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2.
ESMO Open ; 6(1): 100044, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33516148

RESUMO

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.


Assuntos
Inibidores de Checkpoint Imunológico , Segunda Neoplasia Primária , Humanos , Incidência , Segunda Neoplasia Primária/epidemiologia
3.
J Clin Oncol ; 15(2): 499-508, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9053471

RESUMO

PURPOSE: A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas. PATIENTS AND METHODS: One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status > or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, > or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P < .0001), and overall survival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI. CONCLUSION: TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Linfoma/sangue , Linfoma/tratamento farmacológico , Linfotoxina-alfa/sangue , Proteínas de Neoplasias/sangue , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/metabolismo , Antígenos CD/sangue , Antígenos de Neoplasias/sangue , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Humanos , Linfoma/imunologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Risco , Análise de Sobrevida , Resultado do Tratamento
4.
Am J Med ; 106(2): 191-7, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10230749

RESUMO

PURPOSE: We sought to describe the infections that occur after large-dose chemotherapy, which was followed by autologous peripheral blood progenitor cell transplantation, and to determine their risk factors. PATIENTS AND METHODS: We retrospectively analyzed the occurrence and the characteristics of infections in 277 consecutive patients who received intensive chemotherapy for non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27), or multiple myeloma (n = 43) in a single institution. Conditioning regimens included total body irradiation in 47% of the cases. Infections occurring within the 30 days after transplant were defined as early infections, whereas infections after that time in patients who had achieved a neutrophil count greater than 1.0 x 10(9)/L (1,000 per microL) were considered as late infections. RESULTS: Within the first 30 days, 172 patients had unexplained fever (62%); infections were documented in 83 patients (30%), most commonly bacteremia (57 patients). Late infections occurred in 64 (26%) of 244 evaluable patients and consisted mainly of varicella zoster virus infections (n = 36) and pneumonia (n = 16). Administration of total body irradiation [odds ratio (OR) = 2.50; 95% confidence interval (CI) 1.4 to 4.5; P = 0.002) and previous use of fludarabine (OR 2.5; CI 1.2 to 5.2; P = 0.02) and a diagnosis of myeloma (OR 2.6; CI 1.2 to 5.6; P = 0.04) were significantly associated with late infections. CONCLUSIONS: This study confirms that infectious toxicity after peripheral blood progenitor cell transplantation is usually moderate, although bacteremia remains a serious problem. Late infections are encountered in about 25% of patients and are more common in those with myeloma, or those who received total body irradiation or fludarabine.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/cirurgia , Infecções/etiologia , Linfoma não Hodgkin/cirurgia , Mieloma Múltiplo/cirurgia , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Bacteriemia/etiologia , Feminino , Febre de Causa Desconhecida/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
5.
Br J Cancer ; 77(12): 2357-62, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9649158

RESUMO

A prospective study was performed to assess the use of plasma measurement of tumour necrosis factor (TNF), lymphotoxin alpha (LT alpha) and their soluble receptors (p55 and p75) for prognostic risk assignment in 61 patients with Hodgkin's disease. Plasma levels of TNF, p55 and p75, but not of LT alpha, were higher in Hodgkin's disease patients than in healthy controls. Plasma levels of TNF, p55 and p75 were associated with several prognostic factors for Hodgkin's disease, including those related to the host (age, performance status) and to the tumour (disease stage, extranodal site involvement, bulky tumour, serum levels of LDH and beta2-microglobulin, histology). Elevated plasma levels of TNF, p55 and p75 were also associated with several parameters reflecting an immune activation, including the presence of B symptoms, elevated serum levels of gammaglobulins, alkaline phosphatase and fibrinogen, as well as peripheral monocytosis, anaemia and low serum albumin levels. Finally, elevated TNF ligand receptor plasma markers were associated with a lower incidence of complete response to therapy and predicted shorter free-from-progression survival and overall survival of the patients. These results indicate that the plasma levels of TNF and its soluble receptors correlate with clinical features and outcome of patients with Hodgkin's disease.


Assuntos
Antígenos CD/sangue , Doença de Hodgkin/sangue , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Terapia Combinada , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Ligantes , Linfotoxina-alfa/sangue , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Estudos Prospectivos , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagem
6.
Ann Oncol ; 8(7): 701-4, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9296227

RESUMO

BACKGROUND: Despite improved detection of mantle cell lymphoma (MCL), results of its treatment with conventional therapies remain disappointing and the survival rate poor. The role of high-dose chemotherapy has recently been investigated but no potential benefit has been clearly established. We report here our experience with MCL patients treated with intensive chemotherapy and autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Of the 16 MCL patients who received high-dose chemotherapy and ASCT beginning in 1989, six were treated in first-line and 10 in sensitive relapse. Twelve of 16 patients received regimens which included total body irradiation. All patients received peripheral blood stem cells (PBSC) with the exception of one, who underwent bone marrow transplantation. RESULTS: Three patients died of toxic effects of treatment, Three months after transplant, seven achieved complete response, (CR) and two partial responses (PR), two were stable and two had progressed. With a median follow-up after transplant of 22 months, five of the six surviving patients were without progression, and three were in CR. The median times for event-free survival (EFS) and overall survival (OS) were, respectively, 249 and 317 days. The expected three-year EFS and OS were 24%. The median survival after diagnosis was only 29 months. None of the criteria appeared to be significantly associated with a better outcome, but first-line intensification and a short delay after initial diagnosis may be favorable. CONCLUSION: In this study we were not able to confirm the hypothetical benefit of high-dose chemotherapy and PBSC transplantation in mantle cell lymphoma, even though this approach may be promising in a subgroup of patient.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
7.
Br J Haematol ; 103(1): 235-42, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9792315

RESUMO

Peripheral blood progenitor cells (PBPC) were mobilized and harvested in 200 patients treated for non-Hodgkin's lymphoma (n = 148), Hodgkin's disease (n = 22) and multiple myeloma (n = 30). The variables predicting the collection of a minimal (>2.5 x 10(6)/kg) or a high (>10 x 10(6)/kg) CD34+ cell count were analysed. Patients were mobilized with haemopoietic growth factors following either standard chemotherapy (n = 49) or high-dose cyclophosphamide, given alone (n = 55) or combined with high-dose VP16 (n = 86). 10 patients received haemopoietic growth factors only. The first mobilization resulted in a PBPC harvest with enough CD34+ cells in 179/200 patients (90%). High-dose cyclophosphamide, with or without VP16, did not mobilize a higher progenitor cell yield than standard chemotherapy. When performing multiple regression analysis in the 190 patients who received chemotherapy-containing mobilization, only the number of previous chemotherapy regimens and the exposure to fludarabine predicted for a failure to collect a minimal PBPC count (P=0.06 and 0.0008 respectively). The target to collect a high CD34+ cell count was negatively associated with the number of previous chemotherapy regimens (P=0.002). When only non-Hodgkin's lymphoma patients were considered for multivariate analysis, low-grade histology with fludarabine appeared to be associated with poor PBPC cell yield (P=0.08 and 0.005 respectively). This data confirms that PBPC harvest should be planned early in the disease course in transplant candidates, and can be obtained after a standard course of chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citocinas/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Antígenos CD34/metabolismo , Feminino , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucaférese , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Blood ; 91(9): 3148-55, 1998 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9558369

RESUMO

Optimal numbers of CD34(+) cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34(+) cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 x 10(9)/L) and unsustained platelet recovery (>50 x 10(9)/L) were analyzed in three groups defined by the number of CD34(+) cells reinfused: a low group with less than or equal to 2.5 x 10(6) CD34(+) cells/kg, a high group with greater than 15 x 10(6) CD34(+) cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P < .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34(+) cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 x 10(6) CD34(+) cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.


Assuntos
Antígenos CD34/análise , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Feminino , Hematopoese , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
9.
Ann Oncol ; 10(10): 1191-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10586336

RESUMO

BACKGROUND: Fludarabine was associated with a good response and was well tolerated in patients with follicular lymphoma in phase II trials and this treatment may be associated with less adverse events than treatment with CHVP plus interferon in elderly patients. PATIENTS AND METHODS: One hundred thirty-one patients older than 59 years with a follicular lymphoma and poor prognosis were randomized between the association of CHVP (12 cycles in 18 months) plus interferon (5 MU TIW for 18 months) or fludarabine alone (25 mg/m2/d x 5 days for 6 cycles, then 20 mg/m2/day for 6 further cycles for 18 months). Poor prognosis was defined by the presence of a large tumor mass, poor performance status, the presence of B symptoms, above normal LDH level, or > or = 3 mg/l beta-microglobulin level. RESULTS: Patients treated with CHVP plus interferon had a higher response to treatment, a longer time to progression and a longer survival than those treated with fludarabine alone (P < 0.05 for all analyses). With a median follow-up of 29 months, the 2-year failure-free survival was 63% for the CHVP-plus-interferon arm compared to 49% for the fludarabine arm and the two-year survival was 77% and 62%, respectively. This benefit was confirmed in a multivariate analysis including initial prognostic parameters. Fludarabine alone was associated with less neutropenia than CHVP plus interferon. Interferon was decreased or stopped in 39% of the patients because of severe fatigue. CONCLUSIONS: CHVP plus interferon over 18 months was associated with a better outcome, even though the combination of interferon plus chemotherapy was less well tolerated than fludarabine.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Vidarabina/análogos & derivados , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Interferons/administração & dosagem , Interferons/efeitos adversos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prognóstico , Análise de Sobrevida , Teniposídeo/administração & dosagem , Teniposídeo/efeitos adversos , Vidarabina/efeitos adversos , Vidarabina/uso terapêutico
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