Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 351
Filtrar
1.
Blood ; 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35007321

RESUMO

The goal of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for ET and PV patients at high-risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment naïve, high-risk ET/PV patients. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (p=0.80) at 12 months. At 24/36 months, CR was 20%/17% for HU and 29%/33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, while grade 3/4 adverse events were more frequent with PEG (46% vs. 28%). At 12 months of treatment there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment PEG was more effective in normalizing blood counts and reducing driver mutation burden, while HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk ET/PV patients. (Funded by the National Cancer Institute, 5P01CA108671-09; clinicaltrials.gov number (NCT01259856).

2.
Clin Case Rep ; 10(1): e05212, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35028141

RESUMO

The translocation t(8;9)(p22;p24) results in the production of a chimeric PCM1-JAK2 fusion protein leading to the constitutive activation of the Janus Kinase 2 that renders this disease potentially sensitive to ruxolitinib. Here, we report an interesting case of PCM1-JAK2 myeloproliferative neoplasm evolving in myeloid sarcoma and B precursor ALL.

4.
Cancers (Basel) ; 13(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34638230

RESUMO

Long non-coding RNAs (lncRNAs) have been recently described as key mediators in the development of hematological malignancies. In the last years, circulating lncRNAs have been proposed as a new class of non-invasive biomarkers for cancer diagnosis and prognosis and to predict treatment response. The present study is aimed to investigate the potential of circulating lncRNAs as non-invasive prognostic biomarkers in myelofibrosis (MF), the most severe among Philadelphia-negative myeloproliferative neoplasms. We detected increased levels of seven circulating lncRNAs in plasma samples of MF patients (n = 143), compared to healthy controls (n = 65). Among these, high levels of LINC01268, MALAT1 or GAS5 correlate with detrimental clinical variables, such as high count of leukocytes and CD34+ cells, severe grade of bone marrow fibrosis and presence of splenomegaly. Strikingly, high plasma levels of LINC01268 (p = 0.0018), GAS5 (p = 0.0008) or MALAT1 (p = 0.0348) are also associated with a poor overall-survival while high levels of LINC01268 correlate with a shorter leukemia-free-survival. Finally, multivariate analysis demonstrated that the plasma level of LINC01268 is an independent prognostic variable, suggesting that, if confirmed in future in an independent patients' cohort, it could be used for further studies to design an updated classification model for MF patients.

5.
Hematol Oncol ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34714558

RESUMO

Functional parameters from positron emission tomography (PET) seem promising biomarkers in various lymphoma subtypes. This study investigated the prognostic value of PET radiomics in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP given either every 14 (testing set) or 21 days (validation set). Using the PyRadiomics Python package, 107 radiomics features were extracted from baseline PET scans of 133 patients enrolled in the Swiss Group for Clinical Cancer Research 38/07 prospective clinical trial (SAKK 38/07) [ClinicalTrial.gov identifier: NCT00544219]. The international prognostic indices, the main clinical parameters and standard PET metrics, together with 52 radiomics uncorrelated features (selected using the Spearman correlation test) were included in a least absolute shrinkage and selection operator (LASSO) Cox regression to assess their impact on progression-free (PFS), cause-specific (CSS), and overall survival (OS). A linear combination of the resulting parameters generated a prognostic radiomics score (RS) whose area under the curve (AUC) was calculated by receiver operating characteristic analysis. The RS efficacy was validated in an independent cohort of 107 DLBCL patients. LASSO Cox regression identified four radiomics features predicting PFS in SAKK 38/07. The derived RS showed a significant capability to foresee PFS in both testing (AUC, 0.709; p < 0.001) and validation (AUC, 0.706; p < 0.001) sets. RS was significantly associated also with CSS and OS in testing (CSS: AUC, 0.721; p < 0.001; OS: AUC, 0.740; p < 0.001) and validation (CSS: AUC, 0.763; p < 0.0001; OS: AUC, 0.703; p = 0.004) sets. The RS allowed risk classification of patients with significantly different PFS, CSS, and OS in both cohorts showing better predictive accuracy respect to clinical international indices. PET-derived radiomics may improve the prediction of outcome in DLBCL patients.

6.
Mediterr J Hematol Infect Dis ; 13(1): e2021057, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527209

RESUMO

SARS-COV2 pandemic has caused profound challenges in health care systems worldwide. Patients affected by hematological neoplasms appear to be particularly at risk of developing COVID-19 complications, with unfavorable outcomes. Here, we present the case of a 57-years-old woman diagnosed with severe COVID-19 pneumonia and concurrent acute myeloid leukemia (AML). At the time of diagnosis, it was decided to postpone leukemia therapy to enable adequate COVID-19 pneumonia treatment. When her conditions related to pneumonia improved, the combination of Azacitidine-Venetoclax was used as first-line treatment instead of conventional intensive chemotherapy. At the end of the first two cycles, the patient showed complete remission, and a post-remission consolidation with allogeneic hematopoietic stem cell transplantation has been planned. This case suggests that Azacytidine-Venetoclax induction may represent a valid and safe alternative to intensive chemotherapy in the challenging setting of patients with a concomitant diagnosis of AML and severe COVID-19 infection.

7.
Blood ; 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34343258

RESUMO

Nucleophosmin (NPM1) mutations in acute myeloid leukemia (AML) affect exon 12, but sporadically also exon 9 and 11, all causing changes at protein C-terminal end (loss of tryptophans and creation of a nuclear export signal-NES motif) that lead to aberrant cytoplasmic NPM1 (NPM1c+), detectable by immunohistochemistry. Combining immunohistochemistry and molecular analyses in 929 AML patients, we found non-exon 12 NPM1 mutations in 5/387 (1.3%) NPM1c+ cases. Besides mutations in exon 9 (n=1) and exon 11 (n=1), novel mutations in exon 5 were discovered (n=3). One more exon 5 mutation was identified in additional 141 AML patients selected for wild-type NPM1 exon 12. Furthermore, 3 NPM1 rearrangements (i.e. NPM1/RPP30, NPM1/SETBP1, NPM1/CCDC28A) were detected and characterized among 13,979 AML samples screened by cytogenetic/FISH and RNA sequencing. Functional studies demonstrated that in AML cases the new NPM1 proteins harboured an efficient extra NES, either newly created or already present in the fusion partner, ensuring its cytoplasmic accumulation. Our findings support NPM1 cytoplasmic relocation as critical for leukemogenesis and reinforce the role of immunohistochemistry in predicting any AML-associated NPM1 genetic lesions. Also, this study highlights the need for developing new specific assays for molecular diagnosis and monitoring of NPM1-mutated AML.

9.
Br J Haematol ; 195(2): 244-248, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34331348

RESUMO

Fedratinib, an oral Janus kinase-2 (JAK2) inhibitor, reduces splenomegaly and improves symptom burden in patients with myelofibrosis. Regulatory approval of fedratinib 400-mg daily was based on results of an updated analysis of the pivotal phase III, placebo-controlled JAKARTA trial in patients with JAK-inhibitor-naïve myelofibrosis. At week 24, spleen volume response rate was 47% and symptom response rate was 40% with fedratinib 400 mg, versus 1% and 9% respectively, with placebo. Common adverse events were diarrhoea, nausea, anaemia, and vomiting. No Wernicke encephalopathy occurred in patients receiving fedratinib 400 mg/day. These updated data support use of first-line fedratinib in patients with myelofibrosis.

12.
Clin Lymphoma Myeloma Leuk ; 21(10): 686-693, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34158265

RESUMO

BACKGROUND: The Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study has provided an opportunity to evaluate the real-world outcomes of patients with myeloma. The aim of this study was to compare the outcome according to the different subtypes of myeloma using CALM data. PATIENTS: This study compared overall survival (OS), progression-free survival (PFS), and complete remission (CR) and the impact of novel versus non-novel drug containing induction regimens prior to autologous hematopoietic cell transplantation (HCT) of 2802 patients with "usual" and "rare" myelomas. RESULTS: Our data suggest that IgM and non-secretory myeloma have superior PFS and OS compared with IgD myeloma and outcomes comparable to those for usual myeloma. Patients who received novel agent induction had higher rates of CR prior to transplant. Non-novel induction regimens were associated with inferior PFS but no difference in OS. Although not the primary focus of this study, we show that poor mobilization status is associated with reduced PFS and OS, but these differences disappear in multivariate analysis suggesting that poor mobilization status is a surrogate for other indicators of poor prognosis. CONCLUSION: We confirm that IgD myeloma is associated with the worst prognosis and inferior outcomes compared with the other isotypes.

14.
Transplant Cell Ther ; 27(5): 406.e1-406.e11, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965179

RESUMO

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade ≥II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and ≤8/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence.


Assuntos
Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Alelos , Medula Óssea , Humanos , Itália , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Sistema de Registros
16.
Bone Marrow Transplant ; 56(8): 1944-1952, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33824436

RESUMO

Therapeutic management of patients with primary or secondary myelofibrosis (MF) who experience relapse or graft failure following allogeneic haematopoietic cell transplantation (allo-HCT) remains heterogeneous. We retrospectively analyzed 216 patients undergoing a second allo-HCT for either relapse (56%) or graft failure (31%) between 2010 and 2017. Median age was 57.3 years (range 51-63). The same donor as for the first allo-HCT was chosen in 66 patients (31%) of whom 19 received an HLA-identical sibling donor, whereas a different donor was chosen for 116 patients (54%). Median follow-up was 40 months. Three-year overall survival (OS) and relapse-free survival (RFS) were 42% and 39%, respectively. Three-year non-relapse mortality (NRM) and relapse rates were 36% and 25%, respectively. Grade II-IV and III-IV acute GVHD occurred in 25% and 11% of patients, respectively, and the 3-year incidence of chronic GVHD was 33% including 14% for extensive grade. Graft-failure incidence at 1 year was 14%. In conclusion, our data suggest that a second allo-HCT is a potential option for patients failing first allo-HCT for MF albeit careful patient assessment is fundamental to identify individual patients who could benefit from this approach.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Mielofibrose Primária , Humanos , Pessoa de Meia-Idade , Mielofibrose Primária/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante
17.
Cancers (Basel) ; 13(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925541

RESUMO

In many clinical studies published over the past 20 years, adolescents and young adults (AYA) with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph- ALL) were considered as a rather homogeneous clinico-prognostic group of patients suitable to receive intensive pediatric-like regimens with an improved outcome compared with the use of traditional adult ALL protocols. The AYA group was defined in most studies by an age range of 18-40 years, with some exceptions (up to 45 years). The experience collected in pediatric ALL with the study of post-induction minimal residual disease (MRD) was rapidly duplicated in AYA ALL, making MRD a widely accepted key factor for risk stratification and risk-oriented therapy with or without allogeneic stem cell transplantation and experimental new drugs for patients with MRD detectable after highly intensive chemotherapy. This combined strategy has resulted in long-term survival rates of AYA patients of 60-80%. The present review examines the evidence for MRD-guided therapies in AYA's Ph- ALL, provides a critical appraisal of current treatment pitfalls and illustrates the ways of achieving further therapeutic improvement according to the massive knowledge recently generated in the field of ALL biology and MRD/risk/subset-specific therapy.

18.
Blood Adv ; 5(5): 1452-1462, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33666652

RESUMO

Myelofibrosis (MF) belongs to the family of classic Philadelphia-negative myeloproliferative neoplasms (MPNs). It can be primary myelofibrosis (PMF) or secondary myelofibrosis (SMF) evolving from polycythemia vera (PV) or essential thrombocythemia (ET). Despite the differences, PMF and SMF patients are currently managed in the same way, and prediction of survival is based on the same clinical and genetic features. In the last few years, interest has grown concerning the ability of gene expression profiles (GEPs) to provide valuable prognostic information. Here, we studied the GEPs of granulocytes from 114 patients with MF, using a microarray platform to identify correlations with patient characteristics and outcomes. Cox regression analysis led to the identification of 201 survival-related transcripts characterizing patients who are at high risk for death. High-risk patients identified by this gene signature displayed an inferior overall survival and leukemia-free survival, together with clinical and molecular detrimental features included in contemporary prognostic models, such as the presence of high molecular risk mutations. The high-risk group was enriched in post-PV and post-ET MF and JAK2V617F homozygous patients, whereas pre-PMF was more frequent in the low-risk group. These results demonstrate that GEPs in MF patients correlate with their molecular and clinical features, particularly their survival, and represent the proof of concept that GEPs might provide complementary prognostic information to be applied in clinical decision making.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Humanos , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Transcriptoma
19.
Front Med (Lausanne) ; 8: 609440, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681246

RESUMO

The novel coronavirus, SARS-CoV-2, continues to spread rapidly. Here we discuss the dramatic situation created by COVID-19 in Italy, particularly in the province of Bergamo (the most severely affected in the first wave), as an example of how, in the face of an unprecedented tragedy, acting (albeit belatedly)-including imposing a very strict lockdown-can largely resolve the situation within approximately 2 months. The measures taken here ensured that Bergamo hospital, which was confronted with rapidly rising numbers of severely ill COVID-19 patients requiring hospitalization, was able to meet the initial challenges of the pandemic. We also report that local organization and, more important, the large natural immunity against SARS-CoV-2 of the Bergamo population developed during the first wave of the epidemic, can explain the limited number of new COVID-19 cases during the more recent second wave compared to the numbers in other areas of Lombardy. Furthermore, we highlight the importance of coordinating the easing of containment measures to avoid what is currently observed in other countries, especially in the United States, Latin American and India, where this approach has not been adopted, and a dramatic resurgence of COVID-19 cases and an increase in the number of hospitalisations and deaths have been reported.

20.
Blood Cancer J ; 11(3): 53, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33677466

RESUMO

Polycythemia vera (PV) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) characterized by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow, mainly due to a Janus kinase 2 gene mutation (JAK2V617F). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2V617F cell growth, has demonstrated good efficacy and safety in three phase 1/2 studies in patients with PV. This manuscript focuses on the 4-year mean (2.8 year median) follow-up of an open-label, long-term study that enrolled 51 patients with PV (out of a total of 54 with MPN) who received clinical benefit from givinostat in these previous studies or on compassionate use, and who continued to receive givinostat at the last effective and tolerated dose. The primary objectives are to determine givinostat's long-term safety and tolerability, and efficacy evaluated by the investigators according to internationally recognized response criteria. During follow-up, only 10% of PV patients reported Grade 3 treatment-related adverse events (AEs), while none had Grade 4 or 5 treatment-related AEs. The overall response rate for the duration of follow-up was always greater than 80% in patients with PV. In conclusion, givinostat demonstrated a good safety and efficacy profile in patients with PV, data supporting long-term use in this population.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...