Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

Cost-effectiveness analysis of gemtuzumab ozogamicin for the treatment of de novo CD33-positive Acute Myeloid Leukaemia (AML) in Italy.

BACKGROUND: Based on the results from the ALFA-0701 study, gemtuzumab ozogamicin (GO) has been approved by the European Medicine Agency and by the Italian Drug Agency for the first line treatment of de novo acute-myeloid leukemia (AML). In this analysis, we assessed the cost-effectiveness of GO in combination with daunorubicin and cytarabine (DA), vs DA alone, adopting the perspective of the Italian National Health Service. METHODS: For this analysis, a cohort state transition model was developed. The model was designed to capture health states and events that occur throughout the entire disease course and that impact costs and outcomes. The ALFA-0701 study was the main source of clinical data for this analysis. In the model, patients had the same baseline characteristics and experienced the same clinical improvements as in the ALFA-0701 study. Economic data (resource consumption and unit costs) were adapted to reflect expenditure for the Italian National Health Service. Utilities per health state and disutilities due to adverse events were based on the literature and on the general population for those functionally cured. A lifetime horizon was adopted, with both costs and outcome being discounted of 3.0%, annually. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results. RESULTS: In the base case (lifetime horizon; primary source of data: study ALFA-0701; perspective: Italian National Health Service; discount rate on costs and outcomes: 3.0%), GO + DA was more effective DA both in terms of life-year (LY) survival (6.42 LY vs 5.75 LY, respectively) and quality-of-life adjusted survival (4.69 QALY vs 4.19 QALY, respectively). The overall costs were almost similar in the two groups (slightly lower with GO + DA than with DA; €162,424 and €162,708, respectively). The use of GO increased the costs of drug therapy but saved costs of relapse and costs associated with transplantation (HSCT). CONCLUSIONS: If results of the ALFA-0701 study are applied to the Italian healthcare environment, then gemtuzumab ozogamicin, in combination with daunorubicin and cytarabine, would clinical outcomes and reduce lifetime costs, compared with daunorubicin and cytarabine alone for the first line treatment of de novo AML. TRIAL REGISTRATION: Not applicable.

The cost-effectiveness of glasdegib in combination with low-dose cytarabine, for the treatment of newly diagnosed acute myeloid leukemia in adult patients who are not eligible to receive intensive induction chemotherapy in Canada.

AIM: The clinical efficacy and safety of DAURISMO (glasdegib) combined with low-dose cytarabine (LDAC) were demonstrated in the BRIGHT AML 1003 study among newly diagnosed acute myeloid leukemia patients who are not eligible to receive intensive chemotherapy. This study aims to evaluate its cost-effectiveness versus LDAC alone and azacitidine from a Canadian payer perspective. MATERIALS AND METHODS: A partitioned-survival model was developed with three health states: progression-free survival (PFS), relapse/progression and death. Clinical inputs were obtained from the BRIGHT AML 1003 study for glasdegib and LDAC, and from the two trial publications and indirect treatment comparison for azacitidine. Drug acquisition/administration, disease management, adverse event and end-of-life costs were considered. All costs were measured in Canadian dollars. Cost-effectiveness of glasdegib + LDAC was assessed against LDAC alone in main population, and against azacitidine by bone marrow blasts (BMB). A weighted average ICER was calculated to represent the current treatment use of Canadian clinical practice. The reference-case analysis was conducted probabilistically, and numerous probabilistic scenario analyses were conducted. RESULTS: The incremental cost-effectiveness ratios (ICERs) compared to LDAC alone was CAD $177,065 (a mean gain of 0.41 QALYs and an incremental cost of CAD $72,695), to azacitidine in 20-30% and >30% BMB group were CAD $178,201 (a mean gain of 0.34 QALYs and an incremental cost of CAD $59,889) and dominant (a mean gain of 0.28 QALYs while reducing costs by CAD $7,856) respectively, resulting in a weighted average ICER of CAD $81,310 per QALY. LIMITATIONS AND CONCLUSIONS: Though uncertainties remain with the generated PFS curve, the derived azacitidine curves, administration and vial wastage, the model has been built under the best available evidence and relied on clinical opinions where there were data gaps. The weighted average ICER suggests that glasdegib + LDAC is cost-effective at a CAD $100,000 willingness-to-pay threshold.

Cost-effectiveness analysis of rituximab with methotrexate, cytarabine and thiotepa for the treatment of patients with primary central nervous system lymphoma.

The International Extranodal Lymphoma Study Group-32 (IELSG32) randomized patients with primary central nervous system lymphoma (PCNSL) for induction treatment with methotrexate-cytarabine, methotrexate-cytarabine-rituximab, or methotrexate-cytarabine-thiotepa-rituximab (MATRix) and reported significantly improved complete remission with the MATRix regimen. This study assessed cost-effectiveness among these three induction strategies for PCNSL. A Markov model was developed based on the IELSG32 trial over a 20 year time horizon from the Canadian health care system perspective. Costs for induction, consolidation, inpatient treatment administration, follow-up, adverse events, relapsed disease, and palliative care were included. Methotrexate-cytarabine-rituximab was subject to extended dominance by the other two strategies. The MATRix regimen compared to methotrexate-cytarabine produced 3.05 quality-adjusted life year (QALY) gains at added costs of $75,513, resulting in an incremental cost-effectiveness ratio of $24,758/QALY gained. The MATRix regimen was the optimal strategy in the majority of simulations (98% probability at willingness-to-pay of $50,000/QALY gained) and results appeared robust across sensitivity analyses.

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m2) vs. 4-h (2 g/m2) infusion. NCI SR patients received a dexamethasone-based three-drug and NCI HR/CNS 3 SR patients a prednisone-based four-drug induction. End induction MRD (minimal residual disease) was obtained but did not impact treatment. DI improved the 10-year continuous complete remission (CCR) rate; 75.5 ± 2.5% vs. 81.8 ± 2.2% p = 0.002, whereas MTX administration did not; 4-h 80.8 ± 1.9%; 24-h 81.4 ± 1.9% (p = 0.7780). Overall survival (OS) at 10 years did not differ with DI: 91.4 ± 1.6% vs. 90.9 ± 1.7% (p = 0.25) without but was higher with the 24-h MTX infusion; 4-h 91.1 ± 1.4%; 24-h 93.9 ± 1.2% (p = 0.0209). MRD predicted outcome; 10-year CCR 87.7 ± 2.2 and 82.1 ± 2.5% when MRD was <0.01% with/without DI (p = 0.007) and 54.3 ± 8% and 44 ± 8% for patients with MRD ≥ 0.01% with/without DI (p = 0.11). DI improved CCR for patients with B-ALL with and without end induction MRD.

The economic impact of the transition from branded to generic oncology drugs.

Background: Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the cost-effectiveness (ce) or cost-utility (cu) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods: We re-examined the ce or cu of regimens previously evaluated in Canadian Cancer Trials Group (cctg) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in ce or cu. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results: The four randomized controlled trials included (representing 1979 patients) were cctg br.10 (early lung cancer, adjuvant vinorelbine-cisplatin vs. observation, n = 172), cctg br.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), cctg co.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and cctg ly.12 (relapsed or refractory lymphoma, gemcitabine-dexamethasone-cisplatin vs. cytarabine-dexamethasone-cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (icer) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (qaly) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions: Genericization of a costly oncology drug can modify the ce and cu of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems.

Health state utilities associated with treatment options for acute myeloid leukemia (AML).

Aims: Acute myeloid leukemia (AML) treatment typically involves remission induction chemotherapy followed by consolidation chemotherapy. New treatments for AML have recently been introduced, including a chemotherapy formulation called CPX-351, which is administered via less time-intensive IV infusion than the standard "7 + 3" continuous infusion regimen of cytarabine plus an anthracycline. The purpose of this study was to estimate utilities that could be used in economic modeling of AML treatment. Materials and methods: In time trade-off interviews, participants from the UK general population valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML. The decrease in utility when adding these chemotherapy regimens represents the disutility of each regimen. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: Two hundred participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. Adding any chemotherapy significantly decreased utility (p < 0.0001). Induction had a mean disutility of -0.11 with CPX-351 and -0.15 with 7 + 3. Mean disutility for consolidation ranged from -0.03 with outpatient CPX-351 to -0.11 with inpatient 5 + 2. Utilities are also reported for other AML treatments (e.g. transplant, low-intensity chemotherapy). Limitations: One limitation is that the differences in adverse event profiles between the treatment regimens were based on clinician opinion. Future use of CPX-351 in clinical trials or clinical settings will provide additional information on its adverse event profile. Conclusions: While all chemotherapy regimens were associated with disutility, regimens with shorter hospitalization and less time-intensive infusion were generally perceived as preferable. These utilities may be useful in cost-utility models comparing the value of AML treatments.

Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens.

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG.

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

Midostaurina en el tratamiento de la leucemia mieloide aguda / Midostaurina en el tratamiento de la leucemia mieloide aguda

INTRODUCCIÓN: La leucemia mieloide aguda es la segunda forma más común de leucemia y la causa más frecuente de muerte relacionada con leucemia en Estados Unidos. La incidencia de LMA aumenta con el avance de la edad y el pronóstico empeora sustancialmente con el aumento de esta. La leucemia mieloide aguda (LMA) es un tipo de cáncer en el cual la médula ósea (MO) produce de manera anormal mieloblastos, glóbulos rojos y plaquetas. El tabaquismo, el tratamiento previo con quimioterapia, la exposición a la radiación y las sustancias químicas como el benceno, pueden constituir factores de riesgo para el desarrollo de LMA en adultos. Los trastornos genéticos, tales como la anemia de Fanconi, el síndrome de Shwachman, el síndrome de Diamond-Blackfan y el síndrome de Down, se asocian con un aumento del riesgo de presentar LMA. Dicha leucemia puede presentarse como resultado de la progresión de otros tipos de enfermedades, como la policitemia vera, la mielofibrosis primaria, la trombocitemia esencial y los síndromes mielodisplásicos (SMD). EPIDEMIOLOGÍA: La LMA es el tipo de leucemia aguda más común en los adultos. La frecuencia de LMA entre los 30 y 34 años es alrededor de 1 caso por cada 100,000 personas y entre los 65 y 69 años alrededor de 10 casos por cada 100,000 personas, la incidencia continúa aumentando en mayores de 70 años con un pico entre los 80 y 84 años. TECNOLOGÍA: El FLT3 es un receptor de tirosin-kinasa tipo III expresado en las células hematopoyéticas inmaduras que actúa como mediador clave de la hematopoyesis temprana. Las mutaciones del dominio yuxtamembranoso del gen se encuentran presentes en el 25% de los pacientes con LMA. Estas mutaciones alteran las propiedades biológicas de la LMA y se asocian con peor pronóstico. OBJETIVO: Evaluar la eficacia y seguridad de la Midostaurina (M) en el tratamiento de la Leucemia Mieloide Aguda. COMENTARIOS FINALES: De los resultados conocidos del único estudio clínico de Fase III con 717 pacientes, la sobrevida global a 57 meses con Midostaurina, mejoró en 4,6 meses y obtuvieron una reducción del 23% en la probabilidad de morir por cualquier evento. En los otros estudios la tendencia de los resultados es similar. Observando específicamente, la remisión completa se logra en mayor porcentaje en los pacientes FLT3 mutados con Midostaurina, que en los otros grupos. Según los resultados, la Midostaurina se posiciona como una opción terapéutica a considerar en los pacientes con LMA FLT3 mutado.

Outpatient administration of BEAM conditioning prior to autologous stem cell transplantation for lymphoma is safe, feasible, and cost-effective.

High-dose BEAM chemotherapy (BCNU, etoposide, Ara-C, and melphalan) followed by autologous hematopoietic stem cell transplantation is frequently used as consolidative therapy for patients with recurrent or refractory Hodgkin or non-Hodgkin lymphoma. The BEAM regimen has traditionally been administered over 6 days in the hospital, with patients remaining hospitalized until hematologic recovery and clinical stability. In an effort to reduce the length of hospitalization for these patients, our institution has transitioned from inpatient (IP) to outpatient (OP) administration of BEAM conditioning. Here, we report the results of an analysis of the feasibility, cost, complications, and outcomes for the initial group of patients who received OP BEAM compared to a prior cohort of patients who received IP BEAM. Patient and disease characteristics were comparable for the two cohorts, as were engraftment kinetics. Length of hospital stay was reduced by 6 days for the OP cohort (P < 0.001), resulting in a cost savings of more than $17,000 per patient. Fewer complications occurred in the OP cohort, including severe enteritis (P = 0.01), organ toxicities (P = 0.01), and infections (P = 0.04). Overall survival rate up to 3 years posttransplant was better for the OP cohort (P = 0.02), likely due to differences in posttransplant therapies. We conclude that OP administration of BEAM conditioning is safe and may offer significant advantages, including decreased length of hospitalization, reduced costs, decreased risks for severe toxicities and infectious complications, and likely improvement in patient satisfaction and quality of life.

Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer.

OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.

Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer

OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.

Successful importation of cytarabine into the United States during a critical national drug shortage.

PURPOSE: The importation of cytarabine into the United States during a critical national drug shortage is described. SUMMARY: In March 2011, the hospital pharmacy team at an acute care hospital was struggling to supply cytarabine for four specific patients, all of whom needed critical maintenance therapy after induction. Cytarabine was not available from any source in the United States, and the team had no realistic projected release dates for back orders. Idis UK, a pharmaceutical distributor, was asked to identify available drug and eventually found an unrestricted source of cytarabine in Switzerland. Once available drug was identified, a price quote for the supply amount was written for our consideration. This was inspected carefully to ensure that the drug, strength, dosage form, and any other ingredients listed were indeed what were expected. The pharmacy department worked with the hospital's department of finance and accounting to submit the necessary financial paperwork. Payment was electronically sent to the distributor before the drug was shipped. Before the order for cytarabine was placed, the associated risks and benefits were assessed. The patients provided consent to treatment with the unapproved product. Acceptance of the price quote and instructions to order the drug were e-mailed to the distributor. The necessary documentation was completed and included with the shipment. The importation process, from initial inquiries to delivery, took 21 days. CONCLUSION: The importation of cytarabine amid a drug shortage required a complex process that involved the efforts of an overseas distributor, the cooperation of multiple health professionals, and meticulous attention to detail.

Analysis of efficacy and cost-effectiveness of high-dose arabinoside versus daunorubicin chemotherapy in older adult patients with acute myeloid leukemia by cytogenetic risk profile: retrospective review from China.

High-dose arabinoside (HiDAC) and daunorubicin (DNR)-based chemotherapy are the primary consolidation treatment options for older adults (50-60 years old) with acute myeloid leukemia in China. We analyzed the event-free survival (EFS) and hospital treatment charges of older adult patients with different cytogenetic risk profiles. In patients with a better/intermediate risk profile, the average total treatment cost of HiDAC was similar to that of DNR (P = 0.11). A 5-year follow-up of patients with better/intermediate cytogenetic risk profiles revealed that the median EFS of patients who received HiDAC was significantly longer than for patients who received the DNR-based regimen (27 vs. 20 months, P = 0.03). Average cost per year of life saved was 18,746.84 USD for HiDAC, compared to 32,733.37 USD for DNR. In contrast, for patients with a poor cytogenetic risk profile, the average total treatment cost for HiDAC was higher than for DNR (P < 0.005). In addition, the median EFS in the HiDAC protocol group was significantly lower than in the DNR group (11 vs. 20 months, P = 0.003). Meanwhile, in this risk group, the average cost per year of life saved was 103,237.70 USD compared to 32,277.93 USD, respectively, in the HiDAC and DNR regimens. We conclude that HiDAC is a more efficacious and cost-effective consolidation treatment regimen in the better/intermediate risk group, while the DNR-based regimen is more cost-effective in the poor risk group.

Cerebellar assessment for patients receiving high-dose cytarabine: a standardized approach to nursing assessment and documentation.

Cerebellar toxicity is a known potential adverse effect of high-dose cytarabine chemotherapy. Oncology nurses are expected to assess patients receiving high-dose cytarabine for cerebellar toxicity prior to administering each dose. Information regarding cerebellar assessment techniques and documentation of findings is limited in the nursing literature. This article provides nurses with a standardized approach for cerebellar function assessment and documentation of assessment finding for patients receiving high-dose cytarabine therapy.

Improved outcome for Chinese children with acute promyelocytic leukemia: a comparison of two protocols.

OBJECTIVE: Acute promyelocytic leukemia (APL) is now highly curable, except in many developing countries. Introduction of current treatment strategies may improve the outcome for children with APL in these countries. METHODS: The diagnosis was based on the FAB classification and detection of PML-RAR alpha rearrangement. From December 1999 to September 2004, 16 eligible children were treated with an intensive in-house protocol including high-dose AraC and anthracycline. Subsequently, 14 cases were treated with a less intensive protocol modified from the PETHEMA LPA99. RESULTS: The 3.5 years event-free survival (EFS) was 37.5% (95% CI, 13.8-61.2%) for patients treated on initial protocol. The treatment failures were: six patients abandoned treatment (37.5%), two who died of intracranial hemorrhage at diagnosis (6.3%) and sepsis in remission (6.3%) respectively, and two who relapsed (12.5%). Those treated on modified PETHEMA had a 3.5 years EFS of 79.6% (95% CI, 52.9-106.3%). Treatment failures included: one who died of intracranial hemorrhage at diagnosis (7.1%) and one who relapsed (7.1%). The patients on modified PETHEMA had a significantly higher EFS (P = 0.012), lower frequency of sepsis during treatment (7.7% vs. 77.8%; P = 0.0015), and lower hospitalization cost (median US$ 4,700 vs. US$ 20,000; P < 0.0001) than those on in-house protocol. CONCLUSION: Treatment with the less intensive protocol based on the PETHEMA LPA99 study of childhood APL successfully reduced chemotherapy toxicity and lowered hospitalization costs without increasing relapses. This led to decreases in treatment-related morbidity and the treatment abandonment rate, thus improving overall outcome.

[The results of a multicenter trial of acute lymphoblastic leukemia treatment on ALL-MB 91/ALL-BFM 90m in children: analysis of efficacy and toxicity].

AIM: A comparative analysis of efficacy and toxicity of two chemotherapy regimens: standard German protocol ALL-BFM 90m and less intensive original test protocol ALL-MB 91 in a multicenter trial of acute lymphoblastic leukemia (ALL) in children. MATERIAL AND METHODS: In 1995-2002 a total of 834 patients with newly diagnosed ALL aged 0-18 years were admitted to 10 clinics of Russia. Of them, 713 were randomized in two groups: treatment program ALL-BFM 90m (n = 355) and ALL-MB 91 program (n = 358). RESULTS: In 7-year follow-up median, 10-year event-free survival (EFS) and overall survival (OS) did not differ significantly between the groups and was 67 +/- 3 and 68 +/- 3% (ALL-MB 91) and 74 +/- 2, 71 +/- 3% (ALL-BFM 90m), respectively. Though the rate of isolated recurrences in CNS in patients on the protocol ALL-MB 91 was 2.8%, they developed only in 0.8% patients of the standard risk group. Anemia, thrombocytopenia and agranulocytosis developed less frequently, hospital stay was significantly shorter on the test protocol vs the control one (p < 0.01). CONCLUSION: EFS and OS on the test (ALL-MB 91) and control (ALL-BFM 90m) protocols were equivalent in lower toxicity and cost of therapy.