[Show abstract][Hide abstract] 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 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.
No preview · Article · May 2012 · Clinical lymphoma, myeloma & leukemia
[Show abstract][Hide abstract] ABSTRACT: Relapse after 5 years of complete remission (CR) is uncommon in acute myeloid leukemia (AML). Among 2347 patients seen between 1980 and 2008, 1366 achieved CR; 942 relapsed. Eleven (1.16% of all relapses) relapsed after a CR of >5 years. The median age was 66 years (range, 37-79). Initial therapy was cytarabine plus anthracycline in six, amsacrine-based in three, and other in two. The median CR1 duration was 81 months (range, 60-137). At relapse, the karyotype was different from the initial finding in five of eight (63%) patients with available data. Treatment for relapse included cytarabine with anthracycline in eight, and other in three patients, with a second CR (CR2) achieved in four (36%). The median CR2 duration was 1 month (range, 0-37), and median survival after relapse was 6.4 months (range, 1-39). Late relapses in AML are infrequent, with poor response to therapy. Karyotype at relapse is frequently different, raising the question of second AML versus relapse with the original clone.
No preview · Article · Mar 2010 · Leukemia & lymphoma
[Show abstract][Hide abstract] ABSTRACT: The diagnosis of cancer is based on the demonstration of malignant cells obtained via biopsy or needle aspiration. For some patients, diagnostic options may be limited either because of tumor location, underlying comorbid conditions, or lack of access to care.
275 of 282 consecutive patients presenting to the University of Texas M.D. Anderson Cancer Center with a suspicion of cancer between April 1, 2000 and January 23, 2003 were evaluated retrospectively. We analyzed differences in means of diagnosis, complication rates, clinical characteristics, and comorbid medical conditions between patients with and without a cancer diagnosis. Logistic regression analysis was used to determine the independent predictors of a diagnosis of cancer.
179 (65%) patients had a cancer diagnosis. Endoscopic ultrasonography with fine needle aspiration (EUS/FNA) and image-guided percutaneous biopsy (IGPB) were the most commonly used diagnostic techniques. Complications occurred in 6% of all cases. Independent predictors of a cancer diagnosis included age of 50 years or older, jaundice, weight loss, percentage of monocytes greater than 7, and platelet count greater than 440x10/L; the ROC statistic was 0.796 (CI, 0.738-0.854; P<0.001). Controlling for age, there was no difference in comorbidity between patients with and without a cancer diagnosis.
EUS/FNA and IGPB play an important role in the diagnosis of certain types of malignancy and are associated with a low risk for complications. Advanced age, prior history of malignancy, weight loss, abnormally high percentage of monocytes, and thrombocytosis may be predictive of a cancer diagnosis in patients with suspected malignancy. Comorbid medical conditions are common among patients and occur at rates similar to the general population. Further study is necessary to determine organ-specific predictors of malignancy and to better understand the relationship between cancer and coexisting medical conditions.
No preview · Article · Jul 2005 · The American Journal of the Medical Sciences