Significant Difference In Relapse Rate Research Articles

Prognostic Significance Of Copy Number Alterations In B-Lineage Adult Acute Lymphoblastic Leukemia Patients Enrolled In Risk-Adapted Protocols From The Pethema Group

▪ IntroductionIn the last years genome wide profilings have identified recurrent Copy Number Alterations (CNA) in genes potentially involved in the pathogenesis of Acute Lymphoblastic Leukemia (ALL). These studies have identified deletions in B-cell development genes (IKZF1, EBF1, PAX5, TCF3, etc.), cell cycle regulation genes (CDKN2A/B, RB1, TP53, etc.), glucocorticoid resistance genes (BTG1, CREBBP) and growth factor receptors genes (CRLF2, CSF2RA, IL3RA) among others. Some of these CNA (i.e. IKZF1, CDKN2A, CRLF2) have been reported to have prognostic significance in several pediatric series but there are very few data regarding their impact in B-lineage adult ALL. Our aim was to analyze the frequency and prognostic significance of CNA in a series of 125 B-lineage adult ALL patients treated according to risk-adapted protocols from the Spanish PETHEMA Group. MethodsBone marrow or peripheral blood (with significant blast burden) samples from 125 B-lineage adult ALL patients enrolled in risk-adapted protocols from the PETHEMA Group were analyzed at diagnosis. MLPA assays (MRC-Holland) were performed for the following genes: IKZF1, IKZF2, IKZF3, EBF1, CDKN2A/B, PAX5, ETV6, BTG1, RB1, hsa-miR-31, X/Y PAR1 region genes (CRLF2, CSF2RA, IL3RA) and 14q32.33 region genes (IGH D, MTA1, KIAA0284). Fragment analysis was made by Genescan in an ABI-3130 sequencer (Applied Biosystems). Data normalization provided a value indicative of the presence or absence of CNA: 0-0.20 homozygous deletion, 0.21-0.70 heterozygous deletion, 0.71-1.30 normal, 1.31-1.70 heterozygous duplication and 1.71-2.20 homozygous duplication. ResultsThe median age [range] was 40 [15-74] years, 71 (57%) males, median WBC count 12.11 x109/L [0.4-388]. Immunophenotype: pro-B 14 (11%), common 71 (58%), pre-B 26 (21%), mature-B 10 (8%), unavailable 2 (2%). Cytogenetics: normal 16 (13%), hyperdiploid 6 (5%), hypodiploid 2 (2%), t(9:22) 20 (16%), t(1;19) 8 (6%), 11q23/MLL 11 (9%), 8q24/C-MYC 7 (5%), complex 1 (1%), iAMP21 2 (2%), other translocations or deletions 31 (25%), no growth 20 (16%). CNA frequencies of the 125 patients are shown in the table.TableDeletionDuplicationNormalIKZF138 (30%)1 (1%)86 (69%)EBF111 (9%)7 (5%)107 (86%)CDKN2A/B44 (35%)-81 (65%)PAX533 (26%)4 (4%)88 (70%)hsa-miR-3123 (18%)-102 (82%)ETV67 (6%)1 (1%)117 (93%)BTG111 (9%)3 (2%)111 (89%)RB120 (16%)-105 (84%)14q32.33 region20 (16%)11 (9%)94 (75%)X/Y PAR16 (5%)16 (13%)103 (82%)IKZF2-4 (3%)121(97%)IKZF32 (2%)8 (6%)115 (92%)IKZF1 deletions were significantly associated with EBF1 deletions, high WBC count and Philadelphia (Ph) chromosome. In the IKZF1 deleted cohort whole gene deletions were as frequent as Ik6 isoforms (28% each). A high codeletion rate was detected in genes located in 9p (CDKN2A/B with PAX5, CDKN2A/B with hsa-miR-31 and PAX5 with hsa-miR-31). CDKN2A/B also showed concomitant deletions with ETV6 while PAX5 showed codeletions with BTG1. CDKN2A/B and PAX5 deleted patients had higher WBC counts than non-deleted individuals.Clinical follow-up data was available for 123 patients of the whole series and for the 105 patients of the Ph-negative cohort. Multivariate analysis showed that advanced age, BTG1 deletions and EBF1 deletions were negative prognostic factors for achieving Complete Remission (CR) and WBC count and IKZF1 deletions significantly reduced CR duration in both cohorts. Interestingly, there were significant differences in relapse rates between whole and partial gene IKZF1 deletions. IKZF1 haploinsufficient patients had a probability of CR duration at 3 years of 83% ± 30% vs. 6% ± 12% of partial gene deletion carriers. Advanced age and IKZF1 deletions were predictors for overall survival in the Ph-negative cohort and age>30 years, IKZF1 deletions and hsa-miR-31 deletions were associated with poor prognosis in the whole series. ConclusionsIn B-lineage adult ALL, deletions of IKZF1, EBF1, BTG1 or hsa-miR-31 are markers with prognostic significance in addition to age and WBC count. Patients with partial IKZF1 gene deletions have a significantly higher probability of relapse than those with whole gene loss. These genetic abnormalities could help to better define prognostic subgroups in adult patients with B-lineage ALL.Supported by the grants PI10/01417 and RD12-0036-0029 from Instituto Carlos III and a grant from the Spanish Society of Hematology and Hemotherapy (2012). Disclosures:No relevant conflicts of interest to declare.

Outpatient Cytarabine Administration Is Safe and Effective For Consolidation In Acute Myeloid Leukemia

IntroductionAlthough most patients with Acute Myeloid Leukemia (AML) achieve complete remission with induction chemotherapy, further consolidation with chemotherapy or stem cell transplantation (SCT) is recommended in order to prolong remission duration and prevent relapse. Since the 1990's, high dose cytarabine has been a standard consolidation regimen, with a goal of 3-4 cycles every 28 days and dose adjustments for advanced age. However, there is no data to define the optimal number of cycles or predict if delays in consolidation delivery alter its efficacy. Furthermore, it has not been demonstrated whether outpatient cytarabine is a safe and feasible alternative to repeated inpatient admissions. Our institution has moved to outpatient administration of cytarabine consolidation for eligible patients (reside within 30 minutes of the hospital in private home or American Cancer Society Hope Lodge with full-time caregiver) in an attempt to reduce hospitalization days, cost, and improve patient quality of life by limiting inpatient days. We hypothesized that outpatient administration of cytarabine consolidation is safe and effective without increased treatment delays or AML relapse and represents a potentially cost-saving approach in selected patients. MethodsWe performed a retrospective chart review of 50 consecutive adult AML patients treated with cytarabine consolidation at the University of Kansas from January 1, 2005, to October 1, 2012. Data collected included AML prognostic category, age, inpatient/outpatient cytarabine consolidation, number of cycles, time between treatment cycles, reasons for any delays and duration of remission. ResultsThe median age was 52 (ages 20-70). 42% of patients had favorable risk disease, while 20% were high risk and 36% were intermediate risk. High risk patients who received cytarabine consolidation did so due to the lack of suitable stem cell donor or as a bridge while securing a donor for SCT. Intermediate risk patients who received cytarabine consolidation had no matched sibling or unrelated donor or declined SCT in first complete remission. At the time of this writing, 44% were in remission while 56% had relapsed, with a median duration of remission of 391 days (range 94-991 days). Factors which determined whether patients were treated with cytarabine consolidation as an inpatient or outpatient included insurance coverage for outpatient cytarabine and availability of local housing/caregiver. Patients who received inpatient versus outpatient cytarabine were older (median ages of 57 and 44 respectively, p<.01). Inpatient cytarabine was given to 54% of patients, 77% of whom have relapsed. In contrast, outpatient cytarabine was given to 46% of patients, with a significantly lower rate of relapse at 32% (p=0.002). Patients treated with outpatient consolidation more frequently had favorable or intermediate risk AML (92% vs 69% inpatient). The difference in relapse rates remained significant on logistic regression analysis controlling for cytogenetic risk category (p=0.048), although the sample size is small. Delays of more than 7 days between consolidation cycles occurred in 67% of all patients. The most common reasons for delay were infection and prolonged cytopenias. Using Cox regression analysis, there was no significant difference in rates of delayed consolidation cycles between patients treated inpatient or outpatient. There was no statistically significant difference seen in relapse rates whether or not delays in treatment occurred (p=0.13). There were no recorded incidents of ambulatory pump failure. Out of 71 cycles of outpatient cytarabine administered, there were 20 re-hospitalizations, and 20% of patients had re-hospitalization during at least one outpatient consolidation cycle. ConclusionsThe delivery of cytarabine consolidation in the outpatient setting appears safe with no increase in delays in chemotherapy delivery. Although the statistically significant difference in relapse rate favors outpatient cytarabine consolidation, this may reflect inherent AML biology as more patients had favorable risk AML. There was no evidence to suggest inferior outcomes with this approach. This small retrospective sample demonstrates the feasibility of outpatient cytarabine consolidation, avoiding costly and inconvenient hospitalization without compromising the on-time delivery of chemotherapy or clinical outcome. Disclosures:No relevant conflicts of interest to declare.

Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties.

BackgroundFlu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines’ levels.MethodsIn a randomized, double blind study of 45 IFNβ-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented.Results25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed.ConclusionVitamin D supplementation to IFN−β treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN−β related FLS.Trial registrationClinicalTrials.gov ID: NCT01005095

A robust prognostic signature for hormone-positive node-negative breast cancer

BackgroundSystemic chemotherapy in the adjuvant setting can cure breast cancer in some patients that would otherwise recur with incurable, metastatic disease. However, since only a fraction of patients would have recurrence after surgery alone, the challenge is to stratify high-risk patients (who stand to benefit from systemic chemotherapy) from low-risk patients (who can safely be spared treatment related toxicities and costs).MethodsWe focus here on risk stratification in node-negative, ER-positive, HER2-negative breast cancer. We use a large database of publicly available microarray datasets to build a random forests classifier and develop a robust multi-gene mRNA transcription-based predictor of relapse free survival at 10 years, which we call the Random Forests Relapse Score (RFRS). Performance was assessed by internal cross-validation, multiple independent data sets, and comparison to existing algorithms using receiver-operating characteristic and Kaplan-Meier survival analysis. Internal redundancy of features was determined using k-means clustering to define optimal signatures with smaller numbers of primary genes, each with multiple alternates.ResultsInternal OOB cross-validation for the initial (full-gene-set) model on training data reported an ROC AUC of 0.704, which was comparable to or better than those reported previously or obtained by applying existing methods to our dataset. Three risk groups with probability cutoffs for low, intermediate, and high-risk were defined. Survival analysis determined a highly significant difference in relapse rate between these risk groups. Validation of the models against independent test datasets showed highly similar results. Smaller 17-gene and 8-gene optimized models were also developed with minimal reduction in performance. Furthermore, the signature was shown to be almost equally effective on both hormone-treated and untreated patients.ConclusionsRFRS allows flexibility in both the number and identity of genes utilized from thousands to as few as 17 or eight genes, each with multiple alternatives. The RFRS reports a probability score strongly correlated with risk of relapse. This score could therefore be used to assign systemic chemotherapy specifically to those high-risk patients most likely to benefit from further treatment.

Comparison of the efficacy of buprenorphine and clonidine in detoxification of opioid-dependents.

Since the number of drug users is increasing, applying a method of detoxification with fewer side effects during withdrawal from opioids and greater reliability seems to be necessary. In addition, without maintenance treatment, there will be limited success of treatment. This study aimed to compare success rates of detoxification with sublingual buprenorphine and clonidine and to evaluate addiction relapse in patients using naltrexone in a six-month follow-up. This double-blind trial was carried out on opioid dependent patients in a psychiatric hospital in Kerman (Iran) during 2007-09. The subjects were randomly selected from individuals who had referred for detoxification. They were allocated to two groups to receive either clonidine (n = 21) or buprenorphine (n = 14). The success rates of the two methods were assessed at the end of the course and patients were discharged while prescribed with 25 mg daily use of naltrexone. They were followed up for six months and the continuous use of naltrexone and relapse of substance abuse were evaluated. A total number of 35 patients entered the study. Success of detoxification with naltrexone was confirmed in all cases. One person (8.4%) in the clonidine group and no patient in the buprenorphine group had a clinical opiate withdrawal scale (COWS) score of more than 12 (P > 0.05). The mean levels of objective signs and subjective symptoms of withdrawal and the desire for drug abuse had significant reductions during detoxification period in both groups (P < 0.001). However, the difference in these variables between the two groups was not statistically significant (P > 0.05). Naltrexone was used for an average of one month in 43% and 64% of subjects in the clonidine and buprenorphine groups, respectively. In addition, 62% of patients in the clonidine group and 92.8% of subjects in the buprenorphine group received maintenance treatment. Nevertheless, the mean number of days staying in treatment was not significantly difference between the two groups (P > 0.05). Buprenorphine is as effective as clonidine in controlling withdrawal symptoms. A greater percentage of patients detoxified by buprenorphine received maintenance treatment, but there was not a significant difference in relapse rates between the two methods.

Curcumin for maintenance of remission in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon characterized by episodes of disease activity and symptom-free remission.There is paucity of evidence regarding the efficacy and safety of complementary or alternative medicines for the management of UC. Curcumin, an anti-inflammatory agent, has been used in many chronic inflammatory conditions such as rheumatoid arthritis, esophagitis and post-surgical inflammation. The efficacy of this agent for maintenance of remission in patients with UC has not been systematically evaluated. The primary objective was to systematically review the efficacy and safety of curcumin for maintenance of remission in UC. A computer-assisted literature search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Inflammatory Bowel Disease Specialized Trial Register was performed on July 11, 2012 to identify relevant publications. Proceedings from major gastroenterology meetings and references from published articles were also searched to identify additional studies. Randomized placebo-controlled trials (RCT) of curcumin for maintenance of remission in UC were included. Studies included patients (of any age) who were in remission at the time of recruitment. Co-interventions were allowed. Two authors independently extracted data and assessed the methodological quality of the included studies using the Cochrane risk of bias tool. Data were analyzed using Review Manager (RevMan 5.1). We calculated the relative risk (RR) and 95% confidence interval (95% CI) for each dichotomous outcome. For continuous outcomes we calculated the mean difference (MD) and 95% CI. Only one trial (89 patients) fulfilled the inclusion criteria. This trial randomized 45 patients to curcumin and 44 patients to placebo. All patients received treatment with sulfasalazine or mesalamine. The study was rated as low risk of bias. Curcumin was administered orally in a dose of 2 g/day for six months. Fewer patients relapsed in the curcumin group than the placebo group at six months. Four per cent of patients in the curcumin group relapsed at six months compared to 18% of patients in the placebo group (RR 0.24, 95% CI 0.05 to 1.09; P = 0.06). There was no statistically significant difference in relapse rates at 12 months. Twenty-two per cent of curcumin patients relapsed at 12 months compared to 32% of placebo patients (RR 0.70, 95% CI 0.35 to 1.40; P = 0.31). A total of nine adverse events were reported in seven patients. These adverse events included sensation of abdominal bulging, nausea, transient hypertension, and transient increase in the number of stools. The authors did not report which treatment group the patients who experienced adverse events belonged to. The clinical activity index (CAI) at six months was significantly lower in the curcumin group compared to the placebo group (1.0 + 2.0 versus 2.2 + 2.3; MD -1.20, 95% CI -2.14 to -0.26). The endoscopic index (EI) at six months was significantly lower in the curcumin group than in the placebo group (0.8 + 0.6 versus 1.6 + 1.6; MD -0.80, 95% CI -1.33 to -0.27). Curcumin may be a safe and effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine. However, further research in the form of a large scale methodologically rigorous randomized controlled trial is needed to confirm any possible benefit of curcumin in quiescent UC.

Multiple sclerosis and pregnancy: experience from a nationwide database in Germany

The objective of this study was to evaluate exposure to disease-modifying therapies (DMTs) during pregnancy in 335 pregnancies of multiple sclerosis (MS) patients and to further determine whether exclusive breastfeeding of MS mothers has any relevant influence on postpartum relapse rate. Only limited data are available on whether DMT exposure during pregnancy affects relapse rate during pregnancy or after birth. Currently, findings on beneficial effect of exclusive breastfeeding on MS disease course are controversially discussed. We enrolled pregnant women with MS who contacted us directly or via their treating physicians to be included in our nationwide MS and pregnancy database. We identified 78 pregnancies under interferon-beta (IFNβ) preparations, 41 under glatiramer acetate (GLAT), and 216 pregnancies without DMT exposure during pregnancy. As expected, annualized relapse rate (ARR) decreased continuously during pregnancy in nonexposed mothers (p < 0.001) to then increase after birth. In IFNβ- or GLAT-exposed women this typical pattern was not as obvious. Congenital anomalies were within normal ranges in exposed pregnancies. In total, 170 women were identified who exclusively breastfed (EBF). Significantly reduced postpartum relapse rate during the first 3 months after birth were registered in the EBF group as compared with nonexclusively breastfeeding (NEBF) or nonbreastfeeding women (NBF) women with MS (p < 0.0001). Relapse rate (RR) in the year before pregnancy had been similar throughout all groups. We did not observe any significant differences in RR of NEBF and NBF women. Exclusive breastfeeding showed some beneficial effects on postpartum relapse rate in our cohort. Our data support that IFNβ and GLAT do not seem to represent a major teratogenic risk in pregnancy.

Efficacy of 3-day versus 5-day antibiotic therapy for clinically diagnosed nonsevere pneumonia in children from developing countries

Pneumonia is the leading cause of mortality in young children in developing countries. A short course of antibiotics in the treatment of nonsevere pneumonia has been suggested as feasible and could lead to decreased costs, risk of adverse events, and development of antimicrobial resistance. This review evaluates the evidence regarding the duration of antibiotic treatment in this population. The PubMed, EMBASE, Cochrane Library, and other databases were searched. Studies were selected for inclusion if they enrolled patients in developing countries between the ages of 2 months to 18 years clinically diagnosed with nonsevere pneumonia, and compared the clinical outcomes of a short course of oral antibiotics with a long course. The outcomes of interest included failure rate, relapse rate, and safety. Four randomized controlled trials were identified, which enrolled 9235 patients cumulatively. All patients were aged between 2 to 59 months and diagnosed using World Health Organization defined criteria. All four trials showed no significant difference in relapse rates between 3-day and 5-day courses. In one study, the 3-day course was associated with higher rates of treatment failure and adverse events, with no adverse event classified as severe. Overall, short and long courses of antibiotics produce similar outcomes treating clinically diagnosed, nonsevere pneumonia in children in developing countries between the ages of 2 to 59 months. Three out of four studies in this review, representing two-thirds of the patients in aggregate, showed no significant difference in treatment failure or relapse rates between a 3-day and 5-day course of antibiotics.

CNS Remission at the Time of Autologous Stem Cell Transplantation Improves Outcome for Patients with Non-Hodgkin's Lymphoma with Pre-Existing CNS Involvement: a CIBMTR Analysis

AbstractAbstract 371Various small, retrospective single institutional and registry analyses have suggested that pre-existing central nervous system (CNS) involvement was not a contraindication for autologous hematopoietic stem cell transplantation (aHSCT) for patients with non-Hodgkin's lymphoma (NHL). The outcomes of 151 adult patients with NHL with pre-existing CNS involvement (CNS+), identified as CNS involvement identified at any time in the course of their disease, undergoing aHSCT were analyzed and compared to 4688 patients who underwent the procedure but with no pre-existing CNS involvement (CNS−) during the years 1990–2005. There were significant baseline differences between the groups with CNS+ patients more likely to be younger, have lower performance status, higher age adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, increased # of extranodal disease sites, and to have a shorter interval between diagnosis and aHSCT. There were no discernible differences in sex, immunophenotype, B symptoms at diagnosis, bone marrow involvement, # prior lines of therapy, conditioning regimens or disease status at aHSCT. Median follow-up of survivors was equivalent (CNS+: 77 months vs CNS− 73 months). Comparing the CNS+ with the CNS− groups, the univariate probabilities of DFS were 30 vs 35%, OS were 42 vs 49%, respectively. Cumulative incidence for relapse was 61 vs 57% and for NRM was 9 vs 8%, respectively. No statistically significant differences were identified between the two groups although there was a trend to higher relapse and lower OS for the CNS+ transplant group. Further analysis was performed on the CNS+ cohort, stratifying by disease status at time of aHSCT. Marked increase in relapse rates (72 vs 49%) with associated lower DFS (19 vs 46%) and OS (31 vs 58%) were found in patients with active CNS disease (Figure 1). With recognition that there were differences in disease presentation and risk features, a propensity analysis was performed on the original CNS− cohort to allow a case match control study, matched for number of high risk features but differing based upon CNS involvement. 135 CNS+ patients selected for B cell phenotype and common NHL subtypes were compared to 535 CNS− patients. On multi-variate analysis, no statistically significant differences in relapse rates, NRM, DFS and OS (Figure 2) were found comparing these groups in the case control study. Validation of the CNS− case match study population showed no differences in OS of the matched CNS− group with the non-matched CNS- population. In summary, NHL patients with CNS involvement in the course of their disease, despite often presenting with more adverse features, can achieve excellent long-term outcomes with aHSCT. However, optimal outcomes are only achieved when CNS disease control is present at the onset of the aHSCT. [Display omitted] [Display omitted] Disclosure:No relevant conflicts of interest to declare.

Probiotics for maintenance of remission in ulcerative colitis

<h3>Background</h3> Several studies have demonstrated the importance of intestinal bacterial flora in the pathogenesis of inflammatory bowel disease. It has therefore been suggested that modifying the bacterial flora with probiotics will attenuate the inflammatory process and prevent relapses in ulcerative colitis (UC). <h3>Aim</h3> To evaluate the available evidence on the use of probiotics for the maintenance of remission in UC and to assess the occurrence of adverse events associated with the use of probiotics. <h3>Design</h3> Systematic review and meta-analysis of randomised controlled trials (RCTs) published between 1966 and October 2009. <h3>Methods</h3> Data sources were MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Inflammatory Bowel Disease Specialised Register, and reference lists of retrieved articles. We aimed to include trials which compared probiotics with either placebo or other interventions. Data extraction and assessment of methodological quality were performed independently by two reviewers. <h3>Results</h3> Three RCTs met the inclusion criteria. All three trials compared probiotics with mesalazine and no placebo-controlled studies were identified. Meta-analysis of the results of the three RCTs, which involved 555 patients, showed no statistically significant difference in relapse rates between patients who received probiotics and those who received mesalazine (pooled odds ratio 1.45, 95% CI 0.99 to 2.13). The incidence of adverse events was not statistically significantly different between the probiotic and mesalazine groups (pooled odds ratio 1.21, 95% CI 0.80 to 1.84). <h3>Conclusion</h3> The available evidence does not demonstrate a statistically significant difference between probiotics and mesalazine for the maintenance of remission in UC. However, two of the included studies had relatively small sample sizes and there is insufficient evidence to make any definite conclusions about the efficacy of probiotics for induction of remission in UC. Further well-designed randomised controlled trials including those that compare probiotics with placebo are needed to investigate whether probiotics are effective for the maintenance of remission in UC.

Determining the Oncological Risk of Autologous Lipoaspirate Grafting for Post-Mastectomy Breast Reconstruction

This study compares the incidence of local and regional recurrence of breast cancer between two contiguous time windows in a homogeneous population of 137 patients who underwent fat tissue transplant after modified radical mastectomy. Median follow-up time was 7.6 years and the follow-up period was divided into two contiguous time windows, the first starting at the date of the radical mastectomy and ending at the first lipoaspirate grafting session and the second beginning at the time of the first lipoaspirate grafting session and ending at the end of the total follow-up time. Although this study did not employ an independent control group, the incidence of local recurrence of breast cancer was found to be comparable between the two periods and in line with data from similar patient populations enrolled in large multicenter clinical trials and who did not undergo postsurgical fat tissue grafting. Statistical comparison of disease-free survival curves revealed no significant differences in relapse rate between the two patient subgroups before fat grafting and after fat grafting. Although further confirmation is needed from multicenter randomized clinical trials, our results support the hypothesis that autologous lipoaspirate transplant combines striking regenerative properties with no or marginal effects on the probability of post-mastectomy locoregional recurrence of breast cancer.

Effectiveness of coping skills training in relapse prevention and resiliency enhancement in people with substance dependency

The aim of this study was to determine the effectiveness of coping skills training based on “Marlatt Relapse Prevention Model” in relapse prevention and resiliency enhancement in people with substance dependency. In a semi-experimental study, 27 subjects with diagnosis of opiate use disorders in Jameiate Aftab Center of Tehran who had been successfully detoxified, were divided into two experimental group (13 subjects) and control group (14 subjects) that had been selected using available sampling method. The experimental group underwent 12 sessions of coping skills training and the control group did not receive any treatment. All subjects in the study were assessed by Conner-Davidson Resiliency Scale (CD-RIS) and morphine test before treatment, after treatment, and after a 4-month follow up stage. Data were analyzed using descriptive methods, χ2test, and ANCOVA. χ2 test result showed that experimental and control groups (p<0/001) had a significant difference in relapse rates. In addition, ANCOVA showed a significant difference between two groups in resiliency enhancement at periods of post test and follow up (p<0/001). Study results indicated that coping skills training is effective in resiliency enhancement and relapse prevention in people with substance dependency.

The role of higher thoracic irradiation doses in patients with limited stage of small-cell lung cancer: Retrospective study

Background: Small-cell lung cancer is highly chemo- and radiosensitive tumor. We evaluated two different radiotherapy doses applied sequentially with chemotherapy in relation to time to progression, progression free survival, and overall survival in patients with limited disease of small cell lung cancer. Methods: From 1998 to 2003, 81 patients were treated for small-cell lung carcinoma. Median age was 57 years (range, 36-77 years) and female: male ratio was 1:4. Patients were initially treated with four cycles of chemotherapy during three weeks (cisplatin 80mg/m2 IV, day 1 and etoposide 100 mg/m2 IV, days 1 - 3). One month later, patients received up to 44 Gy, 2 Gy per day, 5 days per week (group I, 41 patients) or above 44 Gy, standard fractionation (group II, 40 patients), to mediastinum and tumor. Range of higher radiotherapy doses was 54 Gy to 64 Gy, standard fractionation. We evaluated if different radiotherapy doses had any influence on time to progression, progression free survival, and overall survival. Results: The median follow up time was 23 months (range, 12-72 months) for both groups of patients (81). The median time to progression in group I of patients (41) was 13 months (range, 11-29 months) while median time to progression in group II of patients (40) was 20 months (min=9, max=60). There was no statistically significant difference in relapse rate between two groups of patients (p&gt;0.05, Fisher test). However, there was difference but not statistically significant in one-year progression free survival (p=0.05, chi square test) between groups, while there was statistically significant difference in two-year progression free survival favoring higher doses of radiotherapy (p&lt;0.05, chi-square test). The median overall survival was 18 months (range, 12-35 months) for group I of patients and 28 months (range, 15-72 months) for group II of patients. There was no statistically significant advantage between two groups of patients for one-year overall survival (p&gt;0.05, chi-square test). However, there was statistically significant difference in overall survival favoring higher radiotherapy doses for two-year overall survival (p&lt;0.05, chi-square test). Conclusion: We found that higher radiotherapy doses had an impact on long-term time to progression, progression free survival, and overall survival (2 years) of patients.

Interferon for the treatment of genital warts: a systematic review

BackgroundInterferon has been widely used in the treatment of genital warts for its immunomodulatory, antiproliferative and antiviral properties. Currently, no evidence that interferon improves the complete response rate or reduces the recurrence rate of genital warts has been generally provided. The aim of this review is to assess, from randomized control trials (RCTs), the efficacy and safety of interferon in curing genital warts.MethodsWe searched Cochrane Sexually Transmitted Diseases Group's Trials Register (January, 2009), Cochrane Central Register of Controlled Trials (2009, issue 1), PubMed (1950-2009), EMBASE (1974-2009), Chinese Biomedical Literature Database (CBM) (1975-2009), China National Knowledge Infrastructure (CNKI) (1979-2009), VIP database (1989-2009), as well as reference lists of relevant studies. Two reviewers independently screened searched studies, extracted data and evaluated their methodological qualities. RevMan 4.2.8 software was used for meta-analysisResults12 RCTs involving 1445 people were included. Among them, 7 studies demonstrated the complete response rate of locally-used interferon as compared to placebo for treating genital warts. Based on meta-analysis, the rate of Complete response of the two interventions differed significantly (locally-used interferon:44.4%; placebo:16.1%). The difference between the two groups had statistical significance (RR 2.68, 95% CI 1.79 to 4.02, P < 0.00001). 5 studies demonstrated the complete response rate of systemically-used interferon as compared to placebo for treating genital warts. Based on meta-analysis, the rate of Complete response of the two interventions had no perceivable discrepancy (systemically-used interferon:27.4%; placebo:26.4%). The difference between the two groups had no statistical significance (RR1.25, 95% CI 0.80 to 1.95, P > 0.05). 7 studies demonstrated the recurrence rate of interferon as compared to placebo for treating genital warts. Based on meta-analysis, the recurrence rate of the two interventions had no perceivable discrepancy(interferon 21.1%; placebo: 34.2%). The difference between the two groups had no statistical significance (RR0.56, 95% CI 0.27 to 1.18, P > 0.05). However, subgroup analysis showed that HPV-infected patients with locally administered interferon were less likely than those given placebo to relapse, but that no significant difference in relapse rates was observed between systemic and placebo. The reported adverse events of interferon were mostly mild and transient, which could be well tolerated.ConclusionInterferon tends to be a fairly well-tolerated form of therapy. According to different routes of administration, locally-used interferon appears to be much more effective than both systemically-used interferon and placebo in either improving the complete response rate or reducing the recurrence rate for the treatment of genital warts.

Long-term follow-up after ovarian borderline tumor: Relapse and survival in a large patient cohort

Objectives To assess long-term survival and relapse rate of patients diagnosed with a borderline tumor of the ovary (BOT) with special focus on the influence of primary surgery. Study design All women diagnosed and treated for BOT between 1983 and 2006 at our institution were included in this retrospective study. Clinical data including operative procedure, stage and histology at first diagnosis as well as follow-up data were analyzed with reference to survival times and relapse rates. Results Altogether 113 patients could be identified, including 19 women treated with fertility sparing surgery (19.2%). Mean follow-up time was 9.6 ± 6.6 years. Relapse occurred during the follow-up period in 10 patients (10.1%) with a mean time to recurrence of 2.0 ± 1.7 years. Patients with recurrent disease had a statistically significantly worse survival: 5- and 10-year survival rates were 90.0 and 80.0% compared with 98.9 and 94.4% for those without ( p = 0.0208), respectively. Relapse rate was 7.1% in early borderline patients (Ia: 4/56) and 14% (>Ia: 6/43) for all others ( p = 0.436). Patients with invasive implants had a statistically significantly higher relapse rate ( p = 0.0112). No significant difference in relapse rates or survival was observed between the histological subtypes. Five- and 10-year survival rates of women treated with fertility sparing surgery ( n = 19) were 100% and thus not worse than those of radically operated patients (5- and 10-year survival 95.1 and 90.1%). Relapse rates in both groups were comparable with 10.5 and 10.0% ( p = 0.723). The surgical procedure with lymphadenectomy vs. without had no influence on relapse or survival, neither did laparoscopy vs. laparotomy. Conclusion Our findings confirm the good prognosis of BOT in general. Patients with invasive implants have higher relapse rates. Fertility sparing surgery in women at childbearing age can be an adequate treatment option in early stage disease.

Long-Term Smoking Cessation Outcomes Among Childhood Cancer Survivors in the Partnership for Health Study

Partnership for Health (PFH) was found to increase smoking cessation among smokers in the Childhood Cancer Survivors Study (CCSS) at the 8- and 12-month postbaseline follow-up. This report provides outcomes at 2 to 6 years postbaseline; the primary outcome is a four-category smoking status variable (quit at all follow-ups, quit at final follow-up only, smoker at all follow-ups, and smoker at final follow-up only); quit attempts among those who reported smoking at the final follow-up is a secondary outcome. PFH was a randomized control trial with two conditions, peer phone counseling (PC) and self-help (SH), that involved smokers (n = 796) enrolled in the CCSS cohort. Long-term quit rates were higher in PC versus SH participants. Long-term smoking cessation outcomes were lower among those who were nicotine dependent, of lower educational levels, and among men, and were higher among those who used nicotine replacement therapy and who had higher levels of situational self-efficacy. There were no significant differences in relapse rates between conditions or in quit attempts among continued smokers. Cessation rates continue to be significantly higher among participants in the PC condition versus SH, although the differences were not large. This article highlights differences in long-term engagement with smoking cessation among those who received the intervention.

Outcome of Patients with Myeloproliferative Disorders Treated with Allogeneic Hematopoietic Stem Cell Transplantation

Myeloproliferative disorders (MPD) are characterized by marrow clonal proliferation leading to ineffective hematopoiesis. Between 1998 and 2007, 27 patients (pts) with myeloproliferative disorders were treated with hematopoietic stem cell transplantation. Patients included 9 males (33%) and 18 females (67%) with a median age of 52 years (range 30–68). Diseases included Philadelphia chromosome-negative chronic myelogenous leukemia (CML) (n=2, 7%), myelofibrosis (n=21, 78%), polycythemia vera (n=2, 7%) and essential thrombocythemia (n=2, 7%). Twelve patients (44%) had abnormal cytogenetics, 24 pts (89%) had splenomegaly and 9 pts (33%) had a prior splenectomy. Preparative regimens included busulfan and cyclophosphamide (n=11, 41%), cyclophosphamide and total body irradiation (n=3, 11%), fludarabine and busulfan (n=3, 11%), fludarabine and cyclophosphamide (n=1, 4%), fludarabine and melphalan (n=7, 26%), and fludarabine with low dose total body irradiation (n=2, 7%). Patients with unrelated donors also received ATG. Twelve patients received an unrelated donor product, 7 pts received bone marrow and 20 pts received peripheral blood stem cells.The 5-year overall Kaplan-Meier product-limit survival estimates (figure 1.) was 60.9%. The day 100 transplant-related mortality was 18.5%, all in patients receiving either cyclophosphamide and total body irradiation or cyclophosphamide and busulfan. Overall, there were twice as many deaths in patients receiving a non-fludarabine-based regimen (n=7, 25.9%) compared with patients receiving a fludarabine-based regimen (n=3, 11.1%) though the difference was not statistically significant (p=0.15). The overall incidence of grade II–IV acute GVHD was 44% and chronic GVHD was 64%. The overall relapse rate was 16%. No significant differences in relapse rates by acute (p=0.40) and chronic GVHD (p=0.53) or by fludarabive vs non-fludarabine based regimens (p=0.24) were observed. In univariate Cox proportional hazard models, chronic GVHD was the only significant factor associated with worse survival (p=0.035).In conclusion, myeloproliferative disorders can be successfully treated with allogeneic hematopoietic stem cell transplantation. Chronic GVHD significantly reduces overall survival. The optimal preparative regimen still remains to be determined. [Display omitted]

Prognostic Significance of NQO1 Polymorphism and GST-M1 Deletion in De Novo Acute Myeloid Leukemia

Background: Although the most powerful prognostic factor of acute myeloid leukemia (AML) patients is the karyotype of the leukemic blast, data have not been obtained almost entirely in patients with heterogeneous cytogenetics. Further, some patients with favorable cytogenetics may show the poor treatment outcomes. Previous reports suggested that the single nucleotide polymorphisms of genes coding drug detoxification enzymes such as cytochrome P450 family or DNA repair system may influence the treatment outcomes in the patients with AML. We evaluated the role of polymorphisms in XRCC1, XRCC4, CYP1A1, GST-T1, GST-M1, NOQ1, and NAT2*6A in predicting therapeutic outcomes of adults with AML.Methods:XRCC1 (rs25487), XRCC4 (rs1056503), NQO1 (rs1800566), CYP-4501A1*2B (rs1048943), NAT2*6A (rs1799930) gene polymorphisms and deletion of GST-M1/GST-T1 were evaluated in 460 bone marrow (BM) samples obtained at initial diagnosis from de novo AML patients. Genotyping method is pyrosequencing using genomic DNA from BM samples. Homozygous deletions of GST-M1 and GST-T1 genes were detected with a multiplex PCR technique. All patients except APL (acute promyelocytic leukemia) received one or two rounds of intensive induction chemotherapy consisting of 3 days of idarubicin and 7 days of cytarabine. APL patients treated with AIDA regimen consisting of 45 days of ATRA (all-trans retinoic acid) and 3 days of idarubicin.Results: Of total 460 patients, ninety-nine patients (21.5%) were APL. Seventy-one (15.4%) were AML with t(8;21), twenty-three (5%) were AML with inv(16), and 179 patients (38.9%) showed normal cytogenetics. The median age of patients was 44 years (range, 14–75 years). In all cytogenetic risk group, the patients carrying homozygous NQO1 gene polymorphism (TT) showed significantly lower rate of complete remission (CR) than in those with negative or heterogyzous polymorphisms (TT: 72.7% vs. CC/CT: 85.9%, p=0.03). There was no significant difference in relapse rate, leukemia-free survival (LFS) and overall survival between homo- and heterozygote groups in these polymorphsims. In subgroup analysis, APL patients carrying TT genotype in NQO1 also showed lower rate of CR (TT: 77.8% vs. CC/CT: 95.4%, p=0.04). In AML patients except APL, NQO1 homozygous polymorphsim (TT) was also associated with lower CR rate (TT: 69.6% vs. CC/CT: 84.2%, p=0.005). In normal cytogenetics, the patients with del GST-M1 showed shorter LFS compared with those carrying GST-M1 (18.0 ± 5.7ms. vs. 34.6 ± NA. p=0.04).Conclusions: This study revealed an association between NQO1 polymorphism and GST-M1 deletion and the treatment outcomes for AML patients. Further study and larger sample size are needed to reach the definite conclusion on these associations. However, a stratified treatment plan in remission induction chemotherapy such as augmentation or addition of other chemotherapeutic agents may be warranted for AML patients harvoring homozygous NQO1 polymorphism (TT) or del GST-M1.

The combined evaluation of interim contrast-enhanced computerized tomography (CT) and FDG-PET/CT predicts the clinical outcomes and may impact on the therapeutic plans in patients with aggressive non-Hodgkin’s lymphoma

We investigated the concomitant interim response of patients with aggressive non-Hodgkin's lymphoma (NHL) using multi-detector row computerized tomography (CT) and (18)F-fluoro-2-deoxy-D: -glucose-positron emission tomography (PET)/CT for prediction of clinical outcomes. One hundred six newly diagnosed patients with aggressive NHL were enrolled. Both the CT and PET/CT were serially performed at the time of diagnosis and after three to four cycles of chemotherapy (interim). The patients were categorized into four different responsive groups according to the interim PET/CT and CT: (1) complete metabolic response (CMR)-complete response unconfirmed (CRu), (2) CMR-partial response (PR), (3) partial metabolic response (PMR)-Cru, and (4) PMR-PR. Fifty-five patients with CMR-CRu, 20 patients with CMR-PR, seven patients with PMR-Cru, and 23 patients with PMR-PR were distributed. In addition, one patient experienced a disease progression. There was a significant difference in relapse rates between PET/CT-positive (67.3%) and PET/CT-negative patients (17.3%; P < 0.01). Also, there was a significant difference between patients with PMR-PR (32.0% and 26.1%) and CMR-CRu (89.3% and 80.0%) for 3-year overall survival (OS) and event-free survival (EFS), respectively. A multivariate analysis revealed that high international prognostic index (> or =3) at diagnosis, T-cell phenotype, and PMR-PR in interim PET/CT and CT were independent prognostic significances for OS. Moreover, bulky disease (>10 cm), T-cell phenotype, and PMR-PR showed significant associations for EFS. PMR-PR in interim response was the predictive prognostic determinant for both OS and EFS, with a hazard ratio of 3.93 (1.61-9.60) and 3.60 (1.62-7.98), respectively. The combined evaluation of interim PET/CT and CT was found to be a significant predictor of disease progression, OS, and EFS.

Preventing relapse of depression in primary care: a pilot study of the “Keeping the blues away” program

To determine the effectiveness of "Keeping the blues away" (KBA), a manualised depression relapse prevention program for general practice, in reducing the relapse of depression compared with usual care (with the aim of halving the relapse rate), and in reducing depression severity and improving the process of care. A cluster randomised controlled trial conducted in 2004-2005 in South Australian general practices. 43 general practitioners from 23 urban and rural practices recruited 110 patients with depression (age range, 18-75 years). GP training manual or patient manual and relaxation CD; 20 hours of training on depression, the study protocol, assessment tools and skills. Relative risk (RR) of depression relapse; depression severity and quality of life scores. There were no significant differences in relapse rates between the groups (chi(2)(1) = 1.51; P = 0.23), although there was a non-significant tendency for relapse to be reduced in the KBA group (RR = 0.77; 95% CI, 0.50-2.05). Older patients (> or = 50 years) in the KBA group showed a significantly lower probability of relapse than those in the control group (P = 0.018). There was a decrease in depression scores in both groups. KBA participants had more severe depression at baseline, and the reduction in severity in those with symptoms for > 6 months was nearly significant (P = 0.06). KBA was positively received by GPs and patients. Although this pilot study of a small sample did not achieve its primary outcome of reducing depression relapse by 50%, KBA was found to be a promising program for older patients and for those with more severe or persistent symptoms.