scholarly journals Long-Term Survival Benefit of Eculizumab Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from the International PNH Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2188-2188
Author(s):  
Louis Terriou ◽  
Christopher J. Patriquin ◽  
Morag Griffin ◽  
Jong Wook Lee ◽  
Philippe Gustovic ◽  
...  
Keyword(s):  
Rare Disease ◽  
Board Of Directors ◽  
Survival Probability ◽  
Advisory Committees ◽  
Term Survival ◽  
Treatment Status ◽  
History Of ◽  
Baseline Characteristics

Abstract Background Eculizumab, the first C5 inhibitor approved for paroxysmal nocturnal hemoglobinuria (PNH), transformed PNH treatment by improving survival to that of an age- and sex- matched general population. Previous analyses demonstrating the survival benefit of eculizumab in patients with PNH leveraged historical data and were limited by small patient numbers and short follow-up durations; few evaluated survival of patients receiving eculizumab compared with untreated patients. The objective of the current analysis was to describe the baseline characteristics and overall survival of a large international cohort of eculizumab-treated patients compared with a contemporaneous untreated cohort using data from the prospective, observational International PNH Registry (NCT01374360). Methods Data from patients enrolled in the Registry after March 16, 2007 with complete information for birth date, sex, enrollment date, and treatment status were included (database cut-off, April 12, 2021). Ever-treated patients were those who received eculizumab for a minimum treatment period of 35 days while enrolled in the Registry; never-treated patients did not receive eculizumab at any time before or during Registry participation. Univariate and multivariate analyses were performed using a Cox proportional hazards that incorporated the following parameters at baseline as covariates: treatment status, presence of high disease activity (HDA), age, sex, history of bone marrow failure (BMF), history of thrombotic events (TE), transfusion dependence, and estimated glomerular filtration rate ≤60 mL/min/1.73 m 2. HDA was defined as lactate dehydrogenase (LDH) ratio ≥1.5 × upper limit of normal (ULN) and ≥1 of the following: history of major adverse vascular events (including TE); anemia (hemoglobin <10 g/dL), or physician-documented abdominal pain, dyspnea, dysphagia, fatigue, hemoglobinuria, or erectile dysfunction at any time before and including baseline. Baseline was defined as the date of eculizumab treatment initiation (ever-treated patients) or date of Registry enrollment (never-treated patients). Survival time was analyzed using a left-truncation approach that mapped time in patients' survival based on disease start date, defined as the earliest date of first-reported PNH diagnosis, PNH symptom, or first consistent flow cytometry result. Results Baseline characteristics of the 4627 patients included in the analysis (mean [SD] age at disease start, 40.2 [18.71] years; 53% female; 75% white) were comparable between the ever-treated and never-treated groups (n=1892 and n=2735, respectively). Compared with never-treated patients, more ever-treated patients had LDH ≥1.5 × ULN (90% vs 35%), and fewer had <10% PNH granulocytes (3% vs 57%) or history of BMF (45% vs 76%). The univariate Cox proportional hazard ratio (HR) for mortality in ever-treated vs never-treated patients was 0.48 (95% CI, 0.39-0.60; P<0.0001), indicating a 52% increase in survival in the treated group (Table). Among ever-treated patients, those with HDA at baseline experienced the largest reduction in mortality risk (HR [95% CI], 0.46 [0.33-0.64]; n=174); however, decreased mortality was also evident in ever-treated patients without HDA (HR, 0.65 [0.39-1.10]; n=212) or with unknown HDA status (HR, 0.50 [0.32-0.76; n=120) at baseline. Overall survival probability by treatment status was consistently greater in ever-treated vs never-treated patients through 20 years of follow-up; survival probability at 20 years was 82% (ever-treated) vs 69% (never-treated). Although long-term survival probability was greatest throughout follow-up in ever-treated patients with HDA at baseline, increased survival among ever-treated patients was evident in all 3 HDA status groups (Figure). Conclusion In this analysis of Registry data, treatment with the C5 inhibitor eculizumab improved patient survival compared with a never-treated cohort at a comparable time point in their disease course. Covariates were assessed at baseline only and competing risks and time on treatment were not controlled for, which are potential limitations. Survival benefits conferred by eculizumab treatment were observed regardless of HDA status at baseline, were more pronounced in treated patients with HDA vs those without HDA, and were maintained through 2 decades of real-world follow-up. Figure 1 Figure 1. Disclosures Terriou: Alexion, AstraZeneca Rare Disease: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patriquin: Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Speakers Bureau; Biocryst: Honoraria; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Griffin: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees; BioCryst Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis: Other: Educational grant support. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gustovic: Alexion, AstraZeneca Rare Disease: Current Employment. Patel: Alexion, AstraZeneca Rare Disease: Current Employment. Szer: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Prevail Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Predictive Factors of Response and Survival of Lenalidomide and Rituximab As Initial Treatment of Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1533-1533 ◽  
Author(s):  
Paolo Strati ◽  
Ralph J. Johnson ◽  
Sheryl G Forbes ◽  
Loretta J. Nastoupil ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Initial Treatment ◽  
Research Funding ◽  
Advisory Board ◽  
Advanced Stage ◽  
Advisory Committees ◽  
Long Term Follow Up ◽  
Baseline Characteristics

Introduction. The combination of rituximab and lenalidomide (R2) is active in patients with untreated indolent lymphoma. Recent randomized trials (RELEVANCE) have demonstrated similar efficacy when compared to standard chemo-immunotherapy backbones. Long term follow up of patients receiving R2 as well as predictors of long term remission and survival have yet to be published. Methods. We prospectively evaluated patients with low grade advanced stage FL who received R2 as initial treatment at our institution between 07/2008 and 10/2014. Lenalidomide was given at 20 mg (day 1-21, in a 28 day cycle) for 6 cycles with rituximab monthly. Lenalidomide starting dose was 10 mg if baseline creatinine clearance was < 60 mL/min. Patients with an objective response continued with 10-20 mg of lenalidomide with rituximab for up to 12 more cycles. Response was evaluated according to 2014 Lugano criteria. Results. One-hundred and one patients were included in the analysis, baseline characteristics are shown in the Table. Median number of provided cycles was 7 (range, 1-20). Median dose of lenalidomide was 20 mg (range, 5-20 mg), and 29 (29%) patients required a dose reduction. Fifty-six (55%) patients experienced grade 3-4 treatment-related toxicities, the most common (> 5%) being neutropenia (39%), skin rash (20%), myalgia (16%) and fatigue (16%). Seven (7%) patients discontinued treatment before completion, after a median time of 4 months (range, 1-10 months): 4 because of toxicity (arterial thrombosis in 2, respiratory failure in 1, and skin rash in 1), and 3 because of progression. Ninety-eight patients were evaluable for response, while 3 patients discontinued treatment because of toxicity before first response assessment. Overall response rate was 98%, CR rate 90% (both achieved after a median of 6 months [range, 3-22 months]), and CR rate at 30 months (CR30) was 80%. Only female sex associated with a higher CR rate (96% vs 83%, p=0.05), while no baseline characteristic associated with CR30 rate. After a median follow-up of 88 months (95% confidence interval, 84-92 months), 31 (31%) patients progressed and/or died, 7-year progression-free survival (PFS) was 63%, and 13% of patients had a PFS < 24 months (PFS24). Failure to achieve CR was the only factor associated with significantly decreased PFS (10 months vs not reached, p<0.001) and higher likelihood of PFS24 (46% vs 5%, p<0.001). No association was observed with baseline characteristics, including FLIPI and FLIPI-2 score. At most recent follow-up, transformation was reported in 3 (3%) patients, after 30, 32 and 42 months, respectively. Two (2%) patients have died, 1 of unrelated comorbid health conditions, 1 of progressive disease, and 7-year overall survival was 98%. Second cancers (excluding transformation) were diagnosed in 8 (8%) patients, after a median of 55 months (range, 3-105 months). These included: breast adenocarcinoma (2), melanoma (2), pancreatic adenocarcinoma (1), esophageal adenocarcinoma (1), and therapy-related acute myeloid leukemia. Discussion. Long-term follow-up show very favorable outcomes for patients with advanced stage FL receiving R2 as initial treatment, independent of traditional prognostic factors relevant to patients treated with chemoimmunotherapy, including FLIPI and FLIPI-2 score. Combination strategies, aimed at increasing depth of response to R2, may further improve outcomes observed with this regimen. Table. Disclosures Nastoupil: Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Spectrum: Honoraria. Westin:Janssen: Other: Advisory Board, Research Funding; Unum: Research Funding; Curis: Other: Advisory Board, Research Funding; 47 Inc: Research Funding; Genentech: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; Celgene: Other: Advisory Board, Research Funding; MorphoSys: Other: Advisory Board; Novartis: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding. Wang:AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding; BioInvent: Consultancy, Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Research Funding; Dava Oncology: Honoraria; Celgene: Honoraria, Research Funding; Aviara: Research Funding; Kite Pharma: Consultancy, Research Funding; Guidepoint Global: Consultancy; VelosBio: Research Funding; Loxo Oncology: Research Funding. Neelapu:Pfizer: Consultancy; Precision Biosciences: Consultancy; Merck: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Allogene: Consultancy; Novartis: Consultancy; BMS: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Cellectis: Research Funding; Acerta: Research Funding; Karus: Research Funding; Poseida: Research Funding; Incyte: Consultancy; Cell Medica: Consultancy; Unum Therapeutics: Consultancy, Research Funding. Fowler:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: lenalidomide and rituximab are not yet FDA-approved as frontline treatment for patients with FL

scholarly journals Long-Term AL Amyloidosis Survivors Among Non-Selected Referral Population

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3226-3226
Author(s):  
Eli Muchtar ◽  
Morie A. Gertz ◽  
Martha Q. Lacy ◽  
David Dingli ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Survival Rates ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Term Survival ◽  
Long Term Survival ◽  
Long Term Survivors

Abstract Introduction: Prognosis of AL amyloidosis has improved in recent years; however for many patients prognosis remains poor. We aimed to define patient-, disease- and treatment characteristics which are associated with long-term survival. Method: A retrospective chart review of all patients with biopsy-proven systemic AL amyloidosis, who were seen within 90 days of the confirmed diagnosis. Long-term survival was defined as 5-year and 10-year survival from the time of diagnosis. For 5-year survival we selected patients seen between January 1, 2000 and December 31, 2012 (allowing a minimum of 5-year follow-up, n=1331) and for 10-year survival we screened patients seen between January 1, 2000 and December 31, 2007 (allowing a minimum of 10-year follow-up; n=779). Treatment allocation was defined as the first regimen given, irrespective of subsequent treatment modifications. Results: Of the screening population, 498 patients survived ≥5 years from diagnosis (37% of the 5-year screening cohort) and 168 patients survived 10 years or more (22% of the 10-year screening cohort). Five-year survivors and 10-year survivors as compared to their counterparts were (Table): younger, higher proportion of women, more likely to have single organ involvement, less heart/liver/nerve involvement and more kidney involvement. Long-term survivors also had lower bone marrow plasma cell percentage at the time of diagnosis and lower tumor burden measured by the difference between involved to uninvolved light chain (dFLC). Similarly, long-term survivors had lower Mayo stages and higher systolic blood pressure. No difference in light chain isotype was observed between long-term survivors to long term non-survivors. Long-term survivors were less likely to be seen within 30 days of diagnosis compared to their counterparts (52% among 5-year survivors vs 67% among 5-year non-survivor; P<0.001). FISH abnormalities (data available for 555/1331 patients, 42%) were comparable between groups with regard to t(11;14) (50% among 5-year survival compared to 50% among 5-year non-survivors; P=0.93) and 13q abnormalities (34% vs 36%, respectively; P=0.53). However, trisomies were less frequently encountered in the 5-year survivor group (20% vs 29%, respectively; P=0.01), and far less common among 10-year survivors (11% vs 26%, respectively; P=0.04). Autologous stem cell transplantation (ASCT) was more likely to be associated with long-term survival. Of all patients who underwent ASCT, 74% survived more than 5 years and 49% survived more than 10 years. In comparison, among the standard-intensity therapies, 5-year survival rates for melphalan-dexamethasone, bortezomib-based regimens, immunomodulatory drug-based regimens and single agent dexamethasone/ melphalan-prednisone were 29%, 28%, 30% and 10%, respectively. The corresponding 10-year survival rates were 15%, 20%, 20% and 5%, respectively. Conclusions: Long-term AL survivors have distinct favorable baseline characteristics (including those introduced by referral bias) and ASCT as their initial therapy. Identification of these patients, especially the Mayo 2004 stage III and the Mayo 2012 stage III-IV patients who unexpectedly survived 10 years, will allow for further study and insights. Disclosures Gertz: Teva: Consultancy; Prothena: Honoraria; Alnylam: Honoraria; celgene: Consultancy; Ionis: Honoraria; Physicians Education Resource: Consultancy; Research to Practice: Consultancy; Amgen: Consultancy; janssen: Consultancy; Apellis: Consultancy; Medscape: Consultancy; Abbvie: Consultancy; spectrum: Consultancy, Honoraria; annexon: Consultancy. Lacy:Celgene: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Russell:Vyriad: Equity Ownership. Kumar:KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding.

scholarly journals Long-Term Subgroup Analyses from Azacitidine Vs. Decitabine in Unfit Newly Diagnosed Acute Myeloid Leukemia Patients: Results from the Pethema Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1256-1256
Author(s):  
Jorge Labrador ◽  
Adolfo de la Fuente ◽  
David Martínez-Cuadrón ◽  
Rebeca Rodríguez-Veiga ◽  
Josefina Serrano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Subgroup Analysis ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Real Life ◽  
Advisory Committees ◽  
Baseline Characteristics

Abstract INTRODUCTION The hypomethylating agents (HMAs), decitabine (DEC) and azacitidine (AZA), have made it possible to treat more elderly patients with acute myeloid leukemia (AML). Both HMAs have demonstrated efficacy in monotherapy and in combination with targeted therapies. However, there is little direct comparative data on AZA and DEC in first-line treatment, and we do not know which group of patients might benefit from each drug. Results of the full analysis set (FAS) were presented previously (Labrador J, et al. ASH 2020). Here, we report long-term clinical efficacy from prespecified patient subgroup analyses. METHODS We conducted a retrospective study to compare real-life clinical outcomes between AZA and DEC in patients with AML ineligible for intensive chemotherapy included in the PETHEMA registry, and analyzed clinical variables associated with response and overall survival (OS) between AZA and DEC. RESULTS A total of 626 patients were included for the FAS between 2006 and 2019. 487 (78%) received AZA and 139 (22%) received DEC. Baseline characteristics were comparable in both groups, except for the percentage of bone marrow blasts (44% vs. 34% in the DEC group compared to AZA, p=0.010). In the FAS, there was no difference in the CR, CR/CRi or ORR (CR/RCi + PR) rate: 18%, 20.5% and 32% with AZA vs. 23%, 25% and 39.5% with DEC (p=0.20, p=0.27 and p=0.12). In the subgroup analysis, DEC was associated with higher CR/CRi rate than AZA in patients with ECOG ≥ 2 (95% CI: 0.088 - 0.801), bone marrow blast count &lt; 50% (95% CI: 0.293 - 0.965), secondary AML (95% CI: 0.223 - 0.918) and adverse cytogenetics (95% CI: 0.171 - 0.857) (Figure 1A). DEC was associated with higher ORR rate than AZA in patients with ECOG ≥ 2 (95% CI: 0.116 - 0.782), leukocytes &lt; 10 x10 9/L (95% CI: 0.321 - 0.920) and bone marrow blasts &lt; 50% (95% CI: 0.321 - 0.920) (Figure 1B) 120 days-mortality was 25.4% after AZA and 27.1% after DEC, p=0.70. Patients who did not achieve at least a PR had significantly higher 120-day mortality with both HMAs (OR 8.85 and 8.22 for AZA and DEC, respectively). In the subgroup analysis, patients with leukocytes ≥ 10 x10 9/L (95% CI: 1.069 - 4.157) and those with estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73m 2 (95% CI: 1.249 - 4.664) had higher 120-day mortality with DEC than with AZA (Figure 1C) With a median follow-up of 12 months, median OS was 10.4 months (95% CI: 9.2 - 11.7) for AZA vs. 8.8 months (95% CI: 6.7 - 11.0) for DEC (p = 0.455). The subgroup analysis revealed that patients ≥ 80 years (95%: CI 1.005 - 2.341), with leukocytes ≥ 10 x10 9/L (95% CI 1.039 - 2.062), platelet count &lt;20 x10 9/L (95% CI: 1.150 - 3.422) and those with eGFR ≥ 45 mL/min/1.73m 2 (95% CI: 1.040 - 2.059) did benefit for treatment with AZA compared to DEC (Figure 1D). CONCLUSIONS Our study provides real-life data on the outcomes of AML patients treated with AZA compared to DEC in a large retrospective cohort with long-term follow-up. In addition, we identify for the first time some baseline characteristics that could benefit from AZA or DEC in terms of responses, 120-day mortality and OS. These findings could help us to choose the most appropriate HMA in monotherapy or for the development of new combinations. Figure 1 Figure 1. Disclosures de la Fuente: Novartis: Research Funding; Abbie: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Tormo: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pérez-Simón: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Montesinos: Forma Therapeutics: Consultancy; Tolero Pharmaceutical: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Glycomimetics: Consultancy; Agios: Consultancy; Stemline/Menarini: Consultancy; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau.

scholarly journals Prevalence and Risk Predictive Factors of Comorbid Malignancies in Patients with Chronic Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1900-1900
Author(s):  
Tong-Yoon Kim ◽  
Sung-Eun Lee ◽  
Soo-Hyun Kim ◽  
Soo-Young Choi ◽  
Eun-Jung Jang ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Medical Records ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Advisory Committees ◽  
History Of

Abstract Introduction: As chronic myeloid leukemia (CML) patents are generally diagnosed at old age and live longer by active use of BCR-ABL1 tyrosine kinase inhibitors (TKIs), the occurrence of other malignancy (OM) is becoming a critical issue as a long-term comorbidity. An increased rate of OM has been reported in myeloproliferative disorders and long-term TKI treatment may induce OM in CML. To explore exact prevalence and characteristics of OM, we reviewed medical records of CML patients and compared with those of age-matched Korean population. Methods: The medical records of 1,469 CML patients who diagnosed between January 2000 and December 2014 were reviewed using Korean data-set of Asia CML Registry (ACR). With a cut-off date of July 2016, age-standardized prevalence rates (A-SPR) of OM (except benign tumors and other leukemias) were analyzed and compared with that of general population in Korea Central Cancer Registry (KCCR). In addition, we analyzed cumulative incidence rate of OM and various risk factors. Results: The median duration of follow-up was 84 (1-197) months, and 96 CML patients had at least one OM. Forty three patients had a history of OM before a median 69 (1-161) months of CML diagnosis and 53 patients developed OM after a median 53 (range; 0.2-172) months of CML diagnosis. The OM included 32 thyroid cancers, 19 colorectal cancers, 16 stomach cancers, 9 breast cancers, 4 gynecological cancers (3 cervical cancers and 1 uterine endometrial cancers), 3 lymphoma (2 non-Hodgkin's lymphoma and 1 Hodgkin's lymphoma), 3 biliary cancer, 3 skin cancers, 3 prostate cancers, 2 lung cancer, 2 tongue cancer, 2 liver cancer, 2 esophageal cancer, 1 pancreatic cancer, and 1 bladder cancer.A-SPR of OM was 1.7 times higher in CML patients. Hodgkin's lymphoma (8.7 times), thyroid cancer (2.6 times), biliary cancer (2.6 times), colorectal cancer (2 times), non-Hodgkin's lymphoma (1.8 times), cervical cancer (1.8 times), and breast cancer (1.6 times) had a higher A-SPR. On the other hands, skin cancer (3.3 times), lung cancer (2 times), and liver cancer (2 times) were lower than that of general population. With 53 patients who had OM after CML diagnosis, we analyzed the cumulative incidence. The risk of OM was increased over the follow-up period (2.7% at 7 years) Univariate analysis revealed that patients who were more than 37 years old at CML diagnosis (4.3% vs. 0.4%, p<0.001) and who had family history of cancer (8.2% vs. 2.3%, p=0.002) were associated with a higher OM. After adjusting for factors, multivariate analysis showed that older age (HR of 4.19, P<0.001) and family history (HR of 3.17, P=0.001) were independently associated with increased risk. There was no difference in 7-year overall survival (OS) between patients with OM (n=96) and without OM (n=1,373) (84.9% vs. 86.9%, p=0.573). However advanced cancer stages (stage 3 and 4) of OM significantly affected poor OS ( 88.3% vs. 65.6% P=0.0406). Conclusion: Although comorbid malignancies did not significantly affect CML survival, poor survival in advanced stages and the high risk of other cancers warn the need of systematic screening in long-term CML survivors. In addition, the specific cancer types with a significantly higher A-SPR should be considered for further studies including genetic mechanisms. Disclosures Kim: ILYANG: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Long-Term Survival in Adult Patients with Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL) Who Achieved Minimal Residual Disease (MRD) Response Following Anti-CD19 BiTE® Blinatumomab

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2287-2287 ◽  
Author(s):  
Gerhard Zugmaier ◽  
Nicola Goekbuget ◽  
Andreas Viardot ◽  
Matthias Stelljes ◽  
Svenja Neumann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Research Funding ◽  
Residual Disease ◽  
Advisory Committees ◽  
Term Survival ◽  
Long Term Survival ◽  
Equity Ownership

Abstract Introduction: Relapsed/refractory (r/r) B-precursor ALL in adults has an unfavorable prognosis with a median overall survival of 4–8 months and a 5-year survival of <10%. Long-term follow-up data are presented from an exploratory phase 2 study with blinatumomab, an investigational bispecific T-cell engager (BiTE®) antibody construct that directs cytotoxic T-cells to CD19-expressing target cells (Topp MS et al. Blood 2012;120(21):670). Methods: The primary endpoint was hematologic complete remission (CR) or CR with partial hematologic recovery (CRh*) within 2 cycles of blinatumomab. Secondary endpoints included rate of minimal residual disease (MRD) response (defined as < 10-4), overall survival (OS), and relapse-free survival (RFS). Blinatumomab was administered by continuous intravenous infusion for 28 days followed by a 14-day treatment-free interval. Responding patients had the option to receive 3 additional cycles of treatment or to proceed to allogeneic hematopoietic stem cell transplantation (aHSCT). Results: 36 patients were treated; 25 (69%) responded, with 15 (42%) achieving CR and 10 (28%) CRh*. MRD response was achieved in 22 (88%) of these 25 patients with CR or CRh*. Thirteen patients with CR or CRh* proceeded to aHSCT after blinatumomab treatment. In addition, one patient with hypocellular bone marrow and MRD response after the first cycle underwent aHSCT. Follow-up for RFS is 22.4 months; median RFS is 8.8 months. Median follow-up for OS is 30.2 months; median OS is 12.9 months. Ten patients (28%) are alive at 29.7 months (Figure). We analyzed the characteristics of the 10 living long-term survivors, defined as OS of 2 years or longer, seven of whom were relapse-free. The age of these 10 patients at the time of first infusion ranged from 21 to 72 years; the blast count at screening ranged from 8% to 97% (median, 56%). Four of the 10 patients alive had received aHSCT prior to blinatumomab treatment. Of the six patients without a prior aHSCT, two were primary refractory; two had the first relapse within 12 months and two after 12 months post first diagnosis. In the 10 surviving patients blinatumomab treatment induced CR in seven patients, CRh* in two patients, and blast-free hypo-cellular bone marrow in one patient. All 10 surviving patients had an MRD response following blinatumomab treatment. The patient with hypocellular bone marrow received a transplant after the first cycle before potential recovery of blood counts qualifying for CR/CRh* could occur. Seven of the surviving patients underwent aHSCT after blinatumomab, including four patients who received a second aHSCT after they had already received an aHSCT prior to blinatumomab. One of the three patients who did not undergo aHSCT after CRh* had grade 4 cytokine release syndrome requiring resuscitation after 1 day of blinatumomab treatment and has remained in ongoing remission for 22 months without any further treatment aside from 5 cycles of blinatumomab. Another one of these three patients, who had a grade 3 neurologic event on day 2 of cycle 2, has remained in ongoing remission for 34 months without any further treatment aside from 5 cycles of blinatumomab. The third of these three patients had two CD19-positive relapses after CR following blinatumomab treatment. The patient was retreated with 3 cycles of blinatumomab, resulting twice in CR and MRD response. Two of the 10 surviving patients relapsed after blinatumomab and aHSCT; one patient with a CD 19-negative relapse achieved another hematologic remission by chemotherapy. Summary: These data show that patients with r/r ALL, who achieved MRD response and received subsequent aHSCT following blinatumomab immunotherapy may achieve long-term survival longer than 2 years. Studies with a larger sample size are warranted to confirm these data. Two patients with grade 3 or 4 toxicities showed long-term survival without aHSCT after blinatumomab. Figure Figure. Disclosures Zugmaier: Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Off Label Use: This presentation will discuss the off-label use of blinatumomab, as this agent is not approved for use by the FDA, EMA or any other regulatory authorities.. Goekbuget:Amgen Inc.: Consultancy, Honoraria, Research Funding. Viardot:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Travel support Other; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Travel support, Travel support Other; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Travel support Other. Horst:Amgen Inc.: Honoraria, Research Funding. Brueggemann:Amgen Inc.: Consultancy, Research Funding. Holland:Amgen Inc.: Employment, Equity Ownership. Schmidt:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Mergen:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Bargou:Amgen Inc.: Consultancy, Honoraria. Topp:Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Second TKI Discontinuation in CML Patients That Failed First Discontinuation and Subsequently Regained Deep Molecular Response after TKI Re-Challenge

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 788-788 ◽  
Author(s):  
Thomas Pagliardini ◽  
Franck E. Nicolini ◽  
Stephane Giraudier ◽  
Philippe Rousselot ◽  
Gabriel Etienne ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Chronic Phase ◽  
Disease Free Survival ◽  
Molecular Response ◽  
Advisory Committees ◽  
Term Survival ◽  
Deep Molecular Response ◽  
Tki Discontinuation

Abstract Background: Tyrosine kinase inhibitors (TKIs) are able to induce, in some chronic myeloid leukemia (CML) patients, long-term undetectable molecular disease (UMD). Several studies have now demonstrated that TKIs could be safely discontinued in those patients previously treated with imatinib (STIM, TWISTER, EUROSKI) and more recently with nilotinib and dasatinib (STOP 2G-TKI). All these studies show a Treatment-Free Remission (TFR) rate reaching ~50%. However, a major issue needs to be resolved for the ~50% of patients that fail such TFR strategies. Methods: We have previously reported the possibility of a second imatinib discontinuation in 16 patients who obtained a second UMD state according to the STIM criteria (RE-STIM observational study, Legros et al. Blood 2012). Here, we report a larger cohort of patients who attempt twice TKI-discontinuations with enlarged inclusion criteria: Adults CML patients without prior allogeneic transplantation or progression to advanced phase CML undergoing a 2nd attempt of TKI discontinuation for sustained deep molecular response after a 1st failure. All patients were followed in CML reference centers and according to the EUTOS-ELN accreditation criteria for BCR-ABL assessments with minimal numbers of 32,000 ABL copies/sample. Results: At the time of analysis (1st July 2016), 67 patients (median age: 51 years (range: 25-80 years)) were included. At CML diagnosis, 64 patients were in chronic phase (CP) and 3 patients in accelerated phase (AP). The Sokal risk and the EUTOS long-term survival scores (ELTS) were respectively low in 47% and 68%, intermediate in 36% and 16%, high in 11% and 2% and unknown in 6% and 14% of patients. All patients were treated initially with imatinib and 16% of patients switch to nilotinib (6/11) or to dasatinib (5/11) for intolerance/resistance reasons prior to the 1st TKI discontinuation. The median time on TKI prior to the 1st discontinuation was 63 months (range: 30-146) and the median duration of 1st CMR was 35 months (range: 20-85). The 1st molecular relapse occurred with a median of 2.5 months (range: 0-22) and the second UMD after TKI re-challenge was obtained with a median of 4.4 months (0-40). The reason of the TKI re-challenge was loss of UMD in 43%, loss of MMR in 55% and unknown in 1%. The TKI re-challenge (imatinib 73%, nilotinib 16%, dasatinib 11%) was then administered during a median of 31 months (range: 9-72 months) before the 2nd attempt of discontinuation. At 2nd TKI cessation, 85% of patients were in UMD, 3% in MR4.5, 6 % in MR4, 3% in MMR and 3% unknown. Thirty out of sixty-eight (44%) patients remained treatment-free after a median follow-up of 21.5 months (1-106), see figure. Similarly to 1st attempts, the majority of loss of MMR occurred during the first 6-12 months in this 2nd attempt cohort. Gender, age, disease phase, prognosis scores, prior interferon exposure, initial TKI type, and duration of UMD were not found to have any impact on the outcome after the 2nd attempt in a multivariate analysis. In contrast, a longer time to obtain the first UMD before the 1st attempt was associated with a significantly lower molecular disease-free survival rate after the 2nd discontinuation (p = 0.048). All patients are alive at last follow-up except one who died from an unrelated CML reason (heart attack under imatinib). Conclusion: TKIs could safely and successfully be discontinued a second time in CML pts despite a 1st failure. Figure. Figure. Disclosures Nicolini: BMS: Consultancy, Honoraria; Ariad pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Etienne:BMS: Speakers Bureau; Pfizer: Speakers Bureau; ARIAD: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Guerci-Bresler:Pfizer: Consultancy; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; ARIAD: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Mahon:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ARIAD: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria.

scholarly journals The Evaluation of Residual Disease By Digital PCR, and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after for Stopping Imatinib First-Line in Chronic Phase CML Patients: Results of the STIM2 Study.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 462-462 ◽  
Author(s):  
Franck Emmanuel Nicolini ◽  
Stephanie Dulucq ◽  
Joelle Guilhot ◽  
Gabriel Etienne ◽  
Francois-Xavier Mahon
Keyword(s):  
Board Of Directors ◽  
Predictive Factors ◽  
De Novo ◽  
Age At Diagnosis ◽  
First Line ◽  
Advisory Committees ◽  
Term Survival ◽  
Risk Of Relapse

Abstract Background TKI discontinuation is now a critical goal of CML management and several studies have demonstrated the feasibility of stopping safely imatinib (IM). A sustained deep molecular response (DMR) on long-term TKI therapy seems critical prior to attempting treatment-free remission (TFR). Results from different studies have been reported recently, but they failed to identify robust and reproducible predictive factors allowing a better selection of candidate patients for successful TFR. Aims We prospectively asked whether the use of IM first-line in de novo CP-CML patients and a systematic screen of patients with digital droplet quantitative PCR (ddPCR) for BCR-ABL1 would impact on the TFR rates. Methods In a national prospective phase II trial (Eudract # NCT01343173), we enrolled newly diagnosed CP-CML patients, in sustained MR4.5 (≥2 yrs on at least 5 consecutive points) according to the ELN criteria, checked centrally. Further molecular follow-up was performed in local laboratories, all ELN standardized and aligned on the international scale (IS). Molecular recurrence was defined as the positivity of BCR-ABL1/ABL1 transcripts with at least 1-log increase between 2 consecutive assessments or as loss of MMR on a single assessment. Duplex ddPCR was performed on screening samples after RT, using EAC primers and probes. Pre-mixes were transferred in aDG8 cartridge, and generation of droplets was made on the QX200 droplet generator. Each emulsion was transferred into a 96 wells ddPCR plate and amplified on the Biorad-C1000 Touch Thermocycler. Each patient was analyzed in duplicate. ddPCR was considered positive when the BCR-ABL1/ABL1 % was ≥3 SD. BCR-ABL1/ABL1 ratios were aligned on the IS, a conversion factor was calculated for the RT-ddPCR as previously described (S. Branford et al., Blood 2008). Impact of variables on the risk of relapse were assessed through univariate and multivariate analyses using SAS program. Results The median follow-up after IM cessation was 23.5 (1-64) Mo. One patient died from unrelated cause, and 107 experienced a loss of MMR. The molecular recurrence-free survival (RFS) was 52% (95%CI: 45-59%) at 6 months, and 50% (95%CI: 43-57%) at 24 months. The Sokal and the EUTOS long-term survival (ELTS) scores failed to discriminate patients but a trend was observed for ELTS score (p=0.0547). Other variables analysed such as gender (p=0.6246), age at diagnosis (p=0.966), age at IM cessation (p=0.6197), interval diagnosis-IM (p=0.9621), interval IM initiation-DMR (p=0.9978) did not impact on the rate of relapse. In contrast, IM and DMR duration before IM cessation significantly impacted on the rate of relapse, as this interval is redundant with IM duration (p=0.008). ddPCR was applied to 174 out of 218 patients at IM cessation. A cut-off of 0.0023%IS ratio (= median of positive ratios) was also associated with a higher risk of relapse. The RFS estimate according to this cut-off is shown in Figure 1. In a multivariate analysis, the duration of IM (≥74.8 months) and ddPCR (≥0.0023%IS) were the two identified significant predictive factors with respectively p=0.0366 [HR=0.635, 95%CI: 0.415-0.972] and p=0.0081 [HR=0.635, 95%CI: 0.415-0.972)]. No association was observed between a ddPCR ≥0.0023%IS and gender, Sokal or ELTS score, age at diagnosis, age at IM discontinuation, duration of IM treatment, DMR duration or the time-lapse for obtaining DMR. Conclusion We conclude that the duration of IM and the residual leukemic cell load as determined by a sensitive technique such as ddPCR are key factors for predicting TFR for de novo CP-CML patients who have been treated with IM front-line. Disclosures Nicolini: Sun Pharma Ltd: Consultancy; BMS: Consultancy, Speakers Bureau; Incyte Biosciences: Consultancy, Speakers Bureau. Dulucq:Incyte: Consultancy; BMS: Consultancy. Etienne:Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Incyte: Honoraria, Patents & Royalties, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mahon:Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau; BMS: Speakers Bureau.

scholarly journals Long-Term Follow up of a Comparison of Non-Myeloablative Allografting with Autografting for Newly Diagnosed Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 525-525 ◽  
Author(s):  
Benedetto Bruno ◽  
Barry Storer ◽  
Francesca Patriarca ◽  
Marcello Rotta ◽  
Roberto Sorasio ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Salvage Therapy ◽  
Research Funding ◽  
New Drugs ◽  
High Dose ◽  
Advisory Committees ◽  
Term Survival ◽  
High Dose Melphalan

Abstract Abstract 525 Background: Role and timing of allografting in myeloma are hotly debated. Before the introduction of new drugs, we carried out a trial where the treatment assignment was based only on the presence/absence of an HLA-identical sibling (Bruno et al, N Engl J Med 2007). Methods: Overall, 162/199 (81%) of patients with at least one sibling were HLA-typed. First-line treatments included induction with VAD-based regimens and a cytoreductive autograft, followed by a nonmyeloablative allograft (Tandem auto-allo) or a second melphalan-based autograft (Double-auto). We now report an update at a median follow up of 7.1 years. Results: Response rates [complete (CR) and partial remissions (PR)] at the time and after the non-myeloablative allograft and at the time and after the second autograft did not differ between the two cohorts: 76% and 86%, and 76% and 91% respectively (p=1 and p=0,54). However, CR rate was significantly higher after the non-myeloablative allograft than after the second autograft: 55% versus 26% (p=0,0026). At a median follow up of 7.1 years (range 2.5 – 10.7+), by intention-to-treat analysis, median overall survival (OS) and event free survival (EFS) were significantly longer in patients with HLA-identical siblings (No.80) as compared with those without (No.82): not reached vs. 4.25 years (HR 0.51, CI 95% 0.34–0.76, p=0.001) and 2.8 vs. 2.4 years (HR 0.62, CI 95% 0.44–0.87, p=0.005). By multivariate analysis, independent of age, gender, myeloma protein isotype, Durie&Salmon stage, and disease status at the first autograft; the presence of an HLA-identical sibling was significantly associated with longer OS (HR 0.5, CI 95% 0.3–0.8, p=0.001) and EFS (HR 0.63, CI 95% 0.4–0.9, p=0.01). At a median follow up of 7.3 (range 5.4 – 10.7+ years), median OS was not reached in the 58 patients who received a non-myeloablative allograft and 5.3 years in the 46 who received a second high-dose melphalan autograft (HR 0.55, CI 95% 0.32–0.94, p=0.02), whereas EFS was 39 months and 33 months (HR 0.62, CI 95% 0.40–0.96, p=0.02) respectively. Cumulative incidence of transplant related mortality was 11% and 2% at 2 years respectively. At median follow-ups of 7.3 years from diagnosis (range 5.4 – 10.4+) and 6.5 years from the allograft (range 4.2 – 9.4+), and 7.4 years from diagnosis (range 5.6 – 10.7+) and 6.2 years from the second autograft (range 4.7 – 9.1+), 30/58 (52%) and 37/46 (80%) patients, respectively, were treated for disease relapse/progression. Salvage therapies included bortezomib- or thalidomide-containing regimens in most patients of both cohorts. After 1–3 lines of therapy, 22/30 (73%) had a response, including 5 CR and 17 PR, in the tandem auto-allo group, whereas 21/37 (54%) had a response, including 4 CR and 16 PR after the second autograft. Of note, at a median follow up of 3.9 years from the start of the first salvage therapy, OS was not reached and was 1.7 years in patients who had relapsed/progressed after the allograft and the second high-dose melphalan (HR 0.44, CI 95% 0.24–0.82, p=0.01) respectively. Conclusions: In this study, allografting conferred a long term survival advantage over standard autografting. Salvage therapy was associated with longer OS perhaps due to a synergistic effect between new drugs and residual graft-vs.-myeloma effects. In prospective clinical trials, the combination of graft-vs.-myeloma effects with “new drugs” should be explored and may increase the cure rate of myeloma patients. Disclosures: Bringhen: Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Infective endocarditis in patients who use IV drugs: a single centre cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Alraddadi ◽  
A Alsagheir ◽  
S Gao ◽  
K An ◽  
H Hronyecz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Long Term Outcomes ◽  
Replacement Surgery ◽  
Short Term Mortality ◽  
History Of ◽  
Short And Long Term ◽  
Baseline Characteristics

Abstract Background Managing endocarditis in intravenous drug use (IVDU) patients is challenging: unless patients successfully quit IVDU, the risk of re-infection is high. Clinicians often raise concerns with ethical and resource allocation principles when considering valve replacement surgery in this patient population. To help inform practice, we sought to determine the long-term outcomes of IVDU patients with endocarditis who underwent valve surgery in our center. Method After research ethics board approval, infective endocarditis cases managed surgically at our General Hospital between 2009 and 2018 were identified through the Cardiac Care Network. We reviewed patients' charts and included those with a history of IVDU in this study. We abstracted data on baseline characteristics, peri-operative course, short- and long-term outcomes. We report results using descriptive statistics. Results We identified 124 IVDU patients with surgically managed endocarditis. Mean age was 37 years (SD 11), 61% were females and 8% had redo surgery. During admission, 45% (n=56) of the patients had an embolic event: 63% pulmonary, 30% cerebral, 18% peripheral and 11% mesenteric. Causative organisms included Methicillin-Sensitive Staphylococcus Aureus (51%, n=63), Methicillin-Resistant Staphylococcus Aureus (15%, n=19), Streptococcus Viridans (2%, n=2), and others (31%, n=38). Emergency cardiac surgery was performed for 42% of patients (n=52). Most patients (84%) had single valve intervention: 53% tricuspid, 18% aortic and 13% mitral. Double valve interventions occurred in 15% (n=18). Overall, bioprosthetic replacement was most commonly chosen (79%, n=98). In-hospital mortality was 7% (n=8). Median length of stay in hospital was 13 days (IQR 8,21) and ICU 2 days (IQR 1,6). Mortality at longest available follow-up was 24% (n=30), with a median follow-up of 129 days (IQR 15,416). Valve reintervention rate was 11% (n=13) and readmission rate was 14% (n=17) at a median of 275 days (IQR 54,502). Conclusion Despite their critical condition, IVDU patients with endocarditis have good intra-hospital outcomes. Challenges occur after hospital discharge with loss of follow-up and high short-term mortality. IVDU relapse likely accounts for some of these issues. In-hospital and community comprehensive addiction management may improve these patients' outcomes beyond the surgical procedure. Annual rate 2009–2018 Funding Acknowledgement Type of funding source: None

Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-49
Author(s):  
Samantha Ferrari ◽  
Chiara Pagani ◽  
Mariella D'Adda ◽  
Nicola Bianchetti ◽  
Annamaria Pelizzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
High Risk ◽  
Board Of Directors ◽  
Advisory Board ◽  
Advisory Committees ◽  
Risk Status ◽  
History Of ◽  
Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=&lt;0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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