RESUMO
Chromosomal translocations have long been known for their association with malignant transformation, particularly in hematopoietic disorders such as B-cell lymphomas. In addition to the physiological process of maturation, which creates double strand breaks in immunoglobulin gene loci, environmental factors including the Epstein-Barr and human immunodeficiency viruses, malaria-causing parasites (Plasmodium falciparum), and plant components (Euphorbia tirucalli latex) can trigger a reorganization of the nuclear architecture and DNA damage that together will facilitate the occurrence of deleterious chromosomal rearrangements.
Assuntos
Linfócitos B/metabolismo , Linfócitos B/patologia , Transformação Celular Neoplásica , Translocação Genética/genética , Dano ao DNA , Euphorbia/metabolismo , HIV/metabolismo , Herpesvirus Humano 4/metabolismo , Humanos , Plasmodium falciparum/metabolismoRESUMO
BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).
Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Quimioterapia de Indução , Análise de Intenção de Tratamento , Linfoma de Célula do Manto/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Indução de Remissão , Rituximab , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
As a promising alternative to bone marrow aspiration (BMA), mutational profiling on blood-derived circulating cell-free tumor DNA (cfDNA) is a harmless and simple technique to monitor molecular response and treatment resistance of patients with refractory/relapsed multiple myeloma (R/R MM). We evaluated the sensitivity and specificity of cfDNA compared to BMA CD138 positive myeloma plasma cells (PCs) in a series of 45 R/R MM patients using the 29-gene targeted panel (AmpliSeq) NGS. KRAS, NRAS, FAM46C, DIS3, and TP53 were the most frequently mutated genes. The average sensitivity and specificity of cfDNA detection were 65% and 97%, respectively. The concordance per gene between the two samples was good to excellent according to Cohen's κ coefficients interpretation. An increased number of mutations detected in cfDNA were associated with a decreased overall survival. In conclusion, we demonstrated cfDNA NGS analysis feasibility and accuracy in R/R MM patients who may benefit from early phase clinical trial.
Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Sequenciamento de Nucleotídeos em Larga Escala , Mieloma Múltiplo , Mutação , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Sensibilidade e Especificidade , Idoso de 80 Anos ou mais , Adulto , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Análise Mutacional de DNA/métodos , Prognóstico , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The kinesin spindle protein Eg5 is involved in mitosis, and its inhibition promotes mitotic arrest. EMD 534085, a potent, reversible Eg5 inhibitor, demonstrated significant preclinical antitumor activity. METHODS: This first-in-man, single-center, open-label, phase I dose-escalation study (3 + 3 design) investigated EMD 534085 safety, pharmacokinetics and antitumor activity in refractory solid tumors, Hodgkin's lymphoma, or non-Hodgkin's lymphoma. EMD 534085 (starting dose 2 mg/m²/day) was administered intravenously every 3 weeks. Doses were escalated in 100% steps in successive cohorts of 3 patients until grade 2 toxicity occurred, followed by 50% until the first dose-limiting toxicity (DLT) arose. If <2 of 6 patients experienced a DLT, doses were further increased by 25%. Dose-escalation was stopped if a DLT occurred in ≥2 of 6 patients. RESULTS: Forty-four patients received EMD 534085. Median treatment duration was 43 days (range, 21-337). Thirty-eight patients (86%) received ≥2 cycles. DLTs were grade 4 neutropenia (1 patient each at 108 and 135 mg/m²/day), and grade 3 acute coronary syndrome with troponin I elevation (1 patient at 135 mg/m²/day). The maximum tolerated dose (MTD) was 108 mg/m²/day. The most common treatment-related adverse events were asthenia (50%) and neutropenia (32%). EMD 534085 appeared to have linear pharmacokinetics. Increase in phospho-histone H3 positive cells in paired pre- and on-treatment biopsies showed evidence of target modulation. No complete or partial responses were observed. Best response was stable disease in 23 patients (52%). CONCLUSIONS: EMD 534085 appeared to be well tolerated; MTD was 108 mg/m²/day. Preliminary antitumor results suggested limited activity in monotherapy.
Assuntos
Antineoplásicos/administração & dosagem , Cinesinas/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Quinolinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Esquema de Medicação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/patologia , Quinolinas/sangue , Quinolinas/farmacocinética , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some reports showed increased risk of bacterial infection in this context. In onco-hematology, there are few data about the occurrence of infection after administration of an anti-IL6/IL6R for CRS. METHODS: We retrospectively reviewed all consecutive patients treated in Gustave Roussy Cancer Campus between 2018 and 2021, who received anti-IL6/IL6R for CRS due to bsAb in phase I clinical trials or adoptive cellular therapy (ACT). We constituted a control group including all the patients treated in the same clinical trials or standard of care ACT, naïve of anti-IL6/IL6R. RESULTS: Fifty-two patients have been included. In the anti-IL6/IL6R group (n = 26), five patients developed a grade 2 to 5 infection within a month after anti-IL6/IL6R treatment, including two grade 5 infections. In the control group (n = 26), only one patient had a grade 3 infection. The two patients who had grade 5 infections were treated for diffuse large B cell lymphoma (DLBCL), one with bsAb and the other with CAR T cell. Fifty percent (3/6) of DLBCL patients who received an anti-IL6/IL6R presented an infection, one of which was a grade 5. In solid tumor patients treated with bsAb and anti-IL6/IL6R, only one patient (/9, 11%) developed a grade 2 viral infection. CONCLUSION: It seems that the use of anti-IL6/IL6R in CRS secondary to bsAb administration in solid tumors patients does not significantly increase the risk of infection, as opposed to DLBCL patients where secondary infection might be a concern.
Assuntos
Anticorpos Biespecíficos , Linfoma Difuso de Grandes Células B , Humanos , Síndrome da Liberação de Citocina/induzido quimicamente , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/tratamento farmacológicoRESUMO
PURPOSE: Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression. MATERIAL AND METHODS: Observational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000-2021). RESULTS: Between 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range=[1-216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47-90%) of patients. The median PFS was of 36 months (95% CI 24-NA) and 5 years OS estimate was 79% (95% CI 62-100%). Two patients developed a relapse at a second epidural site. CONCLUSION: FL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.
Assuntos
Neoplasias Epidurais , Linfoma Folicular , Adulto , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina , Neoplasias Epidurais/tratamento farmacológico , Incidência , Linfoma Folicular/radioterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Sequential tumour biopsies are of potential interest for the rational development of molecular targeted therapies. PATIENTS AND METHODS: From June 2004 to July 2009, 186 patients participated in 14 phase I clinical trials in which sequential tumour biopsies (13 trials) and/or sequential normal skin biopsies (6 trials) were optional. All patients had to sign an independent informed consent for the biopsies. RESULTS: Tumour biopsies were proposed to 155 patients and 130 (84%) signed the consent while normal skin biopsies were proposed to 70 patients and 57 (81%) signed the consent. Tumour biopsies could not be carried out in 41 (31%) of the 130 consenting patients. Tumour biopsies were collected at baseline in 33 patients, at baseline and under treatment in 56 patients. Tumour biopsies were obtained using an 18-gauge needle, under ultrasound or computed tomography guidance. Only nine minor complications were recorded. Most tumour biopsy samples collected were intended for ancillary molecular studies including protein or gene expression analysis, comparative genomic hybridization array or DNA sequencing. According to the results available, 70% of the biopsy samples met the quality criteria of each study and were suitable for ancillary studies. CONCLUSIONS: In our experience, the majority of the patients accepted skin biopsies as well as tumour biopsies. Sequential tumour and skin biopsies are feasible and safe during early-phase clinical trials, even when patients are exposed to anti-angiogenic agents. The real scientific value of such biopsies for dose selection in phase I trials has yet to be established.
Assuntos
Pesquisa Biomédica/métodos , Ensaios Clínicos Fase I como Assunto/efeitos adversos , Ensaios Clínicos Fase I como Assunto/métodos , Neoplasias/patologia , Aceitação pelo Paciente de Cuidados de Saúde , Pele/patologia , Adolescente , Adulto , Idoso , Algoritmos , Biópsia/efeitos adversos , Biópsia/métodos , Biópsia/psicologia , Biópsia/estatística & dados numéricos , Ensaios Clínicos Fase I como Assunto/psicologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Segurança do Paciente/estatística & dados numéricos , Adulto JovemRESUMO
INTRODUCTION: Primary AL amyloid polyneuropathy (AL-PN) and neuropathy due to POEMS syndrome (POEMS-N) are rare, associated with a monoclonal gammopathy (MG) IgGλ or IgAλ at a low rate and systemic manifestations. They are invalidating and life-threatening. STATE OF THE ART: AL-PN usually mimics small fiber length-dependent axonal polyneuropathies, but also multifocal or painful neuropathies, POEMS-N corresponds to a rapid ascending CIDP with MG. To confirm the diagnosis of AL-PN, initial investigations should identify amyloidosis on nerve or accessory salivary glands, to establish the type of amyloid after serum free light-chain (FLC) measurements. For the diagnosis of N-POEMS, diagnosis is based on the presence of four criteria proposed by Dispenzieri. These neuropathies are associated with biomarkers, useful for diagnosis and treatment monitoring: elevated serum level of FLC monoclonal in (AL-PN) or VEGF (N-POEMS). PERSPECTIVES: Early diagnosis of these neuropathies and early treatment using high-dose melphalan associated with an autologous hematopoietic stem cell graft or low monthly doses can improve the clinical manifestations and patient survival. CONCLUSIONS: Systematic search for monoclonal gammopathy by immunofixation and serum free light chains is very useful for the management of progressive peripheral neuropathies of unknown origin.
Assuntos
Neuropatias Amiloides/diagnóstico , Neuropatias Amiloides/tratamento farmacológico , Amiloide/metabolismo , Síndrome POEMS/diagnóstico , Neuropatias Amiloides/etiologia , Neuropatias Amiloides/cirurgia , Biomarcadores , Biópsia , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/etiologia , Terapia Combinada , Quimioterapia Combinada , Diagnóstico Precoce , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Cadeias lambda de Imunoglobulina/metabolismo , Melfalan/uso terapêutico , Síndrome POEMS/tratamento farmacológico , Síndrome POEMS/metabolismo , Síndrome POEMS/radioterapia , Paraproteinemias/complicações , Nervos Periféricos/patologia , Prednisona/uso terapêutico , Glândulas Salivares Menores/patologia , Pele/patologia , Talidomida/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
Symptomatic nervous system leukemic infiltration is rarely observed in CLL. Various clinical manifestations including headache, confusion, cranial nerve palsies, focal central deficits and peripheral neuropathies have been seldom reported, occurring in less than 1% of patients. We report herein 2 CLL patients with unusual clinical presentations of nervous system invasion. They presented multiple progressive peripheral deficits due to meningoradiculitis. In both, CSF immunophenotyping analysis identified a majority of T cells (>90%), and less than 10% of B-CLL cells expressing CD5, CD19 and CD20. Our analyses revealed the transformation of CLL into an aggressive B-cell lymphoma in one case (Richter's syndrome). A post mortem study showed massive infiltration of cranial nerves and spinal roots by large B lymphomatous cells. In the other case, CNS oriented chemotherapy led to remission and total neurological recovery. In practice, the etiological diagnosis of neurological deficits in CLL patients is difficult. CSF analysis may be useful, requiring viral PCR, repeated cytological studies and immunophenotyping analysis. Although rare, leptomeningeal leukemic localization has to be discussed, even in the absence of overt Richter syndrome, and may require an early therapeutic test.
Assuntos
Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/patologia , Meningite/etiologia , Meningite/patologia , Radiculopatia/etiologia , Radiculopatia/patologia , Idoso , Idoso de 80 Anos ou mais , Nervos Cranianos/patologia , Evolução Fatal , Humanos , Infiltração Leucêmica/patologia , Masculino , Raízes Nervosas Espinhais/patologiaRESUMO
Primary malignant non-hodgkin lymphoma involving the prostate is rare. Most of the time, it is associated with extraprostatic disease. We report a case of a 72-year-old patient presenting with acute lower urinary tract irritative symptoms, due to large B-cell lymphoma limited to the prostate. Combination of chemotherapy with extern beam radiotherapy provided long-term local control.
Assuntos
Linfoma Difuso de Grandes Células B/terapia , Neoplasias da Próstata/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Diarreia/etiologia , Doxorrubicina/uso terapêutico , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Seleção de Pacientes , Prednisona/uso terapêutico , Neoplasias da Próstata/complicações , Neoplasias da Próstata/diagnóstico , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Doenças Raras , Resultado do Tratamento , Transtornos Urinários/etiologia , Vincristina/uso terapêuticoRESUMO
Immune checkpoint inhibitors (ICIs) are changing the treatments of many patients with cancer. These immunotherapies are generally better tolerated than chemotherapy, and their adverse events are immune-related mimicking autoimmune or inflammatory conditions. Although these immune-related adverse events mainly affect the skin, endocrine glands, digestive tract, joints, liver or lungs, all the organs can be theoretically affected, and the haematopoietic system is not spared. This review of the literature will focus on the haematological immune-related adverse events (Haem-irAEs). By reviewing the largest clinical trials of ICIs, we estimate the frequency of Haem-irAEs at 3.6% for all grades and 0.7% for grades III-IV. Frequency of Haem-irAEs of all grades was found to be higher with anti-programmed cell death 1 (4.1%) or anti-programmed cell death ligand 1 (4.7%) than with anti-cytotoxic T-lymphocyte-associated protein 4 (0.5%) (p < 0.0001). From the 63 cases with Haem-irAEs reported in the literature, the mean time to the onset was found to be 10 weeks after ICI initiation, and the large range for occurrence (1-84 weeks) and the regular incidence suggest that Haem-irAEs could occur at any time after ICI therapy. Among the 63 reported cases with Haem-irAEs, the distribution was immune thrombocytopenia (n = 18, 29%), pancytopenia or immune aplastic anaemia (n = 12, 19%), neutropenia (n = 11, 17%), haemolytic anaemia (n = 10, 16%), cytokine release syndrome with haemophagocytic syndrome (n = 7, 11%) and other Haem-irAEs including bicytopenia or pure red cell aplasia (n = 5, 8%). Haem-irAEs are generally highly severe adverse reactions with a mortality rate of Haem-irAEs reported to be 14% (9 deaths among the 63 cases reported). The more severe and life-threatening Haem-irAEs were both cytokine release syndrome with haemophagocytic syndrome and pancytopenia or aplastic anaemia. Haem-irAEs induced by ICIs are potentially life-threatening. By discussing their pathophysiological aspects and clinical picture, we propose in this review clinical guidelines for management.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Pontos de Checagem do Ciclo Celular/imunologia , Fatores Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
The optimization of radiotherapy in these young and long-lived survivors raises the question about the interest of using modern techniques to allow a better distribution of the dose. The choice of the irradiation technique must take into account the incidence of side effects related to radiation. In this context, the definition of the target volumes as well as the verification and monitoring of the delivered processing are essential. International recommendations for treatment fields are based on the "involved node radiotherapy" concept. The best irradiation technique to use remains to be defined. The use of intensity-modulated radiotherapy improves the coverage and reduces the dose to the organs at risk with a variable gain depending on the topography of the lymph nodes: upper or lower mediastinum, right or left lateralization, the techniques used. The deep inspiration breath-hold technique allows an increase of the pulmonary volume, extension of the mediastinum with an up down of the heart which make possible to move the planning target volume away from the cardiac structures. The volumetric-modulated arctherapy technique with several arches can be particularly interesting to reduce the dose to the breasts, as well as tomotherapy when bulky disease. Proton therapy with the Bragg peak specificity can play a key role in limiting doses to organs at risk, when robust planning that will take into account geometric and physical uncertainties is available. The heterogeneity of Hodgkin lymphomas in terms of volume, shape and initial location are the key elements to take into account when choosing the preferred radiotherapy technique.
Assuntos
Doença de Hodgkin/radioterapia , Radioterapia Conformacional/métodos , Suspensão da Respiração , Doença de Hodgkin/diagnóstico por imagem , Humanos , Irradiação Linfática/métodos , Órgãos em Risco , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Radioterapia Guiada por ImagemRESUMO
BACKGROUND: The development of immune checkpoint blocker development brings new hope in older patients (OPs) because of clinical efficacy and low toxicity. Clinical indications are rising steadily, but very few data are available in the geriatric population where comorbidities, reduced functional reserve and immunosenescence may affect efficacy and tolerance. METHODS: All cases of patients enrolled in immunotherapy phase I trials between January 2012 and December 2016 in the Drug Development Department (DITEP) at Gustave Roussy were retrospectively reviewed. Case-control analysis was performed in OPs (patients ≥ 70 years) matched to younger patients (YPs) (patients < 70 years) by trial and treatment dose. We compared cumulative incidence, grade and type of immune-related adverse events (IrAEs) and survival outcomes. RESULTS: Among the 46 OPs and the 174 YPs enrolled in 14 phase I/II trials, 10 (22%) and 23 (13%) patients experienced grade III-IV IrAEs. Cumulative incidence of grade I-II IrAEs was significantly higher in OPs than YPs (p < 0.05). No significant difference was observed between the two groups for grade III-IV IrAEs (p = 0.50). Older age was not associated with lower dose intensity of treatment (p = 0.14). No significant difference was observed between OPs and YPs in median progression-free survival (hazards ratio 1.41, 95% confidence interval [CI] [0.94-2.11] p = 0.09) or median overall survival (HR 0.92, 95% CI [0.61-1.39] p = 0.77). CONCLUSION: Immune checkpoint blockade appears to be an acceptable treatment option for OPs in the setting of phase I trials.
Assuntos
Ensaios Clínicos Fase I como Assunto , Imunoterapia , Neoplasias/terapia , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ensaios Clínicos Fase I como Assunto/estatística & dados numéricos , Progressão da Doença , Feminino , Humanos , Imunoterapia/métodos , Imunoterapia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The evaluation of first-line intensive combination therapy in small cell carcinoma of the ovary (SCCO). PATIENTS AND METHODS: Debulking surgery; four to six cycles of chemotherapy with cisplatin (P) 80 mg/m(2) day 1, adriamycin (A) 40 mg/m(2) day 1, vepeside (V) 75 mg/m(2)/day days 1-3, cyclophosphamide (EP) 300 mg/m(2)/day days 1-3, every 3 weeks and granulocyte colony-stimulating factor with, in case of a complete remission, high-dose chemotherapy with carboplatin, vepeside, cyclophosphamide and stem-cell support. RESULTS: Twenty-seven patients (median age 25 years); International Federation of Gynecology and Obstetrics stage: five I, four IIC, 17 IIIC-IV and one unknown. Twenty patients underwent complete surgery. Eight patients progressed under chemotherapy. Among 18 patients in complete response (CR), 10 received high-dose chemotherapy (CT) (three stem-cell collection failures, two protocol violations, two disease progression and one refusal). The main grade 3-4 toxic effects were hematologic. There were eight relapses among the 18 CR, four of which were pelvic alone. Among the 27 patients, 13 died and 10 patients are in CR1, three in CR2. The median follow-up is 37 months (8-166) and the median duration of the 18 CR is 30 months (5-111). Overall survival at 1 and 3 years is 58% [confidence interval (CI) 40% to 75%] and 49% (CI 30% to 67%). CONCLUSIONS: Initial dose-intensive therapy achieves interesting overall survival in SCCO.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Hipercalcemia/complicações , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Pequenas/complicações , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Ovarianas/complicações , Estudos Prospectivos , Resultado do TratamentoRESUMO
The most appropriate treatment for lymphoblastic lymphomas (LL) remains uncertain. We treated 27 patients with newly diagnosed LL according to an LMT-89 protocol, which is a modified version of the LMT-81 protocol previously reported in pediatric patients. The median age was 31 years. Mediastinal enlargement was present in 25/27 patients, with pleural effusion in 12. Four patients had central nervous system involvement and 12 had bone marrow involvement and 24/27 (89%) had advanced Ann Arbor stage III-IV disease. Complete remission (CR) was achieved in 20/27 patients, unconfirmed complete remission in three patients (residual mediastinal lesion on computed tomography scan) and four failed induction therapy (ORR: 85%). Twelve patients (44%) remained in continuous CR with a median follow-up of 95 months. Survival at 3 years (when all the events occurred in our series) was 63%. Bone marrow involvement was associated with a poor outcome. Overall survival was 85+/-20% in patients without bone marrow involvement compared to 37+/-30% in patients with bone marrow involvement. The Ann Arbor stage, age and serum lactate dehydrogenase level did not influence outcomes. This LMT-89 protocol is a safe regimen and is highly effective in advanced LL without bone marrow involvement.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Progressão da Doença , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and >2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed <6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P<0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and >2: 5.3 months (P=0.0007). In multivariate analysis, tIPI >2, achievement of response and remission lasting <6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.
Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Taxa de SobrevidaRESUMO
RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%; P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 109/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.