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Acute Lymphoblastic Leukaemia (acute + lymphoblastic_leukaemia)
Kinds of Acute Lymphoblastic Leukaemia Selected AbstractsMyelodysplastic syndrome transformed into Acute lymphoblastic leukaemia (FAB:L3)INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2006S. ZAININA Summary Myelodysplastic syndrome (MDS) is recognized as a preleukaemic disorder with a variable risk of transformation to acute myeloid leukaemia. Usually the blast cells in leukaemia are transformed after MDS displays a myeloid phenotype. Even though lymphoid progression had been reported previously, most displayed myeloid,lymphoid hybrid or early B phenotype. We report a case of an elderly man who had MDS transformed into Acute Lymphoblastic Leukaemia (ALL:L3) which is a rare lymphoid transformation. [source] AML with bilateral retinal detachmentACTA OPHTHALMOLOGICA, Issue 2007E SARKADY Purpose: To present a case of thrombotic ocular and CNS involvement complicating acute myeloid leukaemia (AML). Methods: A 42 year old woman developed blurred vision shortly after diagnosis and treatment of M6 AML. Investigations showed anterior orbital infiltration, retinal detachment and panuveitis. Iris biopsy and vitreous aspirate were negative. She developed right temporal lobe infarction and died following further CNS infarction two months after initial diagnosis. Results: Post mortem examination showed cerebral oedema, multiple cerebral infarctions and hepatosplenomegaly; both eyes contained vitreous exudates, retinal detachment and uveal thickening. Microscopy showed exudative and haemorrhagic retinal detachment, without inflammatory or neoplastic infiltrate, and bilateral uveal leukaemic infiltration with infarction. Neoplastic cells infiltrated the leptomeninges and brain parenchyma with focal vascular occlusion. Lung vessels were occluded by neoplastic cells. The spleen and bone marrow were heavily infiltrated. Partial immunophenotyping suggested a diagnosis of acute promyelocytic leukaemia (APL). Conclusions: Acute leukaemia involves the eye occurs in 39-53% cases. Visual loss is uncommon. Retinal involvement most frequently occurs in the form of superficial haemorrhages, detachment is uncommon. Acute lymphoblastic leukaemia (ALL) treated with L-asparaginase, acute promyelocytic leukaemia (APL) and non-M3 AML may present with a prothrombotic state which may be catastrophic, as occurred in this fatal case. [source] Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematologyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2009W. R. Sperr Abstract Background, Recent data suggest that tryptase, a mast cell enzyme, is expressed in neoplastic cells in myeloid leukaemias. In several of these patients, increased serum tryptase levels are detectable. Materials and methods, We have determined serum tryptase levels in 914 patients with haematological malignancies, including myeloproliferative disorders (n = 156), myelodysplastic syndromes (MDS, n = 241), acute myeloid leukaemia (AML, n = 317), systemic mastocytosis (SM, n = 81), non-Hodgkin,s lymphoma (n = 59) and acute lymphoblastic leukaemia (n = 26). Moreover, tryptase was measured in 136 patients with non-neoplastic haematological disorders, 102 with non-haematological disorders and 164 healthy subjects. Results, In healthy subjects, the median serum tryptase was 5·2 ng mL,1. Elevated serum tryptase levels were found to cluster in myeloid neoplasm, whereas almost all patients with lymphoid neoplasms exhibited normal tryptase. Among myeloid neoplasms, elevated tryptase levels (> 15 ng mL,1) were recorded in > 90% of patients with SM, 38% with AML, 34% with CML and 25% with MDS. The highest tryptase levels, often > 1000 ng mL,1, were found in advanced SM and core-binding-factor leukaemias. In most patients with non-neoplastic haematological disorders and non-haematological disorders analysed in our study, tryptase levels were normal, the exception being a few patients with end-stage kidney disease and helminth infections, in whom a slightly elevated tryptase was found. Conclusions, In summary, tryptase is a new diagnostic marker of myeloid neoplasms and a useful test in clinical haematology. [source] Extramedullary acute lymphoblastic leukaemia in childhoodEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007Julián Sevilla No abstract is available for this article. [source] Children and adults with acute lymphoblastic leukaemia have similar gene expression profilesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005E. Kuchinskaya Abstract:,Objectives:,To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis. Methods:,The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed using the oligonucleotide chip Hu95ver2a, produced by Affymetrix. Results:,Unsupervised hierarchical cluster analysis revealed that, in spite of differences in outcome, patients clustered irrespective of age, first by T-cell or B-precursor immunophenotype, and second by cytogenetic changes within the B-precursor group. The expression pattern analysis allowed the reclassification of some samples into the proper cytogenetic group. We also showed that separate clustering of samples with the BCR/ABL translocation could be explained by different breakpoint regions in the BCR. No significant difference in gene expression was observed between samples with and without CDKN2A deletion within the B-precursor group. Analysis of different age groups revealed a similarity in expression profiles when infants with the MLL translocation and adults over 40 yr of age were compared irrespective of karyotype. Conclusions:,In spite of the difference in clinical outcome, the gene expression pattern in children and adults with ALL is very similar and is primarily dependent on immunophenotype and cytogenetic aberrations. However, when age groups are compared, the expression patterns of infants and adults over 40 show a remarkable similarity. [source] Recurrent palmar,plantar erythrodysaesthesia following high-dose cytarabine treatment for acute lymphoblastic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2002Julie H. Crawford Abstract: Palmar,plantar erythrodysaesthesia (PPE) is an uncommon cutaneous complication of cytotoxic chemotherapy which generally presents as a painful erythema involving the palms and soles. It has been suggested that PPE caused by cytarabine does not recur with subsequent cytarabine re-challenge. We report a patient with recurrent, increasingly severe episodes of PPE, ultimately complicated by a severe bullous eruption, following successive cycles of high-dose cytarabine for the treatment of acute lymphoblastic leukaemia. Contrary to previous recommendations, our experience cautions against the further use of high-dose cytarabine in patients who develop PPE, and is a timely reminder of the potential toxicity of this agent, which is now increasingly being used as first-line treatment in the management of haematologic malignancies. [source] The use of ITS DNA sequence analysis and MALDI-TOF mass spectrometry in diagnosing an infection with Fusarium proliferatumEXPERIMENTAL DERMATOLOGY, Issue 11 2008Florian Seyfarth Abstract:, Although mycoses are among the most common diseases worldwide, infections with Fusarium spp. occur only rarely. Mostly patients suffering from underlying immune deficiency are infected with this mould, resulting in a considerably decreasing prognosis. In immunocompromised patients, cutaneous manifestations are more often associated with Fusarium sp. than with Candida sp. or Aspergillus sp. We describe one patient with acute lymphoblastic leukaemia, who was first treated with chemotherapy after GMALL protocol 07/03. After relapse, the patient was successfully transplanted in second remission with a human leukocyte antigen (HLA)-matched unrelated peripheral blood stem cell graft. Ten months later, the patient died from respiratory insufficiency and recurrence of leukaemia. Previously, Aspergillus antigen was detected in blood. In the latter course, disseminated papules appeared. One of these was examined histologically and mycologically. Conventional cultural diagnostics led to the diagnosis of a fusariosis, further supported by internal transcribed spacer (ITS) sequencing and matrix assisted laser desorption/ionisation,time-of-flight mass spectrometry (MALDI-TOF) mass spectrometry, both determining the isolated strain as Fusarium proliferatum, which is a very infrequent pathogen within this genus. Our investigations underline the potential of MALDI-TOF MS based identification of Fusarium species as an innovative, time and cost efficient alternative to ITS sequencing. [source] Engineering thermal stability of l- asparaginase by in vitro directed evolutionFEBS JOURNAL, Issue 6 2009Georgia A. Kotzia l- Asparaginase (EC 3.5.1.1, l- ASNase) catalyses the hydrolysis of l- Asn, producing l- Asp and ammonia. This enzyme is an anti-neoplastic agent; it is used extensively in the chemotherapy of acute lymphoblastic leukaemia. In this study, we describe the use of in vitro directed evolution to create a new enzyme variant with improved thermal stability. A library of enzyme variants was created by a staggered extension process using the genes that code for the l- ASNases from Erwinia chrysanthemi and Erwinia carotovora. The amino acid sequences of the parental l- ASNases show 77% identity, but their half-inactivation temperature (Tm) differs by 10 °C. A thermostable variant of the E. chrysamthemi enzyme was identified that contained a single point mutation (Asp133Val). The Tm of this variant was 55.8 °C, whereas the wild-type enzyme has a Tm of 46.4 °C. At 50 °C, the half-life values for the wild-type and mutant enzymes were 2.7 and 159.7 h, respectively. Analysis of the electrostatic potential of the wild-type enzyme showed that Asp133 is located at a neutral region on the enzyme surface and makes a significant and unfavourable electrostatic contribution to overall stability. Site-saturation mutagenesis at position 133 was used to further analyse the contribution of this position on thermostability. Screening of a library of random Asp133 mutants confirmed that this position is indeed involved in thermostability and showed that the Asp133Leu mutation confers optimal thermostability. [source] Spatial clustering of childhood cancer in Great Britain during the period 1969,1993INTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Richard J.Q. McNally Abstract The aetiology of childhood cancer is poorly understood. Both genetic and environmental factors are likely to be involved. The presence of spatial clustering is indicative of a very localized environmental component to aetiology. Spatial clustering is present when there are a small number of areas with greatly increased incidence or a large number of areas with moderately increased incidence. To determine whether localized environmental factors may play a part in childhood cancer aetiology, we analyzed for spatial clustering using a large set of national population-based data from Great Britain diagnosed 1969,1993. The Potthoff-Whittinghill method was used to test for extra-Poisson variation (EPV). Thirty-two thousand three hundred and twenty-three cases were allocated to 10,444 wards using diagnosis addresses. Analyses showed statistically significant evidence of clustering for acute lymphoblastic leukaemia (ALL) over the whole age range (estimate of EPV = 0.05, p = 0.002) and for ages 1,4 years (estimate of EPV = 0.03, p = 0.015). Soft-tissue sarcoma (estimate of EPV = 0.03, p = 0.04) and Wilms tumours (estimate of EPV = 0.04, p = 0.007) also showed significant clustering. Clustering tended to persist across different time periods for cases of ALL (estimate of between-time period EPV = 0.04, p =0.003). In conclusion, we observed low level spatial clustering that is attributable to a limited number of cases. This suggests that environmental factors, which in some locations display localized clustering, may be important aetiological agents in these diseases. For ALL and soft tissue sarcoma, but not Wilms tumour, common infectious agents may be likely candidates. © 2008 Wiley-Liss, Inc. [source] Health-related quality of life of children with acute lymphoblastic leukaemia: Comparisons and correlations between parent and clinician reportsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Elizabeth B. Waters Abstract The improving prognosis for children with cancer refocusses attention to long-term outcomes with an emphasis on quality of life. Few studies have examined relationships and differences in reported results between the parent, child and clinician. We examined parent-proxy and clinician-reported functional status and health-related quality of life for children and adolescents with acute lymphoblastic leukemia (ALL). Children and adolescents, 5,18 years, in the maintenance phase of treatment for ALL attending the Haematology/Oncology outpatient clinic at the Royal Children's Hospital, Melbourne, were eligible. Measures included: 1) parent-reported functional health and well-being (Child Health Questionnaire [CHQ]); 2) parent-reported condition specific quality of life (Pediatric Cancer Quality of Life inventory [PCQL]); 3) clinician ratings of physical and psychosocial health; and 4) clinical indicators. Insufficient numbers of older patients prohibited collection of adolescent self-reports. We had a 94% response and 31 participants. Mean time since diagnosis: 1.5 (SD 0.4) years. Parents reported significantly lower functioning and well-being than population norms for all CHQ scales, whereas cancer-specific quality of life was comparable to PCQL norms. Clinician reports of the child's global physical and psychosocial health were moderately associated with each other (rs = 0.56, p < 0.001), and with the parent-reported physical (rs = 0.47, p < 0.01) and psychosocial (rs = 0.56, p < 0.001) CHQ summary scores. Clinician reports of the child's psychosocial health were not associated with any clinical indicators reported regularly. The results demonstrate that the social, physical and emotional health and well-being of children with ALL is significantly poorer than the health of their community-based peers. Routinely collected indicators of clinical progress conceal the psychosocial burden of ALL. Data on health, well-being and quality of life can easily be incorporated into clinical care. © 2002 Wiley-Liss, Inc. [source] DNA Index in childhood acute lymphoblastic leukaemia: a karyotypic method to validate the flow cytometric measurementINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2010P. RACHIERU-SOURISSEAU Summary The DNA index (DI) is a prognostic factor in childhood acute lymphoblastic leukemia (ALL). The accuracy of DI measurement is important for treatment stratification: hyperdiploidy with DI , 1.16 is predictive of favorable prognosis whereas hypodiploidy is associated with poor prognosis. The aim of this study was to validate the accuracy of the DI measured by flow cytometry (FCM) by comparison with the karyotype. From samples of 112 childhood ALL, we created a formula to calculate a theoretical DNA index (tDI) based on the blast cell karyotype, taking into account the additional or missing chromosome material of the major clone. FCM DI correlated with tDI calculated from karyotype (R = 0.987) and with modal chromosome number (DI = 0.0202 × Modal NB + 0.0675 and R = 0.984). In three cases a hypodiploid blast cell population was detected by FCM, while only the duplicated clone was identified by the karyotype. The strong correlation between tDI and DI validates the accuracy of FCM quantification, which is technically fast on fresh or frozen samples. If the karyotype is essential to analyze chromosomal abnormalities, FCM provides complementary information in aneuploid ALLs, either by confirming the cytogenetic data or by detecting additional clones not identified when only using cytogenetic data. [source] Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean populationINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2006M. HUR Summary Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. We investigated the association between MTHFR polymorphisms and the risks of acute and chronic leukaemias. MTHFR C677T and A1298C were genotyped in 396 Korean individuals using multiplex polymerase chain reaction/restriction fragment-length polymorphism. They were acute lymphoblastic leukaemia (ALL, n = 89), acute myeloid leukaemia (AML, n = 55), biphenotypic acute leukaemia (n = 12), chronic myelogenous leukaemia (CML, n = 40), and normal controls (n = 200). C677T genotypes were not associated with the risk of each disease. A1298C variants, however, significantly decreased the risks of ALL and CML compared with 1298AA. Odds ratios and 95% confidence intervals of 1298AC and 1298AC + CC were 0.53 (0.31,0.93) and 0.54 (0.31,0.93) in ALL, and 0.34 (0.14,0.80) and 0.40 (0.18,0.89) in CML, respectively, compared with 1298AA. These findings demonstrate that the development of ALL and CML is more dependent on folate status, and more susceptible to DNA instability than that of AML. In addition, A1298C rather than C677T may be a more important genetic risk modifier in leukaemogenesis at least in the Korean population. [source] Leukaemic infiltration of the mandible in a young girlINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 2 2007RACHAEL E. BENSON Background., This report presents a case of leukaemic infiltration of the mandible in a 10-year-old female of Sudanese extraction. Case report., The patient was in remission from acute lymphoblastic leukaemia when she presented with pain localized to the alveolar ridge overlying the unerupted lower right second permanent molar. Two days later, she developed right inferior alveolar nerve paraesthesia. Radiographic imaging demonstrated cortical line absence around the developing lower right second and third permanent molars, and distal displacement of the lower right third molar. In addition, the cortical outline of the right inferior dental canal lacked clarity. Biopsy confirmed leukaemia recurrence demonstrating the Philadelphia chromosome. Tailored chemotherapy was commenced, and a bone marrow transplant was carried out 12 weeks later. At 6-month dental review, the patient remained exceptionally well with no bone pain and normal sensation in the right lower lip. Conclusion., The importance of regular and long-term dental examination of patients with leukaemia is discussed. [source] O -acetylation of GD3 prevents its apoptotic effect and promotes survival of lymphoblasts in childhood acute lymphoblastic leukaemiaJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2008Kankana Mukherjee Abstract We have previously demonstrated induction of O -acetylated sialoglycoproteins on lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). These molecules promote survival of lymphoblasts by preventing apoptosis. Although O -acetylated sialoglycoproteins are over expressed, the status of O -acetylation of gangliosides and their role in lymphoblasts survival remains to be explored in ALL patients. Here, we have observed enhanced levels of 9- O -acetylated GD3 (9- O -AcGD3) in the lymphoblasts of patients and leukaemic cell line versus disialoganglioside GD3 in comparison to the normal cells. Localization of GD3 and 9- O -AcGD3 on mitochondria of patient's lymphoblasts has been demonstrated by immuno-electron microscopy. The exogenous administration of GD3-induced apoptosis in lymphoblasts as evident from the nuclear fragmentation and sub G0/G1 apoptotic peak. In contrast, 9- O -AcGD3 failed to induce such apoptosis. We further explored the mitochondria-dependent pathway triggered during GD3-induced apoptosis in lymphoblasts. GD3 caused a time-dependent depolarization of mitochondrial membrane potential, release of cytochrome c and 7.4- and 8-fold increased in caspase 9 and caspase 3 activity respectively. However, under identical conditions, an equimolar concentration of 9- O -AcGD3 failed to induce similar effects. Interestingly, 9- O -AcGD3 protected the lymphoblasts from GD3-induced apoptosis when administered in equimolar concentrations simultaneously. In situ de- O -acetylation of 9- O -AcGD3 with sodium salicylate restores the GD3-responsiveness to apoptotic signals. Although both GD3 and 9- O -acetyl GD3 localize to mitochondria, these two structurally related molecules may play different roles in ALL-disease biology. Taken together, our results suggest that O -acetylation of GD3, like that of O -acetylated sialoglycoproteins, might be a general strategy adopted by leukaemic blasts towards survival in ALL. J. Cell. Biochem. 105: 724,734, 2008. © 2008 Wiley-Liss, Inc. [source] Should TPMT genotype and activity be used to monitor 6-mercaptopurine treatment in children with acute lymphoblastic leukaemia?JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2007M. Fakhoury PharmD PhD Summary Background and objective: The activity of thiopurine S -methyltransferase (TPMT), a key enzyme in the metabolism of purine analogues, displays wide inter-subject variability partly due to a genetic polymorphism. Previous studies have suggested adjusting purine analogues dosing according to TPMT activity but measurements are costly and time-consuming. It is still unclear, especially under treatment, whether the simpler TPMT genotyping reliably predicts enzyme activity. Our aim was to study the possible correlation of TPMT genotype with phenotype. Methods: We determined the genotypic status and TMPT activity, at diagnosis and after 6 months of maintenance therapy, of 118 children with acute lymphoblastic leukaemia (ALL). Results and Discussion: Eighty-nine per cent of the children had a homozygous wild-type genotype (group 1), 11% had one or two mutant allele(s) (group 2). At both time points, TPMT activity (U/mL peripheral red blood cell) was significantly higher in group 1 than in group 2 (P < 0·001) but inter-group levels overlapped considerably. There was considerable heterogeneity in the percentage increase in TPMT activity after therapy, and little correlation between metabolites ratio [6-methylmercaptopurine derivative/6-thioguanine nucleotides (6-TGN)] and TPMT activity at the end of 6 months' maintenance treatment. These results show that TPMT activity cannot be used as an accurate tool for 6-mercaptopurine monitoring. Conclusion: Genotyping at diagnosis identifies patients with a homozygous mutant TPMT and may prevent severe and life-threatening toxicity. ALL treatment monitoring should preferentially be based on repeated determinations of intracellular active metabolites (6-TGN) and methylated metabolites. [source] High-dose cytosine arabinoside-induced cutaneous reactionsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2002P Cetkovská Abstract Background High-dose cytosine arabinoside (HDAC) is being used increasingly to treat haematological malignancies. The therapy is associated with various non-haematological negative side-effects, frequently involving the skin. Objective Our aim was to evaluate the actual occurrence of adverse skin reactions to HDAC over the 10-year period from 1989 to 1999. Methods One hundred and seventy-two subjects, 118 with acute myelogenous leukaemia and 54 with acute lymphoblastic leukaemia, between 16 and 71 years of age were treated with 226 post-remission consolidation regimens with HDAC (54 subjects underwent two cycles of treatment). Treatment was combined with standard doses of other cytotoxic drugs. A prospective study of the skin changes was then performed. Results The overall incidence of cutaneous reactions was almost 53%, with rashes occurring in 72.7% and 40.6% of subjects who received total doses of 30 and 24 g/m2, respectively. In the group of subjects who received a second cycle of treatment not all of those who experienced exanthema after the first cycle (44.4%) experienced this reaction after the second cycle (only 33.3%). The most commonly observed reactions were morbilliform eruptions on the trunk and extremities and acral erythema, although severe reactions with swelling and generalized urticaria developed in some cases. Conclusions HDAC-induced cutaneous reactions in 53% of subjects. The skin changes were found to be dose related and most cleared spontaneously without requiring treatment. A clinical grading of cutaneous toxicity has been proposed to allow better comparison of cutaneous adverse effects in different reports. [source] Mucormycotic pseudoaneurysm of the common carotid artery with tracheal involvementMYCOSES, Issue 4 2008S. Hashemzadeh Summary Mucormycosis is an emerging and fatal fungal infection. A high index of suspicion and the knowledge of its potential manifestations are essential for early diagnosis. We describe a patient with acute lymphoblastic leukaemia (L2 subtype) who developed a neck mass following a course of induction chemotherapy. Doppler ultrasonography and angiography of the neck revealed a pseudoaneurysm of the right common carotid artery. The patient then developed haemoptysis. Surgical exploration revealed a necrotic right common carotid artery with anteromedial pseudoaneurysm and adjacent tracheal wall perforation. Local debridement and tracheal repair were performed. Nonseptate hypheal invasion (mucormycosis) was found on the microscopic examination of the excised arterial wall. A subsequent recurrence of pseudoaneurysm was treated with local surgical debridement and intravenous amphotericin B (Fungizone) administration. Although rare, clinicians should be aware of these possible presenting features of mucormycosis as early diagnosis and treatment may potentially improve the survival. [source] Oral mucositis in acute lymphoblastic leukaemia: analysis of 169 paediatric patientsORAL DISEASES, Issue 8 2008SLC Figliolia Chemotherapy-induced oral mucositis is a frequent therapeutic challenge in cancer patients. The purpose of this retrospective study was to estimate the prevalence and risk factors of oral mucositis in 169 acute lymphoblastic leukaemia (ALL) patients treated according to different chemotherapeutic trials at the Darcy Vargas Children's Hospital from 1994 to 2005. Demographic data, clinical history, chemotherapeutic treatment and patients' follow-up were recorded. The association of oral mucositis with age, gender, leucocyte counts at diagnosis and treatment was assessed by the chi-squared test and multivariate regression analysis. Seventy-seven ALL patients (46%) developed oral mucositis during the treatment. Patient age (P = 0.33), gender (P = 0.08) and leucocyte counts at diagnosis (P = 0.34) showed no correlation with the occurrence of oral mucositis. Multivariate regression analysis showed a significant risk for oral mucositis (P = 0.009) for ALL patients treated according to the ALL-BFM-95 protocol. These results strongly suggest the greater stomatotoxic effect of the ALL-BFM-95 trial when compared with Brazilian trials. We concluded that chemotherapy-induced oral mucositis should be systematically analysed prospectively in specialized centres for ALL treatment to establish the degree of toxicity of chemotherapeutic drugs and to improve the quality of life of patients based on more effective therapeutic and prophylactic approaches for prevention of its occurrence. [source] Vitamin supplement use among children with Down's syndrome and risk of leukaemia: a Children's Oncology Group (COG) studyPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 3 2008Cindy K. Blair Summary Vitamin supplements have been proposed for children with Down's syndrome (DS) with claims of improving cognitive abilities, or immune or thyroid function. Several studies have shown decreased levels of zinc in this population. Because children with DS have a 50-fold increased risk of developing acute leukaemia during the first 5 years of life, we explored the relation between child vitamin and herbal supplement use and the risk of leukaemia in a case-control study. During the period 1997,2002, we enrolled 158 children with DS aged 0,18 years that were diagnosed with acute lymphoblastic leukaemia (ALL) (n = 97) or acute myeloid leukaemia (AML) (n = 61) at participating Children's Oncology Group institutions. We enrolled 173 DS children without leukaemia (controls), selected from the cases' primary care clinic and frequency-matched on age. Data were collected via telephone interviews with mothers of the index child regarding use of multivitamins, zinc, vitamin C, iron and herbal supplements, including age at first use, frequency and duration. Among controls, 57% reported regular multivitamin use (,3 times/week for ,3 months) compared with 48% of ALL cases and 61% of AML cases. We found no evidence of an association between children's regular multivitamin use and ALL or AML (adjusted odds ratios [OR] = 0.94 [95% CI 0.52, 1.70] and 1.90 [0.73, 4.91] respectively). There was a suggestion of an increased risk for AML associated with regular multivitamin use during the first year of life or for an extended duration (ORs = 2.38 [0.94, 5.76] and 2.59 [1.02, 6.59] respectively). Despite being the largest study of DS-leukaemia, our sample size was small, resulting in imprecise effect estimates. Future research should include larger sample sizes as well as a full assessment of diet including vitamin supplementation to adequately examine the relation between nutritional status and childhood leukaemia. [source] Allergy and infectious disease histories and the risk of childhood acute lymphoblastic leukaemiaPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2 2005Paula F. Rosenbaum Summary Infectious disease histories were evaluated in a population-based case-control study of childhood acute lymphoblastic leukaemia (ALL) as it has been hypothesised that delays in early infections are associated with an increased risk of disease. Allergy histories were also assessed as part of a broader evaluation of the role of immune factors in ALL. Cases (n = 255) were diagnosed between 1980 and 1991 at one of four referral centres in a 31-county area of New York State; controls (n = 760) were a random sample of live births from the same region, frequency matched to cases by sex, race and birth year. Data were collected by mailed questionnaire, completed by case and control parents in 1995. Allergy and infectious histories before the age at leukaemia diagnosis for cases and an equivalent age for controls were evaluated. The adjusted odds ratio and 95% confidence interval [CI] associated with a positive history of any allergy was 0.58 [95% CI 0.38, 0.88] compared with a negative allergy history. The occurrence of several common childhood illnesses before 25 months of age and ALL were assessed, with both weak positive and weak inverse associations observed. Overall, these analyses provide little support for the hypothesis that infection delay in early life is associated with an increased risk of ALL. Children with positive allergy histories reported significantly more infections than those with negative histories; however, effect modification of the infection-ALL associations by child allergy history was not observed. Nonetheless, these observations suggest the importance of assessing both allergy and infectious histories and their possible interactions when evaluating the association between these immune factors and childhood ALL. [source] Vincristine-induced vocal cord paralysis in an infantPEDIATRIC ANESTHESIA, Issue 2 2002DORALINA L. ANGHELESCU MD We report the development of stridor and dysphagia in a 5-month-old-infant with acute lymphoblastic leukaemia after the administration of four weekly doses of vincristine during induction therapy. Because direct laryngoscopy revealed bilateral vocal cord paralysis, the patient underwent elective intubation. Extubation was performed 7 days later, after direct laryngoscopy confirmed recovery of vocal cord mobility. Vincristine-induced bilateral recurrent laryngeal nerve paralysis is a rare but potentially life-threatening complication. Therefore, it should be suspected when stridor is present, and clinicians should consider visualization of the airway to establish the cause of upper airway compromize in infants receiving vincristine. [source] Childhood acute lymphoblastic leukaemia in relation to population mixing around the time of birth in South HungaryPEDIATRIC BLOOD & CANCER, Issue 7 2006John C. Taylor MSc No abstract is available for this article. [source] DHFR 19-bp insertion/deletion polymorphism and MTHFR C677T in adult acute lymphoblastic leukaemia: Is the risk reduction due to intracellular folate unbalancing?,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Donato Gemmati First page of article [source] Itraconazole-enhanced vindesine neurotoxicity in adult acute lymphoblastic leukaemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2007Suning Chen No abstract is available for this article. [source] Parental communication and children's behaviour following diagnosis of childhood leukaemiaPSYCHO-ONCOLOGY, Issue 4 2005Sally-Ann Clarke Many parents find decisions about what to tell their child with cancer difficult. Open communication is generally considered the best policy and most health care professionals encourage parents to talk openly and honestly about the illness. However, parents differ in their views about what to tell the child. In this study 55 parents of children (36 boys and 19 girls, mean age = 7.33 years) newly diagnosed with acute lymphoblastic leukaemia (ALL) were interviewed about (i) the child's reactions and behaviour following diagnosis, (ii) their views about what to tell their child and (iii) factors influencing parents' communication with the child. Interviews were analysed using thematic analysis. Most children showed behavioural and mood difficulties after diagnosis. Older children were given more information. In addition, parents' perceptions of childhood cancer affect the way they communicate with their child. These findings may be used to inform training packages in order to facilitate improved communication amongst health professionals. Copyright © 2004 John Wiley & Sons, Ltd. [source] Are children of older fathers at risk for genetic disorders?ANDROLOGIA, Issue 4 2003A. Jung Summary. Genetic risks related to paternal age should be of interest to clinical andrologists counselling older men who wish to father a child. Theoretically, the number of (pre-meiotic) mitotic cell divisions during spermatogenesis and their remarkable increase with ageing compared with oogenesis would be in favour of genetic risks for the offspring of older men. But for numerical and structural chromosomal anomalies, such an influence of paternal age has not been found. However, in several autosomal dominant disorders affecting three specific genes (fibroblast growth factor receptor 2 and 3, RET proto-oncogene) the risk for a child to be affected increases with paternal age at time of birth. For other autosomal dominant ,X chromosomal dominant or recessive disorders, the available data are sufficient to support the concept of a positive relationship between paternal age and de novo gene mutations. Studies analysing gene sequences of affected children and their parents would allow further evaluation of this topic. The impact of paternal age on disorders with a complex genetic background, however, is a matter of debate. A significant effect of paternal age could not be shown for nonfamilial Alzheimer's disease, congenital heart defects, nonfamilial schizophrenia, acute lymphoblastic leukaemia or prostate cancer. [source] Structure of Helicobacter pyloril -asparaginase at 1.4,Ĺ resolutionACTA CRYSTALLOGRAPHICA SECTION D, Issue 12 2009Prathusha Dhavala Bacterial l -asparaginases have been used in the treatment of childhood acute lymphoblastic leukaemia for over 30,years. Their therapeutic effect is based on their ability to catalyze the conversion of l -asparagine, an essential amino acid in certain tumours, to l -aspartic acid and ammonia. Two l -asparaginases, one from Escherichia coli and the other from Erwinia chrysanthemi, have been widely employed in clinical practice as anti-leukaemia drugs. However, l -asparaginases are also able to cause severe side effects owing to their intrinsic glutaminase activity. Helicobacter pyloril -asparaginase (HpA) has been reported to have negligible glutaminase activity. To gain insight into the properties of HpA, its crystal structure in the presence of l -aspartate was determined to 1.4,Ĺ resolution, which is one of the highest resolutions obtained for an l -asparaginase structure. The final structure has an Rcryst of 12.6% (Rfree = 16.9%) with good stereochemistry. A detailed analysis of the active site showed major differences in the active-site flexible loop and in the 286,297 loop from the second subunit, which is involved in active-site formation. Accordingly, Glu289, Asn255 and Gln63 are suggested to play roles in modulating the accessibility of the active site. Overall, the structural comparison revealed that HpA has greater structural similarity to E. colil -asparaginase than to any other l -asparaginase, including Er. carotovoral -asparaginase, despite the fact that the latter is also characterized by low glutaminase activity. [source] An isocratic fluorescence HPLC assay for the monitoring of l -asparaginase activity and l -asparagine depletion in children receiving E. colil -asparaginase for the treatment of acute lymphoblastic leukaemiaBIOMEDICAL CHROMATOGRAPHY, Issue 2 2009Christa E. Nath Abstract A novel assay for the determination of l -asparaginase activity in human plasma is described that is based on the HPLC quantitation of l -aspartic acid produced during enzyme incubation. Methods for monitoring l -asparagine depletion are also described. Chromatography of l -aspartic acid, l -asparagine and l -homoserine (the internal standard) involved derivatization with o -pthaldialdehyde, then separation from other amino acids on a Phenomenex Luna C18 column using a 1 mL/min flow rate and a mobile phase consisting of di-potassium hydrogen orthophosphate propionate buffer, pH 6, with 10% methanol and 10% acetonitrile. Fluoresence detection was at excitation/emission wavelengths of 357/455 nm. Under these conditions l -aspartic acid, l -asparagine and l -homoserine had retention times of 3.5, 9.8 and 17.7 min, respectively. The l -asparaginase assay was linear from 0.1 to 10 U/mL activity and interday precision and accuracy were less than 13%. The limit of quantitation was approximately 0.03 U/mL. The assay utility was established in 12 children who received E. colil -asparaginase as treatment for acute lymphoblastic leukaemia. Copyright © 2008 John Wiley & Sons, Ltd. [source] O -acetylated sialic acids: Multifaceted role in childhood acute lymphoblastic leukaemiaBIOTECHNOLOGY JOURNAL, Issue 3 2009Suchandra Chowdhury Abstract Childhood acute lymphoblastic leukaemia (ALL), a malignant transformation of the lymphoblasts, is highly responsive to chemotherapy. However, due to certain inadequacy in detection of minimal residual disease (MRD), relapse is a common phenomenon. To address this question, the present review deals with the induction of an unique O -acetyl derivative of sialic acid on a few disease-associated glycoproteins and glycolipids at the onset of childhood ALL, a finding of our group in the last decade. This information has been successfully utilized for diagnosis and prognosis of the disease. Existing literature is included for comparison. Additionally, cell surface overexpression of 9- O -acetylated sialoglycoproteins and antibodies against them present in patients' sera aid the survival of the malignant lymphoblasts and suggest a multifaceted role played by these molecules. Taken together, monitoring these molecules helps not only in unravelling the biology of this paediatric malignancy but also in personalizing the treatment strategies for the betterment of the patient population. [source] Human thiopurine methyltransferase activity varies with red blood cell ageBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2001L. Lennard Aims, Inherited differences in thiopurine methyltransferase (TPMT) activity are an important factor in the wide interindividual variations observed in the clinical response to thiopurine chemotherapy. The aim of this study was to establish a population range for red blood cell (RBC) TPMT activity in children with acute lymphoblastic leukaemia (ALL) at disease diagnosis. An additional aim was to investigate factors that can influence TPMT activity within the RBC. Methods,Blood samples were collected from children with ALL at disease diagnosis, prior to any blood transfusions, as part of the nationwide UK MRC ALL97 therapeutic trial. RBC TPMT activity was measured by h.p.l.c. RBCs were age-fractionated on Percoll density gradients. Results,Pretreatment blood samples were received from 570 children within 3 days of venepuncture. TPMT activities at disease diagnosis ranged from 1.6 to 23.6 units/ml RBCs (median 7.9) compared with 0.654,18.8 units (median 12.9), in 111 healthy control children (median difference 4.5 units, 95% CI 3.9, 5.1 units, P < 0.001). A TPMT quality control sample, aliquots of which were assayed in 60 analytical runs over a 12 month period, contained a median of 11.98 units with a CV of 11.6%. Seven children had their RBCs age-fractionated on density gradients. TPMT activities in the top gradient (young cells) ranged from 4.2 to 14.1 units (median 7.5) and in the bottom gradient (old cells) 1.5,12.6 units (median 4.7 units), median difference 2.3 units, 95% CI 0.7, 4.1, P = 0.035. Conclusions,Circulating RBCs do not constitute a homogeneous population. They have a life span of around 120 days and during that time undergo a progressive ageing process. The anaemia of ALL is due to deficient RBC production. The results of this study indicate that RBC TPMT activities are significantly lower in children with ALL at disease diagnosis. This may be due, at least in part, to a relative excess of older RBCs. [source] | |||||||||||||||||||||||||||||||||||||