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

scholarly journals Pediatric-Onset Evans Syndrome Is Associated with Broad Immunopathological Manifestations, High Treatment Burden and Mortality in Long-Term Follow-up

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-22
Author(s):  
Thomas Pincez ◽  
Helder Fernandes ◽  
Thierry Leblanc ◽  
Gérard Michel ◽  
Vincent Barlogis ◽  
...  
Keyword(s):  
Complete Response ◽  
Second Line ◽  
Treatment Burden ◽  
Recurrent Infections ◽  
Evans Syndrome ◽  
Long Term Outcomes ◽  
Pediatric Onset ◽  
Over Time

Introduction Pediatric-onset Evans syndrome (pES) is defined by the association between immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) before the age of 18 years and may be associated to various immunopathological manifestations (IMs). No comprehensive study of this rare disease exists, and its long-term outcomes are poorly described. Methods Patients from the nationwide French prospective OBS'CEREVANCE cohort with pES and more than 5 years of follow-up were included (excepted pES secondary to bone marrow transplantation or primary immunodeficiencies known at the inclusion). All patients, including those with less than 5 years of follow-up, were included in survival analyses. Multivariate Cox proportional hazards model was used to analyze factors associated with time-dependent variables. Results Of the 216 patients with pES in the cohort, 151 (88 males and 63 females) were included with a median (min-max) follow-up time after first cytopenia diagnosis of 11.3 (5.1-38) years. Median age at final follow-up was 18.5 (6.8-50.0) years. The proportion of patients achieving a sustained complete response (i.e. persisting until final follow-up) increased after cytopenia onset (Fig. 1A). ITP and AIHA were in complete remission in 40.5% and 54.5%, 74.1% and 62.3%, and 78.4% and 86% of patients at 5, 10, and 15 years, respectively. Clinical IMs (cIMs) developed in 100/151 patients (66%), before the first diagnosis of cytopenia in 21/100 cases. The number of cIMs increased over time (Fig. 1B). The proportions of patients with one and more than one cIM were 50% and 14%, 57% and 19%, and 81% and 44% at 5, 10, and 15 years after the first cytopenia diagnosis, respectively. A broad spectrum of cIMs were present, lymphoproliferation (n = 71), dermatological (n = 26), gastrointestinal/hepatic (n = 23), and pneumological manifestations (n = 16) being the most common. Three patients had a hematological malignancy. Biological IMs (bIMs) were diagnosed in 101/151 patients (67%) and also increased over time, with hypogammaglobulinemia (n = 54) being the most common. Autoimmune neutropenia developed in 43 patients (28.5%) and was independently associated with the number of cIMs (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.5-3.8; p = 0.0002). Severe or recurrent infections were present in 53 patients (35%). The number of second-line treatments received (i.e. other than steroids and immunoglobulins) increased over time without reaching a plateau (Fig. 1C). Half of the patients had received at least one, two, and three different treatments at 2.7, 10.5, and 14.7 years after the first cytopenia diagnosis, respectively. The number of cIMs was independently associated with the number of second-line treatments received (HR, 1.3; 95% CI, 1.08-1.6; p = 0.006). Systemic lupus erythematosus (SLE) was diagnosed in 11/151 patients (7.3%, 1/88 males and 10/63 females) and autoimmune lymphoproliferative syndrome (ALPS) in six (4.0%). Sixteen of the 151 patients followed for more than 5 years (10.6%) died, and seven died before the fifth year of follow-up (23 deaths in total). Survival at 5, 10, and 15 years after the first cytopenia was 97%, 92%, and 84%, respectively (Fig. 1D). Deaths occurred regularly throughout the follow-up period, at a median age of 18.0 (1.7-31.5) years. The most frequent cause of death was infections (n = 12, 52%). Four patients (18%) died of hemorrhage, all were less than 13 years old. The numbers of second-line treatments (HR, 1.3; 95% CI, 1.1-1.6; p = 0.004) and severe or recurrent infections (HR, 3.4; 95% CI, 1.2-9.7; p = 0.02) were independently associated with mortality after 5 years of follow-up. Overall, 20-year-old compared to 10-year-old patients more frequently showed a sustained complete response for AIHA (72% vs. 30%) and ITP (50% vs. 26%), but more frequently had cIMs (74% vs. 37%), bIMs (75% vs. 39%), and ongoing second-line treatments (88% vs. 47%; p < 0.001 for all comparisons). Conclusions Long-term outcomes of pES were associated to IMs and second-line treatment burden, not active cytopenia. The significant mortality rates, mostly among adolescents and young adults, were linked to drug-induced and/or constitutive immunodeficiencies. Few cases were associated with SLE or ALPS, which is consistent with a heterogeneous genetic background. These results highlight the importance of multidisciplinary care during the transition from childhood to adulthood. Figure 1 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.

Long-Term Outcomes in the Treatment of Classical Trigeminal Neuralgia by Gamma Knife Radiosurgery

Neurosurgery ◽  
2016 ◽  
Vol 79 (6) ◽  
pp. 879-888 ◽  
Author(s):  
Nuria E. Martínez Moreno ◽  
Jorge Gutiérrez-Sárraga ◽  
Germán Rey-Portolés ◽  
Adolfo Jiménez-Huete ◽  
Roberto Martínez Álvarez
Keyword(s):  
Trigeminal Neuralgia ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
Response Rates ◽  
Complete Response ◽  
Long Term Outcomes ◽  
Classical Trigeminal Neuralgia ◽  
Facial Numbness

Abstract BACKGROUND: Gamma knife radiosurgery (GKRS) is one of the alternatives for treatment for classical trigeminal neuralgia (TN). OBJECTIVE: To retrospectively analyze long-term outcomes for TN using GKRS achieved at our institution. METHODS: One hundred seventeen patients with medically refractory TN treated by GKRS at our institution were followed up between 1993 and 2011. Mean maximum dose was 86.5 Gy (range: 80-90 Gy; median: 90 Gy). Clinical response was defined based on the Burchiel classification. We considered classes I and II as a complete response. For toxicity, we use the Barrow Neurological Institute facial numbness scale. Mean duration of follow-up was 66 months (range: 24-171 months). RESULTS: Complete response at last follow-up in our patients was 81%, with an excellent response while off medication in 52%. Pain-free rates without medication (class I) were 85% at 3 years (confidence interval [CI]: 78%-94%), 81% at 5 years (CI: 72%-91%), and 76% at 7 years (CI: 65%-90%). Complete response rates (classes I-II) were 91% at 3 years (CI: 86%-97%), 86% at 5 years (CI: 79%-93%), and 82% at 7 years (CI: 72%-93%). Poor treatment response rates differed significantly between patients who had undergone previous surgery and were refractory to management with medication prior to GKRS. New or worsening facial numbness was reported in 32.5% (30% score II and 2.5% score III). No anesthesia dolorosa was reported. Permanent recurrence pain rate was 12%. CONCLUSION: GKRS achieved favorable outcomes compared with surgery in terms of pain relief and complication rates in our cohort of patients, notwithstanding decreasing pain-free survival rates over time. We consider GKRS to be an initial treatment in the management of medically intractable TN in selected patients.

scholarly journals Pathologic Complete Response After Neoadjuvant Chemotherapy and Long-Term Outcomes Among Young Women With Breast Cancer

2017 ◽  
Vol 15 (10) ◽  
pp. 1216-1223 ◽  
Author(s):  
Laura Spring ◽  
Rachel Greenup ◽  
Andrzej Niemierko ◽  
Lidia Schapira ◽  
Stephanie Haddad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Young Women ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Long Term Outcomes

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.

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