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1.
Blood ; 144(5): 541-551, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38717861

RESUMEN

ABSTRACT: We hypothesized that fit older patients with acute myeloid leukemia (AML) treated with decitabine (DEC) would report better health-related quality of life (HRQoL) outcomes than those receiving intensive chemotherapy (IC). We conducted a phase 3 randomized trial to compare DEC (10-day schedule) with IC (3+7) in older fit patients with AML. HRQoL was a secondary end point, and it was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in conjunction with its elderly module (EORTC QLQ-ELD14). The following scales were a priori selected for defining the primary end point: physical and role functioning, fatigue, pain, and burden of illness. HRQoL was assessed at baseline, at regeneration from cycle 2, and at 6 and 12 months after randomization, and also before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 100 days after transplantation. Overall, 606 patients underwent randomization. At 2 months, the risk of HRQoL deterioration was lower in the DEC arm than in the 3+7 arm; 76% (95% confidence interval [CI], 69-82) vs 88% (95% CI, 82-93); odds ratio, 0.43 (95% CI, 0.24-0.76; P = .003). No statistically significant HRQoL differences were observed between treatment arms at the long-term evaluation combining assessments at 6 and 12 months. HRQoL deteriorations between baseline and after allo-HSCT were observed in both arms. However, these deteriorations were not clinically meaningful in patients randomized to DEC, whereas this was the case for those in the 3+7 arm, in 4 of 5 primary HRQoL scales. Our HRQoL findings suggest that lower-intensity treatment with DEC may be preferable to current standard IC (3+7) in fit older patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT02172872.


Asunto(s)
Antimetabolitos Antineoplásicos , Decitabina , Leucemia Mieloide Aguda , Calidad de Vida , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Masculino , Femenino , Decitabina/uso terapéutico , Decitabina/administración & dosificación , Persona de Mediana Edad , Antimetabolitos Antineoplásicos/uso terapéutico , Anciano de 80 o más Años , Trasplante de Células Madre Hematopoyéticas , Azacitidina/uso terapéutico , Encuestas y Cuestionarios , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
2.
Haematologica ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39157875

RESUMEN

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

3.
Am J Hematol ; 99(10): 1939-1950, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38953347

RESUMEN

Myeloproliferative neoplasms represent a group of clonal hematopoietic disorders of which myelofibrosis (MF) is the most aggressive. In the context of myeloid neoplasms, there is a growing recognition of the dysregulation of immune response and T-cell function as significant contributors to disease progression and immune evasion. We investigated cytotoxic T-cell exhaustion in MF to restore immune response against malignant cells. Increased expression of inhibitory receptors like CTLA-4 was observed on cytotoxic T cells from MF patients together with a reduced secretion of IFNɣ and TNFɑ. CTLA-4 ligands CD80 and CD86 were increased on MF granulocytes and monocytes highlighting a possible role for myeloid cells in suppressing T-cell activation in MF patients. Unlike healthy donors, the activation of cytotoxic T cells from MF patients was attenuated in the presence of myeloid cells and restored when T cells were cultured alone or treated with anti-CTLA-4. Moreover, anti-CTLA-4 treatment promoted elimination of neoplastic monocytes and granulocytes in a co-culture system with cytotoxic T cells. To test CTLA-4 inhibition in vivo, patient-derived xenografts were generated by transplanting MF CD34+ cells and by infusing homologous T cells in NSGS mice. CTLA-4 blockade reduced human myeloid chimerism and led to T-cell expansion in spleen and bone marrow. Overall, these findings shed light on T-cell dysfunction in MF and suggest that CTLA-4 blockade can boost the cytotoxic T cell-mediated immune response against tumor cells.


Asunto(s)
Antígeno CTLA-4 , Mielofibrosis Primaria , Linfocitos T Citotóxicos , Humanos , Animales , Mielofibrosis Primaria/inmunología , Mielofibrosis Primaria/patología , Linfocitos T Citotóxicos/inmunología , Ratones , Femenino , Masculino , Anciano , Persona de Mediana Edad , Xenoinjertos , Activación de Linfocitos/efectos de los fármacos
4.
Infection ; 52(1): 259-263, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37759073

RESUMEN

CASE PRESENTATION: A pregnant woman developed hepatitis due to a herpes simplex virus 2 primary infection with a severe systemic inflammatory response. Treatment with acyclovir and human immunoglobulin was given and both mother and baby survived. PURPOSE: We provide the first description of the inflammatory response associated with herpetic hepatitis in pregnancy.


Asunto(s)
Hepatitis A , Hepatitis , Herpes Simple , Complicaciones Infecciosas del Embarazo , Embarazo , Femenino , Humanos , Herpesvirus Humano 2 , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/complicaciones , Aciclovir/uso terapéutico , Hepatitis/complicaciones
5.
Br J Haematol ; 202(4): 715-717, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37092558

RESUMEN

The era of AI-based methods to improve flow cytometry diagnostics in haematology is now at the beginning. The study by Nguyen and colleagues explored an emerging machine learning approach to assess phenotypic MRD in chronic lymphocytic leukaemia patients, showing that such AI-driven computational analysis may represent a robust and feasible tool for advanced diagnostics of haematological malignancies. Commentary on: Nguyen et al. Computational flow cytometry provides accurate assessment of measurable residual disease in chronic lymphocytic leukaemia. Br J Haematol 2023;202:760-770.


Asunto(s)
Neoplasias Hematológicas , Leucemia Linfocítica Crónica de Células B , Humanos , Citometría de Flujo/métodos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Inteligencia Artificial , Neoplasia Residual/diagnóstico
6.
Oncologist ; 28(1): e54-e62, 2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36320128

RESUMEN

BACKGROUND: Oncologists are often concerned that talking about death with patients may hinder their relationship. However, the views of death held by patients have not been thoroughly investigated. This study aimed to describe the perception of death among patients with advanced cancer receiving early palliative care (EPC) and their caregivers. MATERIAL AND METHODS: Qualitative and quantitative analyses were performed on 2 databases: (a) transcripts of open-ended questionnaires administered to 130 cancer patients receiving EPC with a mean age of 68.4 years and to 115 primary caregivers of patients on EPC with a mean age of 56.8; (b) texts collected from an Italian forum, containing instances of web-mediated interactions between patients and their caregivers. RESULTS: Quantitative analysis shows that: (a) patients and caregivers are not afraid of speaking about death; (b) patients and caregivers on EPC use the word "death" significantly more than patients on standard oncology care (SOC) and their caregivers (P < .0001). For both participants on EPC and SOC, the adjectives and verbs associated with the word "death" have positive connotations; however, these associations are significantly more frequent for participants on EPC (verbs, Ps < .0001; adjectives, Ps < .003). Qualitative analysis reveals that these positive connotations refer to an actual, positive experience of the end of life in the EPC group and a wish or a negated event in the SOC group. CONCLUSIONS: EPC interventions, along with proper physician-patient communication, may be associated with an increased acceptance of death in patients with advanced cancer and their caregivers.


Asunto(s)
Actitud Frente a la Muerte , Neoplasias , Pacientes , Anciano , Humanos , Persona de Mediana Edad , Cuidadores/psicología , Cuidadores/estadística & datos numéricos , Neoplasias/patología , Neoplasias/terapia , Cuidados Paliativos , Pacientes/psicología , Pacientes/estadística & datos numéricos , Relaciones Médico-Paciente
7.
Hematol Oncol ; 41(1): 120-127, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36156278

RESUMEN

Chronic lymphocytic leukemia (CLL), the most common leukemia in the western countries, is characterized by immunosuppression due to disease itself and cytotoxic treatments. Since the beginning of COVID-19 pandemic, patients with CLL appear to be a vulnerable population. In addition, phase III mRNA vaccine trials did not provide information about the efficacy in immunocomprised population. In CLL, the antibody-mediated response to SARS-CoV-2 vaccine is impaired. The goal of this study was to evaluate the effects of SARS-CoV-2 vaccination on humoral immune response and on cellular immunity in CLL patients. Humoral immune response to BNT162b2 messenger RNA COVID-19 vaccine was evaluated in 44 CLL patients comprising 20 treatment-naïve, 14 under treatment with ibrutinib and 10 in follow-up after completion of therapy. A positive serological response to SARS-CoV-2 vaccination with IgG titers higher than 13 UA/ml was detected in 54.6% of CLL patients with a higher response in patients who obtained remission after treatment. Reduced antibody response was detected in patients under ibrutinib treatment. T-cell response to overlapping pool of peptides representing the spike region was assessed in paired CLL samples collected before and after 1 month from the second dose of COVID-19 vaccine in treatment-naïve and ibrutinib-treated CLL patients using cytokine secretion assay. Both CD3+ CD4+ and CD3+ CD8+ T cells are able to mount a cellular response to spike peptides with secretion of IFNγ and TNFα before and after vaccination in both treatment naïve and ibrutinib-treated patients and this cellular immune response is independent by COVID-19 vaccination. Collectively, T cell response to spike peptides appeared more blunted in CLL patients under treatment with ibrutinib compared to untreated ones. Our study supports the need for optimization of vaccination strategy to achieve an adequate immune response keeping strict preventive measures by CLL patients against COVID-19.


Asunto(s)
COVID-19 , Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Vacunas contra la COVID-19 , Vacuna BNT162 , Pandemias , COVID-19/prevención & control , SARS-CoV-2 , Inmunidad Celular
8.
Infection ; 51(5): 1577-1581, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37076752

RESUMEN

PURPOSE: People with hematologic malignancies have a significantly higher risk of developing severe and protracted forms of SARS-CoV-2 infection compared to immunocompetent patients, regardless of vaccination status. RESULTS: We describe two cases of prolonged SARS-CoV-2 infection with multiple relapses of COVID-19 pneumonia in patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab. The aim is to highlight the complexity of SARS-CoV-2 infection in this fragile group of patients and the necessity of evidence-based strategies to treat them properly. CONCLUSIONS: Patients with hematological malignancies treated with bendamustine and anti-CD20 antibodies had a significant risk of prolonged and relapsing course of COVID-19. Specific preventive and therapeutic strategies should be developed for this group of patients.


Asunto(s)
COVID-19 , Neoplasias Hematológicas , Linfoma Folicular , Humanos , Rituximab/uso terapéutico , Linfoma Folicular/complicaciones , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Clorhidrato de Bendamustina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , SARS-CoV-2 , Neoplasias Hematológicas/tratamiento farmacológico
9.
Int J Mol Sci ; 24(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37175717

RESUMEN

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Adulto , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple
10.
Br J Haematol ; 199(1): 54-60, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35906881

RESUMEN

COVID-19 continues to be a relevant issue among patients with haematological malignancies (HM). Vaccines are frequently not effective in subjects on active treatment. In this multicentre retrospective study of Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), we collected data from 91 paucisymptomatic HM patients treated with anti-spike neutralizing monoclonal antibodies (nMoAbs) to determine time to viral clearance, referencing it to the expected value of 28 days from an historical group of untreated paucisymptomatic patients. Secondary endpoints included rate of hospitalization, intensive care unit (ICU) admission, COVID-19 related death and safety. SARS-CoV-2 molecular swab negativity was obtained in 86 patients (95%), with a median time of 18 days (IQR 13-26; p < 0.0001). We did not find significant variations according to age, diagnosis, treatment type, vaccination status or nMoAbs type. Rate of hospitalization due to COVID-19 progression was 12% (11/91), with 2 patients (2.2%) requiring ICU admission. With a median follow-up of 2.33 months, the overall mortality was 5.5% (5/91), with 3 deaths due to COVID-19. Side effects were rare and self-limiting. Our data suggest that nMoAbs can limit the detrimental effect of immunosuppressive treatments on COVID-19 clinical progression and time to viral clearance. The original trial was registered at www.clinicaltrials.gov as #NCT04932967.


Asunto(s)
COVID-19 , Neoplasias Hematológicas , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes , Neoplasias Hematológicas/terapia , Humanos , Estudios Retrospectivos , SARS-CoV-2
11.
Oncologist ; 27(2): e168-e175, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35641207

RESUMEN

BACKGROUND: Oncologists' fear of taking away hope from patients when proposing early palliative care (EPC) is a barrier to the implementation of this model. This study explores hope perceptions among bereaved caregivers of onco-hematologic patients who received EPC. MATERIALS AND METHODS: Open-ended questionnaires were administered to 36 primary caregivers of patients who received EPC (26 solid and 10 hematologic cancer patients; mean age: 51.4 years, range age: 20-74), at 2 cancer centers, 2 months to 3 years after a patient death. Definitions of hope in the caregivers' narratives were analyzed through a directed approach to content analysis. Results were complemented with automated lexicographic analysis. RESULTS: Caregivers perceived hope mainly as resilience and as expectations based on what they were told about the patients' clinical conditions. Their hope was bolstered by trusting relationships with the healthcare teams. EPC interventions were recalled as the major support for hope, both during the illness and after the death of the patient. The automated quantitative lexical analysis provided deeper insights into the links between hope, truth, and trust. CONCLUSIONS: Our findings suggest that telling the truth about an incurable onco-hematologic disease and beginning EPC might be the combination of factors triggering hope in the setting of incurable cancer.


Asunto(s)
Aflicción , Neoplasias , Oncólogos , Adulto , Anciano , Cuidadores , Humanos , Persona de Mediana Edad , Cuidados Paliativos , Adulto Joven
12.
Ann Neurol ; 89(4): 769-779, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33459417

RESUMEN

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)-specific T cell therapy in a cohort of hematological patients with PML. METHODS: Between 2014 and 2019, 9 patients with a diagnosis of "definite PML" according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides. RESULTS: None of the patients experienced treatment-related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up. INTERPRETATION: Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769-779.


Asunto(s)
Traslado Adoptivo/métodos , Virus JC , Leucoencefalopatía Multifocal Progresiva/terapia , Linfocitos T , Adolescente , Traslado Adoptivo/efectos adversos , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Leucoencefalopatía Multifocal Progresiva/líquido cefalorraquídeo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Carga Viral
13.
Hematol Oncol ; 40(1): 31-39, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34694649

RESUMEN

The standard management for relapsed or refractory classical Hodgkin lymphoma (cHL) is salvage therapy followed by autologous stem cell transplantation (ASCT). This strategy allows almost 50% of patients to be cured. Post-ASCT maintenance treatment with brentuximab vedotin (BV) confers improved progression-free survival (PFS) to cHL patients at high risk of relapse. We investigated the outcome of 105 cHL patients receiving post-ASCT BV maintenance in the real-life setting of 23 Italian hematology centers. This population included naïve patients and those previously exposed to BV. Median follow-up was 20 months. Patients presented a median of two lines of treatment pre-ASCT, with 51% receiving BV. Twenty-nine percent of patients had at least two high-risk factors (refractory disease, complete response [CR] less than 12 months, extranodal disease at relapse), while 16% presented none. At PET-CT, a Deauville score (DS) of 1-3 was reported in 75% and 78% of pre- and post-ASCT evaluations, respectively. Grade 3-4 adverse events (AEs), mainly peripheral neuropathy, were observed in 16% of patients. Three-year PFS and overall survival (OS) were 62% and 86%, respectively. According to BV exposure, 3-year PFS and OS were 54% and 71%, respectively, for naïve and 77% and 96%, respectively, for previously exposed patients. Refractory disease (hazard ratio [HR] 4.46; p = 0.003) and post-ASCT DS 4-5 (HR 3.14; p = 0.005) were the only two factors significantly associated with PFS reduction in multivariable analysis. Post-ASCT BV maintenance is an effective, safe treatment option for cHL naïve patients and those previously exposed to BV.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
14.
Hematol Oncol ; 40(5): 846-856, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35854643

RESUMEN

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.


Asunto(s)
COVID-19 , Coinfección , Neoplasias Hematológicas , Linfoma , Humanos , Anciano , COVID-19/complicaciones , Prueba de COVID-19 , Neoplasias Hematológicas/complicaciones
15.
Ann Hematol ; 101(2): 297-307, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34859285

RESUMEN

Platelet-derived growth factor receptor B (PDGFRB) gene rearrangements define a unique subgroup of myeloid and lymphoid neoplasms frequently associated with eosinophilia and characterized by high sensitivity to tyrosine kinase inhibition. To date, various PDGFRB/5q32 rearrangements, involving at least 40 fusion partners, have been reported. However, information on genomic and clinical features accompanying rearrangements of PDGFRB is still scarce. Here, we characterized a series of 14 cases with a myeloid neoplasm using cytogenetic, single nucleotide polymorphism array, and next-generation sequencing. We identified nine PDGFRB translocation partners, including the KAZN gene at 1p36.21 as a novel partner in a previously undescribed t(1;5)(p36;q33) chromosome change. In all cases, the PDGFRB recombination was the sole cytogenetic abnormality underlying the phenotype. Acquired somatic variants were mainly found in clinically aggressive diseases and involved epigenetic genes (TET2, DNMT3A, ASXL1), transcription factors (RUNX1 and CEBPA), and signaling modulators (HRAS). By using both cytogenetic and nested PCR monitoring to evaluate response to imatinib, we found that, in non-AML cases, a low dosage (100-200 mg) is sufficient to induce and maintain longstanding hematological, cytogenetic, and molecular remissions.


Asunto(s)
Reordenamiento Génico , Leucemia Mieloide/genética , Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Adulto , Anciano , Aberraciones Cromosómicas , Proteínas del Citoesqueleto/genética , Eosinofilia/genética , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Fusión Oncogénica/genética , Polimorfismo de Nucleótido Simple , Translocación Genética , Adulto Joven
16.
Support Care Cancer ; 30(7): 6007-6012, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35399104

RESUMEN

OBJECTIVE: No-visitor policies adopted to prevent coronavirus disease-19 (COVID-19) spread in hospital wards have deeply impacted communication with patients and their relatives. Whereas in pre-COVID-19 era family-clinician meetings were held in person, during the pandemic interactions often took place over the phone, frequently causing feelings of uncertainty and distress to the close ones at home. The goal of this study was to assess and improve the effectiveness of structured telephone-based communication with hospitalized onco-hematological patients' relatives in COVID-19 era. METHODS: After no-visitor policy was adopted in the Onco-Hematological Unit of Modena, inpatients' relatives were contacted daily for clinical updates. After discharge, a telephone satisfaction survey was administered to all contact people of patients consecutive admitted between December 2020 and January 2021 (n = 97). Mean score of response and potential statistically significative differences depending on respondents' characteristics were assessed. RESULTS: Most relatives were satisfied with the communication received with a mean total score of 4.69 on a 5-point Likert scale (standard deviation: 0.60). Results showed high satisfaction rate with both the informative (mean ± SD: 4.66 ± 0.64) and emotional (mean ± SD: 4.66 ± 0.58) content, with no significant difference depending on respondents' demographic characteristics (p > 0.05). CONCLUSION: A structured telephone-based communication may be a reasonable substitute for face-to-face meetings; especially if regular in time, conducted by the same doctor and integrated with video calls. Our findings might assist health workers in implementing measures to minimize the psychological effects of no-visitor policies during hospitalization. Clinical updates delivery through structured phone calls and video calls could become an opportunity also in post-COVID era.


Asunto(s)
COVID-19 , Neoplasias , Comunicación , Humanos , Neoplasias/terapia , SARS-CoV-2 , Encuestas y Cuestionarios , Teléfono
17.
Int J Mol Sci ; 23(9)2022 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-35563634

RESUMEN

Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cytokine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the relapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunotherapeutic approaches in these settings.


Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Mieloma Múltiple Quiescente , Progresión de la Enfermedad , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Paraproteinemias/terapia , Linfocitos T/patología
18.
Clin Infect Dis ; 73(1): e252-e255, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32840571

RESUMEN

We report two fatal cases of acute liver failure secondary to herpes simplex virus 1 infection in COVID-19 patients, following tocilizumab and corticosteroid therapy. Screening for and prompt recognition of herpes simplex virus 1 reactivation in these patients, undergoing immunomodulatory treatment, may have potentially relevant clinical consequences.


Asunto(s)
COVID-19 , Herpes Simple , Herpesvirus Humano 1 , Fallo Hepático Agudo , Humanos , Inmunomodulación , SARS-CoV-2
19.
Br J Haematol ; 195(3): 371-377, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34272724

RESUMEN

COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04-11·21; P = 0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0·35; 95% CI: 0·11-1·13; P = 0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.


Asunto(s)
Formación de Anticuerpos , COVID-19/complicaciones , Neoplasias Hematológicas/complicaciones , SARS-CoV-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Femenino , Neoplasias Hematológicas/inmunología , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Seroconversión , Adulto Joven
20.
Oncologist ; 26(12): e2274-e2287, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34510624

RESUMEN

BACKGROUND: Little is known about the underlying mechanisms through which early palliative care (EPC) improves multiple outcomes in patients with cancer and their caregivers. The aim of this study was to qualitatively and quantitatively analyze patients' and caregivers' thoughts and emotional and cognitive perceptions about the disease prior to and during the EPC intervention, and in the end of life, following the exposure to EPC. MATERIALS AND METHODS: Seventy-seven patients with advanced cancer and 48 caregivers from two cancer centers participated in semistructured interviews. Their reports were qualitatively and quantitatively analyzed by the means of the grounded theory and a text-analysis program. RESULTS: Participants reported their past as overwhelmed by unmanaged symptoms, with detrimental physical and psychosocial consequences. The EPC intervention allowed a prompt resolution of symptoms and of their consequences and empowerment, an appreciation of its multidimensional approach, its focus on the person and its environment, and the need for EPC for oncologic populations. Patients reported that conversations with the EPC team increased their acceptance of end of life and their expectation of a painless future. Quantitative analysis revealed higher use of Negative Affects (p < .001) and Biological Processes words (p < .001) when discussing the past; Agency words when discussing the present (p < .001); Positive Affects (p < .001), Optimism (p = .002), and Insight Thinking words (p < .001) when discussing the present and the future; and Anxiety (p = .002) and Sadness words (p = .003) when discussing the future. CONCLUSION: Overall, participants perceived EPC to be beneficial. Our findings suggest that emotional and cognitive processes centered on communication underlie the benefits experienced by participants on EPC. IMPLICATIONS FOR PRACTICE: By qualitative and quantitative analyses of the emotional and cognitive perceptions of cancer patients and their caregivers about their experiences before and during EPC interventions, this study may help physicians/nurses to focus on the disease perception by patients/caregivers and the benefits of EPC, as a standard practice. The analysis of words used by patients/caregivers provides a proxy for their psychological condition and support in tailoring an EPC intervention, based on individual needs. This study highlights that the relationship of the triad EPC team/patients/caregivers may rise as a therapeutic tool, allowing increasing awareness and progressive acceptance of the idea of death.


Asunto(s)
Neoplasias , Cuidados Paliativos , Directivas Anticipadas , Cuidadores , Humanos , Neoplasias/terapia
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