المؤلفون: Scully, Marie, de la Rubia, Javier, Pavenski, Katerina, Metjian, Ara, Knöbl, Paul, Peyvandi, Flora, Cataland, Spero, Coppo, Paul, Kremer Hovinga, Johanna A, Minkue Mi Edou, Jessica, De Passos Sousa, Rui, Callewaert, Filip, Gunawardena, Sriya, Lin, Julie

المصدر: Scully, Marie; de la Rubia, Javier; Pavenski, Katerina; Metjian, Ara; Knöbl, Paul; Peyvandi, Flora; Cataland, Spero; Coppo, Paul; Kremer Hovinga, Johanna A; Minkue Mi Edou, Jessica; De Passos Sousa, Rui; Callewaert, Filip; Gunawardena, Sriya; Lin, Julie (2022). Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post-HERCULES study. Journal of thrombosis and haemostasis, 20(12), pp. 2810-2822. Wiley-Blackwell 10.1111/jth.15892

مصطلحات موضوعية: 610 Medicine & health, 340 Law

الوصف: INTRODUCTION Caplacizumab demonstrated efficacy and safety in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in the Phase 3 HERCULES trial. However, data on long-term outcomes following caplacizumab treatment are limited. OBJECTIVES The post-HERCULES trial (NCT02878603) evaluated long-term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use. PATIENTS/METHODS Over 3 years' follow-up, patients could receive open-label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of recurrence. Adverse events (AEs) were assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences (recurrence population). TTP-related events (TTP-related death, recurrence, major thromboembolic events) were assessed in the efficacy ITO population (patients without recurrence during HERCULES or before post-HERCULES). RESULTS Among 104 enrolled patients, incidences of AEs and serious AEs were similar between patients who had received caplacizumab+TPE+IST during HERCULES (n=75) and those treated with placebo+TPE+IST (placebo; n=29). TTP-related events occurred in 8% of patients (4/49) randomized to caplacizumab during HERCULES versus 38% (11/29) randomized to placebo. Nineteen patients had ≥1 recurrence; 13 of these were treated with caplacizumab. First recurrence episode was resolved or resolving for all patients treated with caplacizumab, including 9 patients with repeat caplacizumab use. All second recurrences (6/6) were resolved. Safety profile of caplacizumab for treatment of recurrence was consistent with HERCULES; most bleeding events were non-serious. No major cases of organ dysfunction were observed. CONCLUSIONS Long-term follow-up supports the safety and efficacy of caplacizumab for iTTP and its repeated use for recurrences.

وصف الملف: application/pdf

العلاقة: https://boris.unibe.ch/173249Test/

الإتاحة: https://doi.org/10.1111/jth.15892Test
https://boris.unibe.ch/173249/1/J_of_Thrombosis_Haemost_-_2022_-_Scully_-_Long_term_follow_up_of_patients_treated_with_caplacizumab_and_safety_and_efficacy.pdfTest
https://boris.unibe.ch/173249Test/

المؤلفون: Knoebl, Paul, Cataland, Spero, Peyvandi, Flora, Coppo, Paul, Scully, Marie, Kremer Hovinga, Johanna A., Metjian, Ara, de la Rubia, Javier, Pavenski, Katerina, Minkue Mi Edou, Jessica, De Winter, Hilde, Callewaert, Filip

المصدر: Knoebl, Paul; Cataland, Spero; Peyvandi, Flora; Coppo, Paul; Scully, Marie; Kremer Hovinga, Johanna A.; Metjian, Ara; de la Rubia, Javier; Pavenski, Katerina; Minkue Mi Edou, Jessica; De Winter, Hilde; Callewaert, Filip (2020). Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study. Journal of thrombosis and haemostasis, 18(2), pp. 479-484. Wiley-Blackwell 10.1111/jth.14679

مصطلحات موضوعية: 610 Medicine & health

الوصف: BACKGROUND Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy. Caplacizumab, an anti-von Willebrand Factor Nanobody® , is effective for treating aTTP episodes and is well tolerated. OBJECTIVES AND METHODS In the phase 3 HERCULES trial (NCT02553317), patients with aTTP received double-blind caplacizumab or placebo during daily therapeutic plasma exchange (TPE) and for ≥30 days thereafter. Patients who experienced an exacerbation while on blinded study drug treatment switched to receive open-label caplacizumab plus re-initiation of daily TPE. Exacerbations were defined as recurrence of disease occurring within 30 days after cessation of daily TPE. RESULTS Thirty-one patients (placebo, n = 28; caplacizumab, n = 3) had an exacerbation during double-blind treatment. Twenty-eight patients switched to open-label caplacizumab (placebo, n = 26; caplacizumab, n = 2); the three others discontinued upon exacerbation. Median time to platelet count response (≥150 x 109 /L) was 3.49 days upon receiving caplacizumab. There were no deaths. During open-label treatment, further exacerbation or a major thromboembolic event (vena cava thrombosis) was experienced by one patient (3.6%) each. Consistent with the double-blind phase, the most frequent treatment-emergent adverse events were catheter site hemorrhage (28.6%), headache (21.4%), and epistaxis (17.9%). CONCLUSIONS These results suggest that caplacizumab was efficacious and well tolerated in patients with aTTP who experienced a disease exacerbation during double-blind treatment in HERCULES.

وصف الملف: application/pdf

العلاقة: https://boris.unibe.ch/134991Test/

الإتاحة: https://doi.org/10.1111/jth.14679Test
https://boris.unibe.ch/134991/1/HERCULES.pdfTest
https://boris.unibe.ch/134991Test/

المؤلفون: Dimopoulos, Meletios A., Moreau, Philippe, Augustson, Bradley, Castro, Nelson, Pika, Tomas, Delimpasi, Sosana, De la Rubia, Javier, Maiolino, Angelo, Reiman, Tony, Martinez‐Lopez, Joaquin, Martin, Thomas, Mikhael, Joseph, Yong, Kwee, Risse, Marie‐Laure, Asset, Gaelle, Marion, Sylvia, Hajek, Roman

المصدر: American Journal of Hematology; Jan2023, Vol. 98 Issue 1, pE15-E19, 5p

المؤلفون: Pascual‐Izquierdo, Cristina, del Rio‐Garma, Julio, de la Rubia, Javier, Viejo, Aurora, Mingot, Eva, Cid, Joan, Solanich, Xavier, Fernández‐Sojo, Jesús, Martín‐Sánchez, Jesús, Hernández, Luis, García‐Gala, José María, Alonso, Nieves, González, Victoria, Oliva, Ana, Gómez‐Seguí, Inés, Goterris, Rosa, Guerra, Luisa, García‐Candel, Faustino, Fernández‐Docampo, Marta, Antelo, María Luisa

المصدر: Journal of Clinical Apheresis; Aug2021, Vol. 36 Issue 4, p563-573, 11p

مصطلحات موضوعية: THROMBOTIC thrombocytopenic purpura, DIAGNOSIS, IDIOPATHIC thrombocytopenic purpura, PROGNOSIS, DISEASE management, DISEASE incidence, THERAPEUTIC complications

مصطلحات جغرافية: SPAIN

مستخلص: Background: Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by the presence of anti‐ADAMTS13 autoantibodies. Achieving accurate information on incidence and customary disease management is important to provide appropriate diagnostic and therapeutic resources. The aim of this study was to determine the incidence and outcomes of iTTP in Spain. Study design and methods: A cross‐sectional survey was carried out among Spanish hospitals, focused on iTTP patients ≥16 years old attended between 2015 and 2017, and those at follow‐up before that interval. Incidence, prevalence, mortality, refractoriness, exacerbations, treatment complications, relapses, and sequelae were estimated. Results: Forty‐two hospitals covering roughly 20 million inhabitants answered the survey and reported 203 episodes (138 newly‐diagnosed and 65 relapses), of which 193 (95.1%) were treated. Incidence was 2.67 (95% CI 1.90‐3.45) patients per million inhabitants per year and prevalence 21.44 (95% CI% 19.10‐23.73) patients per million inhabitants. At diagnosis, ADAMTS13 activity and anti‐ADAMTS13 autoantibody were measured in 97% and 84.3% of reported episodes, respectively. Fifteen patients (7.4%) died as a direct consequence of iTTP, 6 of them before receiving any iTTP‐specific treatment. Thirty‐one (16.1%) of the 193 treated episodes were refractory to plasma exchange and corticosteroids, and 51 (26.4%) suffered at least one exacerbation. Conclusion: iTTP incidence and prevalence were somewhat higher than those documented in neighboring countries. Together with data on treatments and outcomes, this information will allow us to better estimate what is needed to improve diagnosis and prognosis of iTTP patients in Spain. [ABSTRACT FROM AUTHOR]

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المؤلفون: Terpos, Evangelos, Katodritou, Eirini, de la Rubia, Javier, Hungria, Vania, Hulin, Cyrille, Roussou, Maria, Delforge, Michel, Bries, Greet, Stoppa, Anne‐Marie, Aagesen, Jesper, Sargin, Deniz, Belch, Andrew, Ahlberg, Lucia, Diels, Joris, Olie, Robert A., Robinson, Jr, Don, Spencer, Mike, Potamianou, Anna, van de Velde, Helgi, Dimopoulos, Meletios A.

المصدر: European Journal of Haematology; Oct2018, Vol. 101 Issue 4, p556-565, 10p

مصطلحات موضوعية: BORTEZOMIB, MULTIPLE myeloma treatment, DEXAMETHASONE, DRUG efficacy, IMMUNOTHERAPY

مستخلص: Abstract: Objective: The efficacy and safety of bortezomib‐based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE^® OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real‐world medical practice. Method: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment‐free interval, progression‐free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. Results: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near‐complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment‐free interval was 7.9 months. After 22.6 months’ median follow‐up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new‐onset any‐grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. Conclusion: These prospective real‐world data demonstrate the effectiveness and safety of bortezomib‐based therapy for RRMM and confirm high response rates and long OS for this population. [ABSTRACT FROM AUTHOR]

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المؤلفون: del Río-Garma, Julio, Alvarez-Larrán, Alberto, Martínez, Clara, Muncunill, Josep, Castell, Dolors, de la Rubia, Javier, Zamora, Concepción, Corral, Mercedes, Viejo, Aurora, Peña, Francisco, Rodríguez-Vicente, Pilar, Contreras, Enric, Arbona, Cristina, Ramírez, Consuelo, Garcia-Erce, José A., Alegre, Adrián, Mateo, Jos, Pereira, Arturo

المصدر: British Journal of Haematology; Oct2008, Vol. 143 Issue 1, p39-45, 7p, 3 Charts

مصطلحات موضوعية: THROMBOTIC thrombocytopenic purpura, HEMOLYTIC anemia, PLASMA exchange (Therapeutics), BLOOD transfusion, COMMUNICABLE diseases, BLOOD plasma

مستخلص: Plasma exchange (PE) with plasma infusion is the treatment of choice for thrombotic thrombocytopenic purpura (TTP) but doubts remain as to whether all kinds of plasma are equally effective. A multicentric cohort study was conducted to compare methylene blue-photoinactivated plasma (MBPIP) with quarantine fresh frozen plasma (qFFP) in the treatment of TTP. One hundred and two episodes of idiopathic TTP were included; MBPIP was used in 63 and qFFP in 39. The treatment schedule consisted of daily PE and costicosteroids, and the main end-point was remission status on day 8. Patients treated with MBPIP required more PEs (median: 11 vs. 5, P = 0·002) and a larger volume of plasma (median: 485 ml/kg vs. 216 ml/kg, P = 0·007) to achieve a remission, and presented more recrudescences while on PE therapy (29 of 63 vs. 8 of 39, P = 0·02) than those receiving qFFP. After adjustment for possible confounding factors, the use of MBPIP was associated with a lower likelihood of remission on day 8 [Odds ratio (OR): 0·17; 95% confidence interval (CI): 0·06–0·47] and a higher risk of recrudescence while on treatment (OR: 4·2; 95% CI: 1·6–10·8). In conclusion, MBPIP is less effective than qFFP in the treatment of TTP. [ABSTRACT FROM AUTHOR]

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المؤلفون: de la Rubia, Javier¹ delarubia_jav@gva.es, Arbona, Cristina¹, de Arriba, Felipe¹, del Cañizo, Consuelo¹, Brunet, Salut¹, Zamora, Concha¹, Díaz, Miguel A.¹, Bargay, Joan¹, Petit, José¹, de la Serna, Javier¹, Insunza, Andrés¹, Arrieta, Rosario¹, Pascual, María J.¹, Serrano, David¹, Sanjuan, Isabel¹, Espigado, Ildefonso¹, Alegre, Adrián¹, Martínez, Dobleta¹, Verdeguer, Amparo¹, del Cañizo, Consuelo (AUTHOR)

المصدر: Transfusion. Jan2002, Vol. 42 Issue 1, p4-9. 6p.

مصطلحات موضوعية: *BLOOD cells, *BLOOD donors, *BLOOD

مستخلص: Background: Predictive factors of the response to rHuG-CSF in normal donors have not been extensively studied.Study Design and Methods: We analyzed factors influencing CD34+ cell yield in the 1st day of collection in 261 healthy donors from the Spanish National Donor Registry. The median age was 38 years (range, 2-72). The median dose of rHuG-CSF was 10 microg per kg per day (range, 5-20) over 4 days. In 103 donors (40%), <4 x 10(6) per kg CD34+ cells were collected. The variables that were analyzed included age, sex, weight, basal complete blood cell count, dose, type of rHuGCSF and schedule of administration, and maximum WBC count before apheresis.Results: By univariate analysis, the maximum WBC count (<50 vs. >or=50 x 10(9)/L, p = 0.004), advanced age (p = 0.008), and number of daily rHuG-CSF doses (one vs. two; p = 0.01) correlated with the number of CD34+ cells collected. By multivariate analysis, donors age (<38 vs. >or=38 years; p = 0.014) and a single daily dose of rHuG-CSF (p = 0.005) were the two variables that significantly predicted a low CD34+ cell yield.Conclusion: Donors' age, with a threshold of 38 years or more, and the rHuG-CSF schedule are the factors that significantly affected CD34+ cell mobilization and collection in healthy donors. [ABSTRACT FROM AUTHOR]

المؤلفون: Brunet, Salut, Urbano-Ispizua, Alvaro, Ojeda, Emilio, Ruiz, Dolores, Moraleda, José Ma., Díaz, Miguel Angel, Caballero, Dolores, Bargay, Joan, de la Rubia, Javier, Solano, Carlos, Zuazu, Javier, Diez, José Luis, de la Serna, Javier, Espigado, Idelfonso, Alegre, Adrián, Torres, J. Pio, Jurado, Manuel, Fernández, Manuel, Vivancos, Pilar, Carreras, Enric

المصدر: British Journal of Haematology; Sep2001, Vol. 114 Issue 3, p544-550, 7p, 4 Charts, 2 Graphs

مصطلحات موضوعية: GRAFT versus host disease, HEMATOPOIETIC stem cell transplantation, HEMATOLOGICAL oncology

مستخلص: To assess the influence of graft-versus-host disease (GVHD) on the outcome of patients with advanced haematological malignancies (AHM) who received a primary, unmodified allogeneic peripheral blood progenitor cells transplant (allo-PBT) from a human leucocyte antigen (HLA) identical sibling donor, we analysed 136 patients with myeloid neoplasms (n = 70) or lymphoproliferative disorders (n = 66), transplanted at 19 Spanish institutions. Median age was 35 years (range 1–61). The cumulative incidence of relapse for all patients was 34% (95% CI, 26–42%), 41% (95% CI, 33–49) for patients without GVHD and 14% (95% CI, 3–25) (P = 0·001) for patients with acute and chronic GVHD. After a median follow-up of 11 months (range 2–49), 60 (44%) patients remained alive with an actuarial probability of overall survival and disease-free survival (DFS) at 30 months of 31% (95% CI, 21–41%) and 28% (95% CI, 17–39%) respectively. In patients surviving > 100 d, the low incidence of relapse in those with acute and chronic GVHD led to a DFS of 57% (95% CI, 38–76%) compared with a DFS of 34% (95% CI, 17–51%) in the remaining patients (P = 0·03). Our results indicate a reduced incidence of relapse for patients with AHM receiving an unmodified allo-PBT and developing acute and chronic GVHD, which results in an improved DFS. [ABSTRACT FROM AUTHOR]

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المؤلفون: Lahuerta, Juan Jose, Martinez-Lopez, Joaquin, De La Serna, Javier, Blade, Joan, Grande, Carlos, Alegre, Adrian, Vazquez, Lourdes, Garcia-Larana, Jose, Sureda, Ana, De La Rubia, Javier, Conde, Eulogio, Martinez, Rafael, Perez-Equiza, Katy, Moraleda, Jose M., Leon, Angel, Besalduch, Juan, Cabrera, Rafael, Gonzalez-San Miguel, Jose D., Morales, Alfonso, Garcia-Ruiz, Juan C.

المصدر: British Journal of Haematology; May2000, Vol. 109 Issue 2, p438-446, 9p, 2 Graphs

مصطلحات موضوعية: MULTIPLE myeloma treatment, STEM cell transplantation, ELECTROPHORESIS, SPONTANEOUS cancer regression

مستخلص: We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50–90% reduction). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17–53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57–86, median not reached) compared with any other response group (univariate comparison P < 0·00000 to P = 0·004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0·6; median survival 56, 44 and 42 months respectively, P = 0·5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0·00000; OS P < 0·00000; both Cox models P < 0·00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF. [ABSTRACT FROM AUTHOR]

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المؤلفون: de la Rubia, Javier^1,2, Roig, Mónica¹, Ibáñez, Ángela³, García, Inmaculada⁴, Vera, José A.⁵, Aguilar, Carlos⁶, del Campo, Raquel⁷, González, Nicolás⁸, Martínez, Rafael⁹, Palomera, Luis¹⁰, Picón, Isabel¹¹, Rodríguez, Juan N.¹², Sanz, Miguel A.¹

المصدر: European Journal of Haematology. Oct2010, Vol. 85 Issue 4, p363-365. 3p. 2 Charts.

مصطلحات موضوعية: *MULTIPLE myeloma treatment, *IMMUNOLOGICAL adjuvants, *DRUG efficacy, *HEMODIALYSIS patients, *MEDICAL research

مصطلحات جغرافية: SPAIN

مستخلص: The article reports on a study which examines the efficacy of immunomodulating agent lenalidomide in the management of patients with multiple myeloma (MM) requiring dialysis in Spain. A total of 15 patients with MM and severe renal impairment requiring dialysis and receiving lenalidomide-based therapy were the subject of the study. Findings of the study revealed that lenalidomide-based therapy is associated with a high response rate and a long duration of response.