Khanh Vu

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

UNLABELLED 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. INTRODUCTION 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). PATIENTS AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Late relapses in acute myeloid leukemia: analysis of characteristics and outcome.

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.

A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center

The purpose was to determine the incidence and prevalence of venous thromboembolism (VTE) in acute leukemia patients from our institution. We conducted a retrospective study on newly diagnosed acute leukemia patients who presented at our institution from November 1999 to May 2005. Descriptive statistics and cross‐tabulation were used to describe patient characteristics. Measures of morbidity were used to address VTE risk. Chi‐square testing, Fishers exact testing, Mann–Whitney analyses, or median testing were used to determine between‐group differences. Data analyses were conducted using Stata version 11 (Stata Corp., College Station, TX). Two hundred and ninety‐nine patients with acute lymphoblastic leukemia (ALL) and 996 patients with acute myeloid leukemia (AML) were included. After excluding patients diagnosed with VTE prior to or at the time of leukemia diagnosis, during the mean time follow‐up period of 2.5 years (range: 0.0025–10.3 years), the overall incidence rate of VTE was 3.7 per 100 person‐years: 4.2 per 100 person‐years for ALL and 3.4 per 100 person‐years for AML. Among all patients, the majority (80.6%) developed VTE within 12 months after diagnosis and during thrombocytopenia. The most common VTE was central venous catheter (CVC)‐associated upper‐extremity deep venous thrombosis. Pulmonary embolism occurred in 15% of ALL patients and 8% of AML patients. VTE recurred in 20.7% of ALL patients and 18.6% of AML patients. VTE occurs frequently in patients with acute leukemia. Studies are needed to identify risk factors for the development and recurrence of VTE among patients with acute leukemia and to establish more effective methods for preventing and treating VTEs in leukemia patients who have thrombocytopenia and/or CVC.

Recurrence of venous thromboembolism among adults acute leukemia patients treated at the University of Texas MD Anderson Cancer Center: Incidence and risk factors

The purpose was to determine the incidence and risk factors for venous thromboembolism (VTE) recurrence among adult acute leukemia patients. We performed a retrospective study of adult acute leukemia patients who were treated at our institution between November 1999 and May 2005. Medical records of 139 patients with an initial VTE were reviewed and followed up to May 2010 for VTE recurrence. Of these 139 patients [86 with acute myelogenous leukemia (AML), 53 with acute lymphocytic leukemia (ALL)], 27 (19.4%, 16 AML and 11 ALL) had VTE recurrence. The overall incidence rate of VTE was 8.6 per 100 person-years (median follow-up time: 0.9years). It was 5.9 and 12.4 per 100 person-years among ALL and AML patients, respectively. The cumulative proportion of recurrent VTE was 2.16%, 10.9%, 16.6%, 25.9%, 30.6%, and 34.2% at 1month, 6months, 1year, 3years, 5years, and 7years, respectively. In a multivariate Cox hazards model, significant predictors for VTE recurrence included catheter thrombosis [adjusted hazard ratio (aHR)]:6.3, 95%CI:1.17-34.0), prior history of hematologic cancer (aHR:4.2, 95%CI:1.5-11.2), chronic lung disease (aHR: 3.4, 95%CI:0.92-12.5), psychological disorder (aHR: 4.3, 95%CI:1.5-12.2), and liver disease (aHR: 3.8, 95%CI: 1.04-14.3). VTE recurrence is common among adult acute leukemia patients and it continues up to 7years after the initial episode. Catheter thrombosis, a history of hematologic malignancy antecedent to acute leukemia, and lung, liver and psychiatric co-morbidities increase the patient risk for VTE recurrence. Further studies should be conducted to improve the prevention of VTE recurrence in leukemia patients.

Diagnostic Evaluation of Patients with a High Suspicion of Malignancy: Comorbidities and Clinical Predictors of Cancer

Background: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. Methods: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. Results: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 440 × 109/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. Conclusions: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.

Baseline characteristics predictive of malignancy among patients presenting with lymphadenopathy: A cancer center experience

Context: Patients who present to tertiary cancer centers solely with radiologic evidence of lymphadenopathy often are diagnosed with malignancy, but it is unclear which baseline characteristics are predictive of a cancer diagnosis. Materials and Methods: We conducted a retrospective data review to determine baseline characteristics predictive of a cancer diagnosis and the optimal follow-up time for such patients. Results: Sixty-six adult patients with lymphadenopathy were evaluated. Thirty-six patients (55%) were diagnosed with cancer; the most common type was lymphoma. Cancer was diagnosed in 94%, 79%, and 70% of patients with supraclavicular, retroperitoneal, and abdominal lymphadenopathy, respectively. Increasing age and hypertension were associated with a cancer diagnosis in the multivariate analysis. The mean time to diagnosis was 15 days (range, 1-140 days). The average follow-up time was 18 months in patients without a cancer diagnosis. Conclusions: Patients presenting solely with lymphadenopathy at a cancer center have a higher likelihood of being diagnosed with cancer if they are at least 50 years old or have hypertension. Supraclavicular lymphadenopathy is highly associated with a malignant diagnosis. We suggest that patients presenting solely with lymphadenopathy should be followed-up for at least 6 months for a definitive diagnosis.

Invasive fungal infections (IFI) in patients (pts) receiving hyper-CVAD

6727 Background: IFI are frequent and life-threatening complications in pts with hematologic malignancies. Pts at high risk for IFI are those with acute myelogenous leukemia (AML), high-risk myelodysplastic syndrome (MDS), and pts undergoing bone marrow transplant. The incidence of IFI in AML/MDS during induction at MDACC is 3%-9% with 39% mortality. Pts who receive hyper-CVAD are susceptible to IFI due to use of steroids and neutropenia. Fluconazole 200mg daily is standard anti-fungal prophylaxis for pts undergoing hyper-CVAD for acute lymphoblastic lymphoma (ALL), lymphoblastic lymphoma (LL), or Burkitts leukemia/lymphoma (BL). OBJECTIVES 1) To determine incidence of IFI during hyper-CVAD 2) to evaluate efficacy of our standard anti-fungal prophylaxis 3) to estimate mortality due to IFI. METHODS Retrospective chart review of pts treated with hyper-CVAD from January 1998-July 2003. Review was conducted until relapse, death, transplant, or end of chemotherapy. From 1992-2003 hyper-CVAD was administered as described by Kantarjian et al (JCO 18:547, 2000). From May 2000-December 2001, the modified hyper-CVAD regimen with or without rituximab was used. This regimen incorporated a course of anthracycline intensification on course 2, and 2 courses of early and late intensification during maintenance. No maintenance was given for BL. RESULTS 170 pts were reviewed, 159 were evaluable. Median age was 41 (r: 15-92), 74% ALL, 20% BL and 6% LL. Overall incidence of IFI was 13% (21/159); 62% due to mold, 38% due to yeast. Overall mortality due to IFI was 24% (5/21), 3 of them occurring in pts who were HIV+/BL and 2 in ALL pts. 3/7 pts with HIV+/BL developed and died due to IFI. CONCLUSION The incidence of IFI in pts with ALL, BL, LL is similar to AML/MDS pts, however, the mortality is lower. Patients with BL/HIV, have a high risk of death due to IFI. New strategies for IFI prevention such as use of protected environment and the use of broad-spectrum anti-fungal prophylaxis should be considered in pts receiving hyper-CVAD. No significant financial relationships to disclose.