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.
Sorigue M, Sancho JM, Pineda A, Garcia O, Lopez D, Moreno M, Tapia G, Batlle M, Ferra C, Vives S, Ibarra G, Feliu E, Ribera JM
Incidence and prognostic significance of nephrotoxicity in patients receiving eshap as salvage therapy for lymphoma.
Leuk. Res.Jul 2017, 5898-101. Epub 4 May 2017
Nephrotoxicity is a well-known side effect of platinum-based chemotherapy. We retrospectively assessed the incidence and prognostic impact of nephrotoxicity with ESHAP rescue chemotherapy in 74 lymphoma patients (61 aggressive lymphomas). A higher incidence of nephrotoxicity (estimated glomerular filtration rate <60mL/min) was found when ESHAP was administred on an outpatient vs. inpatient basis (14/39 vs. 4/35). Patients submitted to ASCT with renal failure had a lower overall survival (OS) than those with normal renal function (2-yr OS probability [95%CI]: 88% [77%-99%] vs. 50% [22%-78%]). Outpatient administration of ESHAP may not be optimal for all patients and the impact of ESHAP-induced renal failure on ASCT outcomes in lymphoma needs to be assessed in prospective studies.
Sorigue M, Garcia O, Baptista MJ, Sancho JM, Tapia G, Mate JL, Feliu E, Navarro JT, Ribera JM
Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.
Med Clin (Barc)27 Dec 2016, . Epub 27 Dec 2016
The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab.
Juncà J, Garcia O, Garcia-Caro M, Vila J, Zamora L, Cabezón M, Alonso E, de la Banda E, Rodríguez-Hernández I, Ribera JM, Millá F
CD34 expression and the outcome of nucleophosmin 1-mutated acute myeloid leukemia.
Ann. Hematol.Dec 2016, 95(12)1949-1954. Epub 5 Sep 2016
CD34 positivity has been considered as an adverse prognostic factor in acute myeloid leukemia (AML). Although nucleophosmin 1-mutated (NPM1m) AML is usually CD34 negative, this marker may be expressed at diagnosis or acquired at relapse in a variable number of cases. Our objective was to ascertain if CD34 expression has any influence on the general outcome of this form of acute leukemia. Analysis of clinical outcome (complete remissions, relapses, disease-free survival, and overall survival) was performed depending on the degree of expression of CD34 determined by flow cytometry, in 67 adult patients with NPM1m AML. CD34 expression did not have any influence on the variables analyzed whatever the percentage of blasts expressing this marker. In contrast to other forms of AML, CD34 expression is not an unfavorable prognostic factor in NPM1m AML, neither at diagnosis nor at relapse.
Sorigué M, Ribera JM, García O, Cabezón M, Vélez P, Marcé S, Xicoy B, Fernández C, Buch J, Cortes M, Plensa E, Gallardo D, Boqué C, Feliu E, Zamora L
Highly variable mutational profile of ASXL1 in myelofibrosis.
Eur. J. Haematol.Oct 2016, 97(4)331-5. Epub 19 Jan 2016
Somatic mutations in ASXL1 seem to have a negative prognostic impact in patients with several myeloid neoplasms, including myelofibrosis (MF). The aim of this work was to determine the prevalence and profile of ASXL1 mutations in MF.
Palomo L, Garcia O, Arnan M, Xicoy B, Fuster F, Cabezón M, Coll R, Ademà V, Grau J, Jiménez MJ, Pomares H, Marcé S, Mallo M, Millá F, Alonso E, Sureda A, Gallardo D, Feliu E, Ribera JM, Solé F, Zamora L
Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features.
Oncotarget29 Jul 2016, . Epub 29 Jul 2016
Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC.
Xicoy B, Germing U, Jimenez MJ, Garcia O, Garcia R, Schemenau J, Pedro C, Luño E, Bernal T, González B, Strupp C, Ardanaz M, Kuendgen A, Cedena MT, Neukirchen J, Calabuig M, Brunet S, Medina A, Amigo ML, Ramos F, Callejas M, Díez-Campelo M, Bailén A, Collado R, Vicente A, Arnan M, Valcarcel D, Arilla MJ, Zamora L, Benlloch L, Sanz G
Response to erythropoietic-stimulating agents in patients with chronic myelomonocytic leukemia.
Eur. J. Haematol.Jul 2016, 97(1)33-8. Epub 22 Oct 2015
The efficacy of erythropoietic-stimulating agents (ESA) in chronic myelomonocytic leukemia (CMML) is unknown. Our objective was to analyze erythroid response (ER) and overall survival (OS) in a series of 94 patients with CMML treated with ESA.
Palomo L, Xicoy B, Garcia O, Mallo M, Ademà V, Cabezón M, Arnan M, Pomares H, José Larrayoz M, José Calasanz M, Maciejewski JP, Huang D, Shih LY, Ogawa S, Cervera J, Such E, Coll R, Grau J, Solé F, Zamora L
Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases.
Am. J. Hematol.Feb 2016, 91(2)185-92. Epub 9 Dec 2015
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder with heterogeneous clinical, morphological and genetic characteristics. Clonal cytogenetic abnormalities are found in 20-30% of patients with CMML. Patients with low risk cytogenetic features (normal karyotype and isolated loss of Y chromosome) account for ∼80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. We hypothesized that single nucleotide polymorphism arrays (SNP-A) karyotyping could detect cryptic chromosomal alterations with prognostic impact in these subgroup of patients. SNP-A were performed at diagnosis in 128 CMML patients with low risk karyotypes or uninformative results for conventional G-banding cytogenetics (CC). Copy number alterations (CNAs) and regions of copy number neutral loss of heterozygosity (CNN-LOH) were detected in 67% of patients. Recurrent CNAs included gains in regions 8p12 and 21q22 as well as losses in 10q21.1 and 12p13.2. Interstitial CNN-LOHs were recurrently detected in the following regions: 4q24-4q35, 7q32.1-7q36.3, and 11q13.3-11q25. Statistical analysis showed that some of the alterations detected by SNP-A associated with the patients' outcome. A shortened overall survival (OS) and progression free survival (PFS) was observed in cases where the affected size of the genome (considering CNAs and CNN-LOHs) was >11 Mb. In addition, presence of interstitial CNN-LOH was predictive of poor OS. Presence of CNAs (≥1) associated with poorer OS and PFS in the patients with myeloproliferative CMML. Overall, SNP-A analysis increased the diagnostic yield in patients with low risk cytogenetic features or uninformative CC and added prognostic value to this subset of patients.
Adema V, Larráyoz MJ, Calasanz MJ, Palomo L, Patiño-García A, Agirre X, Hernández-Rivas JM, Lumbreras E, Buño I, Martinez-Laperche C, Mallo M, García O, Álvarez S, Blazquez B, Cervera J, Luño E, Valiente A, Vallespí MT, Arenillas L, Collado R, Pérez-Oteyza J, Solé F
Correlation of myelodysplastic syndromes with i(17)(q10) and TP53 and SETBP1 mutations.