Gachet S, El-Chaar T, Avran D, Genesca E, Catez F, Quentin S, Delord M, Thérizols G, Briot D, Meunier G, Hernandez L, Pla M, Smits WK, Buijs-Gladdines JG, Van Loocke W, Menschaert G, André-Schmutz I, Taghon T, Van Vlierberghe P, Meijerink JP, Baruchel A, Dombret H, Clappier E, Diaz JJ, Gazin C, de Thé H, Sigaux F, Soulier J
Deletion 6q Drives T-cell Leukemia Progression by Ribosome Modulation.
Cancer DiscovDec 2018, 8(12)1614-1631. Epub 28 Sep 2018
Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14,
Avivi I, Boumendil A, Finel H, Nagler A, de Sousa AB, Santasusana JMR, Vandenberghe E, Afanasyev B, Bordessoule D, Moraleda JM, Garcia EC, Pohlreich D, Garcia GG, Thomson K, Or R, Beelen D, Zuffa E, Giebel S, Berthou C, Salles G, Melpignano A, Montoto S, Dreger P
Autologous stem cell transplantation for primary mediastinal B-cell lymphoma: long-term outcome and role of post-transplant radiotherapy. A report of the European Society for Blood and Marrow Transplantation.
Bone Marrow Transplant.Aug 2018, 53(8)1001-1009. Epub 20 Feb 2018
The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.
Buatois V, Johnson Z, Salgado-Pires S, Papaioannou A, Hatterer E, Chauchet X, Richard F, Barba L, Daubeuf B, Cons L, Broyer L, D'Asaro M, Matthes T, LeGallou S, Fest T, Tarte K, Clarke Hinojosa RK, Genescà Ferrer E, Ribera JM, Dey A, Bailey K, Fielding AK, Eissenberg L, Ritchey J, Rettig M, DiPersio JF, Kosco-Vilbois MH, Masternak K, Fischer N, Shang L, Ferlin WG
Preclinical Development of a Bispecific Antibody that Safely and Effectively Targets CD19 and CD47 for the Treatment of B-Cell Lymphoma and Leukemia.
Mol. Cancer Ther.Aug 2018, 17(8)1739-1751. Epub 9 May 2018
CD47, an ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often upregulated by hematologic and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to coengage CD47 and CD19 selectively on B cells. NI-1701 demonstrates favorable elimination kinetics with no deleterious effects seen on hematologic parameters following single or multiple administrations to nonhuman primates. Potent
Genescà E, Lazarenkov A, Morgades M, Berbis G, Ruíz-Xivillé N, Gómez-Marzo P, Ribera J, Juncà J, González-Pérez A, Mercadal S, Guardia R, Artola MT, Moreno MJ, Martínez-López J, Zamora L, Barba P, Gil C, Tormo M, Cladera A, Novo A, Pratcorona M, Nomdedeu J, González-Campos J, Almeida M, Cervera J, Montesinos P, Batlle M, Vives S, Esteve J, Feliu E, Solé F, Orfao A, Ribera JM
Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.
Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.
GESIDA/PETHEMA recommendations on the diagnosis and treatment of lymphomas in patients infected by the human immunodeficiency virus.
Med Clin (Barc)13 Jul 2018, 151(1)39.e1-39.e17. Epub 19 Jan 2018
The incidence of non-Hodgkin's lymphoma and Hodgkin's lymphoma is higher in patients with HIV infection than in the general population. Following the introduction of combination antiretroviral therapy (cART), the prognostic significance of HIV-related variables has decreased, and lymphoma-related factors have become more pronounced. Currently, treatments for lymphomas in HIV-infected patients do not differ from those used in the general population. However, differentiating characteristics of seropositive patients, such as the need for cART and specific prophylaxis and treatment of certain opportunistic infections, should be considered. This document updates recommendations on the diagnosis and treatment of lymphomas in HIV infected patients published by GESIDA/PETHEMA in 2008.
Muncunill J, Baptista MJ, Hernandez-Rodríguez Á, Dalmau J, Garcia O, Tapia G, Moreno M, Sancho JM, Martínez-Picado J, Feliu E, Mate JL, Ribera JM, Navarro JT
Plasma EBV-load as an early biomarker and prognostic factor of HIV-related lymphomas.
Clin. Infect. Dis.29 Jun 2018, . Epub 29 Jun 2018
Epstein-Barr virus (EBV) has been implicated in lymphomagenesis and can be found infecting tumor cells and in plasma at lymphoma diagnosis, especially in HIV-infected patients. Our aim was to evaluate the usefulness of plasma EBV-load as biomarker and prognostic factor in HIV-related lymphomas.
Sorigue M, Gual-Capllonch F, Garcia O, Sarrate E, Franch-Sarto M, Ibarra G, Grau J, Orna E, Ribera JM, Sancho JM
Incidence, predictive factors, management, and survival impact of atrial fibrillation in non-Hodgkin lymphoma.
Ann. Hematol.4 May 2018, . Epub 4 May 2018
Atrial fibrillation (AF) and cancer are common disorders in the general population but there are few studies in patients with both diseases. More specifically, there are scarce data on AF in patients with non-Hodgkin lymphoma (NHL). We assessed the incidence, predictive factors, management, and survival impact of AF in a cohort of patients with NHL from a single institution between 2002 and 2016 (n = 747). Twenty-three patients were diagnosed with AF before and 40 after the diagnosis of NHL (of the later, 16 were secondary to an extracardiac comorbidity and 24 unrelated to any triggering event [primary AF]). The 5-year cumulative incidence of new-onset AF was 4% (95% confidence interval [CI] 3-6%). Age and hypertension were the only predictive factors for the development of AF. Management of AF was heterogeneous, primarily with anti-vitamin K agents but also antiplatelet therapy in a significant proportion of patients. Among the 63 patients, there were six episodes of ischemic stroke/transient ischemic attack and four venous thromboembolic events, with four major bleeding episodes. Overall survival (OS) was inferior in patients with AF (HR 0.1, 95% CI 0.01-0.7, p = 0.02), largely due to secondary AF. We conclude that the incidence of new-onset AF in NHL patients seemed somewhat higher than in the general population, although with similar predictive factors. The management was heterogeneous, and the risk of ischemic and hemorrhagic events did not seem higher than in cancer-free patients. Survival was particularly poor for patients with secondary AF.