Transplant versus no transplant in myelodysplastic syndrome and acute myeloid leukemia with TP53 mutation; a referral center experience.

A remarkably high rate of post-transplant relapse in patients with TP53-mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non-HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non-HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion (p < .01). A total of 69 TP53 variants including 64 pathogenic variants, and 5 variants of undetermined significance were detected. Nine patients (4 in HSCT and 5 in non-HSCT) had multi-hit TP53 variants. After induction: 57.9% versus 56.6% in the HSCT versus non-HSCT cohort achieved morphologic complete remission. Median time to HSCT was 6 months and median follow-up was 15.1 months for HSCT and 5.7 months for non-HSCT. Median disease-free survival (DFS) and overall survival (OS) were 11.7 and 15.9 months for HSCT, and 4.1 and 5.7 months for non-HSCT cohorts, respectively. Non-relapse mortality at 12 months was 22% versus 44% for HSCT versus non-HSCT. In the HSCT cohort, the rate of grade II-IV acute and chronic graft-versus-host disease (GVHD) was 55% and 18%, respectively. None of the patients from the non-HSCT cohort were alive while four patients from the HSCT cohort were alive, in remission, and without GVHD (GRFS) at the time of abstraction. Better treatment strategies for patients with TP53-mutated MDS/AML remain an area of unmet clinical need.

Prophylactic donor lymphocyte infusion for relapse prevention: a meta-analysis.

OBJECTIVE: Primary disease relapse (PDR) of malignant hematologic conditions after standard hematopoietic stem cell transplant (HSCT) is one of the most challenging diseases; therefore ongoing researches are aiming at relapse prevention and minimizing the transplant-related side effects. Prophylactic donor lymphocytes (pDLI) had been proposed as a valuable strategy for PDR prevention, but early studies had been discouraging due to the limited benefit and possible association with acute graft-versus-host disease (aGVHD). Therefore, we conducted a meta-analysis to evaluate the association between pDLI use, PDR, aGVHD and OS. METHOD: We performed a comprehensive literature search in MEDLINE, Cochrane library and Embase database from inception to May 2019 for studies that evaluated the association between pDLI and PDR. We conducted a random effect meta-analysis of 9 studies involving a total of 748 participants (pDLI = 398, non-pDLI = 350) and reported the pooled odd ratio (OR) for association of pDLI use, PDR, aGVHD and OS. RESULT: We found a significant decreased odd of PDR in the pDLI group (pooled OR = 0.42, 95% CI 0.30-0.58, I2 = 0%), but there was no significant increased odd of aGVHD (pooled OR of 0.98, 95% CI 0.56-1.72, I2 = 0.8%). We also found that there was an increased odd of overall survival (OS) (pooled OR 3.17, 95% CI 1.85-5.45, I2 = 50.2%). CONCLUSION: There are significantly decreased odd of PDR and increased odd of OS in the pDLI group compared to the control group, but there is no statistically significant increased odd of aGVHD as suggested by previous studies. We concluded that pDLI is a potentially valuable method for post-transplant PDR prevention.

Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis.

OBJECTIVES: Both haplo-identical transplant (haplo) and umbilical cord transplant (UC) are valuable graft options for patients without available matched relative. Previous studies showed inconsistent outcomes comparing Post transplant Cyclophosphamide based haplo (PTCy-haplo) and UC; therefore, we attempt to compare the studies by mean of meta-analysis. METHODS: We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database and Google scholar that compared transplantation with PTCy-haplo versus UC. We conducted a random-effect meta-analysis of seven studies involving a total of 3434 participants and reported the pooled odd ratios (OR) of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse and overall survival (OS) between PTCy-haplo and UC groups. RESULTS: We found a significantly decreased risk of aGVHD and relapse in the PTCy-haplo group compared to the UC group with a pooled OR of 0.78, 95% Confidence Interval (CI) 0.67-0.92, I2=0%, and 0.74, 95% CI 0.57-0.97, I2=23.9% respectively. We also found a significantly increased rate of cGVHD and OS with a pooled OR of 1.41, 95% CI 1.02-1.95, I2=56.8%, and 1.77, 95% CI 1.1-2.87, I2=82.5%, respectively. CONCLUSION: Our meta-analysis of clinical trials demonstrated superior outcome from PTCy-haplo group compared to the UC group in terms of decreased rate of aGVHD and relapse as well as the increased rate of OS but inferior in terms of increased cGVHD risk compared to UC transplant.

PROGNOSIS OF DIFFERENTIATED THYROID CARCINOMA IN PATIENTS WITH GRAVES DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Objective: It is still controversial whether differentiated thyroid carcinoma (DTC) in patients with Graves disease (GD) can be more aggressive than non-Graves DTC. We conducted a systematic review and meta-analysis to examine the association between GD and prognosis in patients with DTC. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019. We included published studies that compared the risk of mortality and prognosis between DTC patients with GD and those with non-GD. Data from each study were combined using the random-effects model. Results: Twenty-five studies from February 1988 to May 2018 were included (987 DTC patients with GD and 2,064 non-Graves DTC patients). The DTC patients with GD had a significantly higher risk of associated multifocality/multicentricity (odds ratio, 1.45; 95% confidence interval, 1.04 to 2.02; I2, 6.5%; P = .381) and distant metastasis at the time of cancer diagnosis (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; I2, 0.0%; P = .497), but this was not associated with DTC-related mortality and recurrence/persistence during follow-up. Conclusion: Our meta-analysis demonstrates a statistically significant increased risk of multifocality/multicentricity and distant metastasis at the time of cancer diagnosis in DTC patients with GD than those without GD. Abbreviations: CI = confidence interval; DTC = differentiated thyroid carcinoma; GD = Graves disease; LN = lymph node; OR = odds ratio; PTC = papillary thyroid carcinoma; TC = thyroid carcinoma; TSAb = thyroid-stimulating antibody; TSH = thyroid-stimulating hormone.

Contrast-induced nephropathy is associated with new-onset atrial fibrillation in acute coronary syndrome after cardiac catheterization: Systemic review and meta-analysis.

INTRODUCTION: Contrast-induced nephropathy (CIN) is associated with increased cardiovascular morbidity and mortality in patients with acute coronary syndrome (ACS). Recent studies suggest that CIN is associated with new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) who underwent catheterization. However, a systematic review and meta-analysis of the literature have not been done. We assessed the association between CIN in patients with ACS and new-onset AF by a systematic review of the literature and a meta-analysis. HYPOTHESIS: CIN is associated with new-onset AF in patients with ACS. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to April 2018. Included studies were published cohort studies that compared new-onset AF after cardiac catheterization in ACS patient with CIN versus without CIN. Data from each study were combined using the random effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Five studies from December 2009 to February 2018 were included in this meta-analysis involving 5,640 subjects with ACS (1,102 with CIN and 4,538 without CIN). Contrast-induced nephropathy significantly correlates with new-onset AF after cardiac catheterization (pooled risk ratio = 2.84, 95% confidence interval: 1.66-4.87, p < 0.001, I2  = 58%) CONCLUSIONS: Contrast-induced nephropathy is associated with new-onset AF threefold among patients with ACS after cardiac catheterization. Our study warranted further study to establish the causality between CIN and new-onset AF.

Clinical outcomes of patients receiving three versus four doses of methotrexate with concomitant antithymocyte globulin in match unrelated donor allogeneic stem cell transplant: A single-center experience.

Methotrexate (MTX) doses on days +1, +3, +6, and +11 after match unrelated donor allogeneic stem cell transplant (MUD HSCT) is a common graft-versus-host disease (GVHD) prophylaxis regimen. However, the overlapping toxicity of MTX with conditioning chemotherapy sometimes warrants the omission of the fourth dose of MTX. Prior single-institution studies showed conflicting results comparing the outcomes of patients who received three versus four doses of MTX, but to our knowledge, the effect of concomitant antithymocyte globulin (ATG) has not been reported. Charts of patients who underwent MUD HSCT between 2009 and 2023 were reviewed. Patients received rabbit ATG (Thymoglobulin), given at 0.5 mg/kg on day -3, 2 mg/kg on day -2, and 2.5 mg/kg on day -1. MTX is given at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6, and +11. Severe mucositis was the most common indication for day +11 MTX omission (82%). We identified 292 patients (116 in 3 dose cohort and 176 in 4 dose cohort). Median follow-up was 23 months (range 1-151). Patients in the 4 doses cohort were more frequently male (68% vs. 50%, p < 0.01), received a reduced intensity conditioning regimen (38.0% vs. 22%, p < 0.01), were older (median 58 vs. 54 years, p = 0.02), and received a transplant in the earlier era (median HSCT year 2014 vs. 2018, p < 0.01). A statistically significant difference was not evidenced between the cohorts for the following outcomes: acute GVHD (aGVHD) (HR 1.1, 95% CI 0.9-1.5), chronic GVHD (cGVHD) (HR 1.3, 95% CI 0.8-1.6), relapse-free survival (RFS) (HR 1.0, 95% CI 0.6-1.5), non-relapse mortality (NRM) (HR 1.4, 95% CI 0.9-2.2), and overall survival (OS) (HR 1.2, 95% CI 0.9-1.7). Both cohorts had similar median time to neutrophil engraftment at 14 days. When ATG is incorporated, omission of day +11 MTX does not significantly impact the rate of engraftment or cumulative incidence of aGVHD, cGVHD, RFS, NRM, and OS.

Evolving treatment patterns and improved outcomes in relapsed/refractory mantle cell lymphoma: a prospective cohort study.

Over the last two decades, the frontline therapy for mantle cell lymphoma (MCL) has evolved. However, the impact of subsequent lines of therapy on survival outcomes has not been well characterized. In this study, we investigated the treatment patterns and survival outcomes in patients with relapsed/refractory (R/R) MCL treated with second-line (2 L) therapy. Adult patients with newly diagnosed MCL from 2002 to 2015 were enrolled in a prospective cohort study. Clinical characteristics, 2 L treatment details, and outcomes were compared between patients who received 2 L treatment between 2003-2009 (Era 1), 2010-2014 (Era 2), and 2015-2021 (Era 3). 2 L treatment was heterogenous in all eras, and there was a substantial shift in the pattern of 2 L therapy over time. The estimated 2-year EFS rate was 21% (95% CI, 13-35), 40% (95% CI, 30-53), and 51% (95% CI, 37-68) in Era 1-3 respectively, and the 5-year OS rate was 31% (95% CI, 21-45), 37% (95% CI, 27-50), and 67% (95% CI, 54-83) in Era 1-3, respectively. These results provide real-world evidence on evolving treatment patterns of 2 L therapy based on the era of relapse. The changes in 2 L treatment correlated with improved EFS and OS, suggesting that treatment advances are associated with improved outcomes in patients with R/R MCL.

Factors associated with recurrent postinfarction ventricular tachycardia following ablation.

INTRODUCTION: Ablation of ventricular tachycardia is the main therapy for patients with drug-refractory ventricular tachycardia (VT). Although evidence suggests that VT ablation could lower the incidence of recurrent VT, many cases still develop VT in follow-up. In this study, we performed a systematic review and meta-analysis to examine risk factors for recurrent VT in patients with postinfarction VT who underwent VT ablation. EVIDENCE ACQUISITION: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2020. Included studies were cohort studies, experimental trials, or randomized controlled trials that evaluate the risk of recurrent VT in postinfarction VT patients who underwent VT ablation. Data from each study were combined using random-effects. EVIDENCE SYNTHESIS: Thirteen studies involving 1803 postinfarction patients who underwent VT ablation were included. Inducibility after the procedure (pooled HR=1.71, P<0.001), lower baseline left ventricular ejection fraction (LVEF) (pooled HR=0.98, P<0.001) and higher baseline New York Heart Association (NYHA) classification (pooled HR=1.34, P=0.003) were significantly associated with VT recurrence during the follow-up. There was no significant association between age, gender or diabetes mellitus and VT recurrence. CONCLUSIONS: Our meta-analysis demonstrated that inducibility after the procedure, lower baseline LVEF and higher baseline NYHA classification were associated with an increased risk of VT recurrence in postinfarction VT patients who underwent VT ablation.

Engraftment Syndrome and Acute Graft-versus-Host Disease: A Meta-Analysis.

Engraftment syndrome (ES) has been associated with the surge of neutrophils and cytokines, which is similar to the presumed underlying pathophysiology behind acute graft-versus-host disease (aGVHD). However, there has been no meta-analysis to evaluate the association; therefore, the team attempted to verify an association between ES and aGVHD through meta-analysis. The team searched for titles of articles in MEDLINE (PubMed), the Cochrane Library, and the EMBASE database up until December 2018 that evaluated the association between ES and aGVHD and conducted a random effect meta-analysis of 8 studies involving a total of 1,945 participants to report the pooled odds ratio (OR) for association of ES and aGVHD. The team found a significantly increased odds of developing aGVHD in patients with ES with the pooled OR of 2.76 (95% confidence interval [CI]: 1.64-4.63) and an I2= 64.5%. In conclusion, patients with ES have significantly higher odds of developing aGVHD compared to patients without ES.

Cryptogenic Organizing Pneumonia with a Rare Radiographic Presentation of a Diffuse Micronodular Pattern Mimicking Miliary Lung Infiltration: A Case Report and Review of the Literature.

We reported a case of cryptogenic organizing pneumonia (COP) presenting with an unusual diffuse micronodular pattern (DMP) mimicking miliary lung infiltration. The patient is a 66-year-old man with a past medical history of diabetes mellitus type 2 and hyperlipidemia who presented with progressive dyspnea associated with significant weight loss and night sweats for 2 weeks. Upon admission, the patient's clinical condition rapidly progressed to respiratory failure requiring mechanical ventilation. Initial Chest X-ray (CXR) showed diffuse reticulonodular infiltration mimicking miliary pattern. Chest computed tomography (CT) showed diffuse centrilobular micronodular infiltrations with features of a tree-in-bud pattern consistent with the CXR findings. He was then started on empiric antibiotics for community-acquired pneumonia and underwent a diagnostic bronchoscopy with alveolar lavage and transbronchial biopsies, which yielded negative cultures and unrevealing pathology. Tissue from CT-guided lung biopsy performed later on was also inconclusive. Due to the lack of clinical improvement, he eventually underwent surgical lung biopsy. The pathology result showed organizing pneumonia (OP) pattern with heavy lymphoplasmacytic infiltrates and numerous multinucleated giant cells. His final culture results, microbiological data and serology workup for autoimmune disease were all unremarkable. The patient was diagnosed with COP and was started on systemic corticosteroids. He displayed dramatic clinical improvement and was successfully liberated from the ventilator. Subsequent chest imaging showed resolution of the reticulonodular infiltrations. Early diagnosis for OP and ability to distinguish OP from infectious pneumonitides are critical as the majority of patients with OP respond promptly to corticosteroids. Common findings of radiographic pattern for OP are patchy air space consolidation or ground-glass opacity, yet DMP is another rare radiographic pattern that must be recognized, especially in COP. In summary, this case illustrates a rare radiographic presentation of COP. With early recognition and prompt diagnosis, proper treatment can significantly prevent morbidity and reduce mortality.

Budesonide for Protein Losing Enteropathy in Patients with Fontan Circulation: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent studies have shown that oral budesonide can be used to improve albumin level in patients with protein-losing enteropathy (PLE) following Fontan procedure. However, there has never been a systematic review and meta-analysis to confirm this finding. We performed a systematic review and meta-analysis to explore the therapeutic effect of budesonide in patients with PLE post-Fontan procedure. METHODS: We searched the databases of MEDLINE and EMBASE from inception to January 2019. Included studies were published studies that evaluate albumin level before and after budesonide therapy in patients with PLE following Fontan procedure. Data from each study were combined using the random-effects model. RESULTS: Five studies with 36 post-Fontan operation patients with PLE were included. In random-effects model, there was a statistically significant difference in albumin level between before and after budesonide treatment (weighted mean difference = 1.28, 95% confidence interval: 0.76-1.79). No publication bias was observed on a funnel plot and Egger test with a P value of .676. CONCLUSIONS: The results of this systematic review and meta-analysis show that budesonide can be used to increase albumin level in patients with PLE following Fontan operation. Further studies may focus on the impact of outcome of budesonide in this population.

Total Body Irradiation and Risk of Diabetes Mellitus; A Meta-Analysis

Objective: Hematopoietic stem cell transplant (HSCT) has recently emerged as a cure for previously "incurable" diseases and is being explored and attempted in many other fields including congenital and acquired non-malignant diseases. However, the long-term side effect associated with HSCT especially Total Body Irradiation (TBI) is still understudied. Therefore, we attempted to establish association between TBI and risk of developing Diabetes Mellitus (DM) or impaired glucose metabolism (IGM). Methods: We searched for titles of articles in MEDLINE (PubMed), EMBASE, and Cochrane library in August 2018 that evaluated the association between TBI in the setting of HSCT and DM or IGM. We conducted a random effect meta-analysis of 11 studies involving a total of 13,191 participants and reported the pooled MD (mean difference) for the development of DM/IGM after TBI as part of the conditioning regimen for HSCT. Results: We found a significant increase in the risk of developing DM/IGM after TBI is used as part of the conditioning regimen compared to other types of conditioning regimen with the pooled MD being 5.42, 95% Confidence Interval (CI) 2.51-11.71, I2=92.4%. Conclusion: TBI as a conditioning regimen in the setting of HSCT significantly increases the risk of developing DM/IGM. Therefore, we recommend close monitoring and screening for diabetes mellitus in patients who underwent TBI before HSCT.

Smoking and Risk of Microscopic Colitis: A Systematic Review and Meta-analysis.

BACKGROUND: The association between smoking and inflammatory bowel disease has long been recognized, but its role in the development of microscopic colitis is less well defined. This systematic review and meta-analysis was conducted with the aims to identify all available studies on the association between smoking and risk of microscopic colitis and to synthesize their results. METHODS: The MEDLINE and EMBASE databases were searched from inception to May 2018 for cohort studies and case-control studies that compared the risk of microscopic colitis among current/former smokers vs individuals who have never smoked. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted from the included studies and pooled together using a random-effects model, generic inverse variance method of DerSimonian and Laird. Between-study heterogeneity was quantified using the Q statistic and I2. Publication bias was assessed using funnel plots. RESULTS: Seven studies (2 cohort studies and 5 case-control studies) with 262,312 participants met the eligibility criteria and were included in the meta-analysis. Relative to never-smokers, current smokers had significantly increased odds of microscopic colitis, with a pooled OR of 2.99 (95% CI, 2.15-4.15; I2, 64%). Former smokers also had significantly higher odds of microscopic colitis compared with never-smokers, with a pooled OR of 1.63 (95% CI, 1.37-1.94; I2, 0%). Funnel plots were symmetric and did not provide suggestive evidence of publication bias for both analyses. CONCLUSIONS: The current systematic review and meta-analysis found a significantly higher risk of microscopic colitis among current smokers compared with never-smokers. The risk attenuated among former smokers but remained significantly higher among never-smokers.

Chronic graft-versus-host disease and the risk of primary disease relapse: A meta-analysis.

Both primary disease relapse (PDR) and chronic graft-versus-host disease (cGVHD) have long been the dreaded outcomes for patients with hematologic malignancies. Previous theories have speculated an inverse relationship between the two; therefore, we attempted to verify the described association. We searched for titles of articles in MEDLINE (PubMed), Cochrane library, and EMBASE database that evaluated the association between PDR and cGVHD and conducted a random effect meta-analysis of 11 studies involving a total of 64,239 participants. We found a significantly decreased risk of developing PDR in patients with cGVHD, with a pooled risk ratio of 0.49 (95% confidence interval: 0.40-0.61, I2 = 69.3%). We concluded that patients with cGVHD have a significantly lower risk of developing PDR compared with patients without cGVHD.

Vonoprazan versus proton-pump inhibitors for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and meta-analysis.

Acid secretion inhibitors are usually prescribed to promote the healing of artificial ulcers caused by endoscopic submucosal dissection (ESD) to reduce the risk of gastric perforation and delayed bleeding. Vonoprazan is a newer agent that has been shown to be more potent than a proton-pump inhibitor (PPI). However, it remains unclear whether vonoprazan is more effective than PPI in promoting healing of ulcers caused by ESD. Medline and Embase databases were searched through January 2018 for studies that compared the rate of complete healing of ulcers caused by ESD and post-ESD delayed bleeding in patients who received vonoprazan versus those who received PPI after ESD. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity was quantified using the Q-statistic and I. A total of six studies consisting of 461 patients were identified. The likelihood that ulcers caused by ESD were completely healed at 4-8 weeks after the procedure was significantly higher among patients who received vonoprazan compared with those who received PPI, with a pooled OR of 2.27 (95% CI=1.38-3.73; I=0%). The risk of developing post-ESD delayed bleeding was also numerically lower among those who received vonoprazan, with a pooled OR of 0.79, although the result did not reach statistical significance (95% CI=0.18-3.49; I=29%). This study found that patients who received vonoprazan after ESD had a significantly higher rate of completely healed ulcers compared with those who received PPI.