المؤلفون: Lazzari, Lorenzo, Balaguer-Roselló, Aitana, Montoro, Juan, Greco, Raffaella, Hernani, Rafael, Lupo-Stanghellini, Maria Teresa, Villalba, Marta, Giglio, Fabio, Facal, Ana, Lorentino, Francesca, Guerreiro, Manuel, Bruno, Alessandro, Pérez, Ariadna, Xue, Elisabetta, Clerici, Daniela, Piemontese, Simona, Piñana, José Luis, Sanz, Miguel Ángel, Solano, Carlos, de la Rubia, Javier, Ciceri, Fabio, Peccatori, Jacopo, Sanz, Jaime

المساهمون: Lazzari, Lorenzo, Balaguer-Roselló, Aitana, Montoro, Juan, Greco, Raffaella, Hernani, Rafael, Lupo-Stanghellini, Maria Teresa, Villalba, Marta, Giglio, Fabio, Facal, Ana, Lorentino, Francesca, Guerreiro, Manuel, Bruno, Alessandro, Pérez, Ariadna, Xue, Elisabetta, Clerici, Daniela, Piemontese, Simona, Piñana, José Lui, Sanz, Miguel Ángel, Solano, Carlo, de la Rubia, Javier, Ciceri, Fabio, Peccatori, Jacopo, Sanz, Jaime

مصطلحات موضوعية: Adult, Cyclophosphamide, Humans, Mycophenolic Acid, Retrospective Studies, Sirolimus, Transplantation Conditioning, Unrelated Donors, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute

الوصف: Post-transplant cyclophosphamide (PTCy) has emerged as a promising graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no studies have reported the efficacy of a GvHD prophylaxis based on PTCy with sirolimus (Sir-PTCy) in patients with acute myeloid leukemia (AML). In this retrospective study, we analyze the use of sirolimus in combination with PTCy, with or without mycophenolate mofetil (MMF), on 242 consecutive adult patients with AML undergoing a myeloablative first allo-HSCT from different donor types, in three European centers between January 2017 and December 2020. Seventy-seven (32%) patients received allo-HSCT from HLA-matched sibling donor, 101 (42%) from HLA-matched and mismatched unrelated donor, and 64 (26%) from haploidentical donor. Except for neutrophil and platelet engraftment, which was slower in the haploidentical cohort, no significant differences were observed in major transplant outcomes according to donor type in univariate and multivariate analysis. GvHD prophylaxis with Sir-PTCy, with or without MMF, is safe and effective in patients with AML undergoing myeloablative allo-HSCT, resulting in low rates of transplant-related mortality, relapse/progression, and acute and chronic GvHD in all donor settings.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35680995; info:eu-repo/semantics/altIdentifier/wos/WOS:000808391500001; volume:57; issue:9; firstpage:1389; lastpage:1398; numberofpages:10; journal:BONE MARROW TRANSPLANTATION; http://hdl.handle.net/20.500.11768/132811Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85131605087

الإتاحة: https://doi.org/20.500.11768/132811Test
https://doi.org/10.1038/s41409-022-01725-3Test
https://hdl.handle.net/20.500.11768/132811Test

المؤلفون: Encinas, Cristina, Hernandez-Rivas, José-Ángel, Oriol, Albert, Rosiñol, Laura, Blanchard, María-Jesús, Bellón, José-María, García-Sanz, Ramón, de la Rubia, Javier, de la Guía, Ana López, Jímenez-Ubieto, Ana, Jarque, Isidro, Iñigo, Belén, Dourdil, Victoria, de Arriba, Felipe, Pérez-Ávila, Clara Cuéllar, Gonzalez, Yolanda, Hernández, Miguel-Teodoro, Bargay, Joan, Granell, Miguel, Rodríguez-Otero, Paula

المصدر: Blood Cancer Journal; Apr2022, Vol. 12 Issue 4, p1-8, 8p

مصطلحات موضوعية: MULTIPLE myeloma, DISEASE risk factors, ANTIBIOTIC prophylaxis, SERUM albumin, PATIENTS' attitudes, MONOCLONAL gammopathies

مستخلص: Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0–2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies. [ABSTRACT FROM AUTHOR]

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المؤلفون: Mosquera Orgueira, Adrian, González Pérez, Marta Sonia, Diaz Arias, Jose, Rosiñol, Laura, Oriol, Albert, Teruel, Ana Isabel, Martinez Lopez, Joaquin, Palomera, Luis, Granell, Miguel, Blanchard, Maria Jesus, de la Rubia, Javier, López de la Guia, Ana, Rios, Rafael, Sureda, Anna, Hernandez, Miguel Teodoro, Bengoechea, Enrique, Calasanz, María José, Gutierrez, Norma, Martin, Maria Luis, Blade, Joan

المصدر: Blood Cancer Journal; Apr2022, Vol. 12 Issue 4, p1-9, 9p

مصطلحات موضوعية: MULTIPLE myeloma, MACHINE learning, MONOCLONAL gammopathies, PROGNOSTIC models, DIAGNOSIS

مستخلص: The International Staging System (ISS) and the Revised International Staging System (R-ISS) are commonly used prognostic scores in multiple myeloma (MM). These methods have significant gaps, particularly among intermediate-risk groups. The aim of this study was to improve risk stratification in newly diagnosed MM patients using data from three different trials developed by the Spanish Myeloma Group. For this, we applied an unsupervised machine learning clusterization technique on a set of clinical, biochemical and cytogenetic variables, and we identified two novel clusters of patients with significantly different survival. The prognostic precision of this clusterization was superior to those of ISS and R-ISS scores, and appeared to be particularly useful to improve risk stratification among R-ISS 2 patients. Additionally, patients assigned to the low-risk cluster in the GEM05 over 65 years trial had a significant survival benefit when treated with VMP as compared with VTD. In conclusion, we describe a simple prognostic model for newly diagnosed MM whose predictions are independent of the ISS and R-ISS scores. Notably, the model is particularly useful in order to re-classify R-ISS score 2 patients in 2 different prognostic subgroups. The combination of ISS, R-ISS and unsupervised machine learning clusterization brings a promising approximation to improve MM risk stratification. [ABSTRACT FROM AUTHOR]

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المؤلفون: del Río-Garma, Julio, Bobillo, Sabela, de la Rubia, Javier, Pascual, Cristina, García-Candel, Faustino, García-Gala, Jose M., Gonzalez, Reyes, Abril, Laura, Vidan, Julia, Gomez, Maria Jesús, Peña, Francisco, Arbona, Cristina, Martín-Sanchez, Jesús, Moreno, Gemma, Romón, Iñigo, Viejo, Aurora, Oliva, Ana, Linares, Mónica, Salinas, Ramón, Pérez, Sonia

المصدر: Annals of Hematology; Jan2022, Vol. 101 Issue 1, p59-67, 9p

مصطلحات موضوعية: COMA, THROMBOTIC thrombocytopenic purpura, PROGNOSIS, PLATELET count, MORTALITY, EARLY death, PATIENTS' attitudes

مستخلص: Despite the effectiveness of plasma exchange (PEX) and immunosuppressants in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), a number of patients still die as a result of the disease. Whether caplacizumab could rescue these patients remains still unsettled. The objective of this study was to characterise mortality patterns and prognostic factors in the first episode of aTTP. We queried the Spanish TTP Registry for patients with a diagnosis of aTTP in their presenting episode who fulfilled complete clinical and follow-up data (n = 102). The patients were diagnosed between 2004 and 2018, and all were treated with daily PEX and corticosteroids. Clinical and laboratory data were analysed at diagnosis and during the treatment course. Eight patients (7.7%) died between 12 h and 36 days after presentation, and could be classified into three patterns: death before treatment, early death driven by acute cardiac or neurologic events, and late death due to unremitted aTTP. Stupor or coma at diagnosis and platelet count < 20 × 10⁹ /L by the 6th treatment day were independently associated with increased risk of death. Stupor or coma at diagnosis and lack of response to PEX by the 6th day in patients experiencing the first episode of aTTP are strong predictors of mortality. These patients could be rescued by novel agents aimed at halting the microvascular thrombosis until adequate immunosuppression is achieved. [ABSTRACT FROM AUTHOR]

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المؤلفون: Puig, Noemi, Hernández, Miguel T., Rosiñol, Laura, González, Esther, de Arriba, Felipe, Oriol, Albert, González-Calle, Verónica, Escalante, Fernando, de la Rubia, Javier, Gironella, Mercedes, Ríos, Rafael, García-Sánchez, Ricarda, Arguiñano, José M., Alegre, Adrián, Martín, Jesús, Gutiérrez, Norma. C., Calasanz, María J., Martín, María L., Couto, María del Carmen, Casanova, María

المصدر: Blood Cancer Journal; May2021, Vol. 11 Issue 5, p1-11, 11p

مصطلحات موضوعية: DEXAMETHASONE, CLARITHROMYCIN, AUTOGRAFTS, MULTIPLE myeloma treatment, RANDOMIZED controlled trials

مستخلص: Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene. [ABSTRACT FROM AUTHOR]

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المؤلفون: Blanes, M., Lorenzo, J. I., Ribas, P., Jiménez, A., González, J. D., Cejalvo, M. J., Solano, C., Alegre, A., de la Rubia, Javier

المصدر: Annals of Hematology; Aug2019, Vol. 98 Issue 8, p2013-2015, 3p

مصطلحات موضوعية: MULTIPLE myeloma, BUSULFAN, MELPHALAN, DRUG side effects, STEM cell transplantation

المؤلفون: Gutiérrez Gutiérrez, Norma Carmen, Castellanos, M. V., Martín, M. L., Mateos Manteca, María Victoria, Hernández, J. M., Fernández, M., Carrera, D., Rosiñol, Laura, Ribera, J. M., Ojanguren, J. M., Palomera, Luis, Gardella, S., Escoda, L., Hernández-Boluda, J. C., Bello, J. L., De la Rubia, Javier, Lahuerta, Juan José, San Miguel Izquierdo, Jesús Fernando

مصطلحات موضوعية: Multiple myeloma, Genetic abnormalities, FISH, RB deletion, mieloma múltiple

الوصف: [EN]Fluorescence in situ hybridization (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). However, the existence of associations between cytogenetic abnormalities compels us to re-assess the value of each abnormality. A total of 260 patients with MM at the time of diagnosis, enrolled in the GEM-2000 Spanish transplant protocol, have been analyzed by FISH in order to ascertain the independent influence on myeloma prognosis of IGH translocations, as well as RB and P53 deletions. Survival analyses showed that patients with t(4;14), RB or P53 deletions had a significantly shorter survival than patients without these abnormalities. However, patients with RB deletions without other abnormalities in FISH analysis, displayed a similar outcome to those patients without genetic changes by FISH (46 vs 54 months, P ¼ 0.3). In the multivariate analysis the presence of t(4;14), RB deletion associated with other abnormalities, age 460 years, high proportion of S-phase cells and advanced stage of the disease according to the International Staging System retained their independent prognostic influence. In summary, RB deletion as a sole abnormality does not lead to a shortening in the survival of MM patients, whereas t(4;14) confers the worst prognosis in MM patients treated with high-dose chemotherapy.

العلاقة: Gutierrez, N. C., Castellanos, M. V., Martin, M. L., Mateos, M. V., Hernandez, J. M., Fernandez, M., . & San Miguel, J. F. (2007). Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t (4; 14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia, 21(1), 143-150. doi:10.1038/sj.leu.2404413. Epub 2006 Oct 5. PMID: 17024116.; http://hdl.handle.net/10366/154372Test

الإتاحة: https://doi.org/10.1038/sj.leu.2404413Test
http://hdl.handle.net/10366/154372Test

المؤلفون: Casanova, Bonaventura, Jarque, Isidro, Gascón, Francisco, Hernández-Boluda, Juan, Pérez-Miralles, Francisco, Rubia, Javier, Alcalá, Carmen, Sanz, Jaime, Mallada, Javier, Cervelló, Angeles, Navarré, Arantxa, Carcelén-Gadea, María, Boscá, Isabel, Gil-Perotin, Sara, Solano, Carlos, Sanz, Miguel, Coret, Francisco, Hernández-Boluda, Juan Carlos, de la Rubia, Javier, Sanz, Miguel Angel

المصدر: Neurological Sciences; Jul2017, Vol. 38 Issue 7, p1213-1221, 9p

مصطلحات موضوعية: MULTIPLE sclerosis treatment, HEMATOPOIETIC stem cell transplantation, IMMUNOTHERAPY, NEURODEGENERATION, DEGENERATION (Pathology), CYTARABINE, AUTOGRAFTS, COMPARATIVE studies, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, RESEARCH, EVALUATION research, TREATMENT effectiveness, THERAPEUTICS

مستخلص: The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS. [ABSTRACT FROM AUTHOR]

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المؤلفون: Alvarez-Larrán, Alberto, del Río-Garma, Julio, Pujol, Misericòrdia, de la Rubia, Javier, Hernández-Jodra, Manuel, Borrell, Montserrat, González-Porras, José R., García-Gala, José M., Viejo, Aurora, Enríquez, Lourdes, Arbona, Cristina, García-Erce, José A., Noblejas, Ana G., Pereira, Arturo

المصدر: Annals of Hematology; Oct2009, Vol. 88 Issue 10, p973-978, 6p, 2 Charts

مصطلحات موضوعية: THROMBOTIC thrombocytopenic purpura, PLASMA exchange (Therapeutics), BLOOD transfusion, HEMOLYTIC anemia, HEMOLYSIS & hemolysins, DISEASE relapse

مستخلص: The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds 80%, but the disease relapses in up to 20–30% of the cases. Clinical characteristics and response to treatment of relapsed TTP are not well defined. The objective of the present study was to compare the clinical and biological characteristics at presentation and the response to treatment between de novo and relapsed TTP. For such purpose, a total of 102 episodes of idiopathic TTP (70 de novo and 32 relapses) included in a recent multicentric prospective cohort study were analysed. All patients were homogeneously treated with daily PE and costicosteroids. In comparison with de novo TTP, episodes of relapsed TTP showed a higher Hb level (median, 122 g/l versus 91 g/l, p < 0.001) and lower serum lactate dehydrogenase (2.2- versus 4.5-fold above the upper limit of normality, p < 0.001). Neurological symptoms and fever were less frequently observed in patients with relapsed TTP than in patients with de novo TTP. Patients with relapsed TTP needed fewer PE sessions (five versus ten, p = 0.02) and a smaller volume of plasma (221 ml/kg versus 468 ml/kg, p = 0.004) to achieve remission than those with de novo TTP. There was no significant difference in the rate of recrudescence under treatment, the need of complementary treatments or the frequency of refractoriness to PE therapy. In conclusion, relapsed TTP has a milder clinical profile and responds more easily to PE than de novo TTP. [ABSTRACT FROM AUTHOR]

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المؤلفون: Puig, Noemí, de la Rubia, Javier, Jarque, Isidro, Salavert, Miguel, Montesinos, Pau, Sanz, Jaime, Martín, Guillermo, Sanz, Guillermo, Cantero, Susana, Lorenzo, Ignacio, Sanz, Miguel A

المصدر: International Journal of Hematology; Aug2007, Vol. 86 Issue 2, p186-192, 7p

مصطلحات موضوعية: ANTI-infective agents, ANTINEOPLASTIC agents, AUTOGRAFTS, BACTEREMIA, FEVER, HEMATOPOIETIC stem cell transplantation, OPPORTUNISTIC infections, PREANESTHETIC medication, DISEASE incidence, RETROSPECTIVE studies

مستخلص: Infectious complications are a major cause of morbidity and mortality in patients who undergo autologous stem cell transplantation (ASCT). We examined 476 patients with hematologic malignancies (401) or solid tumors (75) who underwent ASCT between February 1990 and May 2005. Anti-infectious prophylaxis consisted of different combinations of ciprofloxacin, cotrimoxazole, fluconazole, aerosolized amphotericin B, acyclovir, and intravenous immunoglobulins. Overall, 454 patients (95%) developed fever in the first 60 days after ASCT. In the majority of patients, initial antibiotic therapy consisted of broad-spectrum beta-lactamic with or without amikacin. A glycopeptide was administered as initial therapy in 86 cases. Overall, there were 132 (29%) clinically documented infections (37 pneumonias), 79 (17%) microbiologically documented infections (65 bacteremias), and 243 (54%) fevers of unknown origin. Coagulase-negative staphylococci (18, 25%) and E coli (18, 25%) were the organisms most frequently isolated. The pattern of infection did not change throughout the study except for a significantly higher incidence of bacteremia due to gram-positive bacteria in the first 5 years of the study. Infection-related mortality was 5% (21 cases), with pneumonia the most frequent cause of death. ASCT should be considered a low-risk procedure, although new therapeutic approaches for patients developing severe respiratory infections are still needed. [ABSTRACT FROM AUTHOR]

: Copyright of International Journal of Hematology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)