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Recently modified diagnostic criteria for chronic myelomonocytic leukaemia (CMML) have lowered the cut-off for absolute monocytosis. In the largest series to date, we have analysed 313 CMML patients, including 104 with oligomonocytic (OM)-CMML. Five-year survival was longer for OM-CMML than for other patients (p < 0.001). Multivariate analysis identified OM-CMML as a favourable prognostic factor (HR 0.58; p = 0.002). The 5-year cumulative incidence of progression to classical CMML was 47%. Older age and transfusion dependence were adverse prognostic factors for OM-CMML. Our results support the inclusion of OM-CMML in the CMML category as a subtype with superior outcomes.
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Leucemia Mielomonocítica Crônica , Humanos , Leucemia Mielomonocítica Crônica/diagnóstico , Leucocitose , PrognósticoRESUMO
Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations.
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Mutação em Linhagem Germinativa , Transplante de Células-Tronco Hematopoéticas , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Testes Genéticos/métodos , Predisposição Genética para Doença , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/diagnóstico , Sequenciamento do Exoma , Transplante HomólogoRESUMO
OBJECTIVES: To clarify the impact of histological grades in follicular lymphoma. METHODS: We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1-2 and 62 grade 3A. RESULTS: In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1-2 FL patients. Estimated six-year progression-free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%-73%) and 51% (95%CI: 41%-61%) vs grades 1-2:55% (95%CI: 46%-63%) and 57% (95%CI: 49%-65%), P = .782 and P = .521, respectively]. Estimated six-year overall survival was lower, 76% (95%CI: 64%-88%) for the grade 3A group than grades 1-2 83% (95%CI: 77%-89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25-0.27) and 0.05 (95%CI: 0.04-0.06) for G3AFL and G1-2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R-CHOP regimen as induction. CONCLUSIONS: Our results indicate similar long-term outcomes in terms of progression-free survival and time to progression in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years.
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Antineoplásicos Imunológicos/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Adulto , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Feminino , Humanos , Quimioterapia de Indução , Linfoma Folicular/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Primary cutaneous follicular center-cell lymphoma (PCFCL) is one of the most common types of cutaneous B-cell lymphoma. Differences in immunohistochemical expression of BCL2 and CD10 antigens along with the presence of t(14:18) translocation in neoplastic cells have been postulated as relevant clues in differentiating PCFCL from cutaneous lesions secondary to a systemic follicular lymphoma (SCFL). The aim of this study is to evaluate the significance and usefulness of these parameters in a large series of patients. METHODS: Patients with PCFCL and SCFL diagnosed at three university hospitals in Barcelona, from 2000 to 2015 were reviewed. Clinical, histopathological, immunophenotypical, genetic, and outcome parameters were analyzed. RESULTS: Eighty-one cases (59 PCFCL and 22 SCFL) were included. There were no significant differences between PCFCL and SCFL cases regarding clinical presentation, site of involvement, or predominant type of skin lesions. Most patients in both groups showed positivity for BCL2 and CD10, but strong expression of BCL2 and CD10 was associated with SCFL cases. Although more frequent in SCFL, a small proportion of PCFCL cases also showed the t(14:18) on FISH analysis. CONCLUSION: The intensity of BCL2 expression was found to be the single most valuable clue in differentiating PCFCL from SCFL cases on histopathological grounds.
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Biomarcadores Tumorais/análise , Linfoma Folicular/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/análise , Neprilisina/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Translocação Genética/genética , Adulto JovemRESUMO
Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In the study herein, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespective of patients' clinical or genetic features, whereas normal T lymphocytes were less sensitive. Fluorizoline increased the protein levels of the pro-apoptotic B-cell lymphoma 2 family member NOXA in chronic lymphocytic leukemia cells. Furthermore, fluorizoline synergized with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax to induce apoptosis. These results suggest that targeting prohibitins could be a new therapeutic strategy for chronic lymphocytic leukemia.
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Aminoimidazol Carboxamida/análogos & derivados , Apoptose/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hidrocarbonetos Fluorados/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Pirazóis/farmacologia , Pirimidinas/farmacologia , Proteínas Repressoras/metabolismo , Ribonucleosídeos/farmacologia , Sulfonamidas/farmacologia , Tiazolidinas/farmacologia , Regulação para Cima/efeitos dos fármacos , Adenina/análogos & derivados , Aminoimidazol Carboxamida/agonistas , Aminoimidazol Carboxamida/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/agonistas , Sinergismo Farmacológico , Feminino , Humanos , Hidrocarbonetos Fluorados/agonistas , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Piperidinas , Proibitinas , Pirazóis/agonistas , Pirimidinas/agonistas , Ribonucleosídeos/agonistas , Sulfonamidas/agonistas , Tiazolidinas/agonistas , Células Tumorais CultivadasRESUMO
Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first-line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first-line response assessment were considered ICT refractory. Three hundred forty-three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high-risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated ß2-microglobulin were correlated with refractoriness, and refractoriness, high-risk FLIPI score, and ß2-microglobulin were correlated with overall survival (OS). Compared with ICT-sensitive, ICT-refractory patients had a higher incidence of histological transformation (5-year cumulative incidence 25% [14%-39%] vs. 6% [3%-10%], P < .001), a higher rate of refractoriness to second-line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5-year OS probability 38% [95% CI 23%-53%] vs. 87% [82%-92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high-FLIPI scores, B symptoms, and elevated serum ß2-micrglobulin. Immunochemotherapy-refractory patients had a worse prognosis than ICT-sensitive patients, and current treatment options for this subgroup are not satisfactory.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Resistência a Medicamentos , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Myelodysplastic syndromes (MDS) are the commonest hematologic malignancies in the elderly. Since many patients with MDS actually die from age-related ailments, the very disease burden of MDS remains largely unknown. This registry-based study was aimed at investigating the excess mortality attributable to MDS. We analyzed 7,408 adult patients diagnosed with primary MDS from 1980 to 2014. Excess mortality was estimated by comparing the patients' survival with that expected in the matched general population. Median age of patients was 74 years, 58% were males, and 65% belonged to the lower risk categories of the Revised International Prognostic Scoring System (IPSS-R). Excess mortality accounted for three-fourths of the all-cause mortality and was mainly driven by factors unrelated to leukemic transformation. Excess mortality increased with the IPSS-R risk category [Incidence rate ratio (IRR): 2.1, 95% CI: 1.9-2.3; P < .001]. Older age and male sex retained an independent association with higher excess mortality after discounting demographic effects. Excess mortality increased in the most recent periods just in the higher risk IPSS-R categories (IRR: 1.2; 95% CI: 1.1-1.3 when comparing periods 2007-14, 2000-06, and 1980-99). In conclusion, MDS carry a significant excess mortality, even in the lower risk categories, that is mainly driven by factors unrelated to leukemic transformation, and increases with older age, male sex, and poorer risk categories. Excess mortality has increased in recent years in the higher risk patients, which might be ascribed to a parallel increase in age-related comorbidities. Our results claim for more comprehensive treatment strategies for patients with MDS. Am. J. Hematol. 92:149-154, 2017. © 2016 Wiley Periodicals, Inc.
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Síndromes Mielodisplásicas/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Mortalidade/tendências , Prognóstico , Fatores Sexuais , Espanha , Análise de SobrevidaRESUMO
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 â¼80% 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.
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Aberrações Cromossômicas , Leucemia Mielomonocítica Crônica/genética , Metáfase , Polimorfismo de Nucleotídeo Único , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , DNA/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Cariotipagem , Leucemia Mielomonocítica Crônica/mortalidade , Leucemia Mielomonocítica Crônica/patologia , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The aim of this study is to analyse the risk of invasive fungal infection (IFI) and the need for antifungal prophylaxis in patients with acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in 121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5, range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one probable aspergillosis and one proven candidemia) occurred in this series. The incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per patient treated in those with severe neutropenia. Two patients died from IFI, leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per treatment cycle. The numbers needed to treat with prophylaxis to prevent one case of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment course, and 137 azacitidine cycles or 24 patients among those with severe neutropenia. AML/MDS patients treated with azacitidine, including those with severe prolonged neutropenia, have a very low risk of IFI which does not justify the use of antifungal prophylaxis.
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Antibioticoprofilaxia , Antifúngicos/uso terapêutico , Azacitidina/efeitos adversos , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/complicações , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/uso terapêutico , Feminino , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/prevenção & controle , Masculino , Pessoa de Meia-Idade , Doenças Mieloproliferativas-Mielodisplásicas/tratamento farmacológico , Neutropenia/complicações , Números Necessários para Tratar , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Triazóis/uso terapêuticoRESUMO
The use of highly effective rituximab-containing therapy for treating diffuse large B-cell lymphoma (DLBCL) makes it more difficult to salvage relapsed or refractory patients. Autologous stem-cell transplantation (ASCT) is the reference treatment for these patients, but the impact of previous exposure to rituximab on the subsequent results of ASCT remains unknown. We analysed 248 patients with relapsed or refractory DLBCL or grade 3B follicular lymphoma pre-treated with rituximab as part of first-line therapy (R+ group) who received ASCT, in comparison with a control group of 127 patients without previous exposure to rituximab (R- group). The complete remission (CR) rates were similar in both groups. Multivariate analysis identified age-adjusted International Prognostic Index at diagnosis, extranodal involvement and disease status at transplant, and the number of previous chemotherapy lines as independent factors with a negative influence on CR rate. Compared with R- patients, those in the R+ group had a significantly better progression-free survival (63% vs. 48% at 5 years) and overall survival (72% vs. 61% at 5 years). This observation was independent of other prognostic factors that affected these outcomes. In conclusion, ASCT is no less effective in patients with relapsed or refractory aggressive B-cell lymphoma pre-treated with first-line rituximab-containing therapy than in rituximab-naive patients.
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Anticorpos Monoclonais Murinos/administração & dosagem , Transplante de Medula Óssea , Linfoma Difuso de Grandes Células B/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab , Terapia de Salvação/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Introduction: Chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) with ring sideroblasts (RS) or SF3B1 mutation (MDS-RS/SF3B1) differ in many clinical features, but share others, such as anemia. RS and SF3B1 mutation can also be found in CMML. Methods: We compared CMML with and without RS/SF3B1 and MDS-RS/SF3B1 considering the criteria established by the 2022 World Health Organization classification. Results: A total of 815 patients were included (CMML, n=319, CMML-RS/SF3B1, n=172 and MDS-RS/SF3B1, n=324). The percentage of RS was ≥15% in almost all CMML-RS/SF3B1 patients (169, 98.3%) and most (125, 72.7%) showed peripheral blood monocyte counts between 0.5 and 0.9 x109/L and low risk prognostic categories. CMML-RS/SF3B1 differed significantly from classical CMML in the main clinical characteristics, whereas it resembled MDS-RS/SF3B1. At a molecular level, CMML and CMML-RS/SF3B1 had a significantly higher frequency of mutations in TET2 (mostly multi-hit) and ASXL1 (p=0.013) and CMML had a significantly lower frequency of DNMT3A and SF3B1 mutations compared to CMML/MDS-RS/SF3B1. Differences in the median overall survival among the three groups were statistically significant: 6.75 years (95% confidence interval [CI] 5.41-8.09) for CMML-RS/SF3B1 vs. 3.17 years (95% CI 2.56-3.79) for CMML vs. 16.47 years (NA) for MDS-RS/SF3B1, p<0.001. Regarding patients with CMML and MDS, both with SF3B1 mutation, survival did not significantly differ. CMML had a higher risk of transformation to acute myeloid leukemia (24% at 8 years, 95%CI 19%-30%). Discussion: CMML-RS/SF3B1 mutation resembles MDS-RS/SF3B1 in terms of phenotype and clearly differs from CMML. The presence of ≥15% RS and/or SF3B1 in CMML is associated with a low monocyte count. SF3B1 mutation clearly improves the prognosis of CMML.
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Background: Erythropoiesis stimulating agents (ESAs) are the first-line therapy in patients with lower-risk myelodysplastic syndromes (LR-MDS). Some predictive factors for ESAs response have been identified. Type and number of somatic mutations have been associated with prognosis and response to therapies in MDS patients. Objectives: The objective was to evaluate the outcomes after ESAs in patients with LR-MDS and to address the potential predictive value of somatic mutations in ESAs-treated patients. Design: Multi-center retrospective study of a cohort of 722 patients with LR-MDS included in the SPRESAS (Spanish Registry of Erythropoietic Stimulating Agents Study) study. Retrospective analysis of 65 patients with next generation sequencing (NGS) data from diagnosis. Methods: ESAs' efficacy and safety were evaluated in patients receiving ESAs and best supportive care (BSC). To assess the potential prognostic value of somatic mutations in erythroid response (ER) rate and outcome, NGS was performed in responders and non-responders. Results: ER rate for ESAs-treated patients was 65%. Serum erythropoietin (EPO) level <200 U/l was the only variable significantly associated with a higher ER rate (odds ratio, 2.45; p = 0.036). Median overall survival (OS) in patients treated with ESAs was 6.7 versus 3.1 years in patients receiving BSC (p < 0.001). From 65 patients with NGS data, 57 (87.7%) have at least one mutation. We observed a trend to a higher frequency of ER among patients with a lower number of mutated genes (40.4% in <3 mutated genes versus 22.2% in ⩾3; p = 0.170). The presence of ⩾3 mutated genes was also significantly associated with worse OS (hazard ratio, 2.8; p = 0.015), even in responders. A higher cumulative incidence of acute myeloid leukemia progression at 5 years was also observed in patients with ⩾3 mutated genes versus <3 (33.3% and 10.7%, respectively; p < 0.001). Conclusion: This large study confirms the beneficial effect of ESAs and the adverse effect of somatic mutations in patients with LR-MDS.
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Lenalidomide (LEN) can induce red blood cell-transfusion independence (RBC-TI) in 60-70% of del(5q) myelodysplastic neoplasm (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN while RBC-transfusion independent. We enrolled 118 patients with IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis, RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved again RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients who reached RBC-TI allows prolonged maintenance of TI in a large subset of patients.
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BACKGROUND: Current thawing techniques of cryopreserved progenitor cells are based on the use of a water bath. The aim of this study has been to assess the progenitor cell viability and the time of hematopoietic engraftment after transplantation of cell products thawed with a new dry-thawing device. STUDY DESIGN AND METHODS: In the preclinical phase, two cryobags from the same patient were thawed with the standard technique and with the dry system method in parallel (n=5, Protocol A and Protocol B, respectively). In the clinical phase, cryobags were thawed with the dry system and the time to hematopoietic engraftment after autologous transplantation (n=52) was compared with those of a control group of patients whose progenitor cell products were thawed with the standard technique (n=52). RESULTS: There were no statistical differences in nuclear and CD34+ cell viability, total colony-forming cells, and cloning efficiency after thawing with Protocols A and B. Days to neutrophil (>0.5×10(9) and >1×10(9) /L) and platelet engraftment (>20×10(9) and >50×10(9) /L) were not different between patients transplanted with products thawed with Protocols A and B. CONCLUSION: Progenitor cell viability and function are preserved with this dry-thawing system. The time to hematopoietic engraftment of patients after transplantation is comparable to those infused with progenitor cells thawed with the water bath technique. Thawing cell products without the use of water and in a dry environment might favor the use of this dry method.
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Criopreservação/instrumentação , Criopreservação/métodos , Células-Tronco Hematopoéticas/citologia , Adulto , Idoso , Antígenos CD34/metabolismo , Sobrevivência Celular/fisiologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs. Results: Among 467 episodes of monomicrobial CRBSI, 407 were Gram-positive (GP) (87.1%), 49 GN (10.5%) and 11 fungal (2.4%). Hematological patients (369 episodes) were more frequently neutropenic and were more likely to carry central venous catheters and develop GP CRBSI. Patients with STs (98 episodes) had more comorbidities, more frequently carried port reservoirs and commonly presented more GN CRBSI. GN CRBSI significantly increased over the study period, from 5.2% to 23% (p < 0.001), whereas GP CRBSI decreased from 93.4% to 73.3% (p < 0.001). CRBSI episodes involving port reservoirs and peripherally-inserted central catheters were significantly increased (p < 0.001). The most frequent GPs were coagulase-negative staphylococci (CoNS) (57.8%) and Pseudomonas aeruginosa was the most common GN (3%). Multidrug-resistant (MDR) GN represented 32.7% of all GN CRBSIs and increased over time (p = 0.008). The independent risk factors for GN CRBSI in the whole cohort were solid tumor, chronic kidney disease and carrying a port reservoir. Carrying a port reservoir was also a risk factor in patients with STs. Health-care acquisition was identified as a risk factor for GN CRBSI in the whole cohort, as well as in patients with STs and HMs. Inadequate empirical antibiotic treatment (IEAT) occurred regardless of the etiology: 49% for GNs and 48.6% for GPs (p = 0.96). In GP CRBSI, IEAT was mainly due to inadequate coverage against CoNS (87%), whereas in GN CRBSI, IEAT was associated with multidrug resistance (54.2%). Early (48 h and 7-day) and 30-day case-fatality rates were similar when analyzed according to the type of underlying disease and etiology, except for the 30-day case-fatality rate, which was higher in the group of patients with STs compared to those with HMs (21.5% vs. 12.5%, p = 0.027). The 48 h case-fatality rate was significantly higher in patients in whom the catheter had not been removed (5.6% vs. 1%; p = 0.011), and it remained significant for GP CRBSI (6% vs. 1.3%, p = 0.023). Conclusions: GNs are an increasing cause of CRBSI in cancer patients, particularly in solid tumor patients carrying port reservoirs. Multidrug resistance among GNs is also increasing and is associated with higher rates of IEAT. Decreased 48 h survival was associated with the non-removal of the catheter. These findings should be considered when deciding on early therapeutic management for cancer patients with suspected CRBSI.
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Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases without a care standard and show variability in treatment outcomes. This Spanish, observational, prospective study ERASME (CEL-SMD-2012-01) assessed the evolution of newly diagnosed and treatment-naïve high-risk MDS patients (according to IPPS-R). 204 patients were included: median age 73.0 years, 54.4% males, 69.6% 0-1 ECOG, and 94.6% with comorbidities. Active treatment was the most common strategy (52.0%) vs. stem cell transplantation (25.5%) and supportive care/watchful-waiting (22.5%). Overall (median) event-free survival was 7.9 months (9.1, 8.3, and 5.3); progression-free survival: 10.1 months (12.9, 12.8, and 4.3); and overall survival: 13.8 months (15.4, 14.9; 8.4), respectively, with significant differences among groups. Adverse events (AEs) of ≥3 grade were reported in 72.6% of patients; serious AEs reported in 60.6%. 33.1% of patients died due to AEs. Three patients developed second primary malignant neoplasms (median: 8.2 months). Our study showed better outcomes in patients receiving active therapy early after diagnosis.
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Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Masculino , Humanos , Idoso , Feminino , Estudos Prospectivos , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/tratamento farmacológico , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-TroncoRESUMO
Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.
RESUMO
Myelodysplastic neoplasms (MDS) are a heterogeneous group of hematological stem cell disorders characterized by dysplasia, cytopenias, and increased risk of acute leukemia. As prognosis differs widely between patients, and treatment options vary from observation to allogeneic stem cell transplantation, accurate and precise disease risk prognostication is critical for decision making. With this aim, we retrieved registry data from MDS patients from 90 Spanish institutions. A total of 7202 patients were included, which were divided into a training (80%) and a test (20%) set. A machine learning technique (random survival forests) was used to model overall survival (OS) and leukemia-free survival (LFS). The optimal model was based on 8 variables (age, gender, hemoglobin, leukocyte count, platelet count, neutrophil percentage, bone marrow blast, and cytogenetic risk group). This model achieved high accuracy in predicting OS (c-indexes; 0.759 and 0.776) and LFS (c-indexes; 0.812 and 0.845). Importantly, the model was superior to the revised International Prognostic Scoring System (IPSS-R) and the age-adjusted IPSS-R. This difference persisted in different age ranges and in all evaluated disease subgroups. Finally, we validated our results in an external cohort, confirming the superiority of the Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS) over the IPSS-R, and achieving a similar performance as the molecular IPSS. In conclusion, the AIPSS-MDS score is a new prognostic model based exclusively on traditional clinical, hematological, and cytogenetic variables. AIPSS-MDS has a high prognostic accuracy in predicting survival in MDS patients, outperforming other well-established risk-scoring systems.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Rituximab/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Clinical outcomes of novel coronavirus 2019 disease (COVID-19) in onco-hematological patients are unknown. When compared to non-immunocompromised patients, onco-hematological patients seem to have higher mortality rates. AIMS: We describe the characteristics and outcomes of a consecutive cohort of 24 onco-hematological patients with COVID-19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. METHODS AND RESULTS: Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID-19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22-82) years. Median follow-up in survivors was 14 (9-28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1-10) and 10 (3-18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D-dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID-19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID-19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (-55%) and chemotherapy sessions (-19%). A significant increase in phone visits was reported (+581%). CONCLUSION: COVID-19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting.