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Blood Cancer J ; 11(8): 142, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376633


This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.

Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/administração & dosagem , Comorbidade , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto Jovem
Blood Adv ; 5(1): 176-184, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33570629


CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD <10-3 was achieved in 57% of complete response (CR)/CR with incomplete hematological recovery (CRi) patients. Only the presence of mutated TP53 (P = .02) or PTPN11 (P = .004) predicted lower response in multivariate analysis. Interestingly, high-risk molecular prognosis subgroups defined by 2017 European LeukemiaNet risk stratification, including ASXL1 and RUNX1 mutations, were not associated with a significantly lower response rate using CPX-351. With a median follow-up of 8.6 months, median overall survival (OS) was 16.1 months. Thirty-six patients underwent allogeneic stem cell transplantation with a significantly longer median OS compared with nontransplanted patients (P < .001). In multivariate analyses, only spliceosome mutations were associated with better OS (P = .04). In comparison with intensive chemotherapy, there was no difference in OS for patients <60 years. These data confirm the efficacy and safety of CPX-351 in high-risk AML (t-AML and MRC-AML) in a real-life setting. CPX-351 is a treatment of choice for patients aged ≥60 years.

Citarabina , Leucemia Mieloide Aguda , Adulto , Idoso , Daunorrubicina , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Estudos Retrospectivos
Clin Lymphoma Myeloma Leuk ; 20(12): 791-796, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32741743


BACKGROUND: More than one-third of patients with acute myeloid leukemia (AML) will relapse after allogenic hematopoietic cell transplant (allo-HCT). The main challenge is to overcome disease resistance to achieve a new complete remission while avoiding excessive toxicity. Gemtuzumab ozogamicin (GO), a conjugate of calicheamicin linked to the humanized monoclonal anti-CD33 antibody, has been used for refractory or relapsed AML with promising response rates, but liver toxicity of GO has long been considered a limiting factor. PATIENTS AND METHODS: We included 18 consecutive patients with AML relapsing after a first allo-HCT and treated with fractioned GO (fGO) and intensive chemotherapy. The median age was 40 years (range, 18-65). RESULTS: The overall response rate was 72% (13/18), including 7 complete remissions. No death was attributed to treatment toxicity. The main liver toxicity was transient and consisted of transaminase level elevation and hyperbilirubinemia. No cases of veno-occlusive disease were observed after the GO treatment. From the time of salvage treatment initiation, 1- and 2-year OS rates were 54% (95% confidence interval, 28%-74%) and 42% (95% confidence interval, 19%-63%), respectively. CONCLUSIONS: Our study suggests the feasibility, efficacy, and safety of an fGO-based salvage regimen combined with intensive chemotherapy in patients with CD33+ AML in the case of early relapse after an allo-HCT.

Oncotarget ; 11(26): 2560-2570, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32655840


Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of BCR-ABL1 transcript as a result of reciprocal translocation between chromosome 9 and 22. The most common transcripts subtypes are e13a2 (b2a2) and e14a2 (b3a2). The prognostic impact of the type of BCR-ABL1 transcript has been the subject of controversies over time. In the imatinib era, several studies have suggested a deeper and faster response in patients expressing e14a2. However, the impact on response after first line therapy with a second-generation tyrosine kinase inhibitor, nilotinib, is unknown. We retrospectively evaluated 118 patients newly diagnosed with chronic phase CML and treated frontline with nilotinib inside or outside clinical trial in five French centers. Only patients expressing e14a2 or e13a2 transcripts alone were analyzed. At baseline, 55.3% expressed e14a2, 44.7% expressed e13a2. The median age was 51 years and median follow-up was 49 months. Relative risks of CML at diagnosis were similar according to the ELTS score (p = .87). Complete hematological response and complete cytogenetic response rates were similar among groups. Patients expressing e14a2 transcripts compared to e13a2 transcripts had deeper and faster molecular responses, when considering MMR (100% vs 84.1%, p = .007) with a median time of 6.7 and 17.1 months or MR4.5 (100% vs 59.9%, p = .005) with a median time of 39.7 and 70.9 months, respectively. A sustained treatment free remission was observed in 10/10 patients with e14a2 versus 1/3 with e13a2 transcript (p = .04). In conclusion, even treated with nilotinib first line, patients with chronic phase CML expressing BCR-ABL1 e13a2 transcript have a lower rate of deep molecular responses.

Transfusion ; 57(7): 1717-1723, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28439927


BACKGROUND: Patients with hematologic malignancies are at high risk for both thrombosis and bleeding. During the prolonged periods of thrombocytopenia experienced by patients who are receiving intensive chemotherapy, clinicians often hesitate to prescribe any protection against thrombosis. In case of anticoagulant prescription, it is the prescribers' responsibility to weigh risks and benefits for each patient. Current guidelines exist but do not take into account types of thrombosis, patients' comorbidities, or previous bleeding events. STUDY DESIGN AND METHODS: We proposed to gain insight into hematologists' beliefs about antithrombotic prescription in hematologic malignancy patients, to design future clinical trials. Therefore, we conducted a survey in France to evaluate the practices among a panel of hematologists. RESULTS: We found that more than 92% of the respondents prescribed therapeutic anticoagulation in case of pulmonary embolism or deep venous thrombosis. In the case of therapeutic anticoagulation, only 64% of the physicians reconsidered treatment under a platelet threshold of 50 × 109 /L. None of the respondents decided to renounce treatment, nor to discontinue it because of thrombocytopenia, except in distal venous thrombosis or superficial vein thrombosis. One-fifth of clinicians proposed the insertion of a vena cava filter. CONCLUSION: As observed in the United States and Canada, we noticed discrepancies between recommendations and current practices in France. This highlights the urgent need to conduct studies to evaluate both efficacy and safety of antithrombotics in patients with hematologic cancer and thrombocytopenia.

Antineoplásicos/efeitos adversos , Fibrinolíticos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Transfusão de Plaquetas , Trombocitopenia/terapia , Neoplasias Hematológicas/sangue , Humanos , Trombocitopenia/induzido quimicamente