(1) Background: New therapeutic strategies have improved the prognosis of multiple myeloma (MM), changing the accepted view of this disease from being incurable to treatable. (2) Methods: We studied ...1001 patients with MM between 1980 and 2020, grouping patients into ten-year periods by diagnosis 1980-1990, 1991-2000, 2001-2010 and 2011-2020. (3) Results: After 65.1 months of follow-up, the median OS of the cohort was 60.3 months, and OS increased significantly over time: 22.4 months in 1980-1990, 37.4 months in 1991-2000, 61.8 months in 2001-2010 and 103.6 months in 2011-2020 (
< 0.001). Using novel agents in the front-line setting for myeloma patients yielded a significantly better OS than in those treated with conventional therapies, especially when combinations of at least two novel agents were used. The median OS of patients treated with the combination of at least two novel agents in induction was significantly prolonged compared to those treated with a single novel agent or conventional therapy in induction: 143.3 vs. 61.0 vs. 42.2 months (
< 0.001). The improvement was apparent in all patients regardless of age at diagnosis. In addition, 132 (13.2%) patients were long-term survivors (median OS ≥ 10 years). Some independent clinical predictors of long-term survival were identified: ECOG < 1, age at diagnosis ≤ 65 years, non-IgA subtype, ISS-1 and standard-risk cytogenetic. Achieving CR and undergoing ASCT were positively associated with >10 years of survival. (4) Conclusions: The combination of novel agents appears to be the main factor for the improvement in survival in MM, which is becoming a chronic and even curable disease in a subtype of patients without high-risk features.
The means of optimally managing very elderly patients with diffuse large B‐cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80‐100 years, diagnosed with ...DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression‐free survival (PFS) and overall survival (OS). One hundred sixty‐three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow‐up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age < 86 years, cumulative illness rating scale (CIRS) score < 6, intermediate risk (1‐2) R‐IPI, and treatment with R‐CHOP at full or reduced doses. We developed a prognostic model based on the multivariate analysis of the 108 patients treated with R‐CHOP‐like: median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0‐1 vs. 2‐3 risk factors (age > 85 years, R‐IPI 3‐5 or CIRS > 5). In conclusion, treatment with R‐CHOP‐like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series.
We have evaluated 9 new molecular markers (ERG, EVI1, MLL-PTD, MN1, PRAME, RHAMM, and WT1 gene-expression levels plus FLT3 and NPM1 mutations) in 121 de novo cytogenetically normal acute myeloblastic ...leukemias. In the multivariate analysis, high ERG or EVI1 and low PRAME expressions were associated with a shorter relapse-free survival (RFS) and overall survival (OS). A 0 to 3 score was given by assigning a value of 0 to favorable parameters (low ERG, low EVI1, and high PRAME) and 1 to adverse parameters. This model distinguished 4 subsets of patients with different OS (2-year OS of 79%, 65%, 46%, and 27%; P = .001) and RFS (2-year RFS of 92%, 65%, 49%, and 43%; P = .005). Furthermore, this score identified patients with different OS (P = .001) and RFS (P = .013), even within the FLT3/NPM1 intermediate-risk/high-risk subgroups. Here we propose a new molecular score for cytogenetically normal acute myeloblastic leukemias, which could improve patient risk-stratification.
Objectives
The myeloproliferative neoplasms displaying a PDGFRB rearrangement are rare diseases derived from a haematopoietic stem cell. The goals of the study were to assess the incidence of these ...disorders and to define the clinical and biological characteristics as well as the response to the imatinib therapy.
Methods
A total of 556 patients with myeloproliferative neoplasms were studied by means of molecular cytogenetics.
Results
The incidence of myeloproliferative neoplasms (MPN) with PDGFRB rearrangement was low (10 cases, 1.8% of all MPN). Most of the patients showed moderate anaemia (median Hb was 10.0 gr/dL; range from 7.5 to 13 g/dL), leukocytosis (median white blood cells was 21.7 × 109/L with a range from 4 to 43 × 109/L) and eosinophilia (median circulating eosinophils was 2.4 × 109/L with a range of 1.1–5.7 × 109/L) with a median of bone marrow infiltration cells displaying PDGFRB rearrangement of 55% (range, 37–85%). In three cases, a t(5;12) was observed while two patients showed rearrangements of 17q21 region. In two cases, a del(5)(q31) was observed. Most of the patients responded to standard dosage of imatinib, and the response was maintained in the time in those patients with a follow‐up higher than 9 years.
Conclusions
The incidence of patients with PDGFRB rearrangement is low. These patients showed leukocytosis with eosinophilia and anaemia. The efficacy of imatinib therapy in patients showing PDGFRB rearrangement is high. For this reason, in all patients with MPN without any other molecular aberration, PDGFRB rearrangement should be ascertained.
We have analyzed brain and acute leukemia, cytoplasmic (BAALC) gene expression and other genetic markers (ERG, EVI1, MN1, PRAME, WT1, FLT3, and NPM1 mutations) in 127 intermediate-risk acute myeloid ...leukemia (AML) patients: 98 cytogenetically normal and 29 with intermediate-risk cytogenetic alterations. High versus low BAALC expressers showed a higher refractoriness to induction treatment (31% vs 10%; p = .005), lower complete remission rate after salvage therapy (82% vs 97%; p = .010), and lower 3-year overall (23% vs 58%, p < .001) and relapse-free survival (26% vs 52%, p = .006). Similar results were found when cytogenetic subgroups were analyzed separately. Multivariate models confirmed the unfavorable prognosis of this marker. In conclusion, BAALC is a relevant prognostic marker in intermediate-risk AML.
Summary
The prognostic significance of low‐hypodiploidy has not been extensively evaluated in minimal residual disease (MRD)‐oriented protocols for adult acute lymphoblastic leukaemia (ALL). We ...analysed the outcome of hypodiploid adult ALL patients treated within Programa Español de Tratamientos en Hematología (PETHEMA) protocols. The 5‐year cumulative incidence of relapse (CIR) of low‐hypodiploid B‐cell precursor (BCP)‐ALL was significantly higher than that of high‐hypodiploids (52% vs. 12%, P = 0.013). Low‐hypodiploid BCP‐ALL patients aged ≤35 years showed superior survival (71% vs. 21%, P = 0.026) and lower 5‐year CIR (17% vs. 66%, P = 0.090) than low‐hypodiploids aged >35 years. Older adults and elderly low‐hypodiploid BCP‐ALL patients show dismal prognosis although achieving an end‐induction good MRD response.
Summary
The study included 1848 diffuse large B‐cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International ...Prognostic Index (NCCN‐IPI) and explore the effect of adding high Beta‐2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN‐IPI variables in order to develop an improved index. Comparing survival curves, NCCN‐IPI discriminated better than IPI, separating four risk groups with 5‐year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high‐risk population. For the second aim the series was split into training and validation cohorts: in the former the multivariate model identified age, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, Stage III‐IV, and β2M as independently significant, whereas the NCCN‐IPI‐selected extranodal sites, primary extranodal presentation and intense treatments were not. These results were confirmed in the validation cohort. The Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO)‐IPI developed here, with 7 points, significantly separated four risk groups (0, 1–3, 4 or ≥5 points) with 11%, 58%, 17% and 14% of patients, and 5‐year overall survival rates of 93%, 79%, 66% and 39%, respectively. In the comparison GELTAMO IPI discriminated better than the NCCN‐IPI. In conclusion, GELTAMO‐IPI is more accurate than the NCCN‐IPI and has statistical and practical advantages in that the better discrimination identifies an authentic high‐risk group and is not influenced by primary extranodal presentation or treatments of different intensity.
Meningococemia durante el tratamiento con eculizumab Rey-Múgica, María de la Asunción; Hernando-Real, Susana; Carrero-González, Pablo ...
Enfermedades infecciosas y microbiología clínica,
01/2013, Volume:
31, Issue:
1
Journal Article
Abstract The PI3/AKT pathway is up-regulated in acute myeloid leukemia (AML), but its prognostic relevance in cytogenetically normal AML (CN-AML) is unclear. We evaluated RNA levels of AKT and two ...downstream substrates ( FOXO3a-p27 ) in 110 de novo CN-AML, included in the Spanish PETHEMA therapeutic protocols. Patients with high FOXO3a gene expression displayed shorter OS ( p = 0.015) and RFS ( p = 0.048) than low FOXO3a expressers. Features selected in the multivariate analysis as having an independent prognostic value for a shorter survival were WBC > 50 × 109 /L, age >65 years and high FOXO3a expression. We concluded that FOXO3a assessment could contribute to improve the molecular-based risk stratification in CN-AML.
Summary
The Grupo Español de Linfomas y Trasplantes de Médula Ósea International Prognostic Index (GELTAMO‐IPI) stratifies four risk groups in diffuse large B cell lymphoma (DLBCL) patients treated ...with immunochaemotherapy: low (LR), low‐intermediate (LIR), high‐intermediate (HIR), and high (HR). The present study explores the effect of GELTAMO‐IPI in the DLBCL subtypes defined by the immunohistochaemistry‐based Hans algorithm, Germinal Centre B (GCB) and non‐GCB. A multivariate Cox regression model including GELTAMO‐IPI risk groups, cell of origin (COO) subtypes and their product was developed to evaluate interaction between the two variables. The COO subtype was available in 839 patients (380 GCB; 459 non‐GCB) and both the GELTAMO‐IPI and the COO subtype in 780 (353 GCB; 427 non‐GCB). There were no differences in 5‐year overall survival (OS) between the two subtypes. The Cox model revealed interaction between the GELTAMO‐IPI risk groups and the COO subtypes (P = 0·005), indicating that GELTAMO‐IPI has a different effect in the two subtypes. Three risk groups were stratified in both COO subtypes: in the GCB subtype, LR, LIR and the combined HIR+HR had 5‐year OS of 100%, 75% and 52%, respectively. In the non‐GCB subtype, LR, the combined LIR+HIR and HR had a 5‐year OS of, 97%, 82% and 35% respectively. GELTAMO‐IPI identifies a genuine poor outcome group of patients in the DLBCL non‐GCB subtype.
PDF
