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1.
Adv Hematol ; 2022: 5581772, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126524

RESUMO

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505.

3.
Surg Neurol Int ; 12: 387, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513154

RESUMO

BACKGROUND: Burkitt's lymphoma is a non-Hodgkin B-cell lymphoma, occurring mostly in Equatorial Africa. According to the WHO, classification is three different variants: sporadic, endemic, and immunodeficient-associated. Here, we present a patient with "sporadic" primary epidural Burkitt's lymphoma resulting in chronic low back pain (LBP). CASE DESCRIPTION: A 63-year-old female presented with a 2-month history of LBP and the left lower extremity sciatica. The thoracolumbar MRI showed a L5 irregular, osteolytic epidural lesion that was hypointense on T1-weighted images, hyperintense on STIR studies, and inhomogeneously enhanced with contrast. Additional hypointense lesions were also seen at the L2, L3, and L4 levels. The patient underwent a L4-L5 laminectomy for piecemeal epidural resection of tumor, and a L4-S1 transpedicular screws/rod fusion. In addition, a L2-L3 radiofrequency ablation was performed. The histological examination documented a primary "sporadic" spinal Burkitt's lymphoma. The patient subsequently was treated with both radiotherapy/chemoradiotherapy. CONCLUSION: Primary "sporadic" spinal Burkitt's lymphoma is rare. Following tumor resection, adjunctive radiation and chemotherapy are typically warranted.

4.
Ann Hematol ; 100(10): 2547-2556, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34327561

RESUMO

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Adulto Jovem
6.
Blood ; 138(7): 571-583, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-33889952

RESUMO

The efficacy and safety of thrombopoietin receptor agonists (TRAs) in older patients with primary immune thrombocytopenia (ITP) are unknown. We investigated TRA response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROTs) in 384 patients with ITP aged ≥60 years. After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectively, achieved a response; 66.7% maintained the response (median follow-up, 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; although no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. Thirty-four major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, while on TRAs and were associated with thrombosis history (subdistribution hazard ratio, 2.04, P = .05) and platelet count <20 × 109/L (subdistribution hazard ratio, 1.69; P = .04), respectively, at TRA start. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but 1 during persisting TRA treatment (incidence rate, 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRAs; 53 (13.8%) patients maintained SROTs, which were associated with TRA discontinuation in complete response (P < .001). Very old age (≥75 years; 41.1%) was associated with the more frequent start of TRAs in the persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in older patients with ITP, with no fatal hemorrhages and with SROTs in a significant portion of patients. Caution is warranted in patients with a history of thrombosis, and a careful risk/benefit balance should be considered.


Assuntos
Benzoatos , Hidrazinas , Púrpura Trombocitopênica Idiopática , Pirazóis , Receptores Fc , Receptores de Trombopoetina/antagonistas & inibidores , Proteínas Recombinantes de Fusão , Trombopoetina , Trombose , Idoso , Idoso de 80 Anos ou mais , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/mortalidade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Estudos Retrospectivos , Trombopoetina/administração & dosagem , Trombopoetina/efeitos adversos , Trombose/induzido quimicamente , Trombose/mortalidade
7.
Am J Hematol ; 96(8): E269-E272, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33878220
8.
Br J Haematol ; 193(2): 386-396, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33618438

RESUMO

Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off-treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO-RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end-point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end-points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty-one patients were evaluable. Primary end-point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL-10, IL-4, TNF-α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response.


Assuntos
Benzoatos/uso terapêutico , Redução da Medicação/estatística & dados numéricos , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/uso terapêutico , Receptores de Trombopoetina/agonistas , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzoatos/administração & dosagem , Benzoatos/toxicidade , Citocinas/imunologia , Redução da Medicação/métodos , Feminino , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/toxicidade , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/diagnóstico , Pirazóis/administração & dosagem , Pirazóis/toxicidade , Receptores de Trombopoetina/imunologia , Indução de Remissão , Suspensão de Tratamento/estatística & dados numéricos
9.
Am J Hematol ; 96(5): E168-E171, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33580969
10.
Ann Hematol ; 100(3): 653-659, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33495923

RESUMO

The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18 years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according to the administration of AP: (1) treated with AP (N= 34; 51%) and (2) not treated with AP (N=33, 49%). AP consisted of combined trimethoprim/sulfamethoxazole (TMP/SMX) and acyclovir (AC) in half of patients. TPM/SMX as a single agent was adopted in 32% patients and one patient received only AC. Overall, infections were experienced in 15% of patients during follow-up with a similar proportion in the 2 groups (treated and not treated) of patients (14.7% vs 15%). Clinical course of infections was however, less severe in patients treated with AP, where all infections were grade 2 and did not require hospitalization. In neither group of patients was reported Pneumocystis pneumonia. In conclusion, despite the absence of clear evidence, our analysis shows that AP in patients with ITP receiving RTX is frequently adopted, even if in the absence of well-defined criteria. Prophylaxis administration is quite consistent within the same haematological Center; thus, it seems related to clinicians' experience.


Assuntos
Antibioticoprofilaxia , Infecções Oportunistas/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/estatística & dados numéricos , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/epidemiologia , Estudos Retrospectivos , Adulto Jovem
11.
Haematologica ; 106(1): 291-294, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32107338
12.
Leukemia ; 35(1): 235-238, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32286543
13.
Eur J Haematol ; 106(4): 493-499, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33378569

RESUMO

OBJECTIVES: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only. METHODS: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study. RESULTS: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.5, 95% CI = 0.36-0.71) although with some limitations due to the non-randomized and retrospective nature of the study and to the lower number of patients in the IDELA-R group (112 cases) related to the current prescribing practice. To overcome the potential problem of confounding by indication, we adjusted the association between the type of therapy and mortality for all variables significantly associated with OS at Cox univariate analysis. Furthermore, those variables, differently distributed between the two study groups, were introduced into the multivariate Cox model to improve the effectiveness of the analysis. By introducing all these variables into the multiple Cox regression model, we confirmed the protective effect of IB vs IDELA-R (HR = 0.67, 95% CI = 0.45-0.98, P = .04) independent of potential confounders. CONCLUSIONS: Although our analysis presents some constraints, that is, the unavailability of additional potential confounders, and the retrospective nature of the study, this observation may be of help for the daily clinical practice, particularly in the absence of randomized trials comparing the two schedules.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adenina/administração & dosagem , Adenina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoglobulinas/genética , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/etiologia , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Piperidinas/administração & dosagem , Modelos de Riscos Proporcionais , Purinas/administração & dosagem , Quinazolinonas/administração & dosagem , Recidiva , Retratamento , Rituximab/administração & dosagem , Resultado do Tratamento
15.
J Blood Med ; 11: 251-258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801981

RESUMO

PURPOSE: Insufficient knowledge of primary immune thrombocytopenia purpura (ITP) in the elderly, together with a lack of clinical trial data, has resulted in wide variation in treatments. Here, we present a study focused on clinical characteristics of ITP in older subjects at diagnosis integrated with the subsequent course of the disease and treatment history. METHODS: In a retrospective monoinstitutional study, we evaluated >65-year-old patients with primary ITP. Clinical characteristics at the time of diagnosis were described and analyzed. We aimed to delineate whether subsequent lines of therapy influenced the number of relapses. In addition to initial regimens, we reported subsequent treatments and the impact on relapse trends. RESULTS: A total of 50 patients (56% males, mean age 78 years) were included. With regard to clinical variables at diagnosis, statistical significance was found for Eastern Cooperative Oncology Group performance status 1 (46% of patients, p<0.0001), presence of three comorbidities (36% of patients, p<0.0001), World Health Organization grade 0 bleeding (46%, p=0.0001), and World Health Organization grade 1 bleeding (42%, p=0.0009). For bleeding sites, the most frequent were skin or mucosa (40%, p=0.0477). A decrease in platelet count was correlated with moderate or severe bleeding (ρ=-0.52, p=0.0001) and viscera or skin/mucosa + viscera site (ρ=-0.50, p=0.0002). Finally, a decreasing number of patients required treatment from first-line therapy to sixth (p<0.0001). Relapse was most frequent before second-line therapy (54%, p<0.0001) and less frequent before fivth and sixth (4%, p=0.0072; 2%, p=0.0027). CONCLUSION: ITP in older age poses considerable challenges, so specific management strategies should be considered to optimize outcomes. Our findings provide evidence of an inverse relationship between lines of therapy and timing of relapses. This study does not exclude the possibility that agents used after first-line therapy may have an impact on the response and modify the unfavorable course of ITP.

16.
Eur J Haematol ; 104(6): 581-587, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32107795

RESUMO

OBJECTIVE AND METHODS: In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed. RESULTS: The median number of previous treatments was 2 (1-4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1 and 2 of a 21-day cycle. The median number of BvB cycles was 4 (2-7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow-up of 19 months (5-47), median PFS was 18 months (95%CI: 23-29), and the 2-year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G > 2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%). CONCLUSION: Our real-world results suggest that BvB is an effective third-line rescue and bridge-to-transplant regimen for RR-cHL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Brentuximab Vedotin/administração & dosagem , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Recidiva , Resultado do Tratamento , Adulto Jovem
17.
Hematol Oncol ; 37(4): 447-455, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385337

RESUMO

Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real-world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient-level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first-line decitabine therapy at the registered schedule of 20 mg/m2 /iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all-cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy-one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable-intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse-free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7-16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13-2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06-1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first-line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.


Assuntos
Decitabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Causas de Morte , Decitabina/efeitos adversos , Progressão da Doença , Feminino , Humanos , Infecções/etiologia , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Masculino , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Estudos Observacionais como Assunto/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Resultado do Tratamento
18.
Am J Hematol ; 93(1): 58-64, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28983953

RESUMO

Sequential use of the TPO-RAs romiplostim and eltrombopag in ITP patients failing either agent was retrospectively evaluated to assess efficacy and impact of clinical characteristics on outcome. Patients were grouped into 5 categories: efficacy issues: 1st TPO-RA failure; loss of response; non-efficacy issues: platelet fluctuations; patient's preference; adverse event development. Either one TPO-RA sequence was analyzed at 3 month and at last follow-up. 106/546 patients on TPO-RA underwent switch and 65% achieved, regained or maintained a short- term response independent of switch sequence, gender or age; lower response rates were associated with lines of previous therapy; disease duration lowers probability to respond. Clinically, patients switched for efficacy issue did not differ from those switched for non-efficacy issues. Response was achieved/regained in 57.8% of patients switched for efficacy issues, the lowest response rates were observed in non-responders to 1st TPO-RA; 80% of patients switched for non-efficacy issues maintained a response. Platelet fluctuation resolved in 44.4%. Of the 49 patients evaluable for long-term outcome, 27 were in response on therapy; 16 discontinued the TPO-RA for reasons other than efficacy, while only 6 were non responders. We confirm the efficacy of TPO-RA switch; once achieved, response to the 2nd TPO-RA seems durable.


Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores de Trombopoetina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/patologia , Receptores de Trombopoetina/agonistas , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
20.
Oncotarget ; 7(41): 67333-67346, 2016 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-27637084

RESUMO

PURPOSE: Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL. EXPERIMENTAL DESIGN: First, N-HL function was evaluated in vitro, showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training (N = 40) and validation (N = 78) sets. RESULTS: s-Arg-1 was higher in patients with advanced stage (p = 0.045), B-symptoms (p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2.Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012).Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% (p = 0.0004). CONCLUSIONS: We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.


Assuntos
Antineoplásicos/uso terapêutico , Arginase/sangue , Biomarcadores Tumorais/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/enzimologia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Neutrófilos/imunologia , Prognóstico , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
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