Fixed price contracts: the case of pediatric acute lymphoblastic leukemia

This paper describes a new type of hospital contract. It is a contract made with payers and represents an attempt to tackle the issues of cost-containment, physicians' dissatisfaction with control over their practise, cost-effective care and quality of care. The case chosen for this attempt is pediatric acute lymphoblastic leukemia. The basis for setting the price of treatment is the division of the illness into episodes of care that correspond to medical events. There is a fixed fee schedule for each episode, and this fee schedule covers all the expenditures incurred during the episode. The fee schedule is fixed at the onset of the disease and depends solely on medical risk factors. Physicians can use the combination of resources they consider best for their patients and hospital management must find a cost-effective way to provide the required care. The advantage to patients is that they no longer have to obtain payers' agreement but receive state-of-the-art treatment in a teaching hospital.     

Health-related quality of life and utility scores in short-term survivors of pediatric acute lymphoblastic leukemia

Purpose

Increase of survival in pediatric acute lymphoblastic leukemia (ALL) has made outcomes such as health-related quality of life (HRQL) and economic burden more important. To make informed decisions on the use of healthcare resources, costs as well as utilities need to be taken into account. Among the preference-based HRQL instruments, the Health Utilities Index (HUI) is the most employed in pediatric cancer. Information on utility scores during ALL treatment and in long-term survivors is available, but utility scores in short-term survivors are lacking. This study assesses utility scores, health state, and HRQL in short-term (6 months to 4 years) ALL survivors.

Methods

Cross-sectional single-center cohort study of short-term ALL survivors using HUI3 proxy assessments.

Results

Thirty-three survivors (median 1.5 years off treatment) reported 14 unique health states. The majority of survivors (61 %) enjoyed a perfect health, but 21 % had three affected attributes. Overall, HRQL was nonsignificantly lower compared to the norm, although the difference was large and may be clinically relevant. Cognition was significantly impaired (p = 0.03).

Conclusion

Although 61 % of short-term survivors of ALL report no impairment, the health status of the other patients lead to a clinically important impaired HRQL compared to norms. Prospective studies assessing utility scores associated with pediatric ALL should be performed, enabling valid and reliable cost-utility analyses for policy makers to make informed decisions.     

左旋门冬酰胺酶治疗急性淋巴细胞白血病患儿的护理研究

目的探讨应用左旋门冬酰胺酶(L-Asp)治疗急性淋巴细胞白血病患儿的不良反应及护理对策。方法总结分析18例急性淋巴细胞白血病(ALL)患儿应用L-Asp的不良反应,并针对性落实相应的护理措施。结果不良反应发生率为65%,其中低蛋白血症5例,凝血障碍8例,肝功能异常7例,使用L-Asp前谷丙转氨酶(ALT)平均45 U/L,用后平均128 U/L。血象异常16例,用药前后差异有统计学意义。结论用药前后加强监测及病情观察,及时对症处理,能缓解及减轻患儿用药后的不良反应,促进疾病康复,提高生存质量。     

Post-therapy profile of serum total cholesterol, retinol and zinc in pediatric acute lymphoblastic leukemia and non-Hodgkin's lymphoma

OBJECTIVE: To assess serum albumin, total cholesterol, retinol, zinc and hemoglobin in children who had completed treatment for acute lymphoblastic leukemia (ALL) and Non-Hodgkin's lymphoma (NHL). METHODS: The above parameters were analyzed in 105 ALL and NHL and 108 age and sex-matched controls. Serum albumin, serum cholesterol and hemoglobin were estimated by colorimetric methods. Serum retinol was estimated by HPLC and serum zinc was estimated by atomic emission spectrophotometer (ICP-AES). Comparisons were made to stage of treatment (maintenance 6 with post-therapy), type of treatment (chemotherapy and radiation with only chemotherapy) and type of malignancy (ALL with NHL). RESULTS: Only serum albumin in patients included at Maintenance(6) was significantly higher (t = 2.31, p = 0.05) than post-therapy patients. No significant difference in serum values was observed by type of treatment. Only total cholesterol was significantly higher in NHL patients than in ALL patients (t = 1.954, p = 0.05). Patients had comparable serum levels to that of controls. However, in patients and controls more than 75% children had deficient serum retinol levels, (< than 0.6989 micromol/l, or 20 microg/dl). Further, 75% patients and 54.7% controls had serum retinol levels less than 0.3439 micromol/l or 10 microg/dl. CONCLUSION: The results of the present study indicate that cancer and its treatment did not have any long-lasting effect on serum albumin, total cholesterol, retinol, zinc and hemoglobin. Majority of subjects had low serum retinol suggestive of depleted liver reserves. The deficient serum retinol levels (< than 0.6989 micromol/l, or 20 microg/dl) in at least 75% of the patients and controls probably reflect poor dietary intake. A higher percentage of patients with low serum retinol levels may also be attributed to the possibility of urinary losses of retinol that occur during episodes of infection while on immunosuppressive anti-cancer drug therapy.     

Month of birth in childhood acute lymphoblastic leukemia

INTRODUCTION: An association between date of birth influenced by certain environmental factors (such as virus infections) and malignant diseases has been suggested in some previous papers. AIMS AND METHODS: The authors analyzed the birth dates of 814 children, 0-18 years of age, in whom acute lymphoblastic leukemia was diagnosed in the period between the 1st of January 1988 and 31st of December 2000. RESULTS: No association between month of birth and manifestation of leukemia in Hungarian children could be established. CONCLUSION: The results suggest that this approach was not capable of detecting any obvious prenatal environmental factors, including virus endemics, that could have influenced the appearance of leukemia.     

Parental prenatal smoking and risk of childhood acute lymphoblastic leukemia

The association between parental smoking and risk of childhood acute lymphoblastic leukemia (ALL) was investigated in an Australian population-based case-control study that included 388 cases and 868 controls aged <15 years, recruited from 2003 to 2006. Both of the child's parents provided information about their smoking habits for each year from age 15 years to the child's birth. Data were analyzed by logistic regression. Maternal smoking was not associated with risk of childhood ALL, but the odds ratio for paternal smoking of ≥15 cigarettes per day around the time of the child's conception was 1.35 (95% confidence interval: 0.98, 1.86). The associations between parental smoking risk of childhood ALL did not differ substantially by immunophenotypic or cytogenetic subtype. Meta-analyses of paternal smoking, including results from the Australian Study of Causes of Acute Lymphoblastic Leukemia in Children and those of previous studies, produced summary odds ratios of 1.15 (95% confidence interval: 1.06, 1.24) for any paternal smoking around the time of the child's conception and 1.44 (95% confidence interval: 1.24, 1.68) for smoking ≥20 cigarettes per day at that time. Study results suggest that heavier paternal smoking around the time of conception is a risk factor for childhood ALL. Men should be strongly encouraged to cease smoking, particularly when planning to start a family.     

Maternal herpesvirus infections and risk of acute lymphoblastic leukemia in the offspring

A critical role for infection in the etiology of childhood leukemia has repeatedly been suggested. The authors undertook a case-control study nested within national maternity cohorts with altogether 7 million years of follow-up to assess the relative role of three maternal herpesvirus infections in childhood acute lymphoblastic leukemia (ALL). Offspring of 550,000 mothers in Finland and Iceland formed the joint study cohort that was followed up for cancer in the offspring before age 15 years during 1975-1997 through national cancer registries. For each index mother-case pair, three or four matched control mother-control pairs were identified from national population registers. First-trimester sera were retrieved from mothers of 342 ALL and 61 other leukemia cases and from 1,216 control mothers and were tested for antibodies to cytomegalovirus, Epstein-Barr virus (EBV), and human herpesvirus 6. Serum EBV DNA was also analyzed. Conditional logistic regression-based estimates of relative risk (odds ratio) adjusted for birth order and sibship size, and population attributable fractions, were calculated. Only EBV immunoglobulin M positivity in EBV-immunoglobulin-G-positive mothers was associated with a highly significant increased risk of ALL in the offspring (adjusted odds ratio = 2.9, 95% confidence interval: 1.5, 5.8). Results indicate that reactivation of maternal EBV infection is probably associated with childhood ALL.     

Health-related quality of life assessment in Indonesian childhood acute lymphoblastic leukemia

Background  

Most studies on Health-related Quality of Life (HRQOL) in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL) patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL.     

Intrachromosomal amplification of AML1 gene in childhood acute lymphoblastic leukemia

The introduction of routine molecular cytogenetic assays enabled us to reveal hitherto unknown genetic disorders of childhood acute leukemias. Of special interest is the recognition of those rare cytogenetic mutations of negative prognostic value, which are associated with well-known markers of good prognosis. In our present study we review a novel cytogenetic mutation typical for childhood B-cell ALL, the intrachromosomal amplification of chromosome 21, which requires high-risk therapy irrespective of other risk factors, and which is associated with a cryptic 12;21 translocation of good prognostic value.     

Epidemiologic,clinical and cytohematologic characteristics of adult acute lymphoblastic leukemia in Tunisia

Through a national retrospective study, the authors report the clinical and hematological characteristics of 124 acute lymphoblastic leukemia of the adult diagnosed during 5 years (1993-1997). The national prevalence is of 0.28/100.000 inhabitants/year. The sex-ratio is of 1.3. Sixty six per cent of patients were 16-35 years of age, and only 10% of them were more than 60 years of age. A tumoral syndrome was present at 71% of the cases with peripheral adenopathies in 55%, splenomegaly in 40%, hepatomegaly in 19% and a mediastinal tumor in 18% of the cases. The bone pain were rarely signaled (10%) and neuro-meningeal affection was found in only 3% of cases. There was no testicular lesions. The white blood cells count was less than 30.000/mm3 in 60% whereas an important hyperleucocytosis superior than 100.103/mm3 was observed in 20% of the cases. Anemia and thrombopenia were noted in 94% and 90% of the cases respectively. Acute lymphoblastic leukemia typing by cytological study of Bone marrow according to the Fransh-American-Britain criteria (FAB) had found 43%, 48% and 4% for type 1,2 and 3 respectively. In 5% of the cases the type of the acute lymphoblastic leukemia was not precised (diagnosis based on the Bone biopsy).     

Acute promyelocytic leukemia with t(15;17): a case study

Acute promyelocytic leukemia (APL with t15;17) is a disease characterized by abnormal proliferation of promyelocytic cells in the peripheral blood and bone marrow, along with coagulopathy and thrombocytopenia. It is a variation of AML that frequently exhibits a typical chromosomal translocation. Laboratory analysis and confirmatory testing for the fusion gene make diagnosis and treatment of APL with t(15;17) possible.     

细胞自噬在急性淋巴细胞白血病化疗中的作用

目的以紫杉醇处理的Jurkat细胞为模型,研究细胞自噬在儿童急性淋巴细胞白血病化疗过程中的作用。方法 10μg/ml的紫杉醇处理人急性T淋巴细胞白血病Jurkat细胞后,免疫印迹和流式细胞技术检测LC3β蛋白的表达变化,WST-1法检测PTX对Jurkat细胞的抑瘤率。结果 PTX处理Jurkat细胞0h、24h、48h后,抑瘤率分别为(4.2±1.2)%、(46.7±5.3)%、(65.9±9.4)%,组间比P均小于0.05;LC3β的平均荧光强度相对倍数分别(3.1±0.2)倍、(4.6±0.31)倍、(34.2±4.5)倍,组间比P值均小于0.05,与抑瘤率一样呈现时间依赖性增强;免疫印迹也显示PTX处理24h和48h后,LC3β的蛋白表达逐渐增强。结论细胞自噬在ALL化疗过程中活化,可导致化疗抵抗。     

儿童急性淋巴细胞白血病和急性粒细胞白血病发病初期微量元素及营养相关蛋白的变化

目的 探讨儿童急性淋巴细胞白血病和急性粒细胞白血病发病初期某些微量元素及营养相关蛋白的变化。方法应用原子吸收光谱法、散射比浊法、干化学法和化学发光法等,对73例急性淋巴细胞白血病和I26例急性粒细胞白血病发病初期的患儿血清铜、锌、铁、镁、磷、钙、铜蓝蛋白、铁蛋白、转铁蛋白、乳酸脱氧酶、总蛋白、白蛋白、血红蛋自含量和红细胞数量等指标进行检测,并与30名正常儿童相比较,运用t检验分析两个发病组和正常对照组之间这些指标的变化。结果发病组与对照组相比,除锌和磷含量的差异无统计学意义外,其余指标的差异均有统计学意义（P〈0．05）,发病组的铜、镁、铁、铁蛋白、铜蓝蛋白和乳酸脱氯酶含量显著高于对照组（P〈0．05）,而钙、转铁蛋白、总蛋白、白蛋门、血红蛋门含晕和红细胞数量显著低于对照组（P〈0．05）。急性淋巴细胞白血病与急性粒细胞白血病相比,在铁及铜锌代谢的相关指标方面的差异有统计学意义（P〈0．05）。结论儿童急性淋巴细胞白血病和急性粒细胞白血病发病初期,血清中一些微量元素与营养相关蛋白含量与正常状态相比,发生紊乱,失去平衡。     

Childhood acute lymphoblastic leukemia: genetic determinants of susceptibility and disease outcome

The origin of acute lymphoblastic leukemia (ALL), the most common pediatric cancer, can be explained by a combination of genetic factors and environmental exposure. The environmental toxicants to which an individual is exposed are biotransformed and eliminated from the body after metabolic conversion mediated by Phase I and Phase II xenobiotic-metabolizing enzymes. Phase I enzymes catalyze hydroxylation, reduction and oxidation reactions of xenobiotics (carcinogens/drugs), often converting them into more active or toxic compounds. Phase II enzymes catalyze conjugation reactions (glucuronidation, acetylation, methylation), thereby converting the metabolites into non-reactive, water-soluble products that are eliminated from the organism. The genetic polymorphism underlying the variation in enzyme activity can modify susceptibility to diverse adult cancers, probably by influencing the activation and removal of toxicants or drugs. Here we present an overview of the role of genetic variants of certain Phase I and Phase II enzymes in the development of childhood ALL, a good model for such studies because of its short latency period. The genetic contribution to the development of ALL is examined by association studies that analyze the loci of Phase I enzymes (cytochrome P-450, myeloperoxidase) and Phase II enzymes (quinone-oxidoreductase, glutathione-S-transferase, N-acetyltransferase). The loci of the enzyme variants CYPlA1, CYP2E1, NQO1, GSTM1, GSTP1, NAT2 are associated with disease development, and evidence of gene-gene interactions has emerged as well. Despite the improvements in treatment, resistant cases of ALL remain a leading cause of cancer-related death in children. Although the underlying mechanism of drug resistance is not well understood, differences in the capacity of ALL patients to process drugs and environmental carcinogens could play a role by modifying the risk of recurrent malignancy, as well as the response to therapy. Therefore, polymorphic genes encoding carcinogen- and drug-metabolizing enzymes may not only increase the risk of ALL but also influence the risk of relapse in patients. We found that the prognosis of patients with CYPlA1 and NQO1 variants was worse than that of patients who lack these variants. We conclude that genotyping ALL patients for functional polymorphisms of candidate genes can become an important tool in predicting disease outcome.