Is there a difference in childhood T-cell acute lymphoblastic leukaemia and T-cell lymphoblastic lymphoma?

To distinguish the similarities or differences between T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), we retrospectively analyzed the clinical, immunophenotypic, cytogenetic, and molecular characteristics in 37 children diagnosed between December 1990 and December 2003. Comparative Expressed Sequence Hybridisation (CESH) was used to determine gene expressing profile in both diseases. Twenty two patients suffered from T-ALL and 15 patients were diagnosed as T-LBL. Immunophenotyping demonstrated a more immature phenotype in T-ALL and a more mature phenotype in T-LBL. Cytogenetic and molecular genetic aberrations were found in 82% of T-ALL compared with 73% of T-LBL. By CESH gene expression profiling, the investigated cases were segregated into two groups that largely corresponded with T-ALL and T-LBL. The clinical presentation and cytogenetic characteristics are largely similar for T-ALL and T-LBL supporting the concept that both represent a spectrum of one single disease. The differences that were found between both neoplasms, in particular in their phenotype and in their expression profile may suggest that most T-ALL derive from a T-cell progenitor of the bone marrow, while thymocytes represent the normal counterpart of T-LBL.     

Do polymorphisms in ABC transporter genes influence risk of childhood acute lymphoblastic leukemia?

It is widely accepted that pathogenesis of childhood acute lymphoblastic leukemia (ALL) is related to the interplay between specific environmental exposure and inherited background. Major role of some members of the ATP-binding cassette (ABC) family of membrane transporters including MDR1 (ABCB1, P-glycoprotein) and breast cancer resistant protein (BCRP, ABCG2) is protection against environmental toxins. Here, we review several recent reports on potential association between single nucleotide polymorphisms (SNPs) in genes encoding for ABC transporters with predisposition to pediatric ALL.     

Is there a role for complementary therapy in the management of leukemia?

Patients with leukemia often seek additional treatments not prescribed by their oncologist in an effort to improve their cancer treatment outcome or to manage symptoms. Complementary therapies are used in conjunction with traditional cancer treatments to decrease symptoms and side effects associated with cancer or cancer treatment, and to improve patients’ overall quality of life. Complementary therapies are distinct from so-called ‘alternative’ therapies, which are unproven, ineffective and may postpone or interfere with mainstream cancer treatment. Complementary therapies are pleasant, inexpensive, nonpharmacologic and effective. For patients with leukemia, the complementary therapies that are always appropriate include mind–body interventions, such as self-hypnosis, meditation, guided imagery and breath awareness. Massage and reflexology (foot massage) decrease symptoms with effects lasting at least 2 days following treatment. Acupuncture is very beneficial for symptom management without adverse consequences. Physical fitness with regular exercise and healthy dietary habits can significantly decrease side effects of cancer treatments and may prolong survival. Botanical extracts and vitamin supplements may interfere with active cancer treatments, and should be discussed with the oncologist or pharmacist before use.     

Prognosis in childhood and adult acute lymphoblastic leukaemia: a question of maturation?

Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in characteristics and biology of adult versus childhood ALL might be the result of a different origin. According to the two-hit paradigm of Knudson, to develop cancer two genetic events are necessary. It has been suggested, that in childhood ALL the first genetic event happens in the more mature lymphoid committed progenitor cells, whereas in adult ALL the first hit occurs in multipotent stem cells. This review compares patient characteristics, the extent of the disease, leukaemic cell characteristics and treatment between childhood and adult ALL. This is discussed in relation to the hypothesis that the maturation stage of the cells, from which the leukaemia arises, is responsible for the differential behaviour of adult and childhood ALL.     

Can we incorporate geriatric assessment in the management of acute lymphoblastic leukemia in older adults?

Acute lymphoblastic leukemia (ALL) is an uncommon disease. Approximately 14% of new ALL cases occur in adults aged 60 and over, and the three-year overall survival in this population is poor at 12.8%. Older adults with ALL are heterogeneous in terms of their underlying health status, which can make treatment selection challenging given the disease rarity and limited inclusion of older patients in clinical trials. A comprehensive geriatric assessment (CGA) is a compilation of tools to assess multiple domains such as physical function and cognition, and may assist in guiding treatment selection and supportive care interventions. However, studies on the use of CGA are limited in older adults with ALL. In this review, we discuss the utility of CGA in patients with various hematologic malignancies. Using two patient cases of ALL, we also describe how CGA may be use to guide treatment and supportive care interventions.     

Asparaginase in the management of adult acute lymphoblastic leukaemia: Is it used appropriately?

Background

Whereas the disease free survival (DFS) continues to improve in paediatric acute lymphoblastic leukaemia (ALL), the prognosis of adult ALL has not altered significantly for last 2-3 decades. About 85% of children with ALL are leukaemia free at 5 years, but at best, only about 40% adults with ‘standard risk’ ALL remain in remission at that time. This is in spite of almost an equal proportion of adult patients achieving a complete remission as their much younger counterparts. Current data supports the efficacy of asparaginase in the treatment of ALL.

Purpose

This review focuses on the role of asparaginase in the management of adult acute lymphoblastic leukaemia (ALL). It examines the current use of this agent in this disease and the potential for optimising its application and monitoring of efficacy in treatment regimens.

Conclusion

Use of l-asparaginase has revolutionised the anti-leukaemia therapy in ALL. Early and sustained asparagine depletion, at least up to the first 30 weeks of therapy, appears to be crucial. Given the clear correlation between the depth of asparagine depletion and the patient outcome, asparaginase therapy should be monitored for adequate asparagine depletion for achievement of optimum results.     

Tobacco smoke and risk of childhood acute lymphoblastic leukemia: findings from the SETIL case–control study

Purpose

Tobacco smoke could cause childhood acute lymphoblastic leukemia (ALL) through at least three pathways: (1) prenatal parental smoking; (2) fetal exposure through maternal smoking during pregnancy; and (3) childhood exposure to secondhand smoke (SHS). We tested these hypotheses in a large population-based case–control study (SETIL) primarily designed to evaluate the role of electromagnetic fields in childhood hematopoietic malignancies.

Methods

From 1998 to 2003, we enrolled 602 incident cases of ALL from 14 Italian Regions, and 918 controls were individually matched by birthdate, sex, and area of residence. Cases (n = 557) and controls (n = 855) with complete information were analyzed; odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated with logistic regression models conditioned on matching variables and adjusted by birth order, birthweight, duration of breastfeeding, parental age at delivery, education, and occupational exposure to benzene.

Results

No evidence associating paternal smoking in the conception period or maternal smoking during the pregnancy with ALL was found. An association of ALL with maternal exposure to SHS during pregnancy (adjusted OR for mothers exposed more than 4 h/day = 2.18, 95 % CI 1.39–3.42) was observed, but recall bias cannot be excluded. Exposure of the children to SHS was associated with ALL only in unadjusted analysis (unadjusted OR for highly exposed children = 1.64; 95 % CI 1.10–2.45).

Conclusions

This study does not support the hypothesis that parental active smoking is associated with ALL. We found very weak evidence of increased risk of ALL for children exposed to SHS. Maternal exposure to SHS was associated with ALL, but recall bias is likely to inflate our estimates.     

Association of functional polymorphism at the miR-502-binding site in the 3′ untranslated region of the SETD8 gene with risk of childhood acute lymphoblastic leukemia,a preliminary report

MicroRNAs (miRNAs), a class of non-coding RNAs, bind to the 3′ untranslated regions (UTRs) of mRNAs, where they interfere with translation of genes and are implicated in the pathogenesis of diverse diseases. In the present study, we evaluate the impact of rs16917496 polymorphism within the miR-502 miRNA seed region at the 3′UTR of SEDT8 on childhood acute lymphoblastic leukemia (ALL). This case-control study was done on 75 ALL and 115 healthy children. Genotyping of rs16917496 C/T polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that CT as well as CT?+?TT decreased the risk of ALL in comparison with CC genotype (odds ratio (OR)?=?0.29, 95 % confidence intervals (95 % CI)?=?0.11–0.78, P?=?0.014 and OR?=?0.31, 95 % CI?=?0.12–0.82, P?=?0.016, respectively). Our results demonstrated that SETD8 rs16917496 C/T polymorphism was associated with decreased risk of developing pediatric ALL in Zahedan, southeast Iran. Larger studies with different ethnicities are desired to validate our findings.     

Maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia： a meta-analysis

Objective: The authors used a meta-analytic technique to quantify the evidence of an association between ma-ternal alcohol consumption during pregnancy and childhood acute leukemia (AL), which provided a basis for the prevention of childhood AL. Methods: Relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened. Subgroup meta-analysis was conducted according to the type of leukemia. Results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. Combined OR values and 95% CIs were statistically calculated with RevMan 4.2 software; Funnel plots were applied to conduct bias analysis for those included litera-tures. Results: Ten related literatures were included after data screening, 4593 cases in Al. group and 6157 cases in control group respectively. According to heterogeneity test result (χ2=16.26, P<0.05), the combined OR values and 95% Cl were calculated with random effects model, which were 1.02(0.92-1.14), Z=0.41, P=0.68 > 0.05, indicating that there was no significant difference between maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia (AL). Subgroup analysis: for the association between maternal alcohol consumption dudng pregnancy and childhood acute lympho-blastic leukemia (ALL), the combined OR value and 95% CI were 0.92 (0.84-1.00), Z=1.92, P=0.05, indicating that there was significant difference between two groups; for the association between maternal alcohol consumption during pregnancy and childhood acute non-lymphoblastic leukemia (ANLL), the combined OR values and 95% Cl were 0.82 (0.61-1.11), Z=1.30, P=0.19>0.05, indicating that there was no significant difference between two groups. Conclusion: Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in childhood ANLL.     

Central nervous system-directed therapy in the treatment of childhood acute lymphoblastic leukemia and studies of neurobehavioral outcome: children’s cancer group trials

Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) have improved due, in part, to the introduction and subsequent refinements in central nervous system (CNS)-directed therapy. Studies of cognitive, motor, and behavioral functioning, which characterize the patterns and severity of CNS sequelae, are being used increasingly as measurable treatment endpoints. This paper summarizes the advances in CNS-directed therapy derived from Children’s Cancer Group randomized therapeutic trials. Results from neurobehavioral outcome studies built upon these trials are also presented. A section of this review is focused on CNSdirected treatments and the neurodevelopmental outcomes of infants diagnosed with ALL, an especially high-risk patient subset. Future studies of neurobehavioral outcome are briefly elaborated in the context of current chemotherapy approaches used in the treatment of childhood ALL.     

Dexamethasone in the maintenance phase of acute lymphoblastic leukaemia treatment: Is the risk of lethal infections too high?

We report an increased incidence of infectious deaths during maintenance treatment of the ninth protocol for acute lymphoblastic leukaemia of the Dutch Childhood Oncology Group (DCOG-ALL-9). The main difference in maintenance treatment between DCOG-ALL-9 and the DCOG-ALL-7 and DCOG-ALL-8 protocols is the interruption of methotrexate and 6-mercaptopurine by vincristine (2mg/m(2) weekly) and dexamethasone (6mg/m(2) daily) for 14 days every 7 weeks in the DCOG-ALL-9 protocol. The 1107 children treated with the DCOG-ALL-7, DCOG-ALL-8 or DCOG-ALL-9 protocol were included and screened for infectious death during maintenance treatment (July 1988-July 2002). Seven of the 510 children died of severe infections during the maintenance phase of DCOG-ALL-9, compared to none of the 597 patients during the DCOG-ALL-7 and DCOG-ALL-8 protocols (1.37% versus 0.0%; p=0.013). Results from the current study suggest that repeated, prolonged exposure to dexamethasone results in an increase of lethal infections from 0% to 1.37%. In the dosing-schedule used, the advantage of dexamethasone may not outweigh the higher risk of infectious death.     

Pancreatitis during therapy of acute myeloid leukemia: Cytarabine related?

Background: Acute pancreatitis in acute myeloid leukemia (AML) has been rarely associated with cytarabine therapy. This report attempts to characterize this toxicity.Patients and methods: Criteria for pancreatitis was prospectively defined. Seven patients with pancreatitis were identified from an AML database and a clinical study at two tertiary care centers (n = 134). Their records were retrospectively reviewed.Results: Seven patients with pancreatitis complicating AML therapy were identified. Median age was 36 (range 25–73) years. Median amylase was 184 (range 77–552) U/l and median lipase was 1026 (range 630–6087) U/l. The patients had received high dose bolus cytarabine (2 g/m² i.v. bolus every 12 hours; n = 2), and continuous infusion cytarabine followed by high-dose cytarabine (100 mg/m² i.v. CI days 1–7 then 2 g/m² i.v. bolus every 12 hours days 8–10; n = 2), or standard dose continuous infusion cytarabine (200 mg/m²/d; n = 3) prior to developing pancreatitis. Pancreatitis occurred at a median of 10 days following day one of cytarabine administration with resolution at a median of 11 days after initial diagnosis. Six patients did not suffer major complications. One patient died of causes unrelated to pancreatitis. Five of six patients was rechallenged and all remained free of pancreatitis. One patient subsequently did develop pancreatitis on a later rechallenge.Conclusions: Pancreatitis in the setting of AML therapy may be an infrequent and self-limited toxicity of cytarabine. A schedule dependent toxicity with cytarabine was not identified.     

Is there a role for platinum chemotherapy in the treatment of patients with hormone‐refractory prostate cancer?

Docetaxel chemotherapy is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and carboplatin, have moderate single-agent activity in HRPC. Next-generation platinum drugs, including satraplatin and oxaliplatin, may have additional activity in the management of HRPC. Furthermore, neuroendocrine differentiation may play a role in disease progression, providing a rationale for platinum-based chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database for reports related to platinum-based chemotherapy in patients with advanced prostate cancer and evaluated studies that reviewed the role of neuroendocrine differentiation in the progression of HRPC. Older studies from the 1970s and 1980s suggested a lack of activity of cisplatin and carboplatin; however, those studies were flawed at least in part by their methods of response assessment. More recent Phase II studies of carboplatin suggested a moderate level of clinical and palliative activity when it was used as a single agent. However, when carboplatin was combined with a taxane and estramustine, high response rates were observed in several recent clinical trials. In addition, a randomized trial suggested that satraplatin plus prednisone improved progression-free survival compared with prednisone alone. For patients who progressed after docetaxel, no standard options existed in the literature that was reviewed. Several preliminary reports suggested that carboplatin and oxaliplatin may have activity as second-line chemotherapy. Platinum chemotherapy drugs historically have been considered inactive in HRPC, although a review of the data suggested otherwise. Carboplatin, in particular, induced very high response rates when it was combined with estramustine and a taxane, but it also appeared to have activity in patients who progressed after docetaxel. Satraplatin plus prednisone is being investigated in a large Phase III trial as second-line chemotherapy for HRPC. Targeting neuroendocrine cells may provide a new therapeutic approach to HRPC.