scholarly journals Rapid Disappearance of Lupus Anticoagulant in Novel Coronavirus 2019 Patients; Is It the Key to Pandora's Box?

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3206-3206
Author(s):  
Hyunji Kim ◽  
Seongsoo Jang
Keyword(s):  
Subgroup Analysis ◽  
Lupus Anticoagulant ◽  
Conflicts Of Interest ◽  
Early Stage ◽  
Laboratory Data ◽  
High Rate ◽  
Confirmatory Test ◽  
Significant Difference ◽  
Thrombotic Tendency

Abstract Background: Coronavirus 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with severe hypercoagulable conditions and complex venous thrombosis is common. Several recent studies have reported elevated aPTT in COVID-19 patients with a thrombotic tendency, suggesting that the test results may be due to the presence of lupus anticoagulant (LA). LA, one of the antiphospholipid antibodies, is included in the diagnostic criteria for antiphospholipid syndrome (APS), and these syndromes are characterized by a tendency to thrombosis, so it is important to ascertain the meaning of LA in SARS-COV-2 infection. Here, we would like to investigate the changes in LA and the characteristics of coagulation-related factors in COVID-19 patients who have undergone LA testing. Methods: From March 2020 to June 2021, we conducted a medical record review of clinical information and laboratory data for COVID-19 patients at our hospital. Among the 140 confirmed patients, 110 patients who underwent lupus anticoagulant testing were included in the analysis. We also performed a subgroup analysis of COVID-19 patients who were regularly screened for LA. Results: Most of the patients in our study were mild, with 95 survivors except for the deaths of 15 patients. Lupus anticoagulant was identified in 71.6% of survivors and 40.0% of deaths. In the LA confirmatory test of survivors, DRVVT positive 98.5% and SCT positive 5.9% were found (Fig 1). When comparing coagulation parameters according to LA results in survivors, aPTT, CRP, and fibrinogen were found to be statistically significant (all P < 0.05). LA-positive patients had higher aPTT, CRP, and fibrinogen, and D-dimer was no different from LA-negative patients (Table 1). Of the 67 LA-positive patients, 25 patients did not follow up, and 12 patients were unable to clearly determine the duration of the negative transition. Among the 30 patients who underwent a follow-up LA test, short-term regular follow-up of LA testing was performed on patients from March 2021 to June 2021, and additional subgroup analysis was performed on these patients. All patients were confirmed to be DRVVT positive and had no other anti-phospholipid syndrome (APS)-related antibodies, such as anti-cardiolipin antibodies or anti-beta-2-gylcoprotein. LA disappeared rapidly within 4 weeks in all patients (range: 2-24 days). As the LA test result converted from positive to negative, aPTT decreased with a statistically significant difference (P=0.003, Fig 2). Conclusions: As previously reported, LA was found in a high proportion of COVID-19 patients. This is the first study to confirm that the proportion of LA positivity (71.6%) is high in Korean COVID-19 patients. Most of the LA positivity disappeared within 4 weeks instead of 12 weeks. The association between LA and thrombotic tendency in COVID-19 patients appears to be low. Presumably, the transient appearance of LA, which is rapidly disappearance in survivors at a high rate, may indicate that other autoantibodies due to the activation of the immune response were detected in the LA test, can be considered as a good indicator of prognosis. It is only necessary to note that there is no delay in anticoagulant treatment due to aPTT prolongation in the early stage due to LA. In summary, the clinical significance of high LA positive rates and rapid negative transitions in COVID-19 patients is currently unknown but needs confirmation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Total Knee Arthroplasty Is Safe in Jehovah's Witness Patients—A 12-Year Perspective

2019 ◽  
Vol 33 (01) ◽  
pp. 034-041 ◽  
Author(s):  
Theodore S. Wolfson ◽  
David Novikov ◽  
Kevin K. Chen ◽  
Kelvin Y. Kim ◽  
Afshin A. Anoushiravani ◽  
...  
Keyword(s):  
Total Knee Arthroplasty ◽  
Postoperative Complications ◽  
Knee Arthroplasty ◽  
Subgroup Analysis ◽  
Blood Management ◽  
Folate Supplementation ◽  
Level Of Evidence ◽  
Significant Difference ◽  
Total Knee

AbstractDespite the evolution of blood management protocols, total knee arthroplasty (TKA) occasionally requires allogeneic blood transfusion. This poses a particular challenge for Jehovah's Witnesses (JW) who believe that the Bible strictly prohibits the use of blood products. The aim of this study was to compare JW and a matched-control cohort of non-JW candidates undergoing TKA to assess the safety using modern blood management protocols. Fifty-five JW patients (63 knees) who underwent TKA at our institution between 2005 and 2017 were matched to 63 non-JW patients (63 knees). Patient demographics, intraoperative details, and postoperative complications including in-hospital complications, revisions, and 90-day readmissions were collected and compared between the groups. Additionally, subgroup analysis was performed comparing JW patients who were administered tranexamic acid (TXA) between the two groups. Baseline demographics did not vary significantly between the study cohorts. The mean follow-up was 3.1 years in both the JW and non-JW cohorts. Postoperative complications, including in-hospital complications (7.9 vs. 4.8%; p = 0.47), revision TKA (1.6 vs. 1.6%; p = 1.00), and 90-day readmission (1.6 vs. 4.8%; p = 0.31) were not significantly different between the JW and non-JW groups. Subgroup analysis demonstrated JW patients who received TXA had a significantly lower decline in postoperative hemoglobin (Hgb) (8.6 vs. 14.0%; p < 0.01). At a follow-up of up to 12 years, JW patients who underwent TKA have outcomes equivalent to non-JW patients without the need for transfusion. Our findings support that surgeons are more likely to optimize JW patients preoperatively with iron and folate supplementation. Despite these variations in preoperative optimization efforts, no significant difference with regard to Hgb or hematocrit levels was demonstrated. Level of evidence is III, retrospective observational study.

Retinal Morphological Changes during the Two Years of Follow-Up in Parkinson's Disease

2020 ◽  
Author(s):  
Mahmut Atum ◽  
Bekir Enes Demiryurek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
Morphological Changes ◽  
Fiber Layer ◽  
Significant Difference ◽  
Yahr Scale ◽  
And Control

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

scholarly journals Discordances between molecular assays for rifampicin resistance in Mycobacterium tuberculosis: frequency, mechanisms and clinical impact

2020 ◽  
Vol 75 (5) ◽  
pp. 1123-1129
Author(s):  
Annelies Van Rie ◽  
Michael G Whitfield ◽  
Elise De Vos ◽  
Lesley Scott ◽  
Pedro Da Silva ◽  
...  
Keyword(s):  
Healthcare Worker ◽  
Human Error ◽  
High Rate ◽  
Confirmatory Test ◽  
Medical File ◽  
Correct Treatment ◽  
Molecular Assays ◽  
Molecular Tests ◽  
Xpert Assay

Abstract Background Molecular assays are endorsed for detection and confirmation of rifampicin-resistant TB. The frequency, causal mechanisms and impact of discordant results between molecular tests are not well understood. Methods The prevalence of discordant results was determined by pairwise comparison of molecular test results in a cohort of 749 rifampicin-resistant TB patients in three South African provinces. Culture isolates were sent to a research laboratory for WGS and rifampicin MIC determination. Clinical information was collected through medical file review. Results The prevalence of discordances between Xpert MTB/RIF and MTBDRplus was 14.5% (95% CI 10.9%–18.9%), 5.6% (95% CI 2.2%–13.4%) between two consecutive Xpert assays and 4.2% (95% CI 2.2%–7.8%) between two consecutive MTBDRplus assays. Likely mechanisms of discordances were false rifampicin susceptibility on MTBDRplus (due to variants not included in mutant probes or heteroresistance with loss of minor variants in culture), false resistance on molecular assay in rifampicin-susceptible isolates, and human error. The healthcare worker changed the treatment regimen in 33% of patients with discordant results and requested 232 additional molecular tests after a first confirmatory test was performed in 460 patients. A follow-up Xpert assay would give the healthcare worker the ‘true’ rifampicin-resistant TB diagnosis in at least 73% of discordant cases. Conclusions The high rate of discordant results between Xpert and MTBDRplus has important implications for the laboratory, clinician and patient. While root causes for discordant result are multiple, a follow-up Xpert assay could guide healthcare workers to the correct treatment in most patients.

scholarly journals Comparison of Midfoot and Metatarsal Dorsal Wedge Osteotomy to Treat Cavovarus Foot Deformity in Adolescents

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0024
Author(s):  
Jinsong Hong
Keyword(s):  
Retrospective Study ◽  
Analogue Scale ◽  
Early Stage ◽  
Wedge Osteotomy ◽  
Foot And Ankle ◽  
Foot Deformity ◽  
Significant Difference ◽  
Spss Software ◽  
American Orthopaedic

Category: Midfoot/Forefoot Introduction/Purpose: To compare the clinical result of midfoot and metatarsal dorsal wedge osteotomy for the treatment of cavovarus foot deformity in adolescents. Methods: A comparative retrospective study of 24 patients with cavovarus foot deformity in adolescents was conducted between March 2012 and March 2015 in the Guangzhou Orthopaedic Hospital. All patients were flexible deformity. 10 patients were treated with midfoot dorsal wedge osteotomy, while 14 patients received metatarsal dorsal wedge osteotomy. The clinical curative effects, complications and image differences were compared between the two groups. American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score and Visual Analogue Scale (VAS) score were evaluated for each patient during the follow-up. All statistics were analyzed using the SPSS software system. Results: No early stage soft tissue complications occurred in all patients. All the patients obtained an average 21.5 months (ranged,10-30 months) follow-up.X-ray demonstrated that bone healing was obtained, the midfoot dorsal wedge osteotomy group at an average of 11.2 weeks (ranged,10-13 weeks). the metatarsal dorsal wedge osteotomy group at an average of 13.4 weeks (ranged,12-15 weeks). By AOFAS foot score and VAS pain score: There is no significant difference between the two groups (P=0.138). No complications of nonunion, recurrence of de-fortuity or implant failure were seen during follow-up. Conclusion: The midfoot and metatarsal dorsal wedge osteotomy are the effective methods for the treatment of cavovarus foot deformity in adolescents. For severe deformity midfoot metatarsal dorsal wedge osteotomy can provide more powerful correction.

Hodgkin Lymphoma Outcomes: Can We Expect Ethnic Parity in a Hispanic Prevalent Population?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4056-4056
Author(s):  
Michelle Janania Martinez ◽  
Prathibha Surapaneni ◽  
Juan F Garza ◽  
Tyler W Snedden ◽  
Snegha Ananth ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Relative Survival ◽  
Complete Response ◽  
Statistical Testing ◽  
P Value ◽  
Hispanic Population ◽  
Significant Difference ◽  
The Mean

BACKGROUND It is estimated that 8110 persons will be diagnosed with Hodgkin Lymphoma (HL) in the US during 2019, but the advent of new treatment options has increased the cure rate to at least 80%. It has been reported that the rates of HL are lower in the adolescent and young adult (AYA) Hispanic population but significantly higher in the Hispanic population older than 65. The relative survival estimates are stated to be similar between AYA Hispanics (HI) and non-Hispanics (NH) but for ages 65-84, HI have a significantly higher mortality rate. Pediatric studies have suggested that ethnicity plays a role in outcomes in patients with HL but there is limited data in the adult population. There is an unmet need in the field, where dossiers on underrepresented ethnic minorities need to be carefully considered and compared to existing data. Therefore, our study aims to compare survival outcomes in Hispanics vs Non-Hispanics with HL, who were treated at the only NCI designated cancer center of South Texas. To our knowledge this is the largest cohort of HL patients from a single academic institution that serves primarily Hispanics. METHODS We located and retrospectively analyzed a total of 616 patients with diagnosis of Lymphoma (HL and NHL) by International Classification of Diseases (ICD) codes and identified 116 cases of HL; all the patients received care at UT Health San Antonio, between 2008-2018. Key variables for each patient included age, gender, race/ethnicity, comorbidities, insurance status, stage, BM and extranodal involvement, treatment received, outcome at 3 and 5 years and vitality status in 2018. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. The significance of variation in the mean with disease category was assessed with one way ANOVA and the significance of associations between categorical outcomes was assessed with Pearson's Chi Square or Fisher's Exact test as appropriate. Multivariate logistic regression was used to model binary outcomes in terms of covariates and indicators of disease. All statistical testing was two-sided with a significance level of 5%. R1 was used throughout. The study was approved by the local Institutional Review Board. The findings will be available to patients, funders and medical community through traditional publishing and social media. RESULTS We identified 116 patients with HL, of which 73 were HI (63%), 43 NH (36%) and 1 not specified (1%). In regard to race, 92% identified as Caucasian, 4% as African American, 3% other and 1% Asian. The median age at diagnosis was 37.4, (SD 15.13). There were 49 females (42%) and 67 males (58%). The most common funding source was commercial insurance N=54 (47%), followed by a hospital payment plan N=30 (26%), Medicare N=16 (14%), unfunded N=13 (11%) and Medicaid N=3 (2%). Most prevalent co-morbidities were HTN N=28 (24%) and diabetes mellitus N= 23(20%); 50% of patients had no co-morbidities (N=63).At diagnosis ECOG of 0-1 was seen in 108 patients (93%); 8 were Stage I (7%), 39 stage II (33%), 32 stage III (28%), and 37 stage IV (32%). EBV was positive in 26 patients (22%). There were 15 patients that were HIV positive (13%), 54% with CD4 count <200, and 12 (75%) on antiretroviral therapy at diagnosis. Median PFS was 853.85 days (SD 912.92). We excluded patients who were lost to follow up or had not reached 3/5 years. At 3 year follow up there was: complete response in 37 HI (74%) vs 22 NH (92%); disease progression in 8 (16%) vs 0 (0%); death in 5 (10%) vs 2 (8%), respectively (p-value= 0.094). At 5 year follow up there was: complete response in 30 HI (77%) vs 17 NH (90%); progressive disease in 2 (5%) vs 0 (0); death 7 (18%) vs 2 (11%), respectively (p-value = 0.619). At the end of 2018, 41 HI (84%) were alive compared to 22 NH (88%) [p-value 0.74]. CONCLUSION Within the limitations of sample size, our study demonstrates that in the prevalently Hispanic population of our institution, HI patients with HL have no statistically significant difference in outcome when compared to NH patients. Disclosures No relevant conflicts of interest to declare.

Clinical Significance of Indeterminate Lupus Anticoagulant (LAC) Results.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3988-3988
Author(s):  
Khaldoun J. Alkayed ◽  
Kandice Kottke-Marchant
Keyword(s):  
Autoimmune Disease ◽  
Clinical Significance ◽  
Lupus Anticoagulant ◽  
Statistical Significance ◽  
The United States ◽  
Test Results ◽  
Clinical Variables ◽  
Significant Difference ◽  
Initial Cohort

Abstract 3988 Poster Board III-924 Abstract: Introduction The International Society of Thrombosis and Hemostasis (ISTH) criteria for the diagnosis of the lupus anticoagulant (LAC) include: Screening test that demonstrates the prolongation of a phospholipid-dependent (PL-D) clotting time; mixing test that confirms the presence of an inhibitor; the confirmation that the inhibitor is PL-D and exclusion of other coagulopathies. Test results that do not fulfill all the criteria are considered indeterminate. These indeterminate results are common (Kottke-Marchant et al. J Thromb Haemost. 2007; 5 Supplement 2: P-M-455), still there is no published data regarding clinical significance. Patients/methods This study investigated the prevalence of thrombotic events in an initial cohort of unselected patients (n=256) from one tertiary hospital in the United States, who were tested for LAC and other antiphospholipid (aPL) antibodies from a 2 month period in 2006. The laboratory results (PT/INR, aPTT, dilute Russell's viper venom time (DRVVT), STACLOT and platelet neutralization (PNP)) were evaluated. The profile included 3 separate PL -D assays (DRVVT confirm, STACLOT, PNP). Samples containing heparin (>0.1U/ml) were pre-treated with Hepadsorb. The LAC profile was considered indeterminate if PL test results were positive, but without a positive aPTT or DRVVT mixing study. The initial cohort included 83 patients with indeterminate results. From this group, 18 patients were excluded: Four due to incomplete data, 2 due to high heparin level (anti Xa>1.0 U/ml), 5 due to other prothrombotic etiologies and 7 with other positive aPL antibodies. For an assessment of thrombotic history, we performed retrospective chart reviews and tabulated all Sapporo clinical features, malignancy and auto-immune disorders within 5 years before and 2 years after the index laboratory testing. Events that did not fulfill diagnostic criteria for thrombosis, ischemic events or obstetrical complications were excluded. The final analysis sample included 65 patients with indeterminate LAC, 106 with negative and 27 with positive LAC. Results The final indeterminate LAC cohort included 65 patients, with mean follow-up of 18 months. Malignancy was present in 29% and autoimmune disease in 25% of patients. The most common thrombotic events were deep vein thrombosis (DVT) (28%), cerebral ischemic stroke (14%) and pulmonary embolism (14%). When compared to those with negative tests, indeterminate group patients were more likely males, relatively older, and more likely to have DVT, superficial thrombosis (ST) or myocardial infarction (MI) (P= 0.049, 0.021, 0.044, 0.005 and 0.045 respectively). Concurrent coumadin (warfarin) therapy was more prevalent in the indeterminate group, but it did not reach statistical significance (p=0.15). There was no statistical significant difference in the prevalence of cancer or autoimmune disease (P=0.19 and 0.48 respectively). In the multivariate analysis model none of the previous variables reached any statistical significance between the two groups. When compared the above clinical variables between indeterminate results and positive LAC results groups from the same cohort, we failed to show any major statistically significant differences. We noticed very poor retesting rate in the indeterminate group during the follow up period of 2 years (15% only). Conclusions Indeterminate results are common among patients referred for LAC testing. When compared to those with negative results, patients with indeterminate results are more likely to have a history of DVT, superficial thrombosis or MI, but none of the clinical variables reached statistical significance in a multivariate model. On the other hand, patients in the indeterminate group shared demographic and clinical profiles with those in the positive results group. This further highlights the need to study the clinical significance of indeterminate LAC results in a prospective study. Disclosures: No relevant conflicts of interest to declare.

Pediatric Therapy In Adult Acute Lymphoblastic Leukemia: Updated Experience of a Single Centre

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4338-4338
Author(s):  
Stefania Paolini ◽  
Sarah Parisi ◽  
Ilaria Iacobucci ◽  
Cristina Papayannidis ◽  
Maria Chiara Abbenante ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Hematological Toxicity ◽  
Induction Phase ◽  
Single Centre ◽  
Phase Ib ◽  
Small Series ◽  
Significant Difference

Abstract Abstract 4338 Background. Acute lymphoblastic leukemia (ALL) presents with different outcome in children and adults, with event-free-survival (EFS) rates of 70–80% and 30–40% at 5 years, respectively. This reflects both a different disease biology and different therapeutic approaches. Recently, results apparently improved in young adults/adolescents aged 15–21 years, with de novo ALL, when treated with pediatric intensive regimens rather than with typical adult regimens. Similarly, clinical studies are ongoing in older patients, toxicity related-therapy seeming the limiting issue. Aims. We report a single centre experience on adult ALL patients treated with an intensive pediatric-inspired schedule, designed to assess its tolerability and efficacy. Methods. From November 2007 to June 2010 seventeen ALL patients (M/F=12/5) were treated at our Center according to a modified AIEOP LAL2000 regimen. Treatment consisted of 7 days steroid pre-treatment, and four drugs 78-days induction (phase IA and phase IB) after which high risk (HR) patients were treated with three polychemotherapy blocks, while intermediate (IR) and standard risk (SR) patients went on 8-weeks consolidation and subsequent delayed intensification. Allo-SCT was planned for all patients with HLA-matched donor, as alternative to 2-years maintenance therapy. Median age was 31 years (range, 17–47). According to cytogenetic, response to steroid and minimal residual disease patients were classified into HR (n=7), IR (n=6) and SR (n=4). Results. 15/17 patients completed the induction phase IA, two being out for toxicity (grade IV infection and intestinal occlusion). Twelve (71%) obtained a complete remission (CR); three were refractory. However, one of them subsequently achieved CR after polychemotherapy blocks, for an overall response rate of 76% (13/17). Eleven patients then completed the 28-days induction IB. One patient is ongoing. Median induction duration was 92 days (range 82–136). Delays were mostly due to extra-hematological toxicity, the commonest being gastrointestinal (n=12), infective (n=7) and thrombotic (n=3). Delays were accumulated in both induction phases without significant difference between phase IA (median 18.5 days, range 4–37) and phase IB (median 17 days, range 9–66), despite an absolute number of moderate-severe AE superior in phase-IA versus phase-IB (12 vs 5). After induction, 4/12 patients already received consolidation therapy; 2/4 then received allo-SCT. The median duration of consolidation was 51 days (range 22–94). Conversely, 6/12 patients received polychemotherapy-blocks, one patient went directly on alloSCT and the remaining is ongoing. After polychemotherapy-blocks, five out six patients received allo-SCT. The median CR duration was 13 months (range 1+-42+); two patients relapsed, both after allo-SCT. With a median follow-up of 11 months (range 2–43) 11/17 (65%) patients are alive, 9 in CR (5 undergone allo-SCT). Six patients dead, three in CR for infectious complications, 3 for relapsed/refractory disease. Conclusions. Though in a small series, pediatric-like intensive chemotherapy seemed to be feasible in adult ALL. Extra-hematological toxicity, however, caused significant treatment delays during induction. Finally, the overall outcome appeared promising, though longer follow-up and larger populations are needed to draw definitive conclusions. Acknowledgments. BolognAIL, European LeukemiaNet, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO, Project of Integrated Program (PIO), Programma di Ricerca Regione – Università 2007–2009. Disclosures: No relevant conflicts of interest to declare.

Gemcitabine, Dexamethasone and Cisplatin (GDP regimen) As First Salvage Treatment of Patients with Refractory or Relapsed Diffuse large B Cell Non Hodgkin Lymphoma (DLBCL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2696-2696
Author(s):  
Thoraya Mohamed Abdel Hamid ◽  
Mona fawzy Ramadan ◽  
Abeer Bahnassy ◽  
Fouad Abu- Taleb ◽  
Magdy Saber
Keyword(s):  
Conflicts Of Interest ◽  
High Dose ◽  
Chemotherapy Response ◽  
Non Hodgkin Lymphoma ◽  
Study Results ◽  
Significant Difference ◽  
Duration Of Response ◽  
Relapsed Disease ◽  
Time To Relapse

Abstract Abstract 2696 Background: Many chemotherapy regimens have been used for patients with refractory or relapsed DLBCL. No regimen has demonstrated superiority to another in this setting. Specific markers could predict the response to certain agents. Aim: to evaluate the response of GDP regimen in relapsed and refractory DLBCL patients and to assess ribonucleotide reductase subunit M1 (RRM1) as a possible predictor marker to Gemcitabine response. Patients and method: Patients with Relapsed or refractory DLBCL after one previous anthracycline-containing chemotherapy regimen were treated with the GDP regimen. RRM1 was assessed by immunohistochemistry in 55 cases and its expression was correlated to treatment outcome. Patients who could not proceed to stem cell transplantation (SCT) were followed for chemotherapy response and their results are presented. Results: The study included 70 patients with a median age of 40 years (range 18–73). At start of GDP, 19 patients (27.1%) were refractory and 51 (72.9%) were relapsed. After 4 cycles of treatment, 42 patients achieved CR, with a CR rate of 60% (95% CI: 53–68%). The median DFS was 6 months (95% CI: 5 to7 months), this DFS didn't include patients who underwent auto SCT. After a median follow-up of 20 months (range 6 to 30 months), the median OS of the patients who achieved CR was not reached, while those who didn't achieve CR had a median OS of 27.4 months (p= 0.01). Correlation between response and the pretreatment prognostic factors including IPI score or any of its elements, previous line of chemotherapy, time to relapse and status at time of salvage were studied with only significant difference in response to GDP between patients with refractory and those with relapsed disease (CR= 21.1% versus 60% respectively, p < 0.001). There was significant correlation between RRMI study results and response to GDP, 30/31 cases with low RRM1 expression achieved CR (96.8%), while only 7/24 cases with high expression achieved CR (29.2%), (p=0.001). No significant relation could be found between RRM1 expression and DFS. Conclusion: GDP regimen is active for patients with refractory or relapsed DLBCL however, the duration of response is short and high-dose therapy with SCT support is the reference postremission treatment. RRM1expression can predict response to Gemcitabine-based chemotherapy. Disclosures: No relevant conflicts of interest to declare.

The Outcome of CLL Patients with 97% Identity to Germline Is Inferior to Other ‘Mutated’ Cases Defined by a 98% Cut off

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2842-2842
Author(s):  
Zadie Davis ◽  
Anton Parker ◽  
Daniel Catovsky ◽  
David Oscier
Keyword(s):  
Cox Regression ◽  
Conflicts Of Interest ◽  
Early Stage ◽  
Prognostic Significance ◽  
Published Data ◽  
Early Stage Disease ◽  
Ighv Gene ◽  
Significant Difference ◽  
Gene Usage ◽  
The Uk

Abstract Abstract 2842 IGHV gene mutational load and use of specific IGHV genes and stereotypes have all been reported to have prognostic significance in CLL. In the UK CLL4 trial there were significant differences in response rate and progression free survival regardless of whether a 97% or 98% cut off was used, and the percentage of mutations which correlates best with clinical outcome remains controversial. We performed IGHV gene sequencing on 1071 patients with CLL or ‘clinical’ MBL (n= 153) in whom biomarkers, time to first treatment (TTFT) and overall survival (OS) were available. Four hundred and ninety six cases were entered into the UK CLL4 trial and 575 presented or were referred to the Royal Bournemouth Hospital. TTFT and OS were determined for cases with <96% identity and for each mutational point from 96% – 100% identity separately, excluding cases utilising IGHV3-21 assigned to stereotype subset 2. There was a significant difference in median TTFT and median OS between those with 97% identity (TTFT-20.9 and OS-99.3 months) and <97% identity (TTFT-118 and OS-191 months; p<0.001 and p<0.001), but not between cases with 97% and >97% identity (TTFT -13.1 months p=0.052 and OS-84.5 months p=0.177). When TTFT was determined for patients with early stage disease only (stage A CLL or CLL-like MBL, n=571), those with 97% identity, determined using either leader sequence or BIOMED 2 primers, had a significantly longer median TTFT than those with >97% identity (92.0 and 36.4 months respectively; p=0.012) and significantly shorter than those cases with <97% identity (273.1 months; p=0.012). If only stage A cases were analysed, those with 97% identity had a significantly longer median TTFT than those with >97% identity (TTFT; 68 vs. 26 months p=0.034). However, when compared to cases with <97% identity, there was a trend towards a shorter TTFT but significance was not reached (68 vs. 128 months p=0.060). A series of Cox Regression analyses were conducted to see if the prognostic value of the 98% cut off in MBL/stage A cases could be improved. In univariate analyses a model which incorporated <97%, 97%, >97% identity and stereotype subset 2 was the best discriminator of TTFT (p=0.0011) (Figure 1).Figure 1.Four subgroups of MBL/stage A CLL with differing TTFT based on stereotype subset 2 and relationship to 97% germline identityFigure 1. Four subgroups of MBL/stage A CLL with differing TTFT based on stereotype subset 2 and relationship to 97% germline identity Multivariate analysis, selected 97% and >97% identity as independent predictors of shorter TTFT (HR 2.5; 95% CI 1.3–4.9; p=0.007 and HR 4.2; 95% CI 2.9–6.1; p<0.001 respectively) in a model including <97%, 97%, >97% identity to germline, age at diagnosis, gender, expression of ZAP70, expression of CD38, del11q, del17p, stereotypy and stereotype subset 2 (Table 1). Further analyses were performed to investigate whether the differences in TTFT between cases with <97%, 97% or >97% identity could be explained by differences in IGHV gene usage. Sixty-one percent of cases with 97% identity to germline utilised only five genes; IGHV3-21, IGHV3-23, IGHV3-48, IGHV3-53 and IGHV1-18 and these genes were significantly over-represented in cases with 97% compared to either, cases with <97% (p>0.001) or >97% (p>0.001). When subset 2 cases were excluded, there was no difference in TTFT between cases using the above 5 genes and all other IGHV genes at this identity (p=0.288). In contrast to previously published data we found no difference in TTFT between mutated IGHV3-23 cases and other mutated cases (using a 98% cut-off), but IGHV3-23 cases with 97% identity had a shorter TTFT than cases with <97% identity (p<0.001). In conclusion the clinical course of cases with 97% identity, especially if diagnosed early in their disease, appears distinct from other cases defined as having mutated IGHV genes using the conventional 98% cut off. This is not accounted for by differences in IGHV gene usage, the incidence of stereotypy or other biomarkers and may reflect differences in response to BCR stimulation between cases with 97% and <97% identity.Table.Multivariate analysis for TTFT in MBL/stage A CLLOutcomeCovariateHazard Ratio (HR)95% CI for HRSignificance (p)TTFT97% identity2.51.3–4.90.007>97% identity4.22.9–6.1<0.001Subset 23.71.8–7.4<0.001Del11q1.71.1–2.70.014CD381.51.0–2.00.028Age at diagnosis0.980.96–0.99<0.001 Only covariates selected as significant are listed above. Disclosures: No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation For Acute Leukemias In Suzhou (China): Similar Outcome In CR1 Patients Compared With European Group For Blood and Marrow Transplantation (EBMT) Results: A Pair-Matched Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5527-5527
Author(s):  
Jia Chen ◽  
Yin Lu ◽  
Myriam Labopin ◽  
De Pei Wu ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Acute Leukemias ◽  
Blood And Marrow Transplantation ◽  
Significant Difference ◽  
Univariate Analyses ◽  
International Multicenter

Abstract The first affiliated hospital of Soochow University initiated a program of stem cell transplantation for hematological malignancies in 2001 and has done until December 2011 a total of 70 autografts to consolidate acute leukemias (61 adults and 9 children). The EBMT presently handles a registry with information on more than 450 000 transplants including over 100 000 transplants for Acute Leukemias, of which 22800 were autografts. In order to evaluate the outcome of patients transplanted in Suzhou and to compare it with results from the EBMT, we collected the necessary information on all patients transplanted in Suzhou and we did a pair matched analysis with patients reported to the EBMT registry. The median age of the patient population autografted in Suzhou was 32 years (4-63). The median follow up was 34 months (1-136). 59 patients (47 AML, 12 ALL) were autografted in CR1 and 11 in CR2/3. The majority of patients received a non TBI conditioning (87%) and PB as a source of stem cells (87%). For those autografted in CR1, the interval from CR1 to transplant was 203 days (75-404). At 2 years, the OS, LFS, RI and NRM were 73±7%, 52± 7%, 44±8% and 5±3% for AML and 76±14%, 67± 16%, 33±17% and 0% for ALL. 48 adult patients autografted in CR1 from Suzhou were matched with 89 patients from the ALWP EBMT registry. Matching factors were age ± 3 years, Cytogenetics and the number of induction courses to reach CR1 (1 course versus more than 1). Patients from Suzhou were transplanted more recently ; the interval from diagnosis to transplant was longer (242 days vs 172 days, p<0.0001) and TBI was less frequently used (p= 0.004 ). By univariate analyses the results were: Suzhou versus EBMT: OS 76 ± 6 vs 69 ±5 % (p= 0.33), LFS 55 ± 7 vs 60 ± 5% (p= 0.44), RI 40 ± 7 vs 33 ± 5% (p= 0.27), NRM 4 ± 3 vs 7 ± 3% (p = 0.47). By multivariate analyses adjusting for interval from diagnosis to transplant, year of transplant and use of TBI, there was no significant difference for OS (HR: 0.65, 95% CI: 0.19-2.19; p=0.49), LFS (HR: 0.97, 95% CI : 0.44-2.15; p=0.95), RI ( HR: 1.02, 95% CI : 0.46-2.28; p=0.96) . We conclude that the results from Suzhou are not statistically different from those obtained using the EBMT database. These findings as well as the observation in another study of similar outcomes following allogeneic transplants in China and within EBMT are important to consider when planning international multicenter randomized studies. Disclosures: No relevant conflicts of interest to declare.

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