Digitally Based Blood Pressure Self-Monitoring Program That Promotes Hypertension Self-Management and Health Education Among Patients With Low-Income: Usability Study.

BACKGROUND: According to evidence-based clinical guidelines, adults with hypertension are advised to self-monitor their blood pressure (BP) twice daily. Self-measured BP monitoring is a recommended strategy for improving hypertension management. OBJECTIVE: We aimed to determine the feasibility and acceptability of a digitally based BP self-monitoring program that promotes hypertension self-management and health education among low-income patients. We hypothesized that the program would be highly feasible and acceptable and that at least 50% of the patients would use the monitor at the rate required for the reimbursement of the device's cost (16 days of measurements in any 30-day period). METHODS: Withings BPM Connect was deployed to patients at Family Health Centers of San Diego. Program elements included training, SMS text message reminders, and physician communication. Compliance, use, mean BP, and BP control status were calculated. A Kaplan-Meier time-to-event analysis was conducted to compare time to compliance between a strict definition (≥16 days in any rolling 30-day window) and a lenient definition (≥1 day per week for 4 consecutive weeks). A log-rank test was performed to determine whether the difference in time to compliance between the definitions was statistically significant. Mean systolic BP (SBP) and diastolic BP (DBP) before the intervention and after the intervention and mean change in SBP and DBP across patients were calculated. Paired sample t tests (2-tailed) were performed to assess the changes in SBP and DBP from before to after the intervention. RESULTS: A total of 179 patients received the monitors. The mean changes in SBP and DBP from before to after the intervention were +2.62 (SE 1.26) mm Hg and +3.31 (SE 0.71) mm Hg, respectively. There was a statistically significant increase in both SBP and DBP after the intervention compared with before the intervention (P=.04 and P<.001). At the first and last measurements, 37.5% (63/168) and 48.8% (82/168) of the patients had controlled BP, respectively. During the observation period, 83.3% (140/168) of the patients had at least 1 controlled BP measurement. Use decreased over time, with 53.6% (90/168) of the patients using their monitor at week 2 and only 25% (42/168) at week 11. Although only 25.6% (43/168) achieved the strict definition of compliance, 42.3% (71/168) achieved the lenient definition of compliance. The median time to compliance was 130 days for the strict definition and 95 days for the lenient definition. The log-rank test showed a statistically significant difference in time to compliance between the compliance definitions (P<.001). Only 26.8% (45/168) complied with the measurement rate that would result in device cost reimbursement. CONCLUSIONS: Few patients used the monitors at a rate that would result in reimbursement, raising financial feasibility concerns. Plans for sustaining costs among low-income patients need to be further evaluated.

Comparison of IV oncology infusions compounded via robotics and gravimetrics-assisted workflow processes.

PURPOSE: A study was conducted to compare an intravenous (IV) gravimetric technology-assisted workflow (TAWF) platform to an IV robotic system. In the study we reviewed both IV technology platforms using the same gravimetric quality assurance system, which allowed for direct comparison. METHODS: All oncology preparations compounded from January 2016 through December 2018 using either system were included in our retrospective analysis. Final preparation accuracy, IV system precision, and workflow throughput (analyzed using lean process methodologies) were evaluated. RESULTS: Data analysis indicated that use of the IV gravimetric TAWF system was associated with a significantly lower percentage of accuracy errors compared to the IV robotics system (1.58% vs 2.47%, P < 0.001), with no significant difference in absolute precision (1.12 vs 1.12 P = 0.952). Lean analysis demonstrated that overall completion time (17:49 minutes vs 24:45 minutes) and compound preparation time (2:39 minutes vs 6:07 minutes) were less with the IV gravimetric TAWF vs the IV robotics system. CONCLUSION: Implementation of either an IV gravimetric TAWF system or IV robotics system will result in similar compounding accuracy and precision. Preparation time was less with use of the IV gravimetric TAWF vs the IV robotic system, but the IV robotic system required less human intervention. Both systems ensure medication safety for patients, although the IV robotic system has increased safeguards in place. Therefore, the primary driver for implementing these systems is alternative factors such as cost of systems implementation and maintenance, employee safety, and drug waste.

Leveraging advanced preparation of oncology medications: Decreasing turnaround-times in an outpatient infusion center.

INTRODUCTION: Many oncology infusions are provided in hospital-based infusion centers. With hospital-based infusion centers seeing increased volumes, patient wait times continue to be a priority. Extended wait times for oncology infusions have been shown to lead to patient dissatisfaction. METHODS: Advanced Preparation of oncology infusion medications allows pharmacy to verify and prepare specific medications the day before a patient's infusion appointment. Our study targeted lower cost, commonly used medications to prepare in advance. Data analyzed included turnaround time (TAT), medication waste, and oncology infusion preparation volumes. Implementation took place in two phases to allow time for the healthcare team to adjust to the new workflow. Phase I medications include a small amount of medications prepared manually by pharmacy technicians. Phase II medications included all phase I medications plus additional medications that were compounded in the intravenous (IV) robotic compounding system. RESULTS: Our study demonstrated significant decrease in median TAT for medications prepared in advance. 537 infusions were prepared using the Advanced Preparation module with a median TAT of 24.2 minutes (IQR, 18.0-34.0). The pre-implementation median TAT was 45.0 minutes (IQR, 36.0-56.0), which represents a decrease of 20.8 minutes (46.2%) following implementation of the program, (p<0.001). There were a total of 149 advanced preparation doses that were wasted (21.7% of doses). CONCLUSION: We have seen a statistically significant reduction in TAT for Advanced Preparation medications. Low volume of Advanced Preparation medications compared to total infusion volume limited impact on overall TAT.

Descriptive comparison of hospital formulary decisions with published oncology valuation methods.

INTRODUCTION: As cost of cancer therapy continues to increase, several organizations have developed rubrics to ascertain treatment. No studies have evaluated these methods for hospital formulary decision-making. We applied different value measurement tools to formulary decisions from one hospital system to assess their operational utility. METHODS: We evaluated four value systems: National Comprehensive Cancer Network Evidence Blocks, DrugAbacus drug pricing, European Society for Medical Oncology clinical benefit scale, and the American Society of Clinical Oncology net health benefit. Each value score or cost was assessed against our hospital formulary requests between 2012 and 2016. Formulary requests accepted and rejected were compared with respect to their relative numbers of National Comprehensive Cancer Network blocks, difference between DrugAbacus and actual cost, and European Society for Medical Oncology and American Society of Clinical Oncology scores. RESULTS: Twenty-two chemotherapy requests were included, with 20 approvals and 2 rejections. No correlation was observed between number of evidence blocks and formulary acceptance (p = 0.13). Most drugs had a higher actual price than the DrugAbacus suggested cost (p = 0.036). No significant differences were observed in European Society for Medical Oncology (p = 0.90) or American Society of Clinical Oncology (p = 0.70) scores between drugs that were accepted or rejected. When evaluating monthly cost per point of American Society of Clinical Oncology score, a numerical difference between groups was observed (median = $369.7 versus $1256.8 per point, p = 0.61). CONCLUSIONS: Existing oncology value assessment systems only variably inform hospital formulary decisions. The American Society of Clinical Oncology net health benefit score deserves further study as a method to systematically quantify the clinical safety and efficacy of formulary medication addition relative to cost.

Development of an operational productivity tool within a cancer treatment center pharmacy.

PURPOSE: The development and implementation of an operational productivity tool in an academic cancer treatment center are described. SUMMARY: Based on the increasing complexity of care delivery within the oncology setting, solutions were explored within Cleveland Clinic pharmacy's productivity model. Data were electronically captured based on orders processed through the outpatient oncology setting, including hazardous and nonhazardous medications. Based on current workflow, inpatient and outpatient orders were reviewed in productivity metrics. The metric defining the variability of the workload itself was weighted dispense type as it was the best representation of a mixed-skill workflow. After conducting workflow process mapping, discrete measurable steps were assessed and evaluated daily. Operational components of interest included pharmacist verification activities and technician compounding activities. Historical production data were sampled for assigning relative value units (RVUs) respective to time to normalize workload into a common unit (i.e., 1 hour) and to relate work demand in a highly variable setting. RVUs were assigned and delineated by cognitive and distributive activities for pharmacists and technicians, respectively. The Cleveland Clinic department of pharmacy developed a productivity tool to retrospectively measure workload involving time to review, verify, reconstitute, admix, and deliver chemotherapeutic agents. The weighting of each medication allowed for precise and meaningful evaluation of productivity. With RVUs assigned to 2 years of operational metrics, there now exists an opportunity to monitor performance trends within the cancer treatment center pharmacy. The data are readily retrievable within the electronic health record. CONCLUSION: The productivity data provided precise information to assess trends in operations within the pharmacy of an outpatient cancer treatment center.

Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced Gastric Cancer.

STUDY OBJECTIVE: Gastric cancer is the fifth most common malignancy and second leading cause of cancer-related mortality. Chemotherapy options for patients who fail first-line treatment are limited. Thus the objective of this study was to assess the cost-effectiveness of second-line treatment options for patients with advanced or metastatic gastric cancer. DESIGN: Cost-effectiveness analysis using a Markov model to compare the cost-effectiveness of six possible second-line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care. MEASUREMENTS AND MAIN RESULTS: The model was performed from a third-party payer's perspective to compare lifetime costs and health benefits associated with studied second-line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1-way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified WTP threshold, our base case analysis demonstrated that irinotecan alone is the most cost-effective regimen, and both paclitaxel alone and the combination of paclitaxel and ramucirumab were not cost-effective (ICER more than $50,000). Both 1-way sensitivity analyses and PSA demonstrated the model's robustness. PSA illustrated that paclitaxel plus ramucirumab was extremely unlikely to be cost-effective at a WTP threshold less than $400,000/QALY gained. CONCLUSION: Irinotecan alone appears to be the most cost-effective second-line regimen for patients with gastric cancer. Paclitaxel may be cost-effective if the WTP threshold was set at $160,000/QALY gained.

Reduction of Inappropriate Prophylactic Pegylated Granulocyte Colony-Stimulating Factor Use for Patients With Non-Small-Cell Lung Cancer Who Receive Chemotherapy: An ASCO Quality Training Program Project of the Cleveland Clinic Taussig Cancer Institute.

PURPOSE: Routine prophylactic pegylated granulocyte colony-stimulating factor (pGCSF) administration for patients receiving chemotherapy regimens associated with low risk (< 10%) for neutropenic fever (LRNF) is not recommended. Inappropriate use of pGCSF increases patient morbidity and health care costs. METHODS: A multidisciplinary team reviewed the charts of patients with non-small-cell lung cancer (NSCLC) at the Taussig Cancer Institute in whom a new chemotherapy regimen was initiated from April through November 2013. pGCSF use was identified and deemed appropriate if prescribed for chemotherapy associated with high risk of neutropenic fever (> 20%) or intermediate risk (10% to 20%) if other risk factors for neutropenic fever were present. Use with LRNF chemotherapy was recorded as inappropriate. RESULTS: One hundred eighty patients with NSCLC received a new chemotherapy regimen during the specified time period. Thirty-four of 119 patients (28%) treated with LRNF chemotherapy received pGCSF. Each patient received an average of 2.6 doses of pGCSF (total, 89 doses). We implemented three plan-do-study-act cycles: education of providers, development of Taussig Cancer Institute consensus guidelines for pGCSF in NSCLC, and removal of standing pGCSF orders from LRNF chemotherapy in the electronic medical record. Analysis during the change period revealed 4% of patients with NSCLC treated with LRNF chemotherapy received pGCSF. Cost analysis showed an 84% decrease in billed charges per month. No increase in neutropenic fever admissions was found. CONCLUSION: pGCSF was excessively prescribed for patients with NSCLC. Factors contributing to inappropriate use included provider lack of familiarity with guidelines and knowledge with regard to the risk of neutropenic fever for individual chemotherapy regimens, and electronic medical record chemotherapy templates that contain standing GCSF orders. Interventions to address these gaps quickly produced improved compliance with guidelines and led to significant cost savings.

A review in the treatment of oncologic emergencies.

AIM: Oncologic emergencies are often categorized as a group of metabolic abnormalities associated with the diagnosis of cancer or the initiation of chemotherapy for treatment. These syndromes often arise in the acute setting, demanding an accurate knowledge of the associated condition and current treatment. In this review, we evaluate five oncologic emergencies: tumor lysis syndrome, hypercalcemia, hyponatremia, spinal cord compression, and disseminated intravascular coagulation. SUMMARY: Oncologic emergencies are often diverse in etiology and are often associated with the initiation of chemotherapy. Tumor lysis syndrome presents as severe electrolyte abnormalities that need to be addressed urgently, sometimes prior to initiation of chemotherapy. Hypercalcemia of malignancy is treated with aggressive rehydration, furosemide, and intravenous bisphosphonates. If a patient with cancer presents with normovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone should be suspected. Malignant spinal cord compression happens when cancer cells grow in, or near to, the spine and press on the spinal cord and nerves. This causes swelling and a reduction in the blood supply to the spinal cord and nerve roots. Disseminated intravascular coagulation is characterized by systemic activation of blood coagulation, which results in generation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to multiple organ dysfunction syndrome. CONCLUSION: Knowledge of oncology emergencies is critical to the understanding of these emergent syndromes in oncology patients. Each of these disease states requires careful evaluation of the patient's symptoms, monitoring parameters for conditions and supportive care measures and interventions.

Reducing Time to Antibiotic Administration for Febrile Neutropenia in the Emergency Department.

PURPOSE: Febrile neutropenia (FN) is an oncologic emergency, and prolonged time to antibiotic administration (TTA) is associated with increased hospital length of stay (LOS) and worse outcomes. We hypothesized that a febrile neutropenia pathway (FNP) quality initiative project would reduce TTA delays for febrile patients with cancer presenting to the emergency department (ED). METHODS: This prospective study compared ED FNP patients (> 18 years old), between June 2012 and June 2013 with both historical and direct admissions (DA) cohorts at a multispecialty academic center. Interventions included providing patients with FN-Alert cards, standardizing the definition of FN and recognizing it as a distinct chief complaint, revising ED triage level for FN, creating electronic FN order sets, administering empiric antibiotics before neutrophil count result, and relocating FN antibiotics to the ED. The primary outcome was TTA, with a target goal of 90 minutes after ED presentation. RESULTS: In total, 276 FN episodes in 223 FNP patients occurred over the 12-month study period and were compared with 107 episodes in 87 patients and 114 episodes in 101 patients in the historical and DA cohorts, respectively. Use of the FNP reduced TTA from 235 and 169 minutes in historical and DA cohorts, respectively, to 81 minutes, and from 96 to 68 minutes when the order set was not used versus used in the FNP group (P < .001 for all comparisons). Decrease in hospital LOS was not statistically significant. CONCLUSION: The ED FNP is a significant quality initiative with sustainable interventions, and was able to demonstrate value by decreasing TTA compared to both historical and DA controls in cancer patients presenting to the ED.

Use of atropine-diphenoxylate compared with hyoscyamine to decrease rates of irinotecan-related cholinergic syndrome.

BACKGROUND: Cholinergic syndrome is a well established acute adverse reaction associated with irinotecan. Cholinergic side effects can be ameliorated or prevented with anticholinergic agents. To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion. OBJECTIVES: To compare the incidence of cholinergic syndrome with irinotecan using atropine-diphenoxylate or hyoscyamine as premedication. METHODS: We conducted a retrospective, single-center, nonrandomized, cohort study of adult patients treated with atropine-diphenoxylate or hyoscyamine as premedication before receiving irinotecan. For all irinotecan infusions, intravenous atropine was administered for patients experiencing any cholinergic reaction. RESULTS: A total of 532 irinotecan cycles (354 cycles for atropine-diphenoxylate group; 178 cycles for hyoscyamine group) were analyzed in 80 patients. Overall incidence of cholinergic syndrome did not differ between atropine-diphenoxylate (8.2%) and hyoscyamine (9.0%) groups (P = .76). The incidence of cholinergic syndrome after the £rst cycle of irinotecan was similar between the 2 arms, atropine-diphenoxylate (14.6%) and hyoscyamine (10.7%), with P = .74. The most common cholinergic symptoms documented were abdominal pain or cramping, and diarrhea. LIMITATIONS: This study was subjected to vulnerabilities to bias and random error because of its observational retrospective design and small number of participants. CONCLUSIONS: Lack of difference in the incidence of cholinergic syndrome observed in irinotecan-treated patients suggests atropinediphenoxylate and hyoscyamine may both be effective prophylactic options. The findings support the need for a larger, randomized study to assess and compare these agents with other potential premedications such as scopolamine and atropine in prevention of irinotecan-related cholinergic syndrome.

Evaluation of noncytotoxic DNMT1-depleting therapy in patients with myelodysplastic syndromes.

BACKGROUND: Mutational inactivation in cancer of key apoptotic pathway components, such as TP53/p53, undermines cytotoxic therapies that aim to increase apoptosis. Accordingly, TP53 mutations are reproducibly associated with poor treatment outcomes. Moreover, cytotoxic treatments destroy normal stem cells with intact p53 systems, a problem especially for myeloid neoplasms, as these cells reverse the low blood counts that cause morbidity and death. Preclinical studies suggest that noncytotoxic concentrations of the DNA methyltransferase 1 (DNMT1) inhibitor decitabine produce p53-independent cell-cycle exits by reversing aberrant epigenetic repression of proliferation-terminating (MYC-antagonizing) differentiation genes in cancer cells. METHODS: In this clinical trial, patients with myelodysplastic syndrome (n=25) received reduced decitabine dosages (0.1-0.2 mg/kg/day compared with the FDA-approved 20-45 mg/m2/day dosage, a 75%-90% reduction) to avoid cytotoxicity. These well-tolerated doses were frequently administered 1-3 days per week, instead of pulse cycled for 3 to 5 days over a 4- to 6-week period, to increase the probability that cancer S-phase entries would coincide with drug exposure, which is required for S-phase-dependent DNMT1 depletion. RESULTS: The median subject age was 73 years (range, 46-85 years), 9 subjects had relapsed disease or were refractory to 5-azacytidine and/or lenalidomide, and 3 had received intensive chemoradiation to treat other cancers. Adverse events were related to neutropenia present at baseline: neutropenic fever (13 of 25 subjects) and septic death (1 of 25 subjects). Blood count improvements meeting the International Working Group criteria for response occurred in 11 of 25 (44%) subjects and were highly durable. Treatment-induced freedom from transfusion lasted a median of 1,025 days (range, 186-1,152 days; 3 ongoing), and 20% of subjects were treated for more than 3 years. Mutations and/or deletions of key apoptosis genes were frequent (present in 55% of responders and in 36% of nonresponders). Noncytotoxic DNMT1 depletion was confirmed by serial BM γ-H2AX (DNA repair/damage marker) and DNMT1 analyses. MYC master oncoprotein levels were markedly decreased. CONCLUSION: Decitabine regimens can be redesigned to minimize cytotoxicity and increase exposure time for DNMT1 depletion, to safely and effectively circumvent mutational apoptotic defects. TRIAL REGISTRATION: Clinicaltrials.gov NCT01165996. FUNDING: NIH (R01CA138858, CA043703); Department of Defense (PR081404); Clinical and Translational Science Award (CTSA) (UL1RR024989); and the Leukemia and Lymphoma Society (Translational Research Program).

Rates of febrile neutropenia with pegfilgrastim on same day versus next day of CHOP with or without rituximab.

Febrile neutropenia is a complication of myleotoxic chemotherapy that can markedly decrease quality of life and increase healthcare costs. A granulocyte-colony stimulating factor (G-CSF) is used to increase neutrophil production to reduce the risk of developing febrile neutropenia. However, G-CSF administered on the same day as chemotherapy can worsen and prolong neutropenia. To study and compare the effects of pegfilgrastim on the incidence of febrile neutropenia and grade 4 neutropenia in patients receiving pegfilgrastim on the same day (day 1) versus the next day (day 2 or beyond) of chemotherapy, a retrospective, single-center, nonrandomized, cohort study was carried out of adult non-Hodgkin's lymphoma patients who received pegfilgrastim 6 mg subcutaneously on day 1 or beyond of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with or without rituximab every 3 weeks. Six hundred and fifty-five chemotherapy cycles (320 cycles for the same day and 335 cycles for the next day) were evaluable in 141 patients. Among all cycles, the incidence of febrile neutropenia was 9.4 versus 5.1% in the same-day versus the next-day group (P=0.03). The incidence of febrile neutropenia was the highest after the first cycle in the same-day group, which was 19.4, versus 11.1% for the next-day group (P=0.27). There were three deaths among patients who developed febrile neutropenia, including two in the next-day group versus one in the same-day group. In conclusion, our findings support the need for a randomized phase III study to fully evaluate whether a G-CSF is safer when administered on the next day versus the same day of chemotherapy.

Outcomes in obese and overweight acute myeloid leukemia patients receiving chemotherapy dosed according to actual body weight.

Cytotoxic chemotherapy dosages are traditionally calculated according to body surface area (BSA). No guidelines exist for chemotherapy dosing of acute myeloid leukemia (AML) patients at extremes of weight. We investigated the efficacy and safety of chemotherapy dosed according to BSA based on actual body weight (ABW) among under/normal weight, overweight, and obese AML patients. AML patients (excluding acute promyelocytic leukemia) treated with anthracycline and cytarabine-based remission induction chemotherapy from 2002 to 2009 at Cleveland Clinic were divided into three body mass index (BMI) groups: under/normal weight (BMI ≤ 24.9), overweight (BMI 25.0-29.9), and obese (BMI ≥ 30.0). Among 247 AML patients, 81 (33%) were under/normal weight, 81 (33%) were overweight, and 85 (34%) were obese. Complete remission (CR) rates were similar among these groups (69.1, 79.0, and 76.5%, respectively; P = 0.321), as was median survival (10.7, 16.7, and 14.2 months, respectively, P = 0.352) and 30-day mortality (3.7, 2.5, 7.1%, respectively, P = 0.331). There was no difference among groups in days to neutrophil or platelet recovery, hospitalization days for induction chemotherapy, and bacteremia. After adjustment for confounders (age, sex, BMI, white blood cells, cytogenetic risk, etiology, and bacteremia), overall survival was significantly shorter for normal weight compared to overweight (P = 0.006) and obese (0.038) patients. Response rates and adverse events were not significantly different among AML patients of all weight classes when induction chemotherapy was dosed according to ABW. Induction chemotherapy in these patients can be safely dosed using ABW.

Absolute lymphocyte count at day 28 independently predicts event-free and overall survival in adults with newly diagnosed acute lymphoblastic leukemia.

We investigated the prognostic impact of absolute lymphocyte count (ALC) following induction chemotherapy in newly diagnosed adult acute lymphoblastic leukemia (ALL). Patients with ALC ≥350 cells/µL at day 28 had a median overall survival (OS) of 47.4 months when compared with 17.6 months for those with an ALC <350 cells/µL (HR = 1.98, P = 0.007). Among patients who achieved a complete remission, median event-free survival (EFS) for those with ALC ≥350 cells/µL on day 28 was 42.1 months when compared with 13.9 months in those with ALC <350 cells/µL (HR = 2.08, P = 0.006). In multivariable analysis, the ALC on day 28 (<350 cells/µL vs. ≥350 cells/µL, P ≤ .0004 for OS and EFS) along with WBC at diagnosis (≤6.0 or >30.0 K/µL vs. >6.0-30.0 K/µL, P ≤ 0.002 for OS and EFS) and cytogenetics (abnormal vs. normal, P = 0.002 for OS and P = 0.02 for EFS) were independent prognostic factors of both OS and EFS. Combining these three factors segregates patients in three well-defined risk groups. These data suggest that ALC can be used in combination with other prognostic features to better predict outcome and that targeting the immune system to improve ALC may be a worthwhile strategy in ALL.

Race and intensity of post-remission therapy in acute myeloid leukemia.

BACKGROUND: In many cancers, including AML, blacks have poorer overall survival. We investigated whether differences in post-remission therapy (PRT) were a contributing factor. METHODS: We compared PRT cycle number and intensity and time to PRT in blacks and whites, among 460 patients with newly diagnosed AML. RESULTS: Blacks and whites had PRT of equal cycle intensity and number, but black patients experienced a significant delay in starting PRT (2.73 months in blacks vs. 1 month in whites, p=0.047). Overall survival was equivalent in blacks and whites. CONCLUSION: PRT is delayed in blacks but does not explain differences in survival.

Incidence and management of asparaginase-associated adverse events in patients with acute lymphoblastic leukemia.

Asparaginase is an enzyme that breaks down extracellular asparagine into aspartic acid and ammonia. Depletion of extracellular asparagine inhibits the growth of lymphocytic leukemic cells. Unlike normal cells, lymphoblasts lack the enzyme to synthesize asparagine and therefore rely on an exogenous source of this amino acid to maintain cellular protein synthesis. Asparagine depletion results in nutritional deprivation, inhibition of protein synthesis, and subsequent apoptotic cell death in lymphoblasts. Asparaginase therapy is an essential component of the treatment protocol for acute lymphoblastic leukemia. The effect of asparaginase on protein synthesis may result in a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. This review discusses the incidence of asparaginase-related adverse events, compares available asparaginase formulations with respect to the emergence of certain toxicities, and considers management strategies for these toxicities in patients with acute lymphoblastic leukemia.