Genome-wide identification of microRNA signatures associated with stem/progenitor cells in Philadelphia chromosome-positive acute lymphoblastic leukemia.
Mol. Biol. Rep.Feb 2019, 46(1)1295-1306. Epub 2 Feb 2019
Acute lymphoblastic leukemia (ALL) is a malignant transformation with uncontrolled proliferation of lymphoid precursor cells within bone marrow including a dismal prognosis after relapse. Survival of a population of quiescent leukemia stem cells (LSCs, also termed leukemia-initiating cells (LICs)) after treatment is one of the relapse reasons in Ph
Barba P, Morgades M, Montesinos P, Gil C, Fox ML, Ciudad J, Moreno MJ, González-Campos J, Genescà E, Martínez-Carballeira D, Martino R, Vives S, Guardia R, Mercadal S, Artola MT, Cladera A, Tormo M, Esteve J, Bergua J, Vall-Llovera F, Ribera J, Martínez-Sanchez P, Amigo ML, Bermúdez A, Calbacho M, Hernández-Rivas JM, Feliu E, Orfao A, Ribera JM
Increased survival due to lower toxicity for high-risk T-cell acute lymphoblastic leukemia patients in two consecutive pediatric-inspired PETHEMA trials.
Eur. J. Haematol.Jan 2019, 102(1)79-86. Epub 22 Nov 2018
Pediatric-inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T-cell ALL. We analyzed 169 patients with high-risk T-cell ALL included in two consecutive trials of the PETHEMA Group (HR-ALL03 [n = 104] and the more contemporary HR-ALL11 [n = 65]).
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,
The role of stem cell transplantation in the management of Philadelphia chromosome-positive acute lymphoblastic leukemia
Therapeutic Advances in HematologyNov 2018, .
The concurrent administration of tyrosine kinase inhibitors (TKIs) with standard chemotherapy together with allogeneic hematopoietic stem cell transplantation (alloHSCT) has improved the outcome of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Although to date, no study has shown alloHSCT to be inferior to chemotherapy plus TKIs in any subgroup of adult Ph+ ALL, there is some evidence suggesting no additional benefit of alloHSCT in patients with deep molecular responses to intensive chemotherapy with a second-generation, and especially, third-generation TKI. As none of these positive and negative studies are controlled, randomized trials are needed to fully define the role of alloHSCT in Ph+ ALL, especially in those with deep molecular response. However, if studies combining TKIs with new approaches such as immunotherapy lead to durable responses, alloHSCT in the first complete remission could be avoided in the near future in the majority of patients with Ph+ ALL.
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.