Predictive Factors For Relapse Research Articles

Association of CD34 Expression with Future Relapse in Pediatric T-cell Acute Lymphoblastic Leukemia

Background: Developing novel prognostic markers is crucial for childhood T-cell acute lymphoblastic leukemia (T-ALL). Objectives: This study aimed to investigate whether the prognostic impact of CD34, a progenitor marker, is associated with outcomes. Methods: This retrospective cohort study included 82 risk-adapted pediatric patients with T-ALL who were treated under the National Protocol of Childhood ALL in China (NPCLC)-ALL2008 from March 2008 to December 2016. Results: CD34 expression was observed in 37.8% of all T-ALL patients, with a median expression level of 62.7%. Patients with CD34 expression had a favorable event-free survival (EFS, 74.2% [66.3% - 82.1%]) with a hazard ratio of 0.69 (P = 0.33) and a reduced cumulative incidence of relapse (CIR, 22.6% [15.0% - 30.2%]; P = 0.86) at five years. Even after adjusting for potential factors and competing events in multivariable regression models, there was no connection between the CD34 immunophenotype and the risk of recurrence. Conclusions: CD34 expression did not serve as a predictive factor for relapse in this limited series. Larger multicenter studies are recommended to determine whether this biomarker at initial diagnosis can predict outcomes.

De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice

Background and objectivesCombination therapy with an immunomodulator (IMM) and an anti-TNF is commonly recommended in Crohn's disease (CD) and ulcerative colitis (UC) patients. However, little is known about relapse rates after therapeutic de-escalation. This study aimed to evaluate the risk of relapse in a cohort of UC and CD patients with long-standing clinical remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse. MethodsThis retrospective study included patients with UC or CD on combination therapy and clinical remission for at least 6 months. IMM or anti-TNF was stopped upon physician decision. Primary objective was to evaluate the relapse rates after discontinuation of IMM or anti-TNF and to analyze predictors of relapse. ResultsThe study included 88 patients, 48 patients (54.5%) discontinued IMM and 40 (45.5%) anti-TNF. During follow-up, relapse rates were 16.7% and 52.5% in the IMM discontinuation group and anti-TNF discontinuation group, respectively (p<0.001). Multivariate analysis showed that anti-TNF discontinuation (HR=3.01; 95% CI=1.22–7.43) and ileal CD location (HR=2.36; 95% CI=1.02–5.47) were predictive factors for relapse while inflammatory CD phenotype was a protective factor (HR=0.32; 95% CI=0.11–0.90). Reintroduction of anti-TNF upon relapse was effective and safe. ConclusionAnti-TNF discontinuation led to significantly higher relapse rates compared to IMM discontinuation in UC and CD patients on combination therapy. Anti-TNF discontinuation and ileal CD location were identified as predictive factors for relapse while inflammatory CD phenotype was a protective factor. Retreatment after anti-TNF discontinuation was effective and safe.

DOP75 Frequency and effectiveness of dose escalation of biologic therapy in Inflammatory Bowel Disease: The RAINBOW-IBD study of ENEIDA

Abstract Background Despite their effectiveness in inflammatory bowel disease (IBD), biologic drugs often require dose escalation. Primary aim: To describe the frequency and effectiveness of dose escalation of biologics: infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST). Secondary: To study the reasons for and the durability of escalation, and to identify predictive factors for relapse and for therapy discontinuation after it. Methods Adult patients from ENEIDA registry who received biologics were included. Dose escalations were specifically analysed. Survival curves assessing the impact of several variables on the durability and on clinical relapse were compared using the log-rank test. Predictive factors associated with therapy discontinuation and the risk of relapse after dose escalation were assessed by Cox-regression. Results Out of the 19,720 patients with biologics included in ENEIDA, 5,096 (26%) had their dose escalated, which were analysed. The frequency of escalation per patient-year of follow-up was: 5% (95% confidence interval [CI]=4.3-5.6%), 7% (6.3-7.7%), 7% (6.9-7.1%), 10% (9.9-10.1%), and 12% (11.9-12.1%) in patients receiving IFX, ADA, GOL, VED and UST, respectively (Figure 1). The main reason for dose escalation was loss of response (60%). Remission and clinical response were recaptured after dose escalation, respectively, in: 49% and 89% (IFX), 41% and 86% (ADA), 46% and 85% (GOL), 32% and 87% (VED), and 47% and 92% (UST). The probability of maintaining the dose escalated at 12 and 24 months was: 88% and 78% (IFX); 82% and 71% (ADA); 82% and 66% (GOL); 84% and 75% (VED); and 93% and 88% (UST), respectively (Figure 2). Predictive factors of relapse after re-achieving remission with dose escalation were: 1) IFX: previous biologic exposure (Hazard ratio [HR]=1.2, 95%CI=1.1-1.4), and IBD duration (HR=0.97, 95%CI=0.96-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.01-1.35); 3) VED: Crohn’s disease (HR=1.56, 95%CI=1.1-2.2), and IBD duration (HR=0.9, 95%CI=0.8-0.99); and 4) UST: ulcerative colitis (HR=2.4, 95%CI=1.5-3.9). Predictive factors of therapy discontinuation after dose escalation were: 1) IFX: previous biologic exposure (HR=1.2, 95%CI=1.1-1.4), and disease duration (HR=0.98, 95%CI=0.97-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.1-1.25); and 3) UST: ulcerative colitis (HR=1.4, 95%CI=1.1-1.9). Conclusion A proportion of IBD patients dose escalate biologics in the long-term. Dose escalation is an effective strategy to recapture response and remission. The durability of escalation seems to be relatively high over time. Prior biologic experience, IBD type, and a short evolution of IBD were identified as predictive factors of relapse and therapy discontinuation after dose escalation.

P844 Frequency and effectiveness of dose de-escalation of biologic therapy in Inflammatory Bowel Disease: The RAINBOW-IBD study of ENEIDA

Abstract Background Biologic dose escalation is associated with increased costs and potential safety concerns; therefore, de-escalation could be considered in patients in remission after dose escalation. However, data on de-escalation outcomes is scarce. Primary aim: To describe the frequency and the evolution after de-escalation of infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST). Secondary: To investigate the durability of dose de-escalation, the factors associated with relapse after de-escalation, and the effectiveness of a re-escalation. Methods Adult patients from ENEIDA registry who previously had their biologic dose escalated, were included. De-escalations (either decreasing the dose or lengthening the interval of administration) were specifically analysed. Survival curves assessing the impact of several variables on clinical relapse were compared using the log-rank test. Predictive factors associated with the risk of relapse after dose de-escalation were assessed by Cox-regression. Results A total of 669 de-escalations from 5,096 previous dose escalations were performed (13%). The incidence rate of dose de-escalation per patient-year of follow-up was: 6% (95% confidence interval [CI]=5.8-6.2%), 9% (7.4-10.7%), 5% (1-9%), 6% (5.4-6.6%), and 3% (2.9-3.1%) in patients receiving IFX, ADA, GOL, VED and UST, respectively (Figure 1). The favourable evolution after dose de-escalation (maintaining remission or response) was: 106/132 (80%) and 131/132 (99%) for IFX; 157/209 (75%) and 208/209 (99%) for ADA; 5/5 (100%) and 5/5 (100%) GOL; 14/16 (88%) and 16/16 (100%) for VED; and 9/12 (75%) and 11/12 (92%) for UST. The probability of maintaining the dose de-escalated at 12 months was: 86%, 86%, 88%, 82%, and 90% for IFX, ADA, GOL, VED and UST, respectively (Figure 2). Predictive factors of relapse after de-escalation were as follows: 1) IFX: previous biologic exposure (Hazard ratio [HR]=2.7, 95%CI=1.1-6.9), and 2) ADA: age at dose de-escalation (HR=1.08, 95%CI=1.02-1.15). Variables associated with the risk of relapse with other biologics could not be identified. Response and remission were recaptured after re-escalation, respectively, in: 11/12 (92%) and 7/12 (58%) for IFX; 22/22 (100%) and 13/22 (59%) for ADA; 1/1 (100%) and 0/1 (0%) for GOL; 2/2 (100%) and 2/2 (100%) for VED; and 1/1 (100%) and 1/1 (100%) for UST. Conclusion In the largest cohort of patients with dose escalation of biologic treatment in real-life, approximately 10% of the patients have a dose de-escalation in the long-term. If carried out, the durability of the de-escalation seems to be high over time. In those who relapse after dose de-escalation, re-escalation of therapy is effective in more than half of the patients.

Predictor factors for recurrence in atypical meningiomas.

Atypical meningiomas (AMs), World Health Organization (WHO) grade 2, are a group of tumors with uneven and unpredictable clinical behavior. Our aim was to analyze possible tumor recurrence predictors, and to identify factors that improve progression-free survival (PFS). Our retrospective study included 81 patients followed up in the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iaşi, Romania, between 1 January 2010 and 31 December 2020. The histopathological specimens were reviewed according to the WHO 2021 criteria. Analyses included clinical, imaging, pathological and surgical factors. The tumor recurred in 53.1% of the 81 cases within 60 months of surgery. Tumor location (p<0.000), tumor volume (p<0.010), extent of surgical resection (p<0.000) and dural sinus invasion (p<0.001) were predictive factors of recurrence. Gross total resection (Simpson grade I and II) was achieved in 59.2% of patients. Patients with the tumors located in the brain convexity and volume <26.4 cm³ had better survival rates up to recurrence. PFS showed a significant relationship between Simpson grade I-III and biopsy (p<0.000) and was statistically influenced by tumor volume and location, and dural sinus invasion. AMs are a heterogeneous group of tumors, and we identified posterior fossa location, volume ≥26.4 cm³, Simpson grade III and IV resection and dural sinus invasion as predictive factors for relapse and a shorter PFS. Whereas certain characteristics provide some prognostic value, future molecular characterizations of AMs are necessary, which will support the clinical decision-making process.

De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice

Background and objectivesCombination therapy with an immunomodulator (IMM) and an anti-TNF is commonly recommended in Crohn's disease (CD) and ulcerative colitis (UC) patients. However, little is known about relapse rates after therapeutic de-escalation. This study aimed to evaluate the risk of relapse in a cohort of UC and CD patients with long-standing clinical remission after discontinuation of IMM or anti-TNF and to identify predictive factors for relapse. MethodsThis retrospective study included patients with UC or CD on combination therapy and clinical remission for at least 6 months. IMM or anti-TNF was stopped upon physician decision. Primary objective was to evaluate the relapse rates after discontinuation of IMM or anti-TNF and to analyze predictors of relapse. ResultsThe study included 88 patients, 48 patients (54.5%) discontinued IMM and 40 (45.5%) anti-TNF. During follow-up, relapse rates were 16.7% and 52.5% in the IMM discontinuation group and anti-TNF discontinuation group, respectively (p<0.001). Multivariate analysis showed that anti-TNF discontinuation (HR=3.01; 95% CI=1.22–7.43) and ileal CD location (HR=2.36; 95% CI=1.02–5.47) were predictive factors for relapse while inflammatory CD phenotype was a protective factor (HR=0.32; 95% CI=0.11–0.90). Reintroduction of anti-TNF upon relapse was effective and safe. ConclusionAnti-TNF discontinuation led to significantly higher relapse rates compared to IMM discontinuation in UC and CD patients on combination therapy. Anti-TNF discontinuation and ileal CD location were identified as predictive factors for relapse while inflammatory CD phenotype was a protective factor. Retreatment after anti-TNF discontinuation was effective and safe.

P418 Dose escalation of oral 5-aminosalicylic acid for ulcerative colitis with Mayo endoscopic subscore of one improves long-term prognosis: a one-year multicentre, open-label, randomized controlled trial.

Abstract Background Endoscopic healing, one of the treatment targets for ulcerative colitis (UC), is commonly defined as Mayo endoscopic sub-score (MES) ≤1. Furthermore, patients in whom MES of 0 is achieved are at a lower risk of relapse than those with MES of 1. However, it is unclarified whether the therapeutic intervention of dose escalation of oral 5-aminosalicylic acid (5-ASA) improves the prognosis of UC patients in clinical remission with MES of 1. Methods A multicentre, open-label, randomized, controlled trial was conducted among 5 hospitals in Japan from March 2018 to June 2022. Patients with UC, aged 16 years or older, treated with 5-ASA, in clinical remission and confirmed MES of 1 were enrolled. Patients receiving maintenance therapy other than oral 5-ASA and thiopurine (e.g., topical therapy, biologics) were excluded. Patients were randomly assigned to either the therapeutic intervention group (increased the dose of 5-ASA) or the control group (without any intervention). Concomitant use of immunomodulator (IM) was used for the stratification factor in the randomization. The primary endpoint was clinical relapse within one year. Relapse was defined as both (1) pMayo ≥3 or rectal bleeding sub-score ≥1, and (2) addition of any induction treatments for UC including topical agents. Predictive factors for relapse and adverse events (AEs) were investigated as the secondary outcomes. The predictive factors were explored in the multivariable Cox regression analysis. Results Eighty-one patients were enrolled and randomly assigned into the therapeutic intervention or the control group, and two patients were excluded due to important protocol violations after the randomization. Finally, 79 patients (n=39; therapeutic intervention, n=40; control) were included in the full analysis set (FAS). In the FAS, 46 (58.2%) patients were male, and 20 (25.3%) patients were treated with IMs. The relapse within one year was less in the therapeutic intervention group (6/39; 15.4%) than the control group (15/40; 37.5%), significantly (P =0.026) (Fig.1). In the exploratory analysis for the predictors, concomitant use of IM was associated with relapse (hazard ratio, 2.52; 95% confidence interval, 1.04-6.12, P =0.041). There were three AEs in the therapeutic intervention group. Two patients complained of nausea, and the other complained of diarrhea and melena. All the AEs were improved after turning back the treatment to that before the intervention. Fig. 1. The proportion of patients relapsed within one year in the full analysis set (primary analysis). Conclusion The dose escalation of oral 5-ASA reduced the relapse within one year in UC patients in clinical remission with MES of 1.

Predictive factors for relapse in corticosteroid-treated patients with chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterised by an abnormal and marked accumulation of eosinophils in the interstitium and alveolar spaces of the lungs. Systemic corticosteroid (CS) therapy leads to marked improvement. However, relapse is common in the clinical course, and the predictive factors for relapse of CEP are not well known. This study aimed to investigate predictive factors for relapse in CS-treated cases of CEP. We identified consecutive patients with CEP at our institution between 1999 and 2019. We retrospectively reviewed 36 CS-treated patients with CEP who underwent bronchoalveolar lavage (BAL) and high-resolution computed tomography (CT) at diagnosis. We examined relapse at least 1 year after the initiation of CS treatment. Statistical analysis included univariate and multivariate Cox proportional hazard regression analyses; P<0.05 was considered statistically significant. The median (interquartile range) age at diagnosis was 59.5 years (47.8-70.0 years). This study included 13 men and 23 women. Twenty-five patients (69.4%) were never smokers and 15 (41.7%) had asthma. The peripheral blood eosinophil percentage was 35.0% (15.6-55.8%), and the BAL eosinophil percentage was 40.8% (10.7-68.5%). The median serum surfactant protein-D (SP-D) level was 135 ng/mL (82.2-176.7 ng/mL). High-resolution CT revealed centrilobular opacities in 23 patients (63.9%). Relapse of CEP was observed in 20 patients (55.6%). Higher serum SP-D levels and the presence of centrilobular opacities on high-resolution CT were significant predictors of relapse in multivariate Cox proportional hazard regression analysis (P=0.017 and P=0.028, respectively). Additionally, we devised a relapse prediction model for CS-treated CEP using two categorical parameters: the presence of centrilobular opacities and serum levels of SP-D (>135/≤135 ng/mL). Based on these parameters, cases were scored 2, 1, or 0. Patients with a score of 2 experienced relapses earlier than those with scores of 1 and 0 (log-rank test; P=0.006, P=0.003, respectively). Centrilobular opacities on high-resolution CT and higher serum SP-D levels at diagnosis may be predictive factors for relapse in CS-treated patients with CEP.

Cluster analysis reveals eosinophilia and fibrosis as poor prognostic markers in 128 patients with eosinophilic fasciitis

Eosinophilic fasciitis (EF) is an extremely rare disease with polymorphic presentation and prognosis. To further investigate EF features. We performed a retrospective multicentre study of EF patients from 2013 to 2019, clustered patients using multivariate correspondence analysis, and sought prognosis factors. One hundred twenty-eight patients were included. Sixty-nine (50%) patients had skin sclerosis, and eosinophil count was increased in 71 (55%) patients. Multivariate correspondence analysis identified 3 clusters: a "mild," a "late-onset and hypereosinophilic," and a "fibrotic" cluster. Of 109 patients who followed up for more than 1year, 49 (45%) presented a relapse, and 48 (44%) had sequelae. Multivariate analysis revealed that eosinophilia (hazard ratio=1.56; P = .02) and fibrosis (hazard ratio=4.02; P = .002) were predictive factors of relapse, whereas edema (odds ratio=0.31; P = .03), relapse (odds ratio=3.00; P= .04) and fibrosis (odds ratio=1) were predictive factors of sequelae. Following relapse, treatment modifications consisted of an increase in glucocorticoids in 40 (82%) patients and the addition of methotrexate in 31 (63%) patients. These modifications led to clinical improvement and glucocorticoid withdrawal in 37 (76%) and 22 (45%) patients. Retrospective study. EF patients can be divided into 3 homogenous clusters, which, along with fibrosis and eosinophilia, are prognosis factors of relapse and sequelae.

P16‐15: Predictive factors for relapse in corticosteroid‐treated patients with chronic eosinophilic pneumonia

P16‐15: Predictive factors for relapse in corticosteroid‐treated patients with chronic eosinophilic pneumonia

Predictive factors of relapse after dose reduction of oral 5-aminosalicylic acid in patients with ulcerative colitis in the remission phase.

Useful indices to determine whether to reduce the dose of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis (UC) during remission remain unclear. We aimed to analyze the rate and risk factors of relapse after reducing the dose of oral 5-ASA used for maintenance therapy of UC. UC patients whose 5-ASA dose was reduced in clinical remission (partial Mayo score of ≤ 1) at our institution from 2012 to 2017 were analyzed. Various clinical variables of patients who relapsed after reducing the dose of oral 5-ASA were compared with those of patients who maintained remission. Risk factors for relapse were assessed by univariate and multivariate logistic regression analyses. Cumulative relapse-free survival rates were calculated using the Kaplan-Meier method. A total of 70 UC patients were included; 52 (74.3%) patients maintained remission and 18 (25.7%) patients relapsed during the follow-up period. Multivariate analysis indicated that a history of acute severe UC (ASUC) was an independent predictive factor for clinical relapse (p = 0.024, odds ratio: 21, 95% confidence interval: 1.50-293.2). Based on Kaplan-Meier survival analysis, the cumulative relapse-free survival rate within 52 weeks was 22.2% for patients with a history of ASUC, compared with 82.0% for those without. the log-rank test showed a significant difference in a history of ASUC (p < 0.001). Dose reduction of 5-ASA should be performed carefully in patients who have a history of ASUC.

TMB and BRAF mutation status are independent predictive factors in stage IIIC/D/IV melanoma patients receiving adjuvant PD-1 antibodies.

9524 Background: High tumor mutational burden (TMB) is associated with a favorable outcome in metastatic melanoma patients treated with immune checkpoint inhibitors. However, data are limited in the adjuvant setting. As BRAF mutated patients have an alternative with targeted adjuvant therapy, it is important to identify predictive factors for relapse and recurrence-free survival (RFS) in patients receiving adjuvant PD-1 antibodies. Methods: We systematically evaluated all melanoma patients who started adjuvant PD-1 antibody therapy at our center between March 2018 and September 2019 to identify predictive factors for outcome. The median follow-up time from start of adjuvant anti-PD-1 therapy was 22 months. Tumor and normal tissue of all stage IIIC/D/IV patients and of stage IIIA/B patients with relapse were sequenced using a 700 genes panel. Predictive factors for relapse and RFS were identified using univariate and multivariate logistic and Cox regression analysis. RFS was estimated by the Kaplan-Meier method. TMB high was defined as the top 20 % of the cohort, corresponding to TMB values ≥ 20 Var/Mb. Results: A total of 165 patients were included in this study. According to AJCC 8th the initial tumor stages at the beginning of adjuvant anti-PD-1 therapy were as follows: N = 80 stage IIIA/B (48 %), N = 85 stage IIIC/D/IV (52 %). 72/165 patients (44 %) suffered a relapse, 44/72 (61 %) with loco regional and 28/72 (39 %) with distant metastases. Sequencing results were available from 79 / 85 patients with stage IIIC/D/IV. Here we present the results of this cohort. TMB low (OR 17.46, 95%CI 4.03-75.55; p &lt; 0.0001) or absence of BRAF V600E/K mutation (OR 4.13, 95%CI 1.36-12.53; p = 0.012) were statistically significant, independent predictive factors for relapse. Also, with regard to RFS, BRAF mutation status and TMB were statistically significant and independent predictive factors. In the table below we display results for the combined variables. Patients with BRAF V600E/K mutation and TMB high had the best outcome. Conclusions: We identified TMB high as positive predictive marker in stage IIIC/D/IVmelanoma patients with adjuvant PD-1 antibody therapy. In tumors with BRAF V600E/K mutation and concurrent low TMB, adjuvant targeted therapy with BRAF- and MEK-inhibitors may be an alternative. This is also supported by the data on adjuvant dabrafenib and trametinib, which showed a greater advantage in patients with low TMB, presumably due to less tumor heterogeneity.[Table: see text]

A prospective phase I/IIa trial to evaluate the safety and efficacy of GTA002, an off-the-shelf, ex vivo-cultured allogeneic NK cell preparation in patients with acute myeloid leukemia in complete morphological remission who have measurable residual disease.

TPS7053 Background: Acute myeloid leukemia (AML) is a malignant disease with poor long-term prognosis in patients who cannot achieve morphological and molecular remission. Although insights into AML biology and treatment modalities have improved over recent years and even though many patients achieve morphological complete remission (CR), most are still relapsing. These relapses are due to residual leukemia stem cells that can be identified as minimal/measurable residual disease (MRD), with MRD serving as a predictive factor for relapse and mortality. Elimination of MRD in patients having reached CR is seen as essential for optimal and persistent clinical responses. A promising approach is the development of adoptive immunotherapies aimed at directly eradicating tumor cells using T-cells or natural killer (NK) cells. NK cells are part of the body’s innate immune system and play a key role in controlling viral infections and conducting tumor immunosurveillance. Furthermore, NK cells can be applied clinically in an allogeneic setting, enabling the supply of high numbers of immune effector cells, which were not exposed to cytotoxic chemotherapeutics. A proprietary ex vivo expansion and differentiation method in a fully closed, automated manufacturing platform was developed to generate GTA002, an “off-the-shelf” (allogeneic), cryopreserved NK cell preparation, generated from CD34+ hematopoietic stem and progenitor cells derived from umbilical cord blood. The safety and tolerability of the product was already demonstrated in a Phase I trial in elderly patients with AML (PMLA25) (Dolstra et al. 2017). Methods: We are currently conducting a prospective 2-stage, open-label, single arm, multicenter Phase I/IIa trial to evaluate the safety and efficacy of GTA002 in 33 adults with AML who are in CR with MRD and who are not proceeding to allogeneic HSCT (ClinicalTrials.gov Identifier: NCT04632316). Patients enrolled in the clinical trial receive a lymphodepleting conditioning regimen consisting of cyclophosphamide and fludarabine (Cy/Flu) followed by up to 3 NK cell infusions 4 days apart and will be followed up for 12 months. The dose escalation stage of the trial will assess the safety and tolerability of repeat NK cell infusions in a 3+3 design with 3 cohorts and a cumulative dose range of 325 to 3,000 x106 viable NK cells. The expansion stage will evaluate the safety, tolerability and efficacy of NK cell infusions in 24 additional subjects. The primary efficacy endpoint is the cumulative incidence of the MRD response and secondary efficacy endpoints include the duration of the MRD response, event-free survival, overall survival and cumulative incidence of relapse. Enrollment in the first cohort (one single NK cell infusion) started in December 2020. Clinical trial information: EudraCT number 2019-003686-17.

Five-year follow-up on a sample of gamblers: predictive factors of relapse.

Background and AimsFew studies have been conducted on the long-term evolution of gambling disorder (GD). The aim of this study was to identify factors that could predict GD relapse.MethodsData were part of a dataset from a large 5-year cohort of gamblers who were assessed at inclusion and each year thereafter. Participants were recruited from an outpatient addiction treatment center, from various gambling places and through the press. For this specific study, inclusion criteria included (i) transitioning from GD to recovery at a follow-up time and (ii) undergoing at least one follow-up visit afterwards. Participants were evaluated using a structured clinical interview and self-report questionnaires assessing sociodemographic, gambling and clinical characteristics. “Relapse” was defined as the presence of GD (according to the DSM-5) at the N+1th visit following the absence of GD at the Nth visit. A Markov model-based approach was employed to examine predictive factors associated with relapse at a subsequent follow-up visit.ResultsThe sample consisted of 87 participants, aged 47.6 years (sd = 12.6), who were predominantly male (65%). Among the participants, 49 remained in recovery, whereas 38 relapsed. Participants who reported not having experienced at least one month of abstinence and those with a low level of self-directedness at the previous follow-up visit were more likely to relapse.ConclusionsOur findings suggest the existence of factors that are predictive of relapse in individuals with GD who had previously achieved recovery. These results can inspire the development of measures to promote long-term recovery.

Long-Term Clinical Outcome and Predictive Factors for Relapse after Radiation Therapy in 145 Patients with Stage I Gastric B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type.

Simple SummaryHelicobacter pylori-associated gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) constitutes >80% of gastric MALT lymphoma. Eradication therapy has been accepted as a standard approach for initial treatment. However, in patients who present without evidence of infection or who fail to respond to eradication therapy, a solid consensus for treatment is not available. Furthermore, few studies have evaluated the predictive factors for response or relapse after radiation therapy (RT) as heterogeneous, relatively small study populations have been treated with RT, and only a small number of events have been reported after treatment. In this study, we report the long-term clinical outcome of stage I gastric MALT lymphoma treated with RT. We also identified that the tumor’s dominant location in the stomach is a predictive factor for relapse after RT.This study aimed to evaluate the clinical outcomes of radiation therapy (RT) for stage I gastric mucosa-associated lymphoid tissue (MALT) lymphoma and find predictive factors for relapse after RT. This retrospective study included 145 patients without a prior history of treatment, except Helicobacter pylori eradication therapy, who were irradiated for stage I gastric MALT lymphoma. The gastric body was the most commonly involved location of the dominant lesion (66.9%), and H. pylori infection at first diagnosis was detected in 61 (42.1%) patients. The median RT dose was 30 Gy (range, 24–40). Seven patients had an autoimmune disease. All patients except one achieved a complete remission at post-treatment endoscopic biopsy after a median of 2 months (range, 1–36). During the median follow-up at 51 months (range, 2–146), 11 patients experienced relapses: in the stomach (n = 5), in a distant site (n = 4), and in both (n = 2). The five-year overall, local relapse-free, distant relapse-free, and relapse-free survival (RFS) rates were 98.6%, 94.0%, 97.1%, and 92.3%, respectively. In multivariate analysis for RFS, the location of MALT lymphoma other than in the gastric body was significantly associated with an increased risk of relapse (hazard ratio 5.85 (95% CI 1.49–22.9), p = 0.011). RT results in favorable clinical outcomes in patients with stage I gastric MALT lymphoma. Tumor location could be a predictive factor for relapse after RT.

Whipple's disease: diagnosis and predictive factors of relapse.

Whipple's disease is a very rare disease needing a long-term treatment. The most frequent symptoms are recurrent arthralgia or arthritis, chronic diarrhea, abdominal pain, and weight loss. In this article, we have highlighted the main clinical features and diagnostic procedures that lead to the diagnosis and comment on the clinical response, treatment, and the factors of relapse. Subjects were recruited from the Internal Medicine and Rheumatologic Departments of an University Hospital from November 1997 to January 2016. Overall, 12 subjects were finally diagnosed. Mean age was 54.3 years (age range: 30-81), with more male patients (58.3%). Almost all patients had articular symptoms and impaired general condition (91.7%); and a majority had digestive symptoms (75%). Regardless of the symptoms, the most efficient diagnostic tools were the PCR screening on the gastrointestinal biopsies and saliva (83.3 and 72.7% positive results, respectively). More than half of the patients relapsed (55.6%). The relapsing patients were older [63.2 (44-81)] and mostly male with a majority (60%) of digestive symptoms and a delayed diagnosis. In current practice, it is highly difficult to diagnose Whipple's disease. In order to decrease the delay between the first symptoms and the diagnosis, effective tools such as saliva and stools PCR should be used because higher delays of diagnosis lead to a higher number of relapses.

A New Pre-Emptive Strategy for Preventing Relapse Based on BCR/ABL Monitoring for Ph+ ALL Undergoing Allo-HCT: A Retrospective Prophylactic TKIs Study and Prospective Validation in a Clinical Trial Cohort

Background: Relapse is a major cause of treatment-failure in patients with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Whether tyrosine kinase inhibitors (TKIs) used post-transplantation could reduce relapse remains controversial. In this study, a new pre-emptive strategy post-transplantation based on BCR/ABL monitoring was compared with prophylactic strategy for preventing relapse. Methods: One hundred and sixty-seven patients were enrolled in this study, including 103 in pre-emptive and 64 in prophylactic groups. The pre-emptive strategy was based on molecular monitoring of BCR/ABL levels and BCR/ABL mutations, and donor lymphocyte infusion was recommended in those who were not responsive to TKIs. The prophylactic TKIs strategy was based on TKI treatment pre-transplantation. The primary endpoint was relapse. Findings: The 3-year cumulative incidence of relapse post-transplantation was 11% and 34% in pre-emptive and prophylactic groups, respectively (P=0.000). The 3-year cumulative overall survival (OS) were 87% and 64% (P=0.000), and LFS were 83% and 58% (P=0.000), respectively, in pre-emptive and prophylactic groups. Multivariate analysis showed that pre-emptive strategy was the predictive factor for relapse, OS and LFS (all P=0.000). Interpretation: Our data suggests that this new pre-emptive strategy based on BCR/ABL monitoring could reduce relapse and improve overall survival for Ph+ALL patients undergoing allo-HCT compared with prophylactic TKIs. Trial Registration: ClinicalTrials.Gov Identifier (NCT01883219). Funding Statement: This work was supported by the National Key Research and Development Programme of China (Grant No.2017YFA105500, 2017YFA105504), the National Natural Science Foundation of China (No. 81770190, 81700176, 81500149, 81401315), Science and Technology Planning Project of Guangdong Province (2019B020236004), Project of the Zhujiang Science and Technology Star of Guangzhou City (No.201806010029), the Science and Technology Program of Guangzhou City (201707010213), and the Clinical Research Project of Nanfang Hospital, Southern Medical University (LC2016ZD009). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The protocol was reviewed and approved by the institutional review board of each of the participating centers and was conducted in accordance with the Declaration of Helsinki. Patients provided written consent before entering the study.

Predictive factors for relapse in adults with dermatomyositis

Dermatomyositis (DM) is a severe disease that can be chronic with relapses and severe morbidity. The objective of this study was to analyze clinical features at presentation that predict non-paraneoplastic DM relapse in adult patients. A multicenter retrospective study focused on 33 patients diagnosed with DM and treated using corticosteroids from 2000 to 2015. This study also aimed to compare patients with and without relapse based on some predictive factors such as demographic characteristics and clinical symptoms. A Cox model was used to estimate hazard ratios (HRs). We identified 33 patients with an average age of 41.8 ± 12 years (range 18-68 years). The sex ratio of females to males was 2:1. During the 13.5-month follow-up period, two (6%) patients died and 21 (63.6%) suffered from a relapse. In univariate analysis, skin ulceration in the initial presentation of disease (HR = 3.1, range 1.1 to 15.1) was significantly associated with a relapsing course. This study demonstrates that in the initial presentation of the disease skin ulceration is significant in allowing prediction of the occurrence of DM relapse.

Outcomes of Therapy Related Acute Lymphoblastic Leukemia in Adults after Allogeneic Stem Cell Transplantation - Twenty-Year Experience from a Tertiary Care Center

Introduction Therapy related acute leukemias are late complications of treatment with mutagenic agents for both malignant and non-malignant disorders. The prevalence of therapy induced Acute lymphoblastic leukemia(t-ALL) is thought to be much less than that of t-AML/MDS, with our institute reporting a 6.9% prevalence of t-ALL among all patients of adult ALL. There is limited data on role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in t-ALL. Recent reports suggested comparable outcomes with de-novo ALL after allo-HSCT. We aim to report our 20-year experience of allo-HSCT in t-ALL. Patients and Methods We retrospectively reviewed all cases of t-ALL who underwent allo-HSCT at our centre from October 1998 to July 2019. Patients were analysed and compared for demographic features, prior malignancy and its treatment, latent period before ALL, clinical, cytogenetic and molecular characteristics of ALL, induction and consolidation treatment received, transplant details including donor details, conditioning regimens, GVHD prophylaxis as well as post-transplant complications (including transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations), relapse rate, relapse free survival (RFS) and overall survival (OS). Predictors of survival were calculated by Cox-Regression Analysis. Results A total of 18 patients underwent allo-HSCT for t-ALL. M:F ratio was 1:1. Median age at allo-HSCT was 44 years (range 20-70 years). Baseline characteristics, prior malignancy and treatment received are summarized in Table 1. Median latent period from prior malignancy to diagnosis of ALL was 44.8 months (range 6-157 months). Complex cytogenetics was present in 16.7% patients (n=3) while 11q23 rearrangement (KMT2A-MLL) and t(9;22) rearrangement was seen in 33.3% (n=6) and 22.2% (n=4) patients respectively. Median time to allo-HSCT from diagnosis of t-ALL was 5 months. Stem cell donors were matched related, matched unrelated and haplo-identical in 27.8% (n=5), 55.6% (n=10), and 16.7% (n=3) patients, respectively. Conditioning regimen was myeloablative in 44.4% (n=8) patients and reduced intensity in 55.6% (n=10) patients. GVHD Prophylaxis used was ATG-CSA-PTCy in 50% (n=9) patients, CSA/MMF in 22.2% (n=4) patients, and other regimens in 27.8% (n=5) patients. Post HSCT CMV and EBV virus reactivation occurred in- 33.3% (n=6) and 47.1% (n=8) patients, respectively. Acute GVHD (any grade) occurred in 70.6% (n = 12) while chronic GVHD (any grade) occurred in 31.3% (n=5) patients. Transplant related mortality (Death before day 100) occurred in 27.8% (n=5) patients. Four (22.2%) patients relapsed. Median RFS was 4 months (Range 0.5-194 months) while median OS was 5.88 months (Range 0.5-194 months) (Figure 1a&amp;b). One patient (5.5%) had relapse of their primary malignancy (CA Breast) 12 years after allo-HSCT. One year RFS and OS for all patients (excluding patients who have not completed one year of followup after HSCT but have not relapsed or died) was 43.8% and 46.7% respectively. None of the basic disease characteristics, treatment characteristics, or transplant or post-transplant parameters including donor type, conditioning received, GVHD prophylaxis used, occurrence of Acute or chronic GVHD etc. were significantly predictive of OS and RFS on Cox-Regression analysis, though the analysis is limited by the small sample size. Conclusions Therapy related ALL is an uncommon but increasingly recognized disease entity. Our outcomes of Allogeneic HSCT in t-ALL were comparable to that in de novo ALL as per previously reported literature. Multicenter studies on t-ALL with more patients and longer follow up duration may provide us with predictive factors of relapse and survival post allogeneic HSCT. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

The Clinical Structure of Remission from Alcohol Dependence

The review presents the clinical factors of destabilization of remission and relapse in alcohol dependence. Traditionally, among these factors the leading role belongs to the pathological craving for alcohol. However, the craving for alcohol is a rare phenomenon in remission from alcohol dependence and even if expressed significantly it does not always become a predictive factor for relapse. Currently, there are many other clinical relapse-dangerous factors which must be taken into account in the treatment and rehabilitation of alcohol-dependent individuals.