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1.
Pediatr Blood Cancer ; 69(4): e29557, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35107876

RESUMO

Although children and young adults with Hodgkin's lymphoma usually have a favorable prognosis, patients with primary refractory disease and some subsets of relapsed patients still have a dismal outcome. Brentuximab vedotin (BV) in combination with bendamustine may represent a suitable salvage therapy; data on 32 patients aged less than 25 years were retrospectively analyzed. Patients received up to six cycles of treatment of BV 1.8 mg/kg on day 1 and bendamustine 90-120 mg/m2 on days 2 and 3. At the end of treatment, the overall response rate was 81%. The 3-year overall and progression-free survivals are 78.1% and 67%, respectively.


Assuntos
Doença de Hodgkin , Imunoconjugados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/efeitos adversos , Brentuximab Vedotin , Criança , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
Ann Hematol ; 99(12): 2773-2777, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32462330

RESUMO

Since July 2017, different generic imatinib formulations have been introduced in Italy for the treatment of patients with chronic myeloid leukemia (CML). We analyzed 168 chronic phase CML patients treated with branded imatinib for a median of 12 years (range 1-16) at a single institution who switched to a single generic formulation in order to assess the safety and impact on molecular response. The Sokal risk was low/intermediate/high in 63%, 33%, and 4% of patients, respectively. The median duration of generic imatinib treatment was 19 months (range 4-22). Twenty-seven percent of patients were in MMR and 73% were in deep molecular responses (MR4-4.5) at the time of the switch. After 12 months of treatment with generic imatinib, 140 patients were evaluable for response: 23.6% and 76.4% were respectively in MMR and in deep molecular response. When the degree of response was compared with the best molecular response observed with branded imatinib, it was found that 84% of patients maintained the response previously achieved, 6% improved it, and 10% of patients had a molecular fluctuation from the previous deep molecular response to MMR. Only 1 patient lost the MMR and no patient switched to another TKI for inefficacy. In terms of safety, 20% of patients reported new or worsening side effects, but only 2 patients returned to branded imatinib for toxicity. Our data show that the switch to generic imatinib in patients who have been previously treated with branded imatinib appears to maintain efficacy, although a proportion of patients experience new or worsening side effects.


Assuntos
Antineoplásicos/administração & dosagem , Substituição de Medicamentos/métodos , Medicamentos Genéricos/administração & dosagem , Mesilato de Imatinib/administração & dosagem , Leucemia Mieloide de Fase Crônica/diagnóstico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Substituição de Medicamentos/efeitos adversos , Medicamentos Genéricos/efeitos adversos , Dispepsia/induzido quimicamente , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
J Thromb Thrombolysis ; 49(3): 426-430, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31981040

RESUMO

Peripherally inserted central catheters (PICCs) for central venous access are frequently used in patients with hematological malignancies. Their use may be complicated by upper extremity deep venous thrombosis (UEDVT). Additionally, hematological patients are frequently thrombocytopenic and the optimal management of UEDVT in patients with thrombocytopenia is challenging and poorly standardized. We retrospectively analyzed 50 adult patients affected by hematological malignancies who presented a PICC-associated UEDVT. UEDVT treatment was compared in 3 groups: patients with a platelet count ≥ 50 × 109/l (group1) who underwent a therapeutic dose of low molecular weight heparin (LMWH) or fondaparinux 7.5 mg; patients with a platelet count < 50 × 109/l and ≥ 30 × 109/l (group 2) who were treated with a 50% reduced dose of LMWH or fondaparinux 5 mg; patients with platelets < 30 × 109/l (group 3) were observed and treated with anticoagulants when the count was > 30 × 109//l. At the onset of thrombosis, 36 patients were in group 1, 8 in group 2 and 6 in group 3. We observed no hemorrhagic or thrombotic complications related to the anticoagulant therapy; length of treatment was comparable between groups 1 and 2 (51 days group 1 vs 50 days group 2). Reduced doses of LMWH or fondaparinux may represent a safe and effective therapeutic approach in patients with moderate thrombocytopenia (< 50 × 109/l and ≥ 30 × 109/l) and a PICC-associated UEDVT.


Assuntos
Anticoagulantes/administração & dosagem , Cateterismo Venoso Central/efeitos adversos , Catéteres/efeitos adversos , Fondaparinux/administração & dosagem , Neoplasias Hematológicas , Heparina de Baixo Peso Molecular/administração & dosagem , Tromboembolia Venosa/tratamento farmacológico , Adulto , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia
5.
Ital J Pediatr ; 49(1): 41, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36978099

RESUMO

BACKGROUND: In 2016, we performed a one-day investigation to analyze the prevalence of pain, pain intensity, and pain therapy in the Departments of Surgery and Onco-Hematology of the Ospedale Pediatrico Bambino Gesù. To improve the knowledge gap highlighted in the previous study, refresher courses and even personalized audits have been carried out during these years. The purpose of this study is to evaluate if, after 5 years, there have been improvements in the management of pain. METHODS: The study was conducted on 25 January 2020. Pain assessment, pain therapies, pain prevalence and intensity in the preceding 24 h and during the recovery period were recorded. Pain outcomes were compared with previous audit results. RESULTS: Out of the 63 children with at least one documented pain assessment (starting from 100 eligible), 35 (55.4%) experienced pain: 32 children (50.7%) experienced moderate /severe pain while 3 patients (4%) felt mild pain. In the preceding 24 h, 20 patients (31.7%) reported moderate/severe pain while 10 (16%) reported moderate or severe pain during the interview. The average value of the Pain Management Index (PMI) was - 1.3 ± 0.9 with a minimum of -3 and a maximum of 0. 28 patients (87%) undergoing analgesic therapy for moderate/severe pain had a PMI of less than 0 (undertreated pain), while 3 patients (13%) scored value of 0 or higher (adequate pain therapy), 4 patients (12.5%) received multimodal analgesia with opioids and 2 patients (6%) opioids alone. Time-based therapy was prescribed to 20 patients (62.5%), intermittent therapy was prescribed to 7 patients (22%) and 5 patients (15.5%) did not receive any therapy. The prevalence of pain was higher during hospitalization and 24 h before the interview, while at the time of the interview, the proportion was the same. In this audit, the daily prescription modality of the therapy had some improvements (time-based: 62.5% vs. 44%; intermittent: 22%vs 25%; no therapy: 15.5% vs. 31%). CONCLUSION: Pain management in hospitalized children constantly requires special daily attention from health professionals aimed at mitigating the components of intractable pain and resolving those of treatable pain. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number (NCT04209764), registered 24 December 2019, https://clinicaltrials.gov/ct2/show/NCT04209764?term=NCT04209764&draw=2&rank=1 .


Assuntos
Hospitais Pediátricos , Manejo da Dor , Adolescente , Criança , Humanos , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Dor/epidemiologia , Manejo da Dor/métodos , Prevalência
6.
Oncol Rep ; 48(6)2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36321792

RESUMO

Novel therapeutic strategies are needed for paediatric patients affected by Acute Myeloid Leukaemia (AML), particularly for those at high-risk for relapse. MicroRNAs (miRs) have been extensively studied as biomarkers in cancer and haematological disorders, and their expression has been correlated to the presence of recurrent molecular abnormalities, expression of oncogenes, as well as to prognosis/clinical outcome. In the present study, expression signatures of different miRs related both to presence of myeloid/lymphoid or mixed-lineage leukaemia 1 and Fms like tyrosine kinase 3 internal tandem duplications rearrangements and to the clinical outcome of paediatric patients with AML were identified. Notably, miR-221-3p and miR-222-3p resulted as a possible relapse-risk related miR. Thus, miR-221-3p and miR-222-3p expression modulation was investigated by using a Bromodomain­containing protein 4 (BRD4) inhibitor (JQ1) and a natural compound that acts as histone acetyl transferase inhibitor (curcumin), alone or in association, in order to decrease acetylation of histone tails and potentiate the effect of BRD4 inhibition. JQ1 modulates miR-221-3p and miR-222-3p expression in AML with a synergic effect when associated with curcumin. Moreover, changes were observed in the expression of CDKN1B, a known target of miR-221-3p and miR-222-3p, increase in apoptosis and downregulation of miR-221-3p and miR-222-3p expression in CD34+ AML primary cells. Altogether, these findings suggested that several miRs expression signatures at diagnosis may be used for risk stratification and as relapse prediction biomarkers in paediatric AML outlining that epigenetic drugs, could represent a novel therapeutic strategy for high-risk paediatric patients with AML. For these epigenetic drugs, additional research for enhancing activity, bioavailability and safety is needed.


Assuntos
Curcumina , Leucemia Mieloide Aguda , MicroRNAs , Humanos , Criança , Proteínas Nucleares/metabolismo , Curcumina/farmacologia , Histonas , Fatores de Transcrição/metabolismo , Recidiva Local de Neoplasia , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Apoptose , Proteínas de Ciclo Celular/metabolismo
7.
Front Oncol ; 11: 794498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966688

RESUMO

Langerhans cell histiocytosis (LCH) is due to aberrant monoclonal proliferation and accumulation of dendritic cells, ranging from a self-limiting local condition to a rapidly progressive multisystem disease with poor prognosis. Pathogenic cells originate from a myeloid-derived precursor characterized by an activation of the MAPK/ERK signaling pathway in about 70% of cases. In particular, BRAF V600E mutation is usually associated with a more severe clinical course and poor response to chemotherapy. We report on a newborn with multisystem LCH in life-threatening medical conditions. At diagnosis, the patient was successfully treated with the early association of BRAF inhibitor Vemurafenib to standard chemotherapy representing a new approach in first-line treatment. A rapid clinical improvement with a prompt fever regression from day 2 and complete resolution of skin lesions by week 2 were observed; laboratory data normalized as well. Vemurafenib was discontinued after 12 months of treatment. No signs of relapse occurred after 12 months of discontinuation. This case indicates that early combination of target therapy with standard treatment may induce rapid response and prolonged disease remission without significant toxicities in infants. This approach represents a valid and safe option as first-line treatment in multisystem disease, especially in high-risk patients.

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