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ALL Patients (all + patient)
Selected AbstractsGenetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemiaENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2004Renata Canalle Abstract Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. Although exposure to environmental agents appears to predispose individuals to this disease, little attention has been paid to the role of genetic susceptibility to environmental exposures in the etiology of childhood ALL. The enzymes GSTM1, GSTT1, GSTP1, CYP1A1, and CYP2E1 are involved in the bioactivation and detoxification of a variety of xenobiotics present in food, organic solvents, tobacco smoke, drugs, alcoholic drinks, pesticides, and environmental pollutants. Polymorphisms in the genes coding for these enzymes have been associated with increased susceptibility to different cancers, including hematologic malignancies. To investigate whether these polymorphisms represent risk-modifying factors for childhood ALL, a study was conducted involving 113 Brazilian patients of childhood ALL and 221 controls with similar ethnic backgrounds. The data revealed that carriers of the rare GSTP1 Val allele were at higher risk of ALL (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.1,6.8; P = 0.04). No difference was found in the prevalence of the GSTM1 and GSTT1 null genotypes between ALL patients and the controls, and no association was found between CYP1A1*2 and CYP2E1*3 variants and ALL. However, when the mutant CYP1A1 and CYP2E1 alleles were considered together with the GSTM1 and GSTP1 risk-elevating genotypes, the risk of ALL was increased further (OR = 10.3; 95% CI = 1.0,111.8; P = 0.05), suggesting a combined effect. These results imply that genetic variants of xenobiotic metabolizing genes influence the risk of developing childhood ALL. Environ. Mol. Mutagen. 43:100,109, 2004. © 2004 Wiley-Liss, Inc. [source] Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007Juan-Manuel Sancho Abstract Background and aim:,Only 20,30% of elderly patients with acute lymphoblastic leukemia (ALL) are enrolled in clinical trials because of co-morbid disorders or poor performance status. We present the results of treatment of Philadelphia chromosome-negative (Ph,) ALL patients over 55 yr treated in the PETHEMA ALL-96 trial. Patients and methods:,From 1996 to 2006, 33 patients 55 yr with Ph, ALL were included. Induction therapy was vincristine, daunorubicin, prednisone, asparaginase, and cyclophosphamide over 5 weeks. Central nervous system (CNS) prophylaxis involved triple intrathecal (IT) therapy, 14 doses over the first year. Consolidation-1 included mercaptopurine, methotrexate, teniposide and cytarabine, followed by one consolidation-2 cycle similar to the induction cycle. Maintenance consisted of mercaptopurine and methotrexate up to 2 yr in complete remission (CR) with monthly reinduction cycles (vincristine, prednisone and asparaginase) during the first year. Results:,Median (range) age was 65 yr (56,77). Phenotype (30 patients): early-pre-B 7, common/pre-B 18, T 5. Cytogenetics (28 patients): normal 12, complex 10, t(4;11) 2 and other 4. CR was achieved in 19/33 (57.6%) patients, early death occurred in 12 (36.4%) and 2 (6%) were resistant. Overall survival and disease-free survival probabilities (2 yr, 95% CI) were 39% (21%,57%) and 46% (22%,70%), respectively (median follow up of 24 months). Removal of asparaginase and cyclophosphamide from the induction decreased induction death (OR 0.119, CI 95% 0.022,0.637, P = 0.013) and increased survival (20% vs. 52%, P = 0.05). Conclusions:,The prognosis of elderly Ph, ALL patients is poor. In this study, less intensive induction decreased toxic death, allowing delivery of planned consolidation therapy and increased survival probability. [source] Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: Poor prognosis and prenatal originGENES, CHROMOSOMES AND CANCER, Issue 10 2010Jan Zuna The ETV6/ABL1 (TEL/ABL) fusion gene is a rare aberration in malignant disorders. Only 19 cases of ETV6/ABL1 -positive hematological malignancy have been published, diagnosed with chronic myeloid leukemia, other types of chronic myeloproliferative neoplasm, acute myeloid leukemia or acute lymphoblastic leukemia (ALL). This study reports three new cases (aged 8 months, 5 years, and 33 years) of ALL with the ETV6/ABL1 fusion found by screening 392 newly diagnosed ALL patients (335 children and 57 adults). A thorough review of the literature and an analysis of all published data, including the three new cases, suggest poor prognosis of ETV6/ABL1 -positive acute leukemias. The course of the disease in the two pediatric patients is characterized by minimal residual disease monitoring, using quantification of both the ETV6/ABL1 transcript and immunoreceptor gene rearrangements. Eosinophilia could not be confirmed as a hallmark of the ETV6/ABL1 -positive disease. Studies of neonatal blood spots demonstrated that, in the child diagnosed at five years, the ETV6/ABL1 fusion initiating the ALL originated prenatally. © 2010 Wiley-Liss, Inc. [source] High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9GENES, CHROMOSOMES AND CANCER, Issue 8 2006Anne R. M. von Bergh The t(7;12)(q36;p13) is a recurrent translocation involving the ETV6/TEL gene (12p13) and a heterogeneous breakpoint at 7q36. A fusion transcript between HLXB9 and ETV6 in AML with t(7;12) is occasionally found. To study the incidence of t(7;12) in infant and childhood acute leukemia, we screened 320 cases <36 months using FISH. Additionally, 28 pediatric cases >36 months with cytogenetic breakpoints at 12p and 7q were investigated. We studied the presence of an HXLB9-ETV6 fusion transcript and quantified the expression of various genes located in the 7q36 breakpoint region. In total, six AML patients carried the t(7;12) of which five were infants and one child of 18 months. Only one out of 99 infant ALL patients harbored the t(7;12). No t(7;12) was found in older children with AML or ALL. AML patients carrying a t(7;12) had a poor outcome with a 3-year EFS of 0%. A fusion of HLXB9 to ETV6 was found in four AML cases with t(7;12). The 7q36 genes NOM1, LMBR1, RNF32, and SHH were equally expressed among t(7;12)-positive AML versus t(7;12)-negative AML, t(7;12)-negative ALL, or normal bone marrow. However, the HLXB9 expression was highly increased in t(7;12)-positive cases, including those with an HLXB9-ETV6 fusion. We conclude that the t(7;12) is almost exclusively present in infant AML and covers 30% of infant AML, while it is extremely rare in infant ALL and older children. The t(7;12) is associated with a poor outcome and an ectopic expression of HLXB9 is commonly involved in this genetic subtype of leukemia. © 2006 Wiley-Liss, Inc. [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] The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatmentJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2005V. DE STEFANO Summary.,Background:,Thromboembolism can occur during acute leukemia, especially acute lymphoid leukemia (ALL) treated with l -asparaginase. Yet, most reports are anecdotical and scarce data are available on the risk of thrombosis in acute myeloid leukemia (AML). Objectives:,To evaluate the risk of thrombosis in patients with acute leukemia. Patients and methods:,Three-hundred and seventy-nine consecutive adult patients with newly diagnosed acute leukemia were recruited in an observational cohort study conducted from January 1994 to December 2003. Diagnosis was ALL in 69 patients, acute promyelocytic leukemia (APL; FAB subtype M3) in 31, and non-M3 AML in 279. All first or recurrent symptomatic thromboembolic events objectively diagnosed were recorded. Results:,Twenty-four patients of the overall 379 (6.3%; 95% CI 4.1%,9.2%) had a first thrombosis, venous in 80% of the cases and arterial in 20%. At diagnosis, thrombosis was a presenting manifestation in 13 cases (3.4% of the whole cohort): 1.4% in ALL, 9.6% in APL, and 3.2% in non-M3 AML patients. Follow-up was carried out on 343 patients without thrombosis at diagnosis and further 11 thrombotic events (3.2%) were recorded. At 6 months from diagnosis, the cumulative incidence of thrombosis was 10.6% in ALL, 8.4% in APL, and 1.7% in non-M3 AML patients. The patients who received l -asparaginase had a 4.9-fold increased risk of thrombosis in comparison with those who did not (95% CI 1.5,16.0). The fatality rate due to thrombosis was 0.8%. Conclusions:,In patients with acute leukemia, the risk of thrombosis is not negligible. Thombosis can be a presenting symptom at diagnosis in a significant portion of cases with APL (9.6%) and non-M3 AML (3.2%); a similar rate of thrombosis can occur during the subsequent course of the disease. The incidence of symptomatic thrombosis at diagnosis is relatively low in ALL patients (1.4%), but is significantly increased by further treatment up to 10.6%. Strategies of antithrombotic prophylaxis should be investigated in this setting. [source] Successful Application of OPLS-DA for the Discrimination of Wild-Type and Mutated Cells in Acute Lymphoblastic LeukemiaMOLECULAR INFORMATICS, Issue 8 2009Claudio, Giuseppe Molteni Abstract OPLS-DA was successfully applied to select of a limited number of gene transcripts necessary to discriminate wild type and mutated cells in ALL patients. In the above list it was possible to identify candidate genes that could be involved in the molecular mechanisms linking PTPN11 and RAS mutations to B-ALL genesis. OPLS-DA and SIMCA classification provide a set of 50 and 77 variables respectively suitable to discriminate wild type from mutated cells in ALL patients. [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] Prevalence of abnormal bone density of pediatric patients prior to blood or marrow transplantPEDIATRIC BLOOD & CANCER, Issue 4 2009Kathryn J. Klopfenstein MD Abstract Osteoporosis and osteopenia are long-term side effects of bone marrow transplant (BMT). The purpose of this study was to determine the prevalence of bone mineral density (BMD) abnormalities in pediatric patients prior to BMT. Forty-four pediatric patients were evaluated with DEXA scans. The average Z -score was ,0.37. Thirty-six percent had abnormal BMD. Sixty-seven percent of ALL patients had abnormal BMD. Patients with non-malignant diseases were significantly more likely to have abnormal BMD. Patients with ALL had more defects than solid tumor patients. Females had more defects than males. These results demonstrate BMD defects are common in children prior to BMT, especially in patients with ALL. Pediatr Blood Cancer 2009;53:675,677. © 2009 Wiley-Liss, Inc. [source] Total body bone measurements: A cross-sectional study in children with acute lymphoblastic leukemia during and following completion of therapyPEDIATRIC BLOOD & CANCER, Issue 1 2009Kara M. Kelly MD Abstract Background Abnormalities in bone mineral density (BMD) occur in children treated for acute lymphoblastic leukemia (ALL). However, BMD estimates have been performed using varied instruments, reference data, and interpretations. This exploratory cross sectional study to evaluate bone mass in children with ALL, uses an algorithm that serially adjusts for variables known to affect pediatric bone measures by dual energy X-ray absorptiometry (DXA), based on models developed in 1,218 healthy children and adolescents. Procedure Anthropometry, DXA scans, and factors with possible influence on bone mass were evaluated in 21 ALL patients receiving chemotherapy and 20 in the follow-up phase. Main outcome was treatment group differences in Z -scores for total body bone mineral content (BMC), bone area (Area), and areal BMD (aBMD). Results Mean Z -scores for the entire study population for BMC, Area, and aBMD were significantly less than zero. Among possible contributing factors, only calcium intake was a significant co-variate. Comparison between treatment groups showed that least-square mean Z -scores for patients on-therapy for at least 12 months were significantly lower than those off therapy for at least 12 months (P: 0.0008,0.044), except for BMC at last step of the algorithm (adjusted for sex, age, ethnicity, height, weight, and bone area). Conclusions Evaluation of total body DXA by this algorithm is consistent with better general bone status in those off-therapy. However, in this small exploratory study, the lack of significant difference between Z -scores for fully adjusted BMC in on- versus off-therapy groups suggests possible risk of low peak bone mass. Additional longitudinal evaluation is warranted. Pediatr Blood Cancer 2009;52:33,38. © 2008 Wiley-Liss, Inc. [source] Randomized study comparing 4,-epi-doxorubicin (Epirubicin) versus doxorubicin as a part of induction treatment in adult acute lymphoblastic leukemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2002Manisha Bhutani Abstract Doxorubicin or daunorubicin are routinely used to induce remission in acute lymphoblastic leukemia (ALL). Efficacy of epirubicin (an analog of doxorubicin), however, has not been adequately evaluated in ALL management. This randomized study was undertaken to compare the relative efficacy of epirubicin vs. doxorubicin as part of induction chemotherapy in adult ALL. Between January 1990 and June 1998, 79 previously untreated adult ALL patients (age 11,55 years, median 20 years) were randomized to receive either doxorubicin (Group A, n = 39) or epirubicin (Group B, n = 40) as a part of induction therapy. Vincristine and prednisolone were common in each group. The induction treatment was followed by identical consolidation and maintenance therapy. The two groups were compared as regards pretherapy clinical and laboratory parameters, dose intensity of therapy, therapeutic efficacy, myelotoxicity, and survival. Epirubicin was as effective as doxorubicin in terms of complete remission rate (80% vs. 78.3%; P = 0.87) and relapse rate (57.1% vs. 51.7%; P = 0.68). Five-year overall survival (30% vs. 30%, P = 0.98) and disease-free survival (40% vs. 39%, P = 0.92) at median follow-up of 68 months was also similar in the two groups. The incidence of Grade 4 myelotoxicity was comparable in the two groups. Patients 20 years of age or less had better CR rates (90% vs. 65%; P = 0.011) and median overall survival (39 vs. 11 months; P = 0.008) compared to those who were older. From this study epirubicin appears as effective as doxorubicin as part of induction therapy for adult ALL. However, the results need to be validated on the basis of immunophenotype and cytogenetic prognostic characterization. Am. J. Hematol. 71:241,247, 2002. © 2002 Wiley-Liss, Inc. [source] Comprehensive flow cytometry phenotype in acute leukemia at diagnosis and at relapseAPMIS, Issue 5 2010XIN LI Li X, Du W, Liu W, Li X, Li H, Huang S-A. Comprehensive flow cytometry phenotype in acute leukemia at diagnostic and at relapse. APMIS 2010; 118: 353,59. Multiparameter flow cytometry (MFC) plays a vital role in the detection of minimal residual disease (MRD) and diagnosis of relapse in acute leukemia. However, application of a limited panel of antibodies in MFC leads to high rates of false-negative and false-positive results. Thirteen patients with acute lymphoblastic leukemia (ALL) and 12 patients with acute myeloid leukemia (AML) were immunophenotyped by MFC at diagnosis and at relapse using a comprehensive panel of monoclonal antibodies (McAbs) to 27 antigens and CD45/SSC gating. In 23 of 25 patients (92.3%), changes in at least one of progenitor-associated, myeloid and lymphoid antigens between diagnosis and relapse were observed. Antigen changes were observed in 92 of 239 antigens (38.5%) expressed in 25 patients, in 49 of 117 antigens (41.9%) expressed in 13 ALL patients, and in 43 of 122 antigens (35.2%) expressed in 12 AML patients. Phenotypic changes were characterized by the expression of cross-lineage antigens. The intralineage change was observed in the majority of patients. However, myeloid lineage shift was identified by MFC in two patients with T-ALL. Multiple panels of three or more McAbs are likely to be required in the monitoring of MRD and diagnosis of relapse in acute leukemia by MFC. [source] Acute leukemia: Diagnosis improved by flow cytometry in addition to morphologyASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Manju SENGAR Abstract Aims: Immunophenotyping using flow cytometry (FCM) has become an essential component of acute leukemia (AL) diagnosis. This study evaluated the judicious application of FCM as an adjunct to well-informed morpho-cytochemical assessment in patients with acute leukemia. Methods: 100 untreated patients with AL were studied using morpho-cytochemistry and immunophenotyping through FCM. Results: There were 29 patients with acute myeloid leukemia (AML), 47 with B-acute lymphoblastic leukemia (ALL), 20 with T-acute lymphoblastic leukemia (ALL) and four with biphenotypic acute leukemia (BAL). Morpho-cytochemistry without FCM could provide definite diagnosis only in the AML cases. It failed to provide definite diagnosis in ALL patients. Over half (55%) of ALL patients were given the noncommittal label, AL. The remaining 45% patients were labeled a more definite, probable ALL. Conclusion: FCM thus had a role to play in ALL patients to confirm a definite and a probable diagnosis, to define therapeutically and prognostically groups such as B and T lineage ALL and to distinguish AML , M0 from ALL. FCM helps in diagnosing AML cases as well, but is a less essential mode of investigation in this group purely from the perspective of the therapy regime. But its role in defining different subgroups in AML is its major use. While morpho-cytochemistry provides a first-line investigation of great therapeutic value, and more so in AML, it needs to be supplemented by flow cytometry, particularly in ALL. [source] Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapyBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2008Masamitsu Yanada Summary The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0·800 and P = 0·964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2·9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect. [source] Identification of transcripts modulated by ETV6 expressionBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Gino Boily Summary Deletions at chromosome 12p12-13 are observed in 26,47% of childhood pre-B acute lymphoblastic leukaemia (ALL) cases, suggesting the presence of a tumour suppressor gene (TSG). Accumulating genetic and functional evidence points to ETV6 as being the most probable TSG targeted by the deletions. ETV6 is a ubiquitously expressed transcription factor of the ETS family with very few known targets. To understand its function and to elucidate the impact of its absence in leukaemia, we conducted a study to identify targeted genes. Following the induction of ETV6 expression, global expression was evaluated at different time points. We identified 87 modulated genes, of which 10 (AKR1C1, AKR1C3, IL18, LUM, PHLDA1, PTGER4, PTGS2, SPHK1, TP53 and VEGF) were validated by real-time quantitative reverse transcription-polymerase chain reaction. To assess the significance of the validated candidate genes in leukaemia, their expression patterns were determined, as well as that of ETV6, in pre-B ALL patients. The expression of IL18, LUM, PTGER4, SPHK1 and TP53 was significantly correlated with that of ETV6, further suggesting that ETV6 could regulate the expression of these genes in leukaemia. This work constitutes another step towards the understanding of the functions of ETV6 and the impact of its inactivation in childhood leukaemia. [source] P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003Maria Ilaria Del Principe Summary. Concurrent resistance mechanisms, such as P-glycoprotein (PGP) and bcl-2, may contribute to a worse outcome in adult acute lymphoblastic leukaemia (ALL). Between 1990 and 2000, we analysed PGP and bcl-2 by flow cytometry, using two anti-PGP (C219 and JSB-1) monoclonal antibodies (mAbs) and an anti-bcl-2 mAb in 115 de novo adult ALL patients. Both a longer overall survival (OS) and longer disease-free survival (DFS) were observed in PGP-negative patients (23%vs 0% at 3 years, P = 0·011 and 29%vs 0% at 2 years, P = 0·006 for C219 respectively; 42%vs 0% at 1·5 years, P = 0·004 and 53%vs 0% at 8·5 months, P = 0·00006 for JSB-1 respectively). Bcl-2 positivity was associated with a significantly higher complete remission rate (90%vs 66%, P = 0·01). Moreover, in 69 patients not presenting with either t(9;22) or B-mature immunophenotype, PGP negativity (JSB-1) maintained its significant favourable prognostic impact with regard to OS (41%vs 0% at 1·5 years, P = 0·009) and DFS (83%vs 0% at 6 months, P = 0·0005). Importantly, within a subset of 62 patients with normal (n = 31) or unknown (n = 31) karyotype, PGP (JSB-1)-negative patients showed both a significantly longer OS and DFS (63%vs 0% at 1·4 years, P = 0·018 and 84%vs 0% at 6 months, P = 0·001 respectively). In multivariate analysis, JSB-1 (P = 0·008) and cytogenetics (P = 0·02) were found to be independent prognostic factors with regard to DFS. Therefore, in adult ALL, PGP and bcl-2 represent sensitive indicators of clinical outcome, and potential targets of novel molecules aimed at overcoming chemoresistance and recurrent relapses. [source] L-asparaginase as a marker of chemotherapy dose modification in children with acute lymphoblastic leukemiaCANCER, Issue 12 2005Jacques Baillargeon Ph.D. Abstract BACKGROUND The objective of the current study was to compare chemotherapy dose modifications in obese (a body mass index [BMI] > 95%) and nonobese (a BMI , 95%) pediatric patients with acute lymphoblastic leukemia (ALL). METHODS The study cohort was comprised of 199 pediatric patients diagnosed with ALL who were treated at 1 of 2 South Texas pediatric oncology centers between 1990,2000. The relative chemotherapy dose modification during the induction phase of chemotherapy was calculated as the ratio of 1) the actual administered dose of L-asparaginase and 2) the protocol-calculated dose of L-asparaginase. The extent to which the chemotherapy dose modification varied according to obesity status was assessed using stratified Student t tests and an ordinary least-squares regression analysis. RESULTS Obese ALL patients were found to exhibit a 7% decrease in the mean relative modification of L-asparaginase during induction chemotherapy compared with their nonobese counterparts. This finding was statistically significant (P = 0.009), even after adjustment for gender, age, ethnicity, and clinical institution. CONCLUSIONS To the authors' knowledge, the current study is the first published report of an obesity-associated chemotherapy dose modification in pediatric patients with ALL, the most common childhood malignancy. It will be important to examine whether these findings are consistent with those observed in future studies, and ultimately to assess the association between obesity-related dose modifications and long-term cancer outcomes. Cancer 2005. © 2005 American Cancer Society. [source] Can the Use of the Radial Artery Be Expanded to All Patients with Different Surgical Grafting Techniques?JOURNAL OF CARDIAC SURGERY, Issue 1 2005Angiographic Results in 600 Patients, Early Clinical Encouraged by our satisfactory early experience with the use of the RA conduit, we have expanded its use to more than 90% of all coronary surgery patients. The aim of the present study was to review our clinical and angiographic results when the use of the RA conduit was expanded to all patients including those aged 65 years and older and diabetics with different surgical grafting techniques. Methods: The records of 600 consecutive patients who underwent isolated CABG using the RA graft at Harefield Hospital between January 1999 and August 2002 were reviewed retrospectively. Ninety-three (15.5%) patients consented and underwent angiography before discharge at the earliest on the fourth postoperative day, aiming to look at the quality of anastomoses and the patency of the RA grafts. Results: The 600 patients had 613 RA grafts to perform 652 distal RA anastomoses. The proximal ends of 515 (84%) RA grafts were anastomosed to the aorta, 98 (16%) RA grafts were constructed as Y-grafts with 49 (8%) RA off a vein graft hood, and 49 (8%) RA grafts were constructed as T- or Y-grafts off an internal thoracic artery (ITA) graft. The proximal ends of 19 (19/294 or 6.5%) vein grafts were constructed as Y-grafts off the RA grafts. Two hundred and sixty-one (43.5%) patients were above the age of 65 years and 111 (18.5%) patients were diabetics. There were four in-hospital deaths (0.6%) among the study patients. Six (1%) patients developed forearm hematoma/seroma postoperatively. The operation time, the hospital stay, and the incidence of conduit harvest site infection for the patients who had vein grafts in addition to the RA grafts were significantly higher than those of patients who had RA grafts only. On postoperative angiography, 86 out of 93 (92.5%) RA grafts were found to be patent with good quality distal anastomoses. The maximum stenosis of the coronary arteries bypassed by the patent 86 RA grafts was 82.6 ± 6.2%, while it was 56.3 ± 15.4% for the coronary arteries bypassed by the occluded seven RA grafts, p < 0.001. Conclusion: The use of the RA can be expanded to all patients with different surgical grafting techniques and provides satisfactory clinical and angiographic outcomes. [source] Should the Concentration of Vitamin D Be Measured in All Patients With Hypertension?JOURNAL OF CLINICAL HYPERTENSION, Issue 3 2010Angela Boldo MD First page of article [source] Eyelid Tightening and Improved Eyelid Aperture through Nonablative Fractional ResurfacingDERMATOLOGIC SURGERY, Issue 11 2008SEAN A. SUKAL MD BACKGROUND AND OBJECTIVE The effects of fractional resurfacing on eyelid tightening and aperture are unknown. Our purpose was to retrospectively examine the potential for eyelid tightening and eye-aperture opening in patients treated with nonablative fractional resurfacing for facial photorejuvenation. STUDY DESIGN/MATERIALS AND METHODS Fractional laser treatments using a 1,550-nm erbium-doped fiber laser system on the upper and lower eyelids were given at a pulse energy of 17 to 20 mJ at 125 micro-thermal zones (MTZ)/cm2 to a final density of 500 to 750 MTZ/cm2. Each patient had 3 to 7 treatments. Standard pre- and post-treatment photographs were taken at each visit. Physicians who graded 31 preselected patient photographs using a 4-point scale evaluated eyelid tightening. Increase in eyelid aperture was also evaluated. RESULTS All patients had some degree of eyelid tightening; 19% achieved 1% to 25% tightening, 26% achieved 25% to 50%, 26% achieved 50% to 75%, and 29% achieved 75% to 100%. Increase in eyelid aperture was seen in 55.9% of patients. Postoperative wounding, hypopigmentation, hyperpigmentation, persistent erythema, and scarring were not observed. All patients experienced mild or no edema for a few days after treatment. CONCLUSION Fractional resurfacing tightens and increases eyelid aperture without wounding, downtime, or long-term complications. [source] Hidradenitis Suppurativa: Importance of Early Treatment; Efficient Treatment with ElectrosurgeryDERMATOLOGIC SURGERY, Issue 2 2008A. BURHAN AKSAKAL MD BACKGROUND Hidradenitis suppurativa is a challenging condition, both for the physicians and for the patients. Many surgical and medical approaches with different success rates have been undertaken. Early and appropriate intervention is a factor that significantly increases the success rate of the treatment of the disease. OBJECTIVE This study was conducted to evaluate the efficiency of electrosurgery treatment in early hidradenitis suppurativa. MATERIALS AND METHODS This study comprised 12 patients aged between 29 and 38 years (mean, 34 years) with a diagnosis of hidradenitis suppurativa Grade I (n=9) or Grade II (n=3). A surgical method consisted of excision of the areas with nodules and sinuses, up to the level of subcutaneous fat tissue, and leaving the surgical defect for secondary healing. RESULTS All patients completed the study. In 10 of 12 (83%) patients, 26 of 30 (86%) lesions, cure was observed in a mean of 16 days (range 15 to 21 days). Four lesions in 2 patients with Grade II became infected and required a short course of antibiotic therapy. CONCLUSION Electrosurgery will decrease the need for other systemic treatments, owing to its high cure rates. Our results showed that electrosurgery should be considered a top alternative in the treatment algorithm of hidradenitis suppurativa. [source] Treatment of Inflammatory Facial Acne Vulgaris with Intense Pulsed Light and Short Contact of Topical 5-Aminolevulinic Acid: A Pilot StudyDERMATOLOGIC SURGERY, Issue 8 2006JINDA ROJANAMATIN MD BACKGROUND Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) and red light (550,700 nm) has been introduced for effective treatment of facial acne. Untoward side effects are common, however. OBJECTIVE To evaluate the efficacy and safety of the short contact of topical ALA and intense pulsed light (IPL) in treatment of inflammatory facial acne. METHODS Fourteen patients with inflammatory facial acne were treated with IPL on the left side and combination of IPL and topical ALA on the right side at 3- to 4-week intervals for three sessions. Clinical photographs and lesion counts were obtained for evaluation. RESULTS All patients revealed a reduction in number of acne lesions on both sides. On the ALA-pretreated side, lesion counts decreased 87.7% at 12 weeks after the last treatment (p<.01). Meanwhile, lesion counts on the nonpretreated side decreased 66.8% (p<.01). In addition, a number of lesion counts on the ALA-pretreated side decreased. Mild edema and minimal crust developed on the combined-treatment side. CONCLUSION Short contact of topical ALA and IPL or IPL alone showed some beneficial effect in treatment of inflammatory facial acne; however, degree of improvement was better and remained longer with the combined regimen. Side effects were mild and reversible. [source] Botulinum Toxin Type B (MYOBLOC) Versus Botulinum Toxin Type A (BOTOX) Frontalis Study: Rate of Onset and Radius of DiffusionDERMATOLOGIC SURGERY, Issue 5 2003Timothy Corcoran Flynn MD Background. Botulinum toxin types A and B can improve the appearance of facial wrinkles. Differences in the time until onset and the degree of diffusion have been observed anecdotally, but no direct comparative studies have been done. Objective. To compare the rate of onset and the radius of diffusion of botulinum toxin types A and B in the rhytides of the forehead. Methods. Adults with symmetrical moderate to severe forehead wrinkles at full contracture received botulinum toxin type A (BOTOX; 5 U) on one side of the forehead and type B (MYOBLOC; 500 U) on the other side. Photographs taken at rest and full frontalis contracture were analyzed by computer, and a time-lapse motion picture was created. Radius of diffusion and time until full effect were measured. Results. Botulinum toxin type B had a slightly faster onset of action than type A. All patients responded to type B quickly, whereas some had a delayed response to type A. A greater radius of diffusion was consistently observed with botulinum toxin type B, as measured by the greater area of wrinkle reduction at the doses used. Conclusions. In this comparative study of patients with symmetrical forehead wrinkles, botulinum toxin type B produced a greater area of diffusion and a more rapid onset of action than type A. [source] Efficacy of low dose long-term interferon monotherapy in aged patients with chronic hepatitis C genotype 1 and its relation to alpha-fetoprotein: A pilot studyHEPATOLOGY RESEARCH, Issue 7 2007Hideyuki Nomura Aim:, The objective of this study was to examine the efficacy and safety of low dose long-term interferon (IFN) therapy in aged patients with chronic hepatitis C genotype 1. Methods:, The IFN therapy was performed in Shin-Kokura Hospital on 44 patients aged 60 or older with chronic hepatitis C. All patients had high viral loads of genotype 1. Three million units of natural IFN-, was administered intramuscularly or intrasubcutaneously, three times a week for three years. A control group of 44 subjects not treated with IFN, matched for age, gender and hepatic histology, was formed. Results:, Two of the 44 patients showed a sustained virological response. Alanine aminotransferase was below the upper limit of normal in 59% (23/39) of the patients and alpha-fetoprotein was less than 40 ng/mL in 97% (38/39) on the completion of treatment. Sustained biochemical response was observed in 53% (19/36) of the patients. In the liver cirrhosis group, serum albumin values and platelet counts increased in 38% (6/16) and 33% (6/18) of patients, respectively. Hepatocellular carcinoma (HCC) appeared in three patients by 13 months after the start of treatment, but no cases were reported thereafter. The cumulative non-carcinogenesis rate of HCC in the liver cirrhosis group was significantly higher in the IFN treatment group compared to the control group (log,rank test, P = 0.046). Conclusion:, Low dose long-term interferon monotherapy to prevent carcinogenesis of HCC was considered useful in aged patients for whom peg-interferon and ribavirin combination therapy is difficult. [source] The treatment of faecal incontinence following ileostomy takedown after rectal surgery for cancerJOURNAL OF NURSING AND HEALTHCARE OF CHRONIC ILLNE SS: AN INTERNATIONAL INTERDISCIPLINARY JOURNAL, Issue 3 2009Federico Attene MD Aim., The aim of this study was to assess the effectiveness of rehabilitative treatment of the pelvic floor on faecal incontinence after ileostomy take-down. Background., Several conditions can induce surgeons to fashion an excluding ileostomy. In our experience 40% of patients subjected to ileostomy takedown refer faecal incontinence which becomes a chronic condition if not treated. Design., Between 2006 and 2008 we observed fourteen patients with faecal incontinence after ileostomy takedown. Previous manometric assessment of the pelvic floor functionality they underwent rehabilitative treatment by electrostimulation of the anal sphincter. Methods., The rehabilitation program was organised in 10 sessions each of 15 minutes. In each session a double electrode probe was introduced through the anus which is able to conduct electric impulses at a frequency of 75 Hz with an intensity of 15,50 mA and duration of 150 ,s. Results., All patients showed important clinical and manometric improvement. Three patients needed a second rehabilitative treatment with subsequent clinical resolution of faecal incontinence. Conclusions., Improvement in all patients was found although the data are not statistically significant. Consideration of social and psychological implications of treatments is important. Patients need to acquire full control of their body and its functions. Considering that faecal incontinence is a pathology with high social costs it appears necessary to establish an effective and repeatable method of treatment. Electric stimulation seems to be the most adequate tool for this purpose. Relevance to clinical practice., The standardisation of parameters in the treatment protocol of incontinence could allow to extend this therapy to a lot of colo-proctological units. [source] The Incidence of Spontaneous Epidural Abscess in Olmsted County from 1990 Through 2000: A Rare Cause of Spinal PainPAIN MEDICINE, Issue 4 2007Anne E. Ptaszynski MD ABSTRACT Objective., The primary objective of this study is to determine the population-based incidence of spontaneous epidural abscess. The secondary objective is to characterize the clinical course of patients with this rare infectious disease. Design., The records-linkage system of the Rochester Epidemiology Project was used to identify incident cases of spontaneous epidural abscess in residents of Olmsted County, Minnesota, USA, from 1990 through 2000. Setting., Tertiary referral medical center. Patients., All patients were residents of Olmsted County and had spontaneous epidural abscesses that were radiographically or surgically confirmed. Results., Eight patients, including six women, were identified and the mean age was 56 years (range, 40,80). The incidence of epidural abscess was 0.88 cases per 100,000 person-years (95% confidence interval, 0.27,1.48). The median time from symptom onset to diagnosis was 18 days (interquartile range, 4,30 days). Six patients presented with spinal pain and one presented with focal neurological deficits. Risk factors were identified in all patients, including concomitant infections, diabetes mellitus, immunosuppression, and intravenous substance abuse. Staphylococcus aureus was cultured in six patients and streptococcal species were cultured in two patients. Three patients were treated surgically and five received medical treatment. One patient treated surgically and one patient treated medically had residual neurological deficits. One patient, who was immunosuppressed and received medical treatment died of pneumonia. Conclusions., This is the first published report of the population-based incidence of spontaneous epidural abscess. These findings could serve as a reference point for further epidemiological research related to this uncommon infection. [source] Management and outcome in prenatally diagnosed sacrococcygeal teratomasPEDIATRICS INTERNATIONAL, Issue 4 2008Tadao Okada Abstract Background: The aim of the present study was to retrospectively determine the clinical factors affecting the outcome after birth in prenatally diagnosed sacrococcygeal teratomas (SCT). Methods: Six cases of prenatal SCT were identified from January 1985 until August 2005. A retrospective review of case-notes and pathological reports was carried out. Clinical data during the perinatal period, operative findings, postoperative complications and follow up were evaluated in the patients with prenatally diagnosed SCT. Results: SCT presented as type I in two neonates and type III in four between 22 and 33 weeks' gestation. Fetal intervention was not performed for any fetus. Five of six were delivered by cesarean section and the other was delivered vaginally due to small tumor size. Patients were born at between 29 and 39 weeks' gestation and weighed from 1840 to 3500 g. All patients with type III SCT presented with related diseases, including bilateral hydronephrosis, neurological deficit of the communicating peroneal nerve such as paralytic talipes equines, bladder or bowel dysfunction, high-output cardiac failure, or fetal hydrops in one of a set of fraternal twins. A baby with high-output cardiac failure and fetal hydrops underwent urgent cesarean section at 29 weeks' gestation and died 8 days after birth despite intensive care due to multi-organ failure. In five cases, surgery was successful with good outcomes maintained at follow-up of between 8 months and 14 years. Conclusions: Detailed ultrasound should be performed to rule out associated anomalies, and determine the presence or absence of hydrops in prenatally diagnosed SCT. Fetal hydrops, orthopedic impairment such as lower extremity weakness and swelling, and urinary incontinence are important clinical factors affecting the outcome after birth in prenatally diagnosed SCT. In particular, the present study indicated that the association of a fraternal twin and fetal hydrops makes it very difficult to treat SCT perinatally. [source] Enhanced External Counterpulsation in Patients with Coronary Artery Disease-Associated Erectile Dysfunction.THE JOURNAL OF SEXUAL MEDICINE, Issue 3 2007Part I: Effects of Risk Factors ABSTRACT Introduction., Recently it has been demonstrated that enhanced external counterpulsation (EECP) could improve erectile dysfunction (ED) in patients with refractory ischemic heart disease (IHD). Aim., To assess the effect of risk factors on the efficacy and the satisfaction rate of EECP in patients with coronary artery disease (CAD)-associated ED. Main Outcome Measures., To assess the effect of risk factors on EECP efficacy and satisfaction rate, we compared the pre- and post-EECP responses to erectile function domain, Q3, and Q4 in patients with and without risk factors. Overall satisfaction and global efficacy question (GEQ) were also assessed. Methods., A total of 44 male consecutive patients with intractable angina caused by coronary insufficiency which cannot be controlled by conventional therapy were enrolled in this study. Patients were screened and followed up for ED using erectile function domain of the International Index for Erectile Function. A thorough sexual, medical, and psychosocial history was taken from all patients. Results., All patients had severe diffuse triple vessels disease. They all had class III or IV angina. They were receiving the maximal antianginal pharmacotherapy. The mean age ± SD was 57.1 ± 5.6 years. Of the patients, 63.9% were below 60 years, and 86.4% were current or ex-smokers. There were significant differences between pre- and post-EECP regarding erectile function domain, Q3, and Q4. The sociodemographic variables were not significantly different among the studies groups and had not affected the GEQ or overall satisfaction. Overall satisfaction and GEQ were negatively influenced by smoking and presence of more than two risk factors. However, diabetes, hypertension, dyslipidemia, myocardial infraction, and obesity have not had such effects. Conclusions., The efficacy and satisfaction rate of EECP in patients with CAD-associated ED were negatively influenced by presence of risk factors; however, the global efficacy and the overall patients' satisfaction were encouraging. El-Sakka A, Morsy A, and Fagih B. Enhanced external counterpulsation in patients with coronary artery disease-associated erectile dysfunction. Part I: Effects of risk factors. J Sex Med 2007;4:771,779. [source] An assessment of the validity of SOFA score based triage in H1N1 critically ill patients during an influenza pandemicANAESTHESIA, Issue 12 2009Z. Khan Summary Sequential Organ Failure Assessment (SOFA) score based triage of influenza A H1N1 critically ill patients has been proposed for surge capacity management as a guide for clinical decision making. We conducted a retrospective records review and SOFA scoring of critically ill patients with influenza A H1N1 in a mixed medical-surgical intensive care unit in an urban hospital. Eight critically ill patients with influenza A H1N1 were admitted to the intensive care unit. Their mean (range) age was 39 (26,52) years with a length of stay of 11 (3,17) days. All patients met SOFA score based triage admission criteria with a modal SOFA score of five. Five patients required invasive ventilation for a mean (range) of 5 (4,11) days. Five patients would have been considered for withdrawal of treatment using SOFA scoring guidelines at 48 h. All patients survived. We conclude that SOFA score based triage could lead to withdrawal of life support in critically ill patients who could survive with an acceptably low length of stay in the intensive care unit. [source] | ||||||||||||||||||||||||||||