RESUMO
We conducted an observational study (FIRE) to understand the effectiveness and safety outcomes of ibrutinib in patients with chronic lymphocytic leukemia (CLL) in France, after a maximum follow-up of five years. Patients were included according to the French marketing authorization in 2016 (i.e. patients with relapsed or refractory CLL or to previously untreated CLL patients with deletion 17p and/or tumor protein p53 mutations unsuitable for chemoimmunotherapy) and could have initiated ibrutinib more than 30 days prior their enrolment in the study (i.e. retrospective patients) or between 30 days before and 14 days after their enrolment (i.e. prospective patients). The results showed that in the effectiveness population (N = 388), the median progression-free survival (PFS) was 53.1 (95% CI: 44.5-60.5) months for retrospective patients and 52.9 (95% CI: 40.3-60.6) months for prospective patients and no difference was shown between the PFS of patients who had at least one dose reduction versus the PFS of patients without dose reduction (p = 0.7971 for retrospective and p = 0.3163 for prospective patients). For both retrospective and prospective patients, the median overall survival was not reached. The most frequent treatment-emergent adverse event of interest was infections (57.6% retrospective; 71.4% prospective). A total of 14.6% of the retrospective patients and 22.4% of the prospective patients had an adverse event leading to death. Our findings on effectiveness were consistent with other studies and the fact that patients with dose reductions had similar PFS than patients without dose reduction is reassuring. No additional safety concerns than those already mentioned in previous studies could be noticed.Trial registration ClinicalTrials.gov, NCT03425591. Registered 1 February 2018 - Retrospectively registered.
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Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56-88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression-free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia-related changes (multilineage dysplasia, MDS-related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.
Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 4 , Predisposição Genética para Doença , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Translocação Genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Aberrações Cromossômicas , Análise Citogenética , Feminino , Estudos de Associação Genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/mortalidade , Transtornos Mieloproliferativos/terapia , PrognósticoRESUMO
Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cγ2 (PLCG2) genes. Mutational information for patients still on ibrutinib is limited. We report a study aimed to provide a "snapshot" of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least 3 years of treatment. Of 204 patients who initiated ibrutinib via an early-access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after 3 years and 57 provided a fresh blood sample. Thirty patients had a CLL clone ≥0.5 × 109/L, enabling next-generation sequencing (NGS); BTK and PLCG2 mutations were detected in 57% and 13% of the NGS samples, respectively. After median follow-up of 8.5 months from sample collection, the presence of a BTK mutation was significantly associated with subsequent CLL progression (P = .0005 vs no BTK mutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment.
Assuntos
Tirosina Quinase da Agamaglobulinemia/genética , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Fosfolipase C gama/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação , PiperidinasRESUMO
BACKGROUND: Monoclonal gammopathy is a biological reality encountered in approximately 1% of the general population. In the absence of clinical and biological signs, it is considered of undetermined significance; however, it can be a biological signature of a monoclonal lymphocytic or plasma-cell proliferation. Their localisation to the oral mucosa remains rare and difficult to diagnose, particularly in indolent forms that escape imaging techniques. CASE PRESENTATION: Here, we report the case of a 73-year-old woman with a history of IgM kappa gammopathy followed for 13 years. The patient did not have a chronic infection or an autoimmune disease, and all the biological investigations and radiological explorations were unremarkable during this period. The discovery of a submucosal nodule in the cheek led to the diagnosis of MALT lymphoma and regression of half of the IgM kappa level after resection. The review of the literature shows the dominance of clinical signs (i.e., a mass or swelling) in the diagnosis of primary MALT lymphomas of the oral cavity after surgical resection. CONCLUSIONS: Our case illustrates the role of examination of the oral cavity in the context of a monoclonal gammopathy. The absence of clinical and radiological evidence in favor of lymphoplasmacytic proliferation, does not exclude a primary indolent MALT lymphoma of the oral mucosa.
Assuntos
Linfoma de Zona Marginal Tipo Células B , Idoso , Feminino , Humanos , Tecido Linfoide , Boca , Mucosa Bucal , Infecção PersistenteRESUMO
Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event-free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high-risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, ß2-microglobulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was significantly shorter for hypercalcemic patients (P = .001). These associations with adverse prognostic factors translated into lower rates of EFS24 (HR = 1.66; 95% CI, 1.08-2.54) and shorter PFS (P = .0059) and OS (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters. These data suggest that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL.
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Hipercalcemia/epidemiologia , Hipercalcemia/mortalidade , Linfoma Difuso de Grandes Células B/diagnóstico , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , França/epidemiologia , Humanos , Hipercalcemia/terapia , Linfoma Difuso de Grandes Células B/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
Histological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88 L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88 L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88 L265P mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88 WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P = .003). Additionally, the MYD88 WT status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P = .001]), with a 5-year transformation rate of 16% for MYD88 WT vs 2.8% with MYD88 L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P < .001). In conclusion, the MYD88 WT status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.
Assuntos
Transformação Celular Neoplásica/genética , Linfoma , Mutação de Sentido Incorreto , Fator 88 de Diferenciação Mieloide/genética , Proteínas de Neoplasias/genética , Macroglobulinemia de Waldenstrom , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma/genética , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de Tempo , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/mortalidadeRESUMO
The mean age at diagnosis of chronic lymphocytic leukemia (CLL) is 72 years, with 22.8% of patients being older than 80 years. However, the elderly are underrepresented in clinical studies of CLL. We performed a retrospective study of CLL patients aged 80 years or older at the initiation of first-line therapy in hospitals affiliated with the French intergroup on CLL (French Innovative Leukemia Organization) between 2003 and 2013. Here, we describe the clinical and biological characteristics, treatment, and outcomes for 201 patients. The median age of the cohort was 83.2 years (80-92 years). The median Cumulative Index Rating Scale comorbidity score was 5 and the median creatinine clearance was 48 mL/min (Cockcroft-Gault formula). At treatment initiation, Binet stage was A (26.4%), B (27.9%), or C (40.3%). Therapy consisted mainly of chlorambucil (65.7%), bendamustine (10.5%), and rituximab (44.3%) as follows: chlorambucil alone (45.3%) or immunochemotherapy (48.3%) with rituximab + chlorambucil (22.7%), rituximab + bendamustine (10.4%), or rituximab + cyclophosphamide + dexamethasone (5.5%). The overall response rate was 66.2% with 31.8% clinical complete remission. The median overall and progression-free survival from treatment initiation was 53.7 and 18.3 months, respectively. These results suggest that treatment is feasible in this age group, even with immunochemotherapy. Thus, prospective trials should target this population and oncogeriatric evaluation and new targeted therapies should be part of such future trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Fatores Etários , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Aberrações Cromossômicas , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Mutação , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores Socioeconômicos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Atrial fibrillation (AF) occurs in 5-9% of patients treated with ibrutinib for chronic lymphocytic leukaemia (CLL); the clinical consequences and optimal management are unclear. We retrospectively studied 56 CLL patients who received ibrutinib and developed AF. Median time to onset was 3·8 months. AF was persistent in 35/56 (62%) cases despite treatment. Clinical consequences included: three episodes of severe cardiac failure (one fatal) and one stroke; eight non-thrombocytopenic patients (14%) experienced severe bleeding adverse events. Altogether, ibrutinib was permanently discontinued in 26/56 cases (46%). Data to guide optimal management are lacking and clinical practice guidelines are urgently needed.
Assuntos
Antineoplásicos/efeitos adversos , Fibrilação Atrial/etiologia , Leucemia Linfocítica Crônica de Células B/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Adenina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Gerenciamento Clínico , Feminino , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Piperidinas , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Estudos RetrospectivosAssuntos
Linfoma Difuso de Grandes Células B/genética , Mutação , Análise Citogenética , Progressão da Doença , França/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Prognóstico , Análise de SobrevidaAssuntos
Leucemia Linfocítica Crônica de Células B/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Feminino , França/epidemiologia , Humanos , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/genética , Resultado do TratamentoAssuntos
Anemia Hemolítica Autoimune , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Anemia Hemolítica Autoimune/epidemiologia , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/terapia , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , SARS-CoV-2RESUMO
We report our experience on bendamustine and rituximab (BR) combination in 26 patients with chronic lymphocytic leukemia (CLL) complicated by autoimmune hemolytic anemia (AIHA). At the time of BR initiation, 88% of the patients had already been treated for AIHA and CLL was progressive regardless of AIHA in all patients but one. Overall response rates were 81% for AIHA and 77% for CLL. Median time to next treatment was 28.3 months and 26.2 months for AIHA and CLL, respectively. BR therapy may represent a good and safe therapeutic option in this setting where adequate control of CLL seems important for long-term AIHA response.
Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Compostos de Mostarda Nitrogenada/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/mortalidade , Anemia Hemolítica Autoimune/patologia , Cloridrato de Bendamustina , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Análise de SobrevidaRESUMO
Only a minority of chronic lymphocytic leukemia (CLL) patients harboring a positive direct antiglobulin test (DAT) will develop autoimmune hemolytic anemia (AIHA). In a single institution cohort of 378 CLL patients, 56 patients (14.8%) had at least one positive DAT during the course of the disease, either at diagnosis or later. We found no relationship between the time of the first positive DAT and overall survival (OS). However, patients with a positive DAT who did not develop AIHA had the same adverse outcome as patients who developed AIHA. Of the patients who were in Binet stage A at diagnosis, those with a positive DAT had a significantly shorter OS, regardless of their IGHV mutational status, however, there was a strong association with VH1-69. By multivariate analysis, a positive DAT was found to be an independent adverse prognostic factor for OS. Thus, DAT represents a strong adverse prognostic factor and its determination should be repeated during follow-up.
Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Teste de Coombs , Leucemia Linfocítica Crônica de Células B/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/imunologia , Anemia Hemolítica Autoimune/mortalidade , Estudos de Coortes , Complemento C3d/análise , Interpretação Estatística de Dados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoRESUMO
We have investigated the potential of Raman microspectroscopy combined with supervised classification algorithms to diagnose a blood lymphoproliferative disease, namely chronic lymphocytic leukemia (CLL). This study was conducted directly on human blood smears (27 volunteers and 49 CLL patients) spread on standard glass slides according to a cytological protocol before the staining step. Visible excitation at 532 nm was chosen, instead of near infrared, in order to minimize the glass contribution in the Raman spectra. After Raman measurements, blood smears were stained using the May-Grünwald Giemsa procedure to correlate spectroscopic data classifications with cytological analysis. A first prediction model was built using support vector machines to discriminate between the two main leukocyte subpopulations (lymphocytes and polymorphonuclears) with sensitivity and specificity over 98.5%. The spectral differences between these two classes were associated to higher nucleic acid content in lymphocytes compared to polymorphonuclears. Then, we developed a classification model to discriminate between neoplastic and healthy lymphocyte spectra, with a mean sensitivity and specificity of 88% and 91% respectively. The main molecular differences between healthy and CLL cells were associated with DNA and protein changes. These spectroscopic markers could lead, in the future, to the development of a helpful medical tool for CLL diagnosis.
Assuntos
Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfócitos/classificação , Microespectrofotometria/métodos , Análise Espectral Raman/métodos , Humanos , Leucemia Linfocítica Crônica de Células B/sangueRESUMO
BACKGROUND: The rare descriptions, in the literature, of ocular infections due to Pasteurella multocida include: endophtalmitis, keratitis and corneal ulcers, Parinaud's oculoglandular syndrome, and conjunctivitis. Here, we report a rare case of rapidly evolving conjunctivitis due to Pasteurella multocida, occurring after direct inoculation with animal droplets in an immuno-compromised host. CASE PRESENTATION: A 69-year-old, Caucasian male was referred to our department with purulent conjunctivitis, occurring five days after chemotherapy for an angioimmunoblastic-T-cell-lymphoma, and thirty-three hours after being struck in his right eye by his sneezing Dachshund dog. Physical examination revealed purulent conjunctivitis of the right eye associated with inflammatory edema of both lids. Direct bacteriological examination of conjunctival secretions showed gram-negative bacilli and regular, grey non-hemolytic colonies appearing the next day on blood agar. The oxidase test was positive for these colonies. An antibiotherapy associating intravenous amoxicillin and amoxicillin/clavulanate was administered. The outcome was favorable in the next three days allowing discharge of the patient with amoxicillin (2 g tid per os). CONCLUSION: This case report may be of interest for infectious diseases, ophthalmology or oncology specialists, especially nowadays with chemotherapy being administered in day care centres, where unusual home pathogens can be encountered in health related infections. In this case, previous animal contact and conjunctival samples showing Enterobacteriaceae like colonies with positive oxidase test were two important clues which could help clinicians to make the diagnosis of Pasteurella conjunctivitis in every day practice.
Assuntos
Conjuntivite Bacteriana/microbiologia , Cães/microbiologia , Infecções Oculares Bacterianas/microbiologia , Hospedeiro Imunocomprometido , Infecções por Pasteurella/microbiologia , Pasteurella multocida/isolamento & purificação , Zoonoses/microbiologia , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Animais , Conjuntivite Bacteriana/diagnóstico , Conjuntivite Bacteriana/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Humanos , Infusões Intravenosas , Linfoma de Células T/patologia , Masculino , Infecções por Pasteurella/diagnóstico , Infecções por Pasteurella/tratamento farmacológico , Animais de Estimação , Inibidores de beta-Lactamases/uso terapêuticoAssuntos
Doenças Autoimunes , Doenças Hematológicas , Leucemia Linfocítica Crônica de Células B , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Quinazolinonas/administração & dosagem , Adenina/análogos & derivados , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/mortalidade , Intervalo Livre de Doença , Feminino , Doenças Hematológicas/tratamento farmacológico , Doenças Hematológicas/mortalidade , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Piperidinas , Taxa de SobrevidaRESUMO
Primary Central Nervous System Lymphoma (PCNSL) is an aggressive brain tumour with a median survival rarely exceeding 3 months without treatment when seen in association with advanced HIV. High dose methotrexate (HD-MTX) in association with combination antiretroviral therapy (cART) is the recommended chemotherapy. However, HD-MTX may be not feasible due to poor performance status and concerns about toxicity. The 2023 guidelines from the European Association of Neuro-Oncology recommend that for people living with HIV (PLWH) presenting with PCNSL who have morbidities and/or poor functional status precluding the safe use of HD-MTX, other agents with a more favorable toxicity profile such as temozolomide might be considered. However, reports of temozolomide use for PLWH presenting PCNSL are exceedingly rare and this recommendation is extrapolated from its use in immunocompetent patients. We report here an elderly man living with HIV, with PCNSL and poor performance status who achieved long lasting remission with temozolomide plus cART. Our case illustrates the potential effectiveness of temozolomide in association with cART as first line treatment for PCNSL in a patient with poor functional status.
RESUMO
Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with untreated RT of diffuse large B-cell lymphoma histology (NCT03931642). In this multicentre phase 2 study, patients without complete response (CR) after two cycles of R-CHOP were eligible to receive an 8-week blinatumomab induction via continuous vein infusion with stepwise dosing until 112 µg/day. The primary endpoint was the CR rate after blinatumomab induction and secondary endpoint included safety, response duration, progression-free and overall survival. Thirty-nine patients started the first cycle of R-CHOP, 25 of whom received blinatumomab. After blinatumomab induction, five (20%) patients achieved CR, four (16%) achieved partial response, and six (24%) were stable. Considering the entire strategy, the overall response rate in the full-analysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safety-set included fever (36%), anaemia (24%), and lymphopaenia (24%). Cytokine release syndrome (grade 1/2) was observed in 16% and neurotoxicity in 20% of patients. Blinatumomab demonstrated encouraging anti-tumour activity (the trial met its primary endpoint) and acceptable toxicity in patients with RT.
Assuntos
Anticorpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma Difuso de Grandes Células B , Prednisona , Rituximab , Vincristina , Humanos , Masculino , Feminino , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pessoa de Meia-Idade , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Idoso , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Vincristina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Resultado do TratamentoAssuntos
Substituição de Medicamentos/métodos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adenina/análogos & derivados , França , Humanos , Piperidinas , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Quinazolinonas/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness values above -0.015 at SSF = 2 were significantly associated with lower PFS, PFS 24, and TTNT. Kurtosis without filtration was an independent predictor of PFS (SSF = 0; HR = 1.22 (95% CI: 1.04, 1.44), p = 0.013), and TTNT (SSF = 0; hazard ratio = 1.23; 95% CI: 1.04, 1.46; p = 0.013). This study shows that pretreatment unenhanced CT texture analysis-derived tumor skewness and kurtosis may be used as predictive biomarkers of PFS and TTNT in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance.