c-peptide and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Hyperglycemia during hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine, with methylprednisolone premedication) chemotherapy is associated with poor outcomes of acute lymphoblastic leukemia (ALL). To examine whether intensive insulin therapy could improve outcomes, a randomized trial was conducted that compared glargine plus aspart vs. conventional therapy. Intensive insulin did not improve ALL clinical outcomes despite improved glycemic control. Secondary analysis suggests that the choice of antidiabetic pharmacotherapy may influence ALL outcomes.. Hyperglycemia during hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine, with methylprednisolone premedication) chemotherapy is associated with poor outcomes of acute lymphoblastic leukemia (ALL).. To examine whether an intensive insulin regimen could improve outcomes compared with conventional antidiabetic pharmacotherapy, a randomized trial was conducted that compared glargine plus aspart vs. conventional therapy (control). Between April 2004 and July 2008, 52 patients newly diagnosed with ALL, Burkitt lymphoma, or lymphoblastic lymphoma who were on hyper-CVAD in the inpatient setting and had a random serum glucose level >180 mg/dL on ≥2 occasions during chemotherapy were enrolled.. The trial was terminated early due to futility regarding ALL clinical outcomes despite improved glycemic control. Secondary analysis revealed that molar insulin-to-C-peptide ratio (I/C) > 0.175 (a surrogate measure of exogenous insulin usage) was associated with decreased overall survival, complete remission duration and progression-free survival (PFS), whereas metformin and/or thiazolidinedione usage were associated with increased PFS. In multivariate analyses, factors that significantly predicted short overall survival included age ≥ 60 years (P = .0002), I/C ≥ 0.175 (P = .0016), and average glucose level ≥ 180 mg/dL (P = .0236). Factors that significantly predicted short PFS included age ≥ 60 years (P = .0008), I/C ≥ 0.175 (P = .0002), high systemic risk (P = .0173) and average glucose level ≥ 180 mg/dL (P = .0249). I/C ≥ 0.175 was the only significant (P = .0042) factor that predicted short complete remission duration.. A glargine-plus-aspart intensive insulin regimen did not improve ALL outcomes in patients with hyperglycemia. Exogenous insulin may be associated with poor outcomes, whereas metformin and thiazolidinediones may be associated with improved outcomes. Analysis of these results suggests that the choice of antidiabetic pharmacotherapy may influence ALL outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blood Glucose; Burkitt Lymphoma; C-Peptide; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Prospective Studies; Thiazolidinediones; Treatment Outcome; Vincristine; Young Adult

To investigate the prevalence and potential risk factors of obesity after therapy for childhood acute lymphoblastic leukemia (ALL).. 39 ALL patients (age 10.7-20.5 years) who were in first remission for 3.4-14.6 years after standardized treatment with chemotherapy plus cranial irradiation (n = 25) or with chemotherapy alone (n = 14) were examined. After fasting overnight, the following parameters were investigated: body mass index (BMI) of patients and their parents; patients' BMI before ALL therapy; serum free thyroxin, growth hormone-dependent factors, estradiol, testosterone, cortisol, leptin and c-peptide; fat-free mass (bioelectrical impedance); resting metabolic rate (RMR, indirect calorimetry); caloric intake (24-hour recall); and physical activity (questionnaire). RMR data were applied to the fat-free mass and compared with 83 controls.. The prevalence of obesity (criterion: BMI > 2 SDS) was significantly (p < 0.05) higher after ALL therapy (38%; irradiated patients 48%, non-irradiated patients 21%) than before therapy (3%). Compared to non-irradiated patients, irradiated patients had significantly lower RMRs (-1.07 +/- 0.24 vs. -0.32 +/- 0.21 SDS; p < 0.05), reduced physical activity levels (1.41 +/- 0.03 vs. 1.52 +/- 0.03; p < 0.05), and lower concentrations of insulin-like growth factor-binding protein-3 (-0.65 +/- 0.17 vs. 0.25 +/- 0.33 SDS; p < 0.05) and of free thyroxin (1.17 +/- 0.06 vs. 1.38 +/- 0.08 ng/dl; p < 0.05). Caloric intake was adequate.. After ALL during childhood, patients face a higher risk of obesity. In the cranially irradiated patients, the likely causes are low physical activity, RMRs and hormonal insufficiency.

Topics: Adolescent; Adult; Basal Metabolism; Body Composition; Body Mass Index; C-Peptide; Child; Energy Intake; Energy Metabolism; Estradiol; Female; Humans; Hydrocortisone; Leptin; Male; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Testosterone; Thyroxine

Using enzymatic assay and radioimmunoassay, we studied the functional status of pancreatic islet in 50 patients with acute leukemia. Oral glucose tolerance test and insulin and C peptide release were made in 40 patients before and after treatment. 14 patients who revealed diabetic curve and delayed insulin and C peptide release before treatment showed normal values in 6 after therapy. Five patients with impaired glucose tolerance and decreased insulin and C peptide release before treatment showed normalization of these parameters following therapy. Five patients with normal pretreatment values disclosed abnormal post-treatment results. The remaining 16 patients displayed normal results both before and after therapy. Anti-insulin antibodies were negative, and glucagon level was normal in all the 50 patients. The red cell insulin receptor binding rate analysed in 47 patients was significantly higher than in controls (P < 0.001). We considered that the disturbed glucose metabolism in acute leukemia was not uncommon mainly due to the dysfunction of pancreatic islet beta cells as a result of islet damage by leukemic cells, the effect of corticosteroid and chemotherapy and the preexisting diabetes. Impaired glucose metabolism had no influence on therapeutic effect.

Topics: Adolescent; Adult; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Leukemia, Myeloid, Acute; Leukemic Infiltration; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma