 1.54, 95% CI 1.14-2.07; moderate/severe hyperglycemia, HR 1.61, 95% CI 0.89-2.91). In conclusion, hyperglycemia on days 0-7 after allo-SCT was associated with inferior outcomes.

Diabetes mellitus (DM) is well-known as a disorder that increases the risk of infectious diseases. Various reports have shown that innate immunity is impaired in patients with DM, which is considered to be a major cause of increased risk of infectious diseases. However, there is a paucity of data about the actual risk of mold infections in patients with DM. Several treatment procedures, such as solid organ transplantation and hematopoietic stem cell transplantation (HSCT), are intrinsically associated with a high risk of mold infections and also correlated with an increased risk of post-transplant DM. Therefore, we could assume that organ transplant recipients or HSCT recipients with DM are at quite high risk of mold infections. Here, we aim to summarize the information about the increased risk of mold infections in patients with DM, and propose possible interventions such as intensive glucose control to reduce this risk in patients with DM.

The life expectancy of people with type 1 diabetes is improving and now approaches that of those without diabetes. As this population ages, a growing number will be diagnosed with and treated for cancer. Cancer treatments can drastically affect insulin requirement and glycemic control through multiple mechanisms including high doses of glucocorticoids and targeted therapies that directly interfere with cellular pathways involved in the action of insulin. Patients with cancer frequently also have alterations in gastrointestinal motility or appetite and require supplemental enteral or parenteral nutrition. Few studies have evaluated these patients directly, but data on patients with and without diabetes suggest that glycemic control may play a larger role in cancer outcomes than is often recognized. Collaboration between the treating oncologist and diabetologist allows people with diabetes to receive the most effective therapies for their cancers without undue risk of hypoglycemia or adverse outcomes due to hyperglycemia.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for patients with hematological malignancies. However, is associated with substantial rates of morbidity and mortality. We and others have shown that malglycemia is associated with adverse transplant outcome. Therefore, improving glycemic control may improve transplant outcome. In this prospective study we evaluated the feasibility of using Glucommander (a Computer-Guided Glucose Management System; CGGM) in order to achieve improved glucose control in hospitalized HCT patients. Nineteen adult patients contributed 21 separate instances on CGGM. Patients were on CGGM for a median of 43 h. Median initial blood glucose (BG) on CGGM was 244 mg/dL, and patients on 20 study instances reached the study BG target of 100-140 mg/dL after a median of 6 h. After BG reached the target range, the median average BG level per patient was 124 mg/dL. Six patients had a total of 10 events of BG <70 mg/dL (0.9% of BG measurements), and no patients experienced BG level <40 mg/dL. The total estimated duration of BG <70 mg/dL was 3 h (0.2% of the total CGGM time). In conclusion, our study demonstrates that stringent BG control in HCT patients using CGGM is feasible.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into consideration a lack of well-established evidence in the field of allo-HSCT, more studies should be conducted in the future, which will require closer multidisciplinary collaboration between hematologists, endocrinologists and nutritionists.

Allogeneic hematopoietic stem cell transplantation (HSCT) has become an established treatment modality for various hematological diseases. However, in allogeneic HSCT, patients often suffer from severe gastrointestinal complications caused by the conditioning regimen and acute/chronic graft-versus-host disease, which requires support by multidisciplinary nutritional support teams (NST). In addition, pretransplantation nutritional status can affect the clinical outcome after allogeneic HSCT. Therefore, it is important to refer the patient to a NST when becoming aware of nutritional problems before allogeneic HSCT. It is also important to follow nutritional status over the long term, as patients often suffer from various nutritional problems, such as malnutrition and metabolic syndrome, even late after allogeneic HSCT. In summary, NST can contribute to the improvement of nutritional status and possibly prognosis at every stage before and after allogeneic HSCT. Here, we aim to give a comprehensive overview of current understanding about nutritional support in allogeneic HSCT and try to provoke a constructive discussion to stimulate further investigation.

Many patients undergoing hematopoietic cell transplantation (HCT) for hematologic malignancies experience hyperglycemic events during treatment, leading to adverse outcomes. Understanding how hyperglycemia during the acute HCT treatment phase impacts outcomes is vital for preventing and mitigating adverse events. This integrative review evaluates the impact of hyperglycemia on adult patients undergoing HCT.

PubMed, MEDLINE®, and CINAHL® electronic databases were used to identify relevant articles.Data Evaluation: The final sample for this integrative review included 12 empirical quantitative reports of clinical patient outcomes. Of the 12, 10 are retrospective, 1 is case-control, and 1 is prospective.

Content analysis was used to synthesize and summarize findings.Presentation of Findings: A review of published literature found associations between hyperglycemia and infection, time to engraftment, development of acute graft-versus-host disease, length of stay, and overall survival. Patient-related risk factors for hyperglycemia included older age, preexisting diabetes, and insulin resistance (i.e., prediabetes). Patients of normal weight experiencing hyperglycemia had worse outcomes than patients who were overweight or obese. Treatment-related risk factors for hyperglycemia include dose and duration of immunosuppressants, specifically corticosteroids, treatment with antihyperglycemic medications, and use of total parenteral nutrition.

HCT is one of the most complex treatments for hematologic disorders. The transplantation nurse, as part of an interdisciplinary team, plays an essential role in glycemic control during the acute phase of HCT. Understanding the effects of hyperglycemia, as well as factors that place the patient at risk for hyperglycemia, allows the nurse to make well-informed, proactive interventions aimed at glycemic control.

Significant hyperglycemia is commonly observed immediately after solid organ and bone marrow transplant as well as with subsequent hospitalizations. Surgery and procedures are well known to cause pain and stress leading to secretion of cytokines and other hormones known to aggravate insulin action. Immunosuppression required for transplant and preexisting risk are also major factors. Glucose control improves outcomes for all hospitalized patients, including transplant patients, but is often more challenging to achieve because of frequent and sometimes unpredictable changes in immunosuppression doses, renal function, and nutrition. As a result, risk of hypoglycemia can be greater in this patient group when trying to achieve glucose control goals for hospitalized patients. Key to successful management of hyperglycemia is regular communication between the members of the care team as well as anticipating and rapidly implementing a new treatment paradigm in response to changes in immunosuppression, nutrition, renal function, or evidence of changing insulin resistance.

Patients with hematologic malignancies are at high risk for hyperglycemia due to factors such as frequent exposure to glucocorticoids, immunosuppressants, total parenteral nutrition, and medical stress. Hyperglycemia in these patients has been associated with poor outcomes including increased risk of infection, organ dysfunction, durability of remission, graft-versus-host disease, and mortality. However, the appropriate glucose targets are not well established, and there are few prospective data assessing whether glucose control improves outcomes. HbA1c should be interpreted with caution in patients with hematologic malignancies, due to inaccuracies imposed by disordered hematopoiesis and frequent transfusions, and short-term perturbations imposed by acute illness or medications. Management of diabetes or glucocorticoid-induced hyperglycemia in the hospital generally requires insulin therapy, which is tailored based upon nutritional needs, baseline glucose control, and concomitant factors such as type and dose of glucocorticoid administration. Close follow-up and adjustment of therapy, ideally with the assistance of patient self-titration algorithms, is required after discharge. Patients are at increased long-term risk for developing diabetes and therefore should undergo regular screening.

Diabetes mellitus (DM) is a factor in the hematopoietic cell transplantation-comorbidity index. However, the impact of pre-transplant DM on morbidity and cause-specific non-relapse mortality (NRM) remains unclear. We performed a retrospective study with registry data that included a total of 7626 patients who underwent their first allogeneic hematopoietic SCT (HSCT) between 2007 and 2010. The median age was 44 years (range 0-88). Compared with patients without pre-transplant DM (non-DM group, n=7248), patients with pre-transplant DM (DM group, n=378) were older and were more likely to have high-risk disease, a reduced-intensity conditioning regimen and GVHD prophylaxis using tacrolimus. Multivariate analyses showed that pre-transplant DM was associated with increased risks of NRM (hazard ratio (HR)1.46, 95% confidence interval (CI) 1.21-1.76, P<0.01) and infection-related NRM (HR 2.08, 95% CI 1.58-2.73, P<0.01). The presence of pre-transplant DM was associated with an increased risk of overall mortality in a multivariate analysis (HR 1.55, 95% CI 1.35-1.78, P<0.01). In conclusion, pre-transplant DM was a risk factor for NRM, particularly infection-related mortality, after allogeneic HSCT. To improve the clinical outcome in patients with DM, the benefits of strict infection control and appropriate glycemic control should be explored in future trials.

New onset diabetes mellitus is frequently observed following hematopoietic stem cell transplantation (HSCT) and is associated with adverse transplantation outcomes. However, the outcomes of patients with preexisting diabetes mellitus undergoing HSCT are largely unknown. We aimed to explore the impact of preexisting diabetes on transplantation outcomes in HSCT. In a retrospective study, medical charts of 34 HSCT recipients with diabetes mellitus undergoing allogeneic or autologous transplantation were reviewed and compared with 71 HSCT recipients without diabetes. Primary outcome was overall survival. Secondary outcomes included hematopoietic recovery, length of hospital stay, febrile neutropenia, acute and chronic graft-versus-host disease (GVHD), primary disease recurrence, and non-relapse mortality (NRM). On univariate analysis, there was no difference in transplantation outcomes in recipients with diabetes compared with recipients without diabetes. However, after adjusting for potential covariates, multivariate analysis demonstrated that having diabetes before HSCT significantly predicted outcome and decreased overall survival (hazard ratio 0.51, 95% confidence interval: 0.27-0.97, p value: 0.04). This study suggests that patients with diabetes mellitus undergoing allogeneic or autologous HSCT may have inferior survival rates and warrant further attention.

Hyperglycemia is a frequent phenomenon in hospitalized patients that is associated with negative outcomes. It is common in liver transplant patients as a result of stress and is related to immunosuppressant drugs. Although studies are few, a history of diabetes and the presentation of hyperglycemia during liver transplantation have been associated with a higher risk for rejection.

To analyze whether hyperglycemia during the first 48hours after liver transplantation was associated with a higher risk for infection, rejection, or longer hospital stay.

A retrospective cohort study was conducted on patients above the age of 15years that received a liver transplant. Hyperglycemia was defined as a value above 140mg/dl and it was measured in three different manners (as an isolated value, as a mean value, and as a weighted value over time). The relation of hyperglycemia to a risk for acute rejection, infection, or longer hospital stay was evaluated.

Some form of hyperglycemia was present in 94% of the patients during the first 48 post-transplantation hours, regardless of its definition. There was no increased risk for rejection (OR: 1.49; 95%CI: 0.55-4.05), infection (OR: 0.62; 95%CI: 0.16-2.25), or longer hospital stay between the patients that presented with hyperglycemia and those that did not.

Hyperglycemia during the first 48hours after transplantation appeared to be an expected phenomenon in the majority of patients and was not associated with a greater risk for rejection or infection and it had no impact on the duration of hospital stay.

The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM.

Parenteral nutrition (PN) exacerbates hyperglycemia, which is associated with increased morbidity and mortality in various cancer populations. By using a retrospective design, we examined incident hyperglycemia in PN and non-PN recipients and the associations with clinical events and 5-year survival in a cohort treated for myeloma with melphalan and auto-SCT (n=112). Clinical comparisons were made at admission, and 'before' and 'after' initiating PN to discern differences and temporality. Actual infusion times were used for PN patients; time frames based on mean PN infusion days were created for the non-PN recipients. Oral intake was lower 'before' in PN vs non-PN patients (P<0.001); however, no differences in mucositis, emesis, infections or transfusions were detected 'before.' Incident hyperglycemia (≥7.0 mmol/L) was significant 'after' PN initiation, and PN recipients experienced delays in WBC (P<0.05) and platelet engraftment (P=0.009), and required significantly greater RBC (P=0.0014) and platelet (P=0.001) support 'after' than non-PN patients. Neutropenic fever and longer hospital stay were more frequent among PN vs non-PN recipients (P<0.001). Differences in 5-year mortality were not apparent. The findings fail to support clinical benefits of PN administration during auto-SCT for myeloma. Further study is needed to discern if hyperglycemia or feeding per se was deleterious in this patient population.