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A randomized controlled trial of an intensive insulin regimen in patients with hyperglycemic acute lymphoblastic leukemia.

ABSTRACT: 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.

SUBMITTER: Vu K

PROVIDER: S-EPMC3974971 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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A randomized controlled trial of an intensive insulin regimen in patients with hyperglycemic acute lymphoblastic leukemia.

Vu Khanh K Busaidy Naifa N Cabanillas Maria E ME Konopleva Marina M Faderl Stefan S Thomas Deborah A DA O'Brien Susan S Broglio Kristine K Ensor Joe J Escalante Carmen C Andreeff Michael M Kantarjian Hagop H Lavis Victor V Yeung Sai-Ching Jim SC

Clinical lymphoma, myeloma & leukemia 20120601 5

<h4>Unlabelled</h4>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 impr ...[more]

PMID: 22658895

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Project description:BackgroundLittle is known about the effectiveness of the newly emerging technology of exergaming in reducing Cancer Related Fatigue (CRF).ObjectivesThe study's primary aim was to examine the effectiveness of exergaming in reducing CRF; the secondary aims were to improve functional capacity/endurance and promote physical activity (PA) among children with acute lymphoblastic leukemia (ALL).MethodsIn this Randomized Controlled Trial (RCT), 45 children aged 6-14 years were randomly assigned into group-I, n = 22, and group II, n = 23. Group-I played exergaming of moderate intensity for 60 min, twice a week for three weeks. Group II was given an instructional session regarding the benefits of PA with advice to practice PA for 60 min twice a week. CRF, functional capacity/endurance, and PA were measured using the pediatric quality of life multidimensional fatigue scale (Ped-QLMFS), six-minute walk test (6-MWT), and Godin-Shepard Leisure Time Physical Activity Questionnaire (QSLTPAQ) respectively. All measurements were taken thrice; in the first, third, and fifth weeks of intervention.ResultsGroup-I demonstrated a significant reduction of CRF, and a significant increase of functional capacity/endurance compared to group-II over the five weeks study period. The effect of time × intervention interaction was significant. Based on Cohen's guidelines, CRF and functional capacity/endurance had large effect sizes (η2 = 0.41, p = .00) and (η2 = 0.27, p = .00) respectively.ConclusionThe protocol of exergaming used in this RCT effectively reduces CRF and promotes functional capacity/endurance and PA in children with ALL undergoing chemotherapy. It may provide an alternative treatment modality to decrease the healthcare load.Key messagesCancer-related fatigue (CRF) is described as physical exhaustion, sleep disturbance, emotional distress, and cognitive dysfunction.Exergaming reduces CRF and promotes functional capacity/endurance and physical activity in children with acute lymphoblastic leukemia undergoing chemotherapy.Exergaming may provide an alternative treatment modality to decrease the healthcare load.

Project description:Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Project description:AimTo compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China.Materials and methodsThis open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint).ResultsThere were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group.ConclusionsCompared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy.

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A randomized controlled trial of an intensive insulin regimen in patients with hyperglycemic acute lymphoblastic leukemia.

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A randomized controlled trial of an intensive insulin regimen in patients with hyperglycemic acute lymphoblastic leukemia.

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