Early Clearance of Peripheral Blood Blasts but Not White Blood Cells Is a Powerful Prognostic marker for complete Response and Overall Survival in Patients with Acute Myeloid Leukemia (AML) receiving Induction Chemotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1553-1553
Author(s):  
Alfonso Quintas-Cardama ◽  
Hagop Kantarjian ◽  
Guillermo Garcia-Manero ◽  
Mark Brandt ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
White Blood Cells ◽  
Complete Response ◽  
Long Term Outcomes ◽  
Group 1

Abstract Abstract 1553 Background: Most pts with AML will achieve complete remission (CR) following therapy with cytarabine and an anthracycline. Early clearance of blasts in peripheral blood (PB) has been shown to be an important prognostic factor in acute lymphoblastic leukemia. We explored the dynamics of PB blasts in pts with AML undergoing induction chemotherapy with AI (ara-C 1.5g/m2x3d and idarubicin 12mg/m2x3d) at our institution and their impact in long-term outcomes. Patients & Methods: We reviewed the dynamics of PB blasts (i.e. PB blasts=0%) or WBC (i.e. WBC≤0.1×109/dL) clearance in pts with AML receiving AI (n=486). Patients with acute promyelocytic leukemia were excluded. Pt characteristics were as follows: median age 55 yrs (range, 19–73), pts <60 yrs 44 (30%), diploid cytogenetics (n=54, 36%), poor cytogenetics (n=57, 38%), median WBC 4.9 (range, 0.3–97.4), platelets 39 (range, 2–581), hemoglobin 8.4g/dL (range, 3.3–13.2), PB blasts (15% (range, 1–96), BM blasts 45% (1–96). Results: The overall response rate (ORR=CR+CRp) was 65% (58%+7%). Forty-four (30%) pts were resistant to induction therapy. To evaluate the dynamics of PB WBC and PB blast clearance, we divided all pts in 5 groups depending on the day they cleared their WBC or blasts from PB: group 1 (0–1 days), 2 (2–3 days), 3 (4–5 days), 4 (6–8 days), and 5 (beyond day 8). A total of 21, 34, 25, 4, and 3 pts were included in groups 1 through 5. No differences in CR rates were observed across all 5 groups according to the time of clearance of PB WBC (p=0.653). Likewise, similar median overall survival (OS) rates were observed in all 5 groups regardless of the timing of PB WBC clearance (0.2). However, the timing of PB blast clearance was associated with a distinct probability of achieving CR, being 73%, 74%, 65%, 24%, AND 60% for groups 1 through 5 (p=0.003). This translated into distinctly different median OS for the 5 groups (p=0.03) (Figure 1A). When groups 1, 2, and 3 were merged and compared with the merge of groups 4 and 5, the ORR for the resulting two new groups was 71% and 32% (p<0.001) and the corresponding median OS was 40 weeks and 75 weeks (p=0.038) (Figure 1B), suggesting that early PB clearance predicts long-term outcomes. Conclusion: We have shown in a large cohort of uniformly treated pts with AML that early clearance of PB blasts (but not WBC) is an important risk factor for achievement of CR and for OS. Clearance of PB blasts should be considered in prognostication schemas for pts with AML. Disclosures: No relevant conflicts of interest to declare.

Recovery Blasts in the Peripheral Blood in AML Patients Who Obtain a Complete Remission Is a Favorable Prognostic Indicator

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5335-5335
Author(s):  
Nathaniel M. Cook ◽  
James N. Butera ◽  
John L Reagan
Keyword(s):  
Complete Remission ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Prognostic Indicator ◽  
Myelogenous Leukemia ◽  
Kaplan Meier ◽  
Cytogenetic Profile ◽  
Group 2 ◽  
Group 1

Abstract Introduction: Many patients with Acute Myelogenous Leukemia (AML) will transiently develop blasts in the peripheral blood upon recovery of induction chemotherapy, despite going on to obtain a complete remission. These are presumably non-leukemic marrow blasts. Recovery blasts can sometimes reach over 20% in the peripheral blood in remission patients. The significance of recovery blasts cells after induction chemotherapy in patients with AML is not clear. We sought to define the incidence of recovery blastocytosis (RB) and determine if the presence of RB has prognostic relevance. Methods: We performed a retrospective analysis of 72 patients with newly diagnosed AML who underwent induction chemotherapy with 7+3 (cytarabine and daunorubicin) with or without etoposide between the years of 2006 and 2013 at our institution. Patients were included in the analysis as having RB only if their blasts resolved by day 14 of induction chemotherapy, blasts reappeared upon recovery after day 14, recovery blasts were > 5% in the peripheral blood of a duration of >5 days, and subsequently resolved by day 45 and remission was obtained. We recorded patient's absolute and percentage peripheral blast counts on presentation, upon nadir and throughout recovery of induction chemotherapy. The incidence and level of RB in patients who achieved a remission was tabulated. This group (group 1) was compared to the patients who achieved a remission whom did not develop RB (group 2). Results: 45/77 AML patients obtained a CR after induction chemotherapy. Recovery blasts were seen in 9/45 (20%) remission patients (group 1), with a median RB of 9% for a median duration of 8 days. Of these 9 patients, 4 developed RB > 10%, and 2 developed RB >20 % Group 1 did not differ in respect to age, gender, cytogenetic profile, etoposide use, or whether the patient received 1 or 2 induction therapies from the 36/45 remission AML patients who did not develop RB (group 2). Median survival for group 1 was = 1,376 days, and 1,036 days for group 2 (p= .035). Conclusion: Recovery Blasts in the peripheral blood after induction chemotherapy is seen commonly in AML patients who obtain a complete remission. RB can be seen even as high as > 20% in remission patients. AML patients who develop RB on their way to remission after induction chemotherapy have a better overall survival then patients who do not develop RB. Figure 1 Figure 1. Graph 1. Kaplan-Meier survival curves for AML patients with RB (group 1) and without RB (group 2). Disclosures No relevant conflicts of interest to declare.

Importance of Achieving a Complete Response in Multiple Myeloma, and the Impact of Novel Agents

2010 ◽  
Vol 28 (15) ◽  
pp. 2612-2624 ◽  
Author(s):  
Asher A. Chanan-Khan ◽  
Sergio Giralt
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Significance ◽  
Complete Response ◽  
Maximal Response ◽  
Prognostic Impact ◽  
Long Term Outcomes ◽  
First Line ◽  
The Impact

The goal of treatment for multiple myeloma (MM) is to improve patients' long-term outcomes. One important factor that has been associated with prolonged progression-free and overall survival is the quality of response to treatment, particularly achievement of a complete response (CR). There is extensive evidence from clinical studies in the transplant setting in first-line MM demonstrating that CR or maximal response post-transplant is significantly associated with prolonged progression-free and overall survival, with some studies demonstrating a similar association with postinduction response. Supportive evidence is also available from studies in the nontransplant and relapsed settings. With the introduction of bortezomib, thalidomide, and lenalidomide, higher rates of CR are being achieved in both first-line and relapsed MM compared with previous chemotherapeutic approaches, thereby potentially improving long-term outcomes. While standard CR by established response criteria has been shown to have differential prognostic impact compared with lesser responses, increasingly sensitive analytic techniques are now being explored to define more stringent degrees of CR or elimination of minimal residual disease (MRD), including multiparameter flow cytometry and polymerase chain reaction. Demonstrating eradication of MRD by these techniques has already been shown to predict for improved outcomes. Here, we review the prognostic significance of achieving CR in MM and highlight the importance of CR as an increasingly realizable goal at all stages of treatment. We discuss clinical management issues and provide recommendations relevant to practicing oncologists, such as the routine use of sensitive techniques for assessment of disease status to inform evidence-based decisions on optimal patient management.

Inability to Tolerate Standard Therapy Is a Major Reason for Poor Outcome In Older Adults with Acute Lymphoblastic Leukemia (ALL): Results From the International MRC/ECOG Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 493-493 ◽  
Author(s):  
Jonathan I Sive ◽  
Georgina Buck ◽  
Adele Fielding ◽  
Hillard M. Lazarus ◽  
Mark R. Litzow ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Induction Chemotherapy ◽  
Older Patients ◽  
Lymphoblastic Leukemia ◽  
Age Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Dose Reductions

Abstract Abstract 493 The International MRC UKALL XII/ECOG E2993 trial for adults with newly diagnosed acute lymphoblastic leukemia (ALL) recruited 1,914 patients to the main part of the trial from 1995 up to its closure in 2006, of whom 100 were over the age of 55 years (median 57, range 55–65). Beginning in 2003 (MRC) or 2004 (ECOG), patients with Philadelphia chromosome positive (Ph+ve) disease were entered into an Imatinib sub-study. We report here baseline characteristics, treatment course and outcomes, and discuss implications for future management strategies. Direct comparison of the 100 patients over 55 yrs with 1,814 under 55 yrs showed that the groups are comparable for gender, immunophenotype and white cell count but there is an indication that more elderly patients had Ph+ve disease (28% aged ≥55 vs 17% aged <55 of those entered before the start of the Imatinib trial; p=0.02). All patients in this trial received a 2 stage induction regimen, consisting of Daunorubicin, Vincristine, Asparaginase and Steroid followed by Cyclophosphamide, Cytarabine, 6-Mercaptopurine and Methotrexate. CNS prophylaxis with IT Methotrexate and Cytarabine was given during both phases. There was a randomisation to autograft or chemotherapy, but only a small number of patients in this age group were randomised (13 autograft and 13 consolidation chemotherapy). Outcomes Complete remission (CR) rate, event-free survival (EFS) and overall survival (OS) were all worse in the over 55 age group, and even after achieving CR, the 5-year OS rate was reduced. There were more infections in phase I induction (67% vs 45%, p<0.0001) and more deaths during induction chemotherapy (18% vs 4% p<0.0001). Excluding those who died in induction, 47% had drug dose reductions in phase I or phase II vs 27% <55 yrs (P=0.0006). Of these, Asparaginase was the most common in those aged ≥55 years, usually due to hepatotoxicity. Age p-value <55 vs ≥55 <55 ≥55 Number 1814 100 CR No v Yes p<0.0001     No 131 (7%) 27 (27%)         No (died in induction) 70 (4%) 18 (18%)         No (but survived induction) 61 (3%) 9 (9%)  Yes 1641 (90%) 70 (70%)     Unknown 42 (2%) 3 (3%) Deaths 1112/1814 (61%) 78/100 (78%) Relapses 750/1683 (45%) 36/73 (49%) Overall survival at 5 years (95% CI) 41% (38–43%) 21% (12–29%) p<0.0001 Event free survival at 5 years (95% CI) 37% (34–39%) 19% (10–27%) p<0.0001 Relapse free survival at 5 years (95% CI) 50% (48–53%) 38% (25–52%) p=0.08 Overall survival at 5 years (95% CI) in those who achieved CR 44% (41–46%) 30% (18–41%) p=0.03 In those patients aged ≥55 years, baseline factors causing a significantly worse 5-yr EFS were Ph-positivity (0% vs 23%, p=0.005), unfavourable vs standard cytogenetic risk (7% vs 26%, p=0.02) and a presenting WCC >50 × 109/l (0% vs 25% for WCC between 10 and 49.9 × 109/l and 23% for WCC <10 × 109/l, p=0.003). Infection during induction chemotherapy predicted for worse EFS; this was especially significant in those who had infection in both phases of induction (6% vs 38%, p=0.007). In those patients who received chemotherapy and were not transplanted, the differences in outcome were smaller: 5-yr OS 25% in ≥55 years vs 38% in <55 years (p=0.06), 5-yr EFS 22% vs 32% (p>0.1). Conclusion Older adults fared significantly worse than younger adults both in terms of achieving an initial CR and long-term survival. This difference cannot be explained solely by a difference in disease characteristics, and the marked increase in infection and deaths during induction reflect the inability of many older patients to tolerate the intensive level of treatment. This is also supported by the large numbers of drug omissions or dose reductions seen. Our data show that this inability to tolerate induction chemotherapy is a major contributor to the poor outcomes seen in this age group. The less marked differences between age groups when transplant patients are excluded, indicates the significant mortality associated with these procedures in older patients. Alternative approaches to consider in this group include less intensive induction with a steroid and vinca alkaloid combination, in conjunction with targeted therapies (eg Rituximab in B-lineage CD20+ disease, Imatinib Mesylate in Ph+ disease). Even amongst those patients who do achieve CR however, the long-term outcome is worse. Reduced intensity allografts may play a role in carefully selected patients in this age group, and the emerging use of MRD monitoring may also assist in selecting patients for more or less intensive approaches. Disclosures: McMillan: EUSA: Honoraria. Goldstone: Roche: Honoraria, Speakers Bureau.

Impact of Tyrosine Kinase Inhibitor (TKI) in Chronic Myeloid Leukemia (CML) Relapsing After T Cell Depleted Allogeneic Stem Cell Transplantation (SCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2762-2762
Author(s):  
Sawa Ito ◽  
Minoo Battiwalla ◽  
Eleftheria K. Koklanaris ◽  
Jeanine Superata ◽  
Richard Childs ◽  
...  
Keyword(s):  
Overall Survival ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Free Survival ◽  
Survival After Relapse ◽  
Tki Treatment

Abstract Abstract 2762 Although SCT is now uncommon treatment for CML, many patients transplanted for CML have become long term survivors and some continue to relapse late post transplant. It is therefore important to evaluate the management of relapse in CML transplant survivors in the era of TKI treatment. We studied 112 patients with Ph+ CML who underwent HLA identical sibling SCT between 1993 to 2008. The mean age was 36 years (range 13–69). Eighty (71%) were in chronic phase, 17 in accelerated phase, 5 in second chronic phase and 10 in blastic phase. Ninety-nine (88%) received myeloablative conditioning regimen with cyclophosphamide +/− fludarabine and total body irradiation and 13 received a non-myeloablative regimen. GVHD prophylaxis was with cyclosporine. Bone marrow or G-CSF mobilized peripheral blood stem cells from the donor were manipulated to achieve 4-log CD3+ cell reduction ex vivo. Peripheral blood BCR-ABL p210 product was regularly monitored by either double nested PCR (until 2003) or real time PCR (2003 to present). For molecular relapse, patients received donor lymphocyte infusions (DLI) with or without imatinib 400–600mg/day. Patients with hematological relapse received a variety of treatments including second SCT. At a median follow up of 6.2 years, 10 year-relapse free survival and overall survival were 34% and 57% respectively. Overall 49 (43.8%) patients relapsed, 28 with molecular and 22 with hematological relapse. Median time to relapse from HSCT was 379 days (range 16–3718 days). Overall survival was not significantly different between relapsed patients and non-relapsed patients. (10-year OS: 59 % vs 55%, P=0.385). Thirty-five relapsed patients (71.4%) were treated with TKI based therapy. Overall survival after relapse was significantly better after TKI based therapy compared to non-TKI based therapy. (5-year survival after relapse: 78% vs 36%, P=0.004 respectively). The benefit of TKI was greater in hematological relapse (median survival after hematological relapse 1182 days in TKI based vs 72 days in others P=0.025). At 7 years median follow up after relapse, 27 (96.4%) patients with molecular relapse are alive in major molecular remission and 20 (71%) no longer receive TKI. These results show that the outlook for relapse after SCT for CML is favorable in the TKI treatment era and that combination of TKI and DLI can achieve long-term disease free survival post relapse.Figure 1.Overall survival: relapse versus no relapseFigure 1. Overall survival: relapse versus no relapseFigure 2.Overall survival after relapse: TKI based therapy versus othersFigure 2. Overall survival after relapse: TKI based therapy versus others Disclosures: No relevant conflicts of interest to declare.

Evolution Of The Results Of 1500 Liver Transplantations Performed In The Department Of General, Transplant And Liver Surgery Medical University Of Warsaw

2015 ◽  
Vol 87 (5) ◽  
Author(s):  
Marek Krawczyk ◽  
Michał Grąt ◽  
Karolina Grąt ◽  
Karolina Wronka ◽  
Maciej Krasnodębski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Graft Survival ◽  
Liver Surgery ◽  
Long Term Outcomes ◽  
Liver Transplantations ◽  
Group 3 ◽  
Group 2 ◽  
Medical University ◽  
Group 1

AbstractLiver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects.was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw).Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures.Increased number of transplantations performed at the site was associated with increased age of the recipients (p<0.001) and donors (p<0.001), increased rate of male recipients (p<0.001), and increased rate of piggyback operations (p<0.001), and decreased MELD (p<0.001), as well as decreased blood (p=0.006) and plasma (p<0.001) transfusions. Overall survival was 71.6% at 5 years in group 1, 74.5% at 5 years in group 2, and 85% at 2.9 years in group 3 (p=0.008). Improvement of overall survival was particularly observed for primary transplantations (p=0.004). Increased graft survival rates did not reach the level of significance (p=0.136).Long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.

scholarly journals The prognostic significance of hematogones and CD34+ myeloblasts in bone marrow for adult B-cell lymphoblastic leukemia without minimal residual disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hongyan Liao ◽  
Qin Zheng ◽  
Yongmei Jin ◽  
Tashi Chozom ◽  
Ying Zhu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Chemotherapy Cycle ◽  
Minimal Residual

AbstractThis study was aimed to dissect the prognostic significances of hematogones and CD34+ myeloblasts in bone marrow for adult B-cell acute lymphoblastic leukemia(ALL) without minimal residual disease(MRD) after the induction chemotherapy cycle. A total of 113 ALL patients who have received standardized chemotherapy cycle were analyzed. Cases that were not remission after induction chemotherapy or have received stem cell transplantation were excluded. Flow cytometry was used to quantify the levels of hematogones and CD34+ myeloblasts in bone marrow aspirations, and the patients were grouped according to the levels of these two precursor cell types. The long-term relapse-free survival(RFS) and recovery of peripheral blood cells of each group after induction chemotherapy were compared. The results indicated that, after induction chemotherapy, patients with hematogones ≥0.1% have a significantly longer remission period than patients with hematogones <0.1% (p = 0.001). Meanwhile, the level of hematogones was positively associated with the recovery of both hemoglobin and platelet in peripheral blood, while CD34+ myeloblasts level is irrelevant to the recovery of Hb and PLT in peripheral blood, level of hematogones and long-term prognosis. This study confirmed hematogones level after induction chemotherapy can be used as a prognostic factor for ALL without MRD. It is more applicable for evaluation prognosis than CD34+ myeloblasts.

Impact of squamous histology on the response to treatment and long-term outcomes of patients with distal esophageal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 135-135
Author(s):  
Parth Kishore Shah ◽  
Miles Cameron ◽  
Jessica M. Frakes ◽  
Jacques Fontaine ◽  
Domenico Coppola ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell ◽  
Clinical Stage ◽  
Complete Response ◽  
Response To Treatment ◽  
Long Term Outcomes ◽  
The Mean ◽  
The Difference ◽  
The Impact

135 Background: Squamous cell carcinoma (SCC) has been traditionally linked to a better response to treatment and overall survival when compared to adenocarcinoma (AC) of the esophagus. Recent advances in staging, neoadjuvant therapy (NAT) and increasing surgical management of patients with EC have led to improved overall survival of these patients. The aim of this study is to analyze the impact of squamous histology on treatment response and long term outcomes in patients with distal EC. Methods: A retrospective review of patients who underwent esophagectomy for EC at a single institution over a 16 year period (1999-2015) was performed. Pre-operative clinical parameters, stage as well as oncologic management were compared between SCC and AC of the distal esophagus and the difference in response to treatment and overall survival were analyzed using descriptive statistics. Results: Esophagectomy was performed on 945 patients with EC of which 839 patients (89%) had distal EC. The mean age of this group was 63 years and majority were male (87%). Histology was SCC for 78 patients (9.4%) and AC for 747 patients (90.6%). Pretreatment clinical stage was similar between groups (p = 0.16). NAT administration was similar between groups (p = 0.13). Although SCC patients had higher rate of complete response (54% v/s 36%, p = 0.01) we found no difference in the overall survival after surgery (33 months for SCC v/s 40 months for AC, p = 0.72) irrespective of whether they received NAT (p = 0.95) or not (p = 0.55). Conclusions: Squamous cell histology had a favorable impact on the rate of pathologic response for patients with distal EC; however, this improvement did not alter their overall survival. This could provide an insight into the decreasing significance of the histology in the management and expectations from treatment of EC while emphasizing the continuing need for multimodality therapy to assure good outcomes on these patients.

scholarly journals FRI0457 LONG-TERM OUTCOMES AND TREATMENT EFFICACY IN PATIENTS WITH TNF RECEPTOR-ASSOCIATED AUTOINFLAMMATORY SYNDROME (TRAPS) FROM THE EUROFEVER INTERNATIONAL REGISTRY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 825.2-826
Author(s):  
R. Papa ◽  
T. Lane ◽  
F. Bovis ◽  
K. Minden ◽  
I. Touitou ◽  
...  
Keyword(s):  
Complete Response ◽  
European Federation ◽  
Efficacy Rate ◽  
Autoinflammatory Syndrome ◽  
Tnf Receptor ◽  
Aa Amyloidosis ◽  
Long Term Outcomes ◽  
Research Support ◽  
International Registry

Background:Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is one of the best-known monogenic auto-inflammatory disorders resulting from an autosomal dominant variation in the TNF super family receptor 1A (TNFRSF1A) gene (1).Objectives:To define best treatment approach in patients with TRAPS and effect on long-term outcomes.Methods:We reviewed all data on patients with TRAPS enrolled in the Eurofever international registry according the INSAID gene variant classification and the new Eurofever/PRINTO classification criteria (EPCC).Results:Data on 226 patients were available. Patients not fulfilling the EPCC carrying likely benign/benign variants (21 patients, 9%) or VOUS/not classified variants (40 patients, 18%) displayed a milder disease than the patients fulfilling the EPCC with VOUS/not classified variants (38 patients, 17%) or pathogenic/likely pathogenic variants (127 patients, 56%). In particular, in patients not fulfilling the EPCC, less frequent abdominal pain and skin rashes, higher efficacy rate of colchicine and no development of AA amyloidosis have been reported. Almost 90% of patients fulfilling the EPCC required maintenance therapy and anti-interleukin (IL)-1 drugs were the most frequently used, with the highest efficacy rate (>85% complete response), while Etanercept was less effectively used and discontinued in 65% of patients.Conclusion:Anti-IL-1 drugs are the best maintenance treatment in TRAPS with potential to reverse the most serious disease complications of AA amyloidosis and infertility. The diagnosis of TRAPS should be considered very carefully in patients carrying VOUS/not classified variants not fulfilling the EPCC.References:[1]Lachmann HJ, Papa R, Gerhold K, Obici L, Touitou I, Cantarini L, et al. The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry. Annals of the rheumatic diseases 2014;73:2160-7.Acknowledgments:RP would like to thank the European Federation of Immunology (EFIS) for the short-term bursary and HL for her continuous support and guidance during the fellowship at the National Amyloidosis Centre in London.Disclosure of Interests:Riccardo Papa: None declared, Thirusha Lane: None declared, Francesca Bovis: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Isabelle Touitou: None declared, Luca Cantarini: None declared, Marco Cattalini: None declared, Laura Obici: None declared, Annette Jansson: None declared, Alexander Belot: None declared, Beata Woska-Kuśnierz: None declared, Rainer Berendes: None declared, Agustin Remesal: None declared, Marija Jelusic: None declared, Graciela Espada: None declared, Irina Nikishina: None declared, Esther Hoppenreijs: None declared, Maria Cristina Maggio: None declared, Taryn Youngstein: None declared, Tamer Rezk: None declared, Charalampia Papadopoulou: None declared, Paul Brogan Grant/research support from: Roche, Novartis, SOBI, Chemocentryx, Novimmune, Consultant of: Roche, SOBI, UCB, Novartis, Speakers bureau: Roche, SOBI, UCB, Novartis, Philip N Hawkins: None declared, Patricia Woo: None declared, Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Marco Gattorno Consultant of: Sobi, Novartis, Speakers bureau: Sobi, Novartis, Helen J. Lachmann: None declared

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