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1.
Orphanet J Rare Dis ; 17(1): 74, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193636

RESUMO

BACKGROUND: Secondary peripheral chondrosarcomas arising in solitary osteochondromas is an unusual complication, reported in small series. In this study, we aimed to present our experience with this rare variant of chondrosarcoma and compare results with already published data in order to determine prognostic factors for overall and disease-free survival. METHODS: The case study includes retrospective data from patients diagnosed at a single institution from 1943 to 2019. Clinical data were collected reviewing all available medical records from first to last follow-up visits. To exclude the presence of the Multiple Osteochondroma Hereditary Syndrome, few patients, with a suspect of a familial form of the disease, were evaluated for the presence of germline heterozygous variants in EXT1 and EXT2 genes. Results were summarized using descriptive statistics and statistical analysis were performed to reveal associations between variables. RESULTS: Two hundred and fourteen secondary peripheral chondrosarcomas that arose exclusively from solitary osteochondromas diagnosed in a multidisciplinary setting at the IRCCS Istituto Ortopedico Rizzoli were retrospectively identified, 66.4% males and 33.6% females with a median age at diagnosis of 38 years. The local recurrence rate was 17.3%, while the metastases one was 5.1%. Besides age, a high histologic grade is the only factor associated with worse 5-year and 10-year overall survival (log-rank p = 0.0005, HR = 3.74; 95% CI 1.69-8.26). Moreover, high histological grade (HR = 3.75; 95% CI = 1.69-8.34; p = 0.001) and surgical debulking (HR = 3.71; 95% CI = 1.57-8.79; p = 0.003) were associated with a significantly worse disease-free survival. CONCLUSIONS: Our study confirm the low-grade behavior of secondary peripheral chondrosarcomas and demonstrate that the best choice of treatment for those arising in solitary osteochondromas is the wide surgical excision, when possible. Location per se is not a factor that affects prognosis, while the accurate histological grade assessment is correlated with the tumor aggressiveness and a long term follow up is necessary for this rare variant of chondrosarcoma.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Osteocondroma , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Condrossarcoma/genética , Condrossarcoma/patologia , Condrossarcoma/cirurgia , Feminino , Humanos , Masculino , Osteocondroma/patologia , Prognóstico , Estudos Retrospectivos
2.
Int J Nurs Stud ; 127: 104172, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35124474

RESUMO

BACKGROUND: There is need for improvement in effective pressure ulcers preventive strategies. OBJECTIVE: To study whether a multi-layer silicone-adhesive polyurethane foam dressing shaped for the sacrum prevents PUs development in addition to standard PU preventive care for at-risk hospitalized patients. DESIGN: Open-label, parallel group, multi-center randomized controlled trial. PARTICIPANTS AND SETTING: 709 in-hospital patients at risk for pressure ulcers from 25 medical, surgical, and intensive care units of 12 Italian hospitals. METHODS: A multi-layer silicone-adhesive polyurethane foam was applied to the sacrum in addition to standard PUs preventive care in the intervention group. In the control group, standard preventive care alone, including systematic pressure ulcer risk assessment, skin assessment three times per day, routine positioning every 4 h, use of active support surface as appropriate, and incontinence skin care, was guaranteed. Primary outcome was incidence of sacral pressure ulcers of any stage at seven days from hospital admission. Secondary outcomes were incidence of sacral pressure ulcers ≥ II stage, number of days needed to PU development, number of skin adverse events due to the foam dressing, number of dressings used for each patient, number of withdrawing patients due to discomfort caused by the foam dressing. Participants were evaluated at baseline and at seven days. RESULTS: In patients admitted to medical units, 15/113 controls and 4/118 in the intervention group developed sacral pressure ulcers (p = 0.010; absolute reduction 9.2%; NNT for benefit 11, 95% CI 6 to 44). In patients admitted to surgical units, 21/144 controls and 8/142 in the intervention group developed sacral pressure ulcers (p = 0.010; absolute reduction 8.9%; NNT for benefit 11 95% CI 6 to 49). Pressure ulcers incidence was not significantly different between the randomization arms (5.2% experimental vs 10.4% control, p = 0.141) in patients admitted to intensive care units. Overall, 46/358 (12.8%) controls and 17/351 (4.8%) in the intervention group developed sacral pressure ulcers (p<0.001; absolute reduction 8%; number needed to treat (NNT) for benefit 12, 95% CI 8 to 26). Incidence of sacral pressure ulcers ≥ II stage did not differ significantly between the two groups. No adverse skin reactions and discomfort attributable to the foam application were reported. CONCLUSION: A sacral multi-layer silicone-adhesive polyurethane foam in addition to standard preventive care is effective for pressure ulcers prevention in at-risk hospitalized patients admitted to medical and surgical units. TRIAL REGISTRATION: ClinicalTrials.gov NCT03900455. The registration (April 1st, 2019) occurred before the first patient was enrolled (October 21st, 2019).


Assuntos
Lesão por Pressão , Adesivos , Bandagens/efeitos adversos , Humanos , Poliuretanos , Lesão por Pressão/epidemiologia , Silicones
3.
Oncol Res Treat ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35034028

RESUMO

Background Bone tumors are not a frequent occurrence and bone-infarct-associated sarcomas are even rarer. The prognosis of this disease is poor and its treatment remains a challenge. Nevertheless, hardly any analyses in literature report on secondary osteosarcoma (SO) on bone infarct and most of the data available do not provide sufficient details. We evaluated whether this condition could be further characterized and if prognosis could be influenced by the chemotherapy treatment. In particular, we sought to determine (1) the main features of this rare disease; (2) the overall survival (OS) rate; (3) the OS rate associated to chemotherapy treatment; (4) the correspondence between our results and published data in terms of survival. Methods We retrospectively reviewed patients admitted at Rizzoli Orthopedic Institute of Bologna between 1992 and 2018 (1465 total cases of osteosarcoma). We identified a list of 11 cases of SO on bone infarct (cohort 1). We conferred about the epidemiology, surgical and chemotherapy (ChT) treatment and surveillance of infarct-associated osteosarcoma showing the correlation to data present in literature, corresponding to 15 case reports published within 1962-2018 (cohort 2). Results (1) cohort 1 was made of 11 patients: six females and five males, median age was 55 years. Nine (81%) were grade 4, two (19%) grade 3. Tumor predominantly arise on distal femur (64%). Most of patients had localized osteosarcoma at the diagnosis (81%); resection surgery was the elective treatment (73%) followed by amputation (18%). Of 11 patients, seven received also ChT (64%). (2) Five-years OS was 62% (95% CI: 28-84). Median OS was 74 months (95% CI: 12-not reached). The cumulative incidence of cancer-related deaths (CICRD) was 37.7% (95% CI: 11.4-64.5) at 120 months. (3) In the group treated with only surgery OS was 50% at 5 years. For patients treated with any form of ChT, OS was 71% at 5 years (p=0.4773) and hazard ratio (HR) 0.56. The CICRD was 29% (at 2 years of follow-up. Instead, it was of 50% for patients treated only with surgery. (4) Median survival was 74 months and 19 months for cohort 1 and cohort 2 respectively (p=0.09). Data analysis showed a decreased HR for cohort 1 compared to cohort 2 (HR 0.378). Results confirmed also stratifying for age and ChT administration (HR 0.355). Conclusions Based on this work, our opinion is that the choice to undergo the patients to ChT combined to surgery could improve their prognosis.

5.
Br J Haematol ; 196(5): 1184-1193, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34951009

RESUMO

The prognostic role of TP53 disruption has been established in diffuse large B-cell lymphoma (DLBCL). Aim of this analysis was to correlate TP53 mutations by Sanger sequencing, cell of origin (COO) profile by Lymph2Cx panel on the NanoString platform and MYC, BCL2 and BCL6 overexpression or re-arrangements by immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH), with outcome in DLBCL patients enrolled into the FIL-DLCL04 trial (NCT00499018). One hundred and twenty-five DLBCL patients with tumour block available were analyzed. TP53 was mutated in 11/125 (9%) cases; 60/125 patients received high-dose chemoimmunotherapy up-front, as for the randomization arm; COO was reported in 88 patients: 48 germinal centre B-cell like, 25 activated B-cell like and 17 unclassified; 26 patients were double expressors in IHC and 11 double hit in FISH. After a median follow-up of 72 months, five-year failure-free survival (FFS) for TP53 mutated versus wild-type was 24% and 72%, and five-year overall survival (OS) was 34% and 83%, respectively. Adjusted hazard ratio (HR) was 2·28 [95% confidence interval (CI) 0·89-5·86, p = 0·086] and 4·05 (95% CI 1·37-11·97, p = 0·011) for FFS and OS, respectively. In this series of young DLBCL patients, TP53 gene mutation identified a poor prognosis subgroup, regardless of treatment and other biological markers.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Proteína Supressora de Tumor p53/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Prednisona/uso terapêutico , Prognóstico , Rituximab/uso terapêutico , Transplante de Células-Tronco , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
6.
Children (Basel) ; 8(12)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34943340

RESUMO

(1) Background: Sprengel's deformity (SD) is a rare congenital anomaly caused by failure in the descent of the scapula. We aimed to systematically review the current literature reporting data from children undergoing surgery for SD, in order to explore the rate of success and complications of the different surgical techniques, possibly providing recommendations about the management of SD in children. (2) Methods: we electronically searched the literature from Ovid, MEDLINE and the Cochrane Library databases. Demographic data, surgical procedures, outcomes and complications were analyzed. We categorized surgical procedures into five groups. (3) Results: 41 articles met the inclusion criteria, showing a poor overall study quality; 674 patients (711 shoulders) were analyzed. Green's and Woodward's procedures, both aiming the scapular relocation in a more anatomical position, were the most commonly used techniques. We counted 168 adverse events (18 major complications). The best clinical and cosmetic results seem to be achieved when surgery is performed in children aged less than eight years. (4) Conclusions: this paper represents the first systematic review reporting qualitative and quantitative data about the surgical treatment of SD. Surgery for SD seems to be effective in increasing the shoulder's range of motion and improving the cosmetic appearance in almost all cases, with a low rate of major complications.

7.
Blood Adv ; 5(21): 4504-4514, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34597375

RESUMO

The role of consolidation radiotherapy (RT) for bulky lesions is controversial in patients with advanced-stage Hodgkin lymphoma who achieve complete metabolic response (CMR) after doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD)-based chemotherapy. We present the final results of the Fondazione Italiana Linfomi HD0801 trial, which investigated the potential benefit of RT in that setting. In this phase 3 randomized study, patients with a bulky lesion at baseline (a mass with largest diameter ≥5 cm) who have CMR after 2 and 6 ABVD cycles were randomly assigned 1:1 to RT vs observation (OBS) with a primary endpoint of event-free survival (EFS) at 2 years. The sample size was calculated estimating an EFS improvement for RT of 20% (from 60% to 80%). The secondary end point was progression-free survival (PFS). One hundred sixteen patients met the inclusion criteria and were randomly assigned to RT or OBS. Intention-to-treat (ITT) analysis showed a 2-year EFS of 87.8% vs 85.8% for RT vs OBS (hazard ratio [HR], 1.5; 95% confidence interval [CI], 0.6-3.5; P = .34). At 2 years, ITT-PFS was 91.3% vs 85.8% (HR, 1.2; 95% CI, 0.5-3; P = .7). Patients in CMR randomly assigned to OBS had a good outcome, and the primary end point of a 20% benefit in EFS for RT was not met. However, the sample size was underpowered to detect a benefit of 10% or less, keeping open the question of a potential, more limited role of RT in this setting. This trial was registered at www.clinicaltrials.gov as #NCT00784537.


Assuntos
Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Estadiamento de Neoplasias , Vimblastina/uso terapêutico
8.
Am J Med Genet A ; 185(11): 3466-3475, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34477285

RESUMO

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (<10 years), 136 adolescents (10-15 years), and 589 adults. Of the entire population, half patients presented at least one deformity, and one quarter reported at least one limitation. Compared with our previous study, the amount of children was more than doubled and the percentage of mild/moderate cases was notably increased, giving a better disease overview throughout the lifespan and suggesting a different cut-off for dividing Class II in subclasses. We confirmed that MO is characterized by phenotypic heterogeneity, suggesting that an early classification of the disease may offer a useful tool to follow disease pattern and evolution, to support clinical practice, and to propose timely interventions.


Assuntos
Exostose Múltipla Hereditária/genética , Osteocondroma/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Exostose Múltipla Hereditária/classificação , Exostose Múltipla Hereditária/epidemiologia , Humanos , Osteocondroma/classificação , Osteocondroma/epidemiologia , Fenótipo , Adulto Jovem
10.
Children (Basel) ; 8(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206218

RESUMO

BACKGROUND: We aimed to investigate the variation of medical and surgical activities in pediatric orthopedics in Italy, during the year of the COVID-19 pandemic, in comparison with data from the previous two years. The differences among the first wave, phase 2 and second wave were also analyzed. METHODS: We conducted a retrospective multicenter study regarding the clinical and surgical activities in pediatric orthopedics during the pandemic and pre-pandemic period. The hospital databases of seven tertiary referral centers for pediatric orthopedics and traumatology were queried for events regarding pediatric orthopedic patients from 1 March 2018 to 28 February 2021. Surgical procedures were classified according to the "SITOP Priority Panel". An additional classification in "high-priority" and "low-priority" surgery was also applied. RESULTS: Overall, in 2020, we observed a significant drop in surgical volumes compared to the previous two years. The decrease was different across the different classes of priority, with "high-priority" surgery being less influenced. The decrease in emergency department visits was almost three-fold greater than the decrease in trauma surgery. During the second wave, a lower decline in surgical interventions and a noticeable resumption of "low-priority" surgery and outpatient visits were observed. CONCLUSION: Our study represents the first nationwide survey quantifying the impact of the COVID-19 pandemic on pediatric orthopedics and traumatology during the first and second wave.

11.
Clin Nutr ; 40(6): 3688-3701, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34134001

RESUMO

BACKGROUND & AIMS: The refeeding syndrome (RFS) has been recognized as a potentially life-threatening metabolic complication of re-nutrition, but the definition widely varies and, its incidence is unknown. The aim of this systematic review and meta-analyses was to estimate the incidence of RFS in adults by considering the definition used by the authors as well as the recent criteria proposed by the American Society of Parenteral and Enteral Nutrition (ASPEN) consensus. Furthermore, the incidence of refeeding hypophosphatemia (RH) was also assessed. METHODS: Four databases were systematically searched until September 2020 for retrieving trials and observational studies. The incidences of RFS and RH were expressed as percentage and reported with 95% confidence intervals (CI). RESULTS: Thirty-five observational studies were included in the analysis. The risk of bias was serious in 16 studies and moderate in the remaining 19. The incidence of RFS varied from 0% to 62% across the studies. No substantial change in the originally reported incidence of RFS was found by applying the ASPEN criteria. Similarly, the incidence of RH ranged between 7% and 62%. In the subgroup analyses, inpatients from Intensive Care Units (ICUs) and those initially fed with >20 kcal/kg/day seemed to have a higher incidence of both RFS (pooled incidence = 44%; 95% CI 36%-52%) and RH (pooled incidence = 27%; 95% CI 21%-34%). However, due to the high heterogeneity of data, summary incidence measures are meaningless. CONCLUSION: The incidence rate of both RFS and RH greatly varied according to the definition used and the population analyzed, being higher in ICU inpatients and in those with increased initial caloric supply. Therefore, a universally accepted definition for RFS, taking different clinical contexts and groups of patients into account, is still needed to better characterize the syndrome and its approach.


Assuntos
Hipofosfatemia/epidemiologia , Síndrome da Realimentação/epidemiologia , Consenso , Humanos , Hipofosfatemia/diagnóstico , Incidência , Estudos Observacionais como Assunto , Guias de Prática Clínica como Assunto , Síndrome da Realimentação/diagnóstico
12.
Children (Basel) ; 8(4)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917765

RESUMO

BACKGROUND: Multiple osteochondromas is a rare skeletal disorder characterized by the presence of osteocartilaginous protrusions causing bony deformities, especially around the knee. Guided growth by temporary hemiepiphyseal stapling is the treatment of choice to correct the deformity by modulating the residual physeal growth of the lower limbs. Although this procedure is increasingly practiced, inconclusive evidence exists regarding its effectiveness in children with multiple osteochondromas. The study aims to compare the outcomes of temporary hemiepiphyseal stapling for correcting genu valgum in children with multiple osteochondromas vs. idiopathic cases. METHODS: In this retrospective cohort study, we included patients admitted at a single institution from 2008 to 2018. A total of 97 children (77 idiopathic, 20 multiple osteochondromas) were enclosed, accounting for 184 limbs treated by temporary hemiepiphyseal stapling. We investigated if children with multiple osteochondromas had a similar successful rate of correction, rate of complications, and correction velocity compared to children with idiopathic genu valgum. RESULTS: Overall, 151 limbs (82%) achieved complete correction or overcorrection, with idiopathic cases having a significantly higher rate of success compared to pathologic cases (88% vs. 55%; p < 0.001). In addition, multiple osteochondromas children sustained a higher rate of major complications (p = 0.021) and showed significantly lower correction velocity (p = 0.029). CONCLUSION: Temporary hemiepiphyseal stapling is effective in both idiopathic and multiple osteochondromas children, although the latter often achieved incomplete correction, had a higher risk of complications, and required a longer time of stapling. We suggest to anticipate the timing of intervention; otherwise, children with multiple osteochondromas and severe valgus deformity, approaching skeletal maturity, could undergo combined femoral and tibial stapling.

13.
G Ital Cardiol (Rome) ; 22(4): 327-331, 2021 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-33783453

RESUMO

The allocation of clinical and economic resources is an emerging issue in health management. A useful update necessarily depends on the evaluation of long-term outcomes of clinical and surgical resources that can permit emphasis on all amendable fields, improve quality of care, and reduce health costs. The PRIORITY (PRedictIng long term Outcomes afteR Isolated coronary arTery bypass surgerY) study represents the first innovative step toward the updating of health management in a selected field, surgery for coronary artery disease, which is one of the most prevalent diseases and requires allocation of high-cost resources, although information on long-term outcomes is limited. The aims of the PRIORITY study are the identification of preoperative risk factors for long-term outcomes and the development of clinical and administrative preoperative scores that can guide clinicians and the national health system to more appropriate actions for increasing quality of care and reducing costs.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana , Doença da Artéria Coronariana/cirurgia , Humanos , Fatores de Risco , Resultado do Tratamento
15.
Br J Haematol ; 193(2): 280-289, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33476434

RESUMO

Treatment for follicular lymphoma (FL) in the elderly is not well standardized. A phase II, multicentre, single arm trial was conducted in this setting with a brief chemoimmunotherapy regimen. Treatment consisted in four monthly courses of rituximab, bendamustine and mitoxantrone (R-BM) followed by 4 weekly rituximab as consolidation; rituximab maintenance was not applied because the drug was not licensed at the time of enrolment. The primary endpoint was the complete remission rate (CR). Seventy-six treatment-naive FL patients (aged 65-80 and a "FIT" score, according to the Comprehensive Geriatric Assessment) were enrolled. CR was documented in 59/76 patients (78%), partial remission in 12 (16%) and stable/progressive disease in five (6%) with an overall response rate in 71/76 (94%). Median follow-up was 44 months with 3-year progression-free-survival (PFS) and overall-survival of 67% and 92% respectively. Nine deaths occurred, three of progressive disease. The regimen was well tolerated and the most frequent severe toxicity was neutropenia (18% of the cycles). Bcl-2/IGH rearrangement was found in 40/75 (53%) of evaluated patients. R-BM was highly effective in clearing polymerase chain reaction-detectable disease: 29/31 (96%) evaluated patients converted to bcl-2/IGH negativity at the end of treatment. A brief R-BM regimen plus rituximab consolidation is effective and safe in "FIT" elderly, treatment-naïve, FL patients, inducing high CR and molecular remission rates with prolonged PFS.


Assuntos
Cloridrato de Bendamustina/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Mitoxantrona/uso terapêutico , Rituximab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Quimioterapia de Consolidação/métodos , Feminino , Seguimentos , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Masculino , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Gradação de Tumores , Intervalo Livre de Progressão , Estudos Prospectivos , Indução de Remissão/métodos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Segurança , Inibidores da Topoisomerase II/administração & dosagem , Inibidores da Topoisomerase II/efeitos adversos , Inibidores da Topoisomerase II/uso terapêutico
16.
Leukemia ; 35(3): 787-795, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32782382

RESUMO

Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) were estimated from the time of salvage therapy. The previously described threshold of 24 months was used to define patients as early- or late-progressors (POD). Overall, 261 r/r MCL patients were included. Second-line regimens consisted of rituximab-bendamustine (R-B, 21%), R-B and cytarabine (R-BAC, 29%), ibrutinib (19%), and others (31%). The four groups were balanced in terms of clinicopathological features. Adjusting for age and early/late-POD, patients treated with R-BAC had significantly higher complete remission (63%) than comparators. Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7). In patients with early-POD (n = 127), ibrutinib was associated with inferior risk of death than comparators (HR 2.41 for R-B, 2.17 for others, 2.78 for R-BAC). In patients with late-POD (n = 134), no significant differences were observed between ibrutinib and bendamustine-based treatments. Ibrutinib was associated with improved outcome in early-POD patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/mortalidade , Recidiva Local de Neoplasia/mortalidade , Terapia de Salvação , Adulto , Idoso , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Agências Internacionais , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
17.
Lancet Haematol ; 8(1): e34-e44, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357480

RESUMO

BACKGROUND: Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population. METHODS: This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal. Eligible patients had Ann Arbor stage III or IV treatment-naive mantle cell lymphoma (or stage II plus bulky disease [≥5 cm] or B symptoms), and had evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). Patients were aged 18-59 years with Eastern Cooperative Oncology Group (ECOG) performance status 0-3, or aged 60-65 years with ECOG 0-2. After an optional prephase with vincristine and steroids (intravenous vincristine 1·4 mg/m2 on day 1, oral prednisone 100 mg [total dose] on days 1-5), patients were given three courses of R-CHOP (21-day cycle, intravenous rituximab 375 mg/m2 on day 1; intravenous doxorubicin 50 mg/m2, vincristine 1·4 mg/m2, and cyclophosphamide 750 mg/m2 on day 2; oral prednisone 100 mg/m2 on day 2-6). Patients then received one cycle of high-dose CTX (intravenous cyclophosphamide 4 g/m2 on day 1, intravenous rituximab 375 mg/m2 on day 4). After restaging, patients received two cycles of R-HD-cytarabine (high-dose intravenous cytarabine 2 g/m2 every 12 h on days 1-3, intravenous rituximab 375 mg/m2 on days 4 and 10). Patients with complete remission or partial remission proceeded to autologous HSCT and responding patients (complete remission or partial remission) with haematological recovery were randomly assigned (1:1) to receive 24 courses of oral lenalidomide maintenance (15 mg per day for patients with platelets >100 × 109 cells per L or 10 mg per day for platelets 60-100 × 109 cells per L, days 1-21 every 28 days) for 24 months, or observation. The primary endpoint was progression-free survival, measured in the randomised population. This study is registered with EudraCT (2009-012807-25) and ClinicalTrials.gov (NCT02354313). FINDINGS: Between May 4, 2010, and Aug 24, 2015, 303 patients were screened for inclusion and 300 patients were enrolled (median age 57 years, IQR 51-62; 235 [78%] male). 95 patients were excluded before randomisation, mostly due to disease progression, adverse events, and inadequate recovery. 104 patients were randomly assigned to the lenalidomide maintenance group and 101 patients to the observation group. 11 (11%) of 104 patients assigned to lenalidomide did not start treatment (3 withdrew, 6 adverse events or protocol breach, 2 lost to follow-up). At a median follow-up of 38 months after randomisation (IQR 24-50), 3-year progression-free survival was 80% (95% CI 70-87) in the lenalidomide group versus 64% (53-73) in the observation group (log-rank test p=0·012; hazard ratio 0·51, 95% CI 0·30-0·87). 41 (39%) of 104 patients discontinued lenalidomide for reasons including death or progression. Treatment-related deaths were recorded in two (2%) of 93 patients in the lenalidomide group (1 pneumonia, 1 thrombotic thrombocytopenic purpura), and one (1%) of 101 in the observation group (pneumonia). 59 (63%) of 93 patients in the lenalidomide group had grade 3-4 haematological adverse events versus 12 (12%) of 101 patients in the observation group (p<0·0001). 29 (31%) of 93 patients in the lenalidomide group and eight (8%) of 101 patients in the observation group had grade 3-4 non-haematological adverse events (p<0·0001), of which infections were the most common.Serious adverse events were reported in 22 (24%) of 93 patients in the lenalidomide group and five (5%) of 101 patients in the observation group. Pneumonia and other infections were the most common serious adverse events. INTERPRETATION: Despite non-negligibile toxicity, lenalidomide after autologous HSCT improved progression-free survival in patients with mantle cell lymphoma, highlighting the role of maintenance in mantle cell lymphoma. FUNDING: Fondazione Italiana Linfomi and Celgene.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Lenalidomida/administração & dosagem , Linfoma de Célula do Manto , Quimioterapia de Manutenção , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Lenalidomida/efeitos adversos , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Taxa de Sobrevida , Transplante Autólogo , Vincristina/administração & dosagem , Vincristina/efeitos adversos
19.
Front Immunol ; 12: 816231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35145514

RESUMO

Even with high-dose post-transplant cyclophosphamide (PT-Cy) which was initially introduced for graft-versus-host disease (GvHD) prevention in the setting of HLA-haploidentical transplantation, both acute and chronic GvHDs remain a major clinical challenge. Despite improvements in the understanding of the pathogenesis of both acute and chronic GvHDs, reliable biomarkers that predict their onset have yet to be identified. We recently studied the potential correlation between extracellular vesicles (EVs) and the onset of acute (a)GvHD in transplant recipients from related and unrelated donors. In the present study, we further investigated the role of the expression profile of membrane proteins and their microRNA (miRNA) cargo (miRNA100, miRNA155, and miRNA194) in predicting the onset of aGvHD in haploidentical transplant recipients with PT-Cy. Thirty-two consecutive patients were included. We evaluated the expression profile of EVs, by flow cytometry, and their miRNA cargo, by real-time PCR, at baseline, prior, and at different time points following transplant. Using logistic regression and Cox proportional hazard models, a significant association between expression profiles of antigens such as CD146, CD31, CD140a, CD120a, CD26, CD144, and CD30 on EVs, and their miRNA cargo with the onset of aGvHD was observed. Moreover, we also investigated a potential correlation between EV expression profile and cargo with plasma biomarkers (e.g., ST2, sTNFR1, and REG3a) that had been associated with aGVHD previously. This analysis showed that the combination of CD146, sTNFR1, and miR100 or miR194 strongly correlated with the onset of aGvHD (AUROC >0.975). A large prospective multicenter study is currently in progress to validate our findings.


Assuntos
Biomarcadores , Ciclofosfamida/uso terapêutico , Vesículas Extracelulares/metabolismo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Transplante Haploidêntico , Resultado do Tratamento , Adulto Jovem
20.
Cancers (Basel) ; 14(1)2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35008361

RESUMO

BACKGROUND: Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313). METHODS: We developed a score with a clustering algorithm applied to clinical variables. The candidate score was correlated to overall survival (OS) and validated in two independent data series from the European MCL Network (NCT00209222, NCT00209209); Results: Three groups of patients were significantly discriminated: Low, Intermediate (Int), and High risk (High). Seven discriminants were identified by a feature reduction approach: albumin, Ki-67, lactate dehydrogenase, lymphocytes, platelets, bone marrow infiltration, and B-symptoms. Accordingly, patients in the Int and High groups had shorter OS rates than those in the Low and Int groups, respectively (Int→Low, HR: 3.1, 95% CI: 1.0-9.6; High→Int, HR: 2.3, 95% CI: 1.5-4.7). Based on the 7 markers, we defined the engineered MCL international prognostic index (eMIPI), which was validated and confirmed in two independent cohorts; Conclusions: We developed and validated a ML-based prognostic model for MCL. Even when currently limited to baseline predictors, our approach has high scalability potential.

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