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Article ; Online: Validation of thrombotic risk factors in 1381 patients with essential thrombocythaemia: A multicentre retrospective real-life study.

Stuckey, Ruth / Ianotto, Jean-Christophe / Santoro, Marco / Czyż, Anna / Perez Encinas, Manuel M / Gómez-Casares, María Teresa / Noya Pereira, Maria Soledad / de Nałęcz, Anna Kulikowska / Gołos, Aleksandra / Lewandowski, Krzysztof / Szukalski, Łukasz / González-Martín, Jesús M / Wróbel, Tomasz / Sobas, Marta Anna

British journal of haematology

2022 Volume 199, Issue 1, Page(s) 86–94

Abstract: Thrombosis and haemorrhage are frequent in patients with essential thrombocythaemia (ET). The 2016 revised International Prognostic Score for Thrombosis in Essential Thrombocythaemia-thrombosis (r-IPSET-t) score stratifies patients into very-low- (VLR), ... ...

Abstract	Thrombosis and haemorrhage are frequent in patients with essential thrombocythaemia (ET). The 2016 revised International Prognostic Score for Thrombosis in Essential Thrombocythaemia-thrombosis (r-IPSET-t) score stratifies patients into very-low- (VLR), low- (LR), intermediate- (IR) and high-risk (HR) groups. We validated the r-IPSET-t in the biggest population of patients with ET (n = 1381) to date and found it to be a better fit than the earlier IPSET-t score. With an average follow-up of 87.7 months, there were 0.578 thrombotic events/person-year and 0.286 bleeding events/person-year after diagnosis. The 10-year thrombosis-free survival was 88% and 99% for the r-IPSET-t LR and VLR groups (p < 0.001). Cytoreduction was a thrombotic risk factor in younger patients (aged <60 years, hazard ratio 9.49, p = 0.026; aged ≥60 years, hazard ratio 1.04, p = 0.93). In multivariable Cox regression analysis, anti-aggregation after diagnosis was protective for thrombosis (hazard ratio 0.31, p = 0.005) but a risk factor for major bleeding (hazard ratio 10.56, p = 0.021). Of the IPSET-t HR and LR groups, 132/780 and 249/301 were re-classified as LR and VLR respectively (p < 0.001). The European LeukemiaNET (ELN) does not recommend aspirin for VLR patients but in this real-life analysis 83.1% of VLR patients received it. Our results validate the r-IPSET-t score as more predictive for thrombosis than the ELN-recommended IPSET-t and raise concerns about unnecessary cytoreductive and anti-aggregative therapy.
MeSH term(s)	Aspirin/therapeutic use ; Humans ; Prognosis ; Retrospective Studies ; Risk Factors ; Thrombocythemia, Essential/diagnosis ; Thrombosis/diagnosis ; Thrombosis/epidemiology ; Thrombosis/etiology
Chemical Substances	Aspirin (R16CO5Y76E)
Language	English
Publishing date	2022-07-29
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18387
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Article ; Online: Somatic mutations in calreticulin can be found in pedigrees with familial predisposition to myeloproliferative neoplasms.

Lundberg, Pontus / Nienhold, Ronny / Ambrosetti, Achille / Cervantes, Francisco / Pérez-Encinas, Manuel M / Skoda, Radek C

Blood

2014 Volume 123, Issue 17, Page(s) 2744–2745

MeSH term(s)	Calreticulin/genetics ; Exons ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Male ; Mutation ; Myeloproliferative Disorders/genetics ; Pedigree ; Phenotype ; Thrombocytosis/genetics
Chemical Substances	Calreticulin
Language	English
Publishing date	2014-04-22
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2014-01-550863
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Article ; Online: Outcomes after intensive chemotherapy for secondary and myeloid-related changes acute myeloid leukemia patients aged 60 to 75 years old: a retrospective analysis from the PETHEMA registry.

Martínez-Cuadrón, David / Megías-Vericat, Juan E / Gil, Cristina / Bernal, Teresa / Tormo, Mar / Martínez-Sánchez, Pilar / Rodríguez-Medina, Carlos / Serrano, Josefina / Herrera, Pilar / Simón, José A Pérez / Sayas, María J / Bergua, Juan / Lavilla-Rubira, Esperanza / Amigo, Maria Luz / Benavente, Celina / Lorenzo, Jose L López / Pérez-Encinas, Manuel M / Vidriales, María B / Colorado, Mercedes /

De Rueda, Beatriz / García-Boyero, Raimundo / Marini, Sandra / García-Suárez, Julio / López-Pavía, María / Gómez-Roncero, Maria I / Noriega, Víctor / López, Aurelio / Labrador, Jorge / Cabello, Ana / Sossa, Claudia / Algarra, Lorenzo / Stevenazzi, Mariana / Solana-Altabella, Antonio / Boluda, Blanca / Montesinos, Pau

Haematologica

2024 Volume 109, Issue 1, Page(s) 115–128

Abstract: Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without ... ...

Abstract	Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval [CI]: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Retrospective Studies ; Disease-Free Survival ; Cytarabine ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/drug therapy ; Remission Induction ; Hematopoietic Stem Cell Transplantation
Chemical Substances	CPX-351 ; Cytarabine (04079A1RDZ)
Language	English
Publishing date	2024-01-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.282506
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Article ; Online: FLT3 inhibitors in the treatment of acute myeloid leukemia: current status and future perspectives.

Mosquera Orgueira, Adrián / Bao Pérez, Laura / Mosquera Torre, Alicia / Peleteiro Raíndo, Andrés / Cid López, Miguel / Díaz Arias, José Á / Ferreiro Ferro, Roi / Antelo Rodríguez, Beatriz / González Pérez, Marta S / Albors Ferreiro, Manuel / Alonso Vence, Natalia / Pérez Encinas, Manuel M / Bello López, José L / Martinelli, Giovanni / Cerchione, Claudio

Minerva medica

2020 Volume 111, Issue 5, Page(s) 427–442

Abstract: Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene arise in 25-30% of all acute myeloid leukemia (AML) patients. These mutations lead to constitutive activation of the protein product and are divided in two broad types: internal tandem duplication ( ... ...

Abstract	Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene arise in 25-30% of all acute myeloid leukemia (AML) patients. These mutations lead to constitutive activation of the protein product and are divided in two broad types: internal tandem duplication (ITD) of the juxtamembrane domain (25% of cases) and point mutations in the tyrosine kinase domain (TKD). Patients with FLT3 ITD mutations have a high relapse risk and inferior cure rates, whereas the role of FLT3 TKD mutations still remains to be clarified. Additionally, growing research indicates that FLT3 status evolves through a disease continuum (clonal evolution), where AML cases can acquire FLT3 mutations at relapse - not present in the moment of diagnosis. Several FLT3 inhibitors have been tested in patients with FLT3-mutated AML. These drugs exhibit different kinase inhibitory profiles, pharmacokinetics and adverse events. First-generation multi-kinase inhibitors (sorafenib, midostaurin, lestaurtinib) are characterized by a broad-spectrum of drug targets, whereas second-generation inhibitors (quizartinib, crenolanib, gilteritinib) show more potent and specific FLT3 inhibition, and are thereby accompanied by less toxic effects. Notwithstanding, all FLT3 inhibitors face primary and acquired mechanisms of resistance, and therefore the combinations with other drugs (standard chemotherapy, hypomethylating agents, checkpoint inhibitors) and its application in different clinical settings (upfront therapy, maintenance, relapsed or refractory disease) are under study in a myriad of clinical trials. This review focuses on the role of FLT3 mutations in AML, pharmacological features of FLT3 inhibitors, known mechanisms of drug resistance and accumulated evidence for the use of FLT3 inhibitors in different clinical settings.
MeSH term(s)	Aniline Compounds/pharmacology ; Antineoplastic Agents/pharmacology ; Benzimidazoles/pharmacology ; Benzothiazoles/pharmacology ; Carbazoles/pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Forecasting ; Hematopoietic Stem Cell Transplantation ; Humans ; Imidazoles/pharmacology ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/therapy ; Maintenance Chemotherapy/methods ; Mutation ; Phenylurea Compounds/pharmacology ; Piperidines/pharmacology ; Point Mutation ; Protein Kinase Inhibitors/pharmacology ; Pyrazines/pharmacology ; Pyridazines/pharmacology ; Recurrence ; Sorafenib/pharmacology ; Staurosporine/analogs & derivatives ; Staurosporine/pharmacology ; fms-Like Tyrosine Kinase 3/antagonists & inhibitors ; fms-Like Tyrosine Kinase 3/genetics
Chemical Substances	Aniline Compounds ; Antineoplastic Agents ; Benzimidazoles ; Benzothiazoles ; Carbazoles ; Imidazoles ; Phenylurea Compounds ; Piperidines ; Protein Kinase Inhibitors ; Pyrazines ; Pyridazines ; gilteritinib ; ponatinib (4340891KFS) ; quizartinib (7LA4O6Q0D3) ; Sorafenib (9ZOQ3TZI87) ; lestaurtinib (DO989GC5D1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; Staurosporine (H88EPA0A3N) ; midostaurin (ID912S5VON) ; crenolanib (LQF7I567TQ)
Language	English
Publishing date	2020-09-21
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	123586-2
ISSN	1827-1669 ; 0026-4806
ISSN (online)	1827-1669
ISSN	0026-4806
DOI	10.23736/S0026-4806.20.06989-X
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Article ; Online: Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry.

Bernal, Teresa / Moreno, Ainhoa Fernández / de LaIglesia, Almudena / Benavente, Celina / García-Noblejas, Ana / Belmonte, Daniel García / Riaza, Rosalía / Salamero, Olga / Foncillas, Maria Angeles / Roldán, Alicia / Concepción, Víctor Noriega / González, Laura Llorente / Bergua Burgués, Juan Miguel / Lorente de Uña, Soraya / Rodríguez-Macías, Gabriela / de la Fuente Burguera, Adolfo / García Pérez, Maria José / López-Lorenzo, Jose Luis / Martínez, Pilar /

Aláez, Concepción / Callejas, Marta / Martínez-Chamorro, Carmen / Roca, José Rifón / Barciela, Lourdes Amador / Mena Durán, Armando V / Gómez Correcha, Karoll / Lavilla Rubira, Esperanza / Amigo, María Luz / Vall-Llovera, Ferran / Garrido, Ana / García-Fortes, María / de Miguel Llorente, Dunia / Leonardo, Anastasia Aules / Cervero, Carlos / Jordá, Rosa Coll / Pérez-Encinas, Manuel M / Zarzuela, Marta Polo / Figuera, Angela / Rad, Guillermo / Martínez-Cuadrón, David / Montesinos, Pau

Cancer medicine

2023 Volume 12, Issue 14, Page(s) 14892–14901

Abstract: Background: CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched ... ...

Abstract	Background: CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. Methods: Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. Results: Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62-71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18-0.59), p < 0.001. Conclusion: Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.
MeSH term(s)	Humans ; Aged ; Retrospective Studies ; Cytarabine/therapeutic use ; Remission Induction ; Leukemia, Myeloid, Acute
Chemical Substances	CPX-351 ; Cytarabine (04079A1RDZ)
Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6120
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Article ; Online: A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia.

Vives, Susana / Martínez-Cuadrón, David / Bergua Burgues, Juan / Algarra, Lorenzo / Tormo, Mar / Martínez-Sánchez, María Pilar / Serrano, Josefina / Herrera, Pilar / Ramos, Fernando / Salamero, Olga / Lavilla, Esperanza / López-Lorenzo, José L / Gil, Cristina / Vidriales, Belén / Falantes, Jose F / Serrano, Alfons / Labrador, Jorge / Sayas, María J / Foncillas, María Á /

Amador Barciela, María L / Olave, María Teresa / Colorado, Mercedes / Gascón, Adriana / Fernández, María Á / Simiele, Adriana / Pérez-Encinas, Manuel M / Rodríguez-Veiga, Rebeca / García, Olga / Martínez-López, Joaquín / Barragán, Eva / Paiva, Bruno / Sanz, Miguel Á / Montesinos, Pau

Cancer

2021 Volume 127, Issue 12, Page(s) 2003–2014

Abstract: Background: Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, ... ...

Abstract	Background: Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA). Methods: Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase. Results: The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001). Conclusions: FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.
MeSH term(s)	Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Azacitidine ; Cytarabine ; Humans ; Leukemia, Myeloid, Acute/therapy ; Remission Induction ; Treatment Outcome ; Vidarabine/analogs & derivatives
Chemical Substances	Cytarabine (04079A1RDZ) ; Vidarabine (FA2DM6879K) ; Azacitidine (M801H13NRU) ; fludarabine (P2K93U8740)
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.33403
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Article: Characteristics and Outcomes of Adult Patients in the PETHEMA Registry with Relapsed or Refractory

Martínez-Cuadrón, David / Serrano, Josefina / Mariz, José / Gil, Cristina / Tormo, Mar / Martínez-Sánchez, Pilar / Rodríguez-Arbolí, Eduardo / García-Boyero, Raimundo / Rodríguez-Medina, Carlos / Martínez-Chamorro, Carmen / Polo, Marta / Bergua, Juan / Aguiar, Eliana / Amigo, María L / Herrera, Pilar / Alonso-Domínguez, Juan M / Bernal, Teresa / Espadana, Ana / Sayas, María J /

Cancers

2022 Volume 14, Issue 11

Abstract: This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine ... ...

Abstract	This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.
Language	English
Publishing date	2022-06-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14112817
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Article ; Online: The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: A multicentre collaborative study.

Pérez Encinas, Manuel M / Sobas, Marta / Gómez-Casares, María Teresa / Abuin Blanco, Aitor / Noya Pereira, María Soledad / Raya, José María / Andrade-Campos, Marcio M / Álvarez Larrán, Alberto / Lewandowski, Krzysztof / Łukasz, Szukalski / Hernández Boluda, Juan Carlos / Ferrer-Marín, Francisca / Fox, María Laura / Gołos, Aleksandra / Gasior Kabat, Mercedes / Magro Mazo, Elena / Czyż, Anna / Martín Martín, Alejandro / Bellosillo Paricio, Beatriz /

Quinteiro García, Celsa / González Martín, Jesús María / Stuckey, Ruth

European journal of haematology

2020 Volume 106, Issue 3, Page(s) 371–379

Abstract: Objectives: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52-bp deletion or type 2, 5-bp insertion). CALR mutations have generally been associated with a lower ... ...

Abstract	Objectives: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52-bp deletion or type 2, 5-bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. Methods: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. Results: With 7.5 years of median follow-up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5-year thrombosis-free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (P = .002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (P = .046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR-type 2 groups but not JAK2V617F vs CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P = .04) adjusted by age. Conclusions: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.
MeSH term(s)	Calreticulin/genetics ; Follow-Up Studies ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Incidence ; Janus Kinase 2/genetics ; Mutation ; Odds Ratio ; Prognosis ; Retrospective Studies ; Thrombocythemia, Essential/complications ; Thrombocythemia, Essential/diagnosis ; Thrombocythemia, Essential/genetics ; Thrombocythemia, Essential/mortality ; Thrombosis/diagnosis ; Thrombosis/etiology ; Thrombosis/mortality
Chemical Substances	CALR protein, human ; Calreticulin ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2020-12-30
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.13561
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Article ; Online: Anagrelide treatment in early pregnancy in a patient with JAK2V617F-positive essential thrombocythemia: case report and literature review.

Sobas, Marta A / Pérez Encinas, Manuel M / Rabuñal Martinez, María J / Quinteiro García, Celsa / Bello López, José L

Acta haematologica

2009 Volume 122, Issue 4, Page(s) 221–222

MeSH term(s)	Adult ; Amino Acid Substitution ; Female ; Fibrinolytic Agents/therapeutic use ; Humans ; Infant, Newborn ; Janus Kinase 2/genetics ; Point Mutation ; Pregnancy ; Pregnancy Complications, Hematologic/drug therapy ; Pregnancy Outcome ; Quinazolines/therapeutic use ; Thrombocythemia, Essential/complications ; Thrombocythemia, Essential/drug therapy ; Thrombocythemia, Essential/genetics
Chemical Substances	Fibrinolytic Agents ; Quinazolines ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2) ; anagrelide (K9X45X0051)
Language	English
Publishing date	2009
Publishing country	Switzerland
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	80008-9
ISSN	1421-9662 ; 0001-5792
ISSN (online)	1421-9662
ISSN	0001-5792
DOI	10.1159/000253030
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evolving treatment patterns and outcomes in older patients (≥60 years) with AML: changing everything to change nothing?

Martínez-Cuadrón, David / Serrano, Josefina / Gil, Cristina / Tormo, Mar / Martínez-Sánchez, Pilar / Pérez-Simón, José A / García-Boyero, Raimundo / Rodríguez-Medina, Carlos / López-Pavía, María / Benavente, Celina / Bergua, Juan / Lavilla-Rubira, Esperanza / Amigo, María L / Herrera, Pilar / Alonso-Domínguez, Juan M / Bernal, Teresa / Colorado, Mercedes / Sayas, María J / Algarra, Lorenzo /

Vidriales, María B / Rodríguez-Macías, Gabriela / Vives, Susana / Pérez-Encinas, Manuel M / López, Aurelio / Noriega, Víctor / García-Fortes, María / Ramos, Fernando / Rodríguez-Gutiérrez, Juan I / Costilla-Barriga, Lisette / Labrador, Jorge / Boluda, Blanca / Rodríguez-Veiga, Rebeca / Martínez-López, Joaquín / Sanz, Miguel A / Montesinos, Pau

Leukemia

2020 Volume 35, Issue 6, Page(s) 1571–1585

Abstract: There are no studies analyzing how therapeutic changes impact on outcomes of older AML patients. This study analyzes patient´s and disease characteristics, treatment patterns, and outcomes of 3637 AML patients aged ≥60 years reported to the PETHEMA ... ...

Abstract	There are no studies analyzing how therapeutic changes impact on outcomes of older AML patients. This study analyzes patient´s and disease characteristics, treatment patterns, and outcomes of 3637 AML patients aged ≥60 years reported to the PETHEMA registry. Study periods were 1999-2006 (before hypomethylating agents-HMAs availability) vs 2007-2013, and treatments were intensive chemotherapy (IC), non-intensive, clinical trial (CT), and supportive care only (SC). Median age was 72 (range, 60-99), 57% male, median ECOG 1 (range, 0-4), secondary AML 914 (30%), with adverse-risk genetic in 720 (32%). Treatment differed between study periods (1999-2006 vs 2007-2013): IC 58% vs 32%, non-intensive 1 vs 23%, CT 0 vs 2%, SC 27 vs 28% (p < 0.001). Median OS was 4.7 months (1-year OS 29% and 5-years 7%, without differences between periods), 1.2 for SC, 7.8 for non-intensive, 8.6 for IC, and 10.4 for CT (p < 0.001). OS improved in the 2007-2013 period for IC patients (10.3 vs 7.5 months, p = 0.004), but worsened for SC patients (1.2 vs 1.6 months, p = 0.03). Our real-life study shows that, despite evolving treatment for elderly patients during the last decade, OS has remained unchanged. Epidemiologic registries will critically assess whether novel therapies lead to noteworthy advances in the near future (#NCT02606825).
MeSH term(s)	Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation/mortality ; Humans ; Leukemia, Myeloid, Acute/mortality ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate
Language	English
Publishing date	2020-10-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-020-01058-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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