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1.
Br J Haematol ; 204(5): 1752-1756, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38176400

RESUMEN

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.


Asunto(s)
Ácidos Nucleicos Libres de Células , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/mortalidad , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/sangre , Linfoma de Células T Periférico/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Ácidos Nucleicos Libres de Células/sangre , Pronóstico , Adulto , Biomarcadores de Tumor/sangre , Estudios Prospectivos , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
2.
Leukemia ; 28(3): 642-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24220274

RESUMEN

We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m(2)) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Clorhidrato de Bendamustina , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Compuestos de Mostaza Nitrogenada/administración & dosificación , Recurrencia
3.
G Ital Dermatol Venereol ; 148(5): 453-63, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24005137

RESUMEN

AIM: Objective of the study was to determine the most common cutaneous lesions in patients with haematologic malignancies observed at dermatologic consultation and to identify the impact parameters related to the haematologic condition, like disease type/duration, remission, chemotherapy and transplantation, have on skin manifestations. METHODS: A total of 101 consecutive patients with onco-haematological malignancies referred for dermatological consultation over a two-year period were included in this prospective single-centre observational cohort study. RESULTS: The most common finding was infection (19.8%), followed by drug adverse reactions (16.8%) and malignant neoplasia (11.9%). Elderly patients and those with a longer disease duration had a higher frequency of cutaneous neoplasia. Squamous cell carcinoma was the most frequent cutaneous neoplasia; three cases of melanoma were diagnosed and had a high Breslow thickness. Cutaneous involvement due to the haematological malignancies was observed in 5 patients. Common chronic dermatoses (psoriasis and eczema) were found in 10% of patients. Transplant had no effect on the percentage of infections or tumours. CONCLUSION: Patients with haematological malignancies have a higher incidence of adverse drug reactions with peculiar morphologic features and a lower incidence of common chronic dermatoses than patients referred for dermatological consultation by their general practitioner or other hospital services. Infectious dermatoses were less frequent than in solid organ transplanted patients. The complex variety of cutaneous lesions, the differential diagnostic pitfalls and the prognostic relevance of early skin tumour diagnosis, evidence the importance of a correct dermatological approach.


Asunto(s)
Trasplante de Médula Ósea , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/cirugía , Enfermedades de la Piel/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/epidemiología , Estudios de Cohortes , Terapia Combinada , Comorbilidad , Erupciones por Medicamentos/epidemiología , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Estudios Prospectivos , Psoriasis/epidemiología , Derivación y Consulta , Enfermedades Cutáneas Infecciosas/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto Joven
4.
Ann Oncol ; 19(4): 763-8, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18180244

RESUMEN

BACKGROUND: In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program. PATIENTS AND METHODS: Patients should be younger than 65 years with unfavorable stage IA and IIA HL (i.e. stage IA or IIA with bulky disease and/or subdiaphragmatic disease, erythrocyte sedimentation rate higher than 40, extranodal (E) involvement, hilar involvement and more than three involved lymph node areas). RESULTS: Ninety-two patients were allocated to the ABVD arm and 89 to the EVE arm. Complete remission (CR) rates at the end of treatment program [chemotherapy (CT) + RT] were 93% and 92% for ABVD and EVE arms, respectively (P = NS). The 5-year relapse-free survival (RFS) rate was 95% for ABVD and 78% for EVE (P < 0.05). As a consequence of the different relapse rate, the 5-year failure-free survival (FFS) rate was significantly better for ABVD (90%) than for EVE (73%) arm (P < 0.05). No differences in terms of overall survival (OS) were observed for the two study arms. CONCLUSIONS: In unfavorable stage IA and IIA HL patients, no differences were observed between ABVD and EVE arms in terms of CR rate and OS. EVE CT, however, was significantly worse than ABVD in terms of RFS and FFS and cannot be recommended as initial treatment for HL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Adulto , Anciano , Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Quimioterapia Adyuvante , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Cardiopatías/inducido químicamente , Enfermedad de Hodgkin/patología , Humanos , Infecciones/etiología , Italia , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia Adyuvante , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos
5.
Leuk Lymphoma ; 48(2): 367-73, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17325898

RESUMEN

The Intergruppo Italiano Linfomi started, in 1996, a randomized trial for the initial treatment of elderly patients (older than 65 years) with Diffuse Large B-Cell Lymphoma (B-DLCL) comparing 6 courses of Mini-CEOP vs 8 weeks of P-VEBEC chemotherapy. Study objectives were survival, response and Quality of Life (QoL). Two hundred and thirty-two patients were evaluable for final analysis. Complete Response (CR) and Overall Response Rates (ORR) were 54% vs 66% (p = 0.107) and 90% vs 78% (p = 0.021) for P-VEBEC and Mini-CEOP, respectively. With a median follow-up of 72 months, the 5-year Overall Survival (OS), Relapse Free Survival (RFS), and Failure Free Survival (FFS) were 32%, 52%, and 21%, respectively. Subjects achieving a CR showed improvement of QoL regardless of treatment arm. Both Mini-CEOP and P-VEBEC determined a similar outcome for elderly patients with B-DLCL, with a third of patients alive after more than 6 years of follow-up. Both regimens can be considered equally for combination treatment with anti-CD20 monoclonal antibody.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Bleomicina/uso terapéutico , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Epirrubicina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Humanos , Masculino , Prednisona/uso terapéutico , Calidad de Vida , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Vinblastina/uso terapéutico , Vincristina/uso terapéutico
6.
Ann Oncol ; 18(2): 346-50, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17071937

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome. METHODS: We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients. RESULTS: HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (P = 0.0001), irrespective of HCV serostatus. CONCLUSIONS: This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV. HCV-positive nongastric lymphomas of MALT show an indolent course similar to HCV-negative patients and seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.


Asunto(s)
Hepacivirus/aislamiento & purificación , Hepatitis C/virología , Linfoma de Células B de la Zona Marginal/virología , Anticuerpos Antivirales/análisis , Biomarcadores/análisis , Femenino , Mucosa Gástrica/virología , Hepatitis C/patología , Humanos , Linfoma de Células B de la Zona Marginal/patología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Tasa de Supervivencia
7.
Leukemia ; 16(2): 268-75, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11840294

RESUMEN

Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P < 0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.


Asunto(s)
Proteínas de Unión al ADN/genética , Linfoma de Células B Grandes Difuso/genética , Proteínas de Neoplasias/genética , Mutación Puntual , Proteínas Proto-Oncogénicas/genética , Proto-Oncogenes , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Carmustina/administración & dosificación , Cromosomas Humanos Par 3/genética , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Genes bcl-2 , Humanos , Tablas de Vida , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Melfalán/administración & dosificación , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisolona/administración & dosificación , Prednisona/administración & dosificación , Pronóstico , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-bcl-6 , Resultado del Tratamiento , Vincristina/administración & dosificación
9.
Ann Oncol ; 9(1): 55-61, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9541684

RESUMEN

BACKGROUND: B-diffuse large-cell lymphomas (DLCL) have been associated with some molecular lesions, but the role of such lesions as prognostic markers is still controversial. This report concerns an investigation of the frequency and clinical correlation of bcl-6, bcl-2, c-myc rearrangements and 6(q) deletions in B-DLCL. PATIENTS AND METHODS: The presence of these genetic lesions was analyzed in samples of lymph nodes or bone marrow collected at diagnosis in 71 patients with B-DLCL, all treated with an anthracycline-containing chemotherapy regimen. RESULTS: Rearrangement of bcl-6 was found in 11 patients (15%), rearranged bcl-2 in 12 (17%), 6(q) deletions in 10 patients (14%) and c-myc rearrangement in four (6%). Patients with rearranged bcl-6 tended to have a more aggressive disease than patients with germ-line bcl-6 (intermediate-high/high risk according to IPI criteria: 73% vs. 43%), but there were no differences in three-year survival rates (62% vs. 42%) between the two groups. The numbers of involved extranodal sites were similar in patients with rearranged and those with germ-line bcl-6. Patients with bcl-2 rearrangement appeared to have a less aggressive disease than those with germ-line bcl-2 (low/ low-intermediate risk 75% vs. 47%) and a slightly better three-year survival rate (70% vs. 41%) but again the difference was not significant. Both groups with or without 6(q) deletion had similar clinical characteristics and outcomes. The four patients with c-myc rearrangement had aggressive disease and did poorly. CONCLUSIONS: The analysis of molecular lesions in B-DLCL may be useful for a better diagnostic definition; however, in this study we were unable to show that the evaluated genetic lesions had a significant impact on clinical outcome.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 6 , Reordenamiento Génico , Linfoma de Células B/genética , Linfoma de Células B Grandes Difuso/genética , Proto-Oncogenes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Femenino , Genes bcl-2 , Genes myc , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
10.
Haematologica ; 83(4): 312-6, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9592980

RESUMEN

BACKGROUND AND OBJECTIVE: Mantle cell lymphoma (MCL) is a separate histological and clinical entity recently recognized in the new revised European-American Lymphoma Classification. Little information exists regarding its therapy. We report the results of a retrospective study of 27 patients affected by MCL evaluating the clinical characteristics and the results of different therapeutical options used during the period of observation. DESIGN AND METHODS: From 1983 to 1993, we observed 27 patients affected by MCL according to the criteria proposed by European Lymphoma Task Force in a revision of 55 cases classified as NHL E according to Working Formulation (WF) criteria. We analyzed the clinical characteristics, the prognostic factors and the O.S. of these patients. RESULTS: The clinical characteristics of our patients (pts) are similar to those observed in other series: male prevalence, median age 62 years, B symptoms in 9 cases, P.S. > 2 in 11 cases, 3 pts were in stage I and II, 4 in stage III, 20 in stage IV; 18 pts had a bone marrow involvement, 13 pts had spleen enlargement and 14 had extranodal localization; 8 pts had bulky tumor and 5 had LDH above normal. The CR rate was 51.8%, the median O.S. was 43 months, and DFS was 18 months; the pts without bulky disease and with localized disease had a better CR rate. The inclusion of an anthracycline in the regimen did not affect the results. INTERPRETATION AND CONCLUSIONS: Our results were not divergent from those present in literature. The mantle cell lymphoma is an incurable and highly aggressive disease. Autologous bone marrow transplantation as support of high dose chemotherapy or allogenic bone marrow transplantation may be a chance for some patients, but not for the majority of patients, which are older than 65 years. Studies of a larger series and different therapeutical approaches, i.e. using biological modifiers in association or as maintenance after chemotherapy are essential.


Asunto(s)
Linfoma no Hodgkin/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/uso terapéutico , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
11.
Haematologica ; 82(3): 309-13, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9234577

RESUMEN

BACKGROUND AND OBJECTIVE: Idarubicin is an effective drug in acute leukemia but its use in non-Hodgkin lymphomas (NHLs) is not yet well established. We evaluated its efficacy in patients with diffuse large cell lymphoma (DLCL) by means of a randomized trial comparing two 12-week regimens (VACOP-B and VICOP-B) which differed only in the anthracycline drug used (doxorubicin vs idarubicin). METHODS: From January 1992 to December 1994, 104 patients aged less than 65 years with de novo advanced stage DLCL were enrolled. Fifty-two patients were treated with VACOP-B (doxorubicin 50 mg/sqm) and 52 with VICOP-B (idarubicin initially 8 mg/sqm and thereafter 10 mg/sqm). RESULTS: Clinical characteristics of the two groups were not significantly different. One HBsAg+ patient died of hepatic necrosis in the VICOP-B arm, and severe (WHO grade > 2) toxicities occurred in 7 patients treated with VACOP-B and in 5 treated with VICOP-B; the only significant difference was for mucositis (p = 0.02). Complete remission (CR) was obtained in 79% of patients receiving VACOP-B and in 56% (idarubicin 8 mg/sqm) and 75% (idarubicin 10 mg/sqm) of those in the VICOP-B group (p = n.s.). Prognostic factors that negatively affected CR were advanced stage in VACOP, bone marrow infiltration in both schedules. At a median follow-up of two years, overall survival (67% VACOP and 61% VICOP) and disease-free survival (65% and 67%, respectively) were not significantly different. INTERPRETATION AND CONCLUSIONS: Idarubicin is slightly less toxic than doxorubicin; at a dose of 10 mg/sqm the former is easily tolerated and shows the same efficacy as doxorubicin in the treatment of DLCL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Cardiomiopatías/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/efectos adversos , Infecciones/etiología , Tablas de Vida , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Prednisona/administración & dosificación , Prednisona/efectos adversos , Inducción de Remisión , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos
12.
Ann Oncol ; 7(9): 919-24, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9006742

RESUMEN

BACKGROUND: A cooperative study was undertaken to evaluate the efficacy and toxicity of a very brief course of chemotherapy followed by locoregional radiotherapy in patients with localized-stage intermediate- to high-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHOD: From January 1988 to November 1994, 84 patients with localized stages IA and IIA intermediate- to high-grade NHL underwent a combined modality treatment. All patients underwent a six-week chemotherapy regimen, ACOP-B (doxorubicin 50 mg/sqm and cyclophosphamide 350 mg/sqm on weeks 1, 3, 5; vincristine 1.4 mg/sqm and bleomycin 10 mg/sqm on weeks 2, 4, 6; prednisone 50 mg p.o. daily throughout the first two weeks and thereafter every other day), followed by locoregional radiotherapy (36 Gy). RESULTS: The median age was 58 years, with 35% older than 65 years; 52 patients had stage I and 32 stage II; 39 patients had extranodal +/- nodal involvement, and 4 had testicular involvement. Treatment was well tolerated, with only 38% suffering from mild mucositis and no toxic deaths. Seventy-nine patients achieved CR after ACOP-B and 83 at the end of the program. With a median follow-up of four years, relapse-free survival was 79% with 15 relapses (93% disseminated). Two patients with testis lymphoma had CNS relapses. Overall survival was 90% at four years. CONCLUSION: This combined program is effective and probably curative in localized stage intermediate- to high-grade NHL, with low toxicity, also in elderly people. Patients with NHL of the testis, as primary site, require CNS prophylaxis due to the high likelihood of CNS relapse.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/radioterapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia/efectos adversos
13.
Leuk Lymphoma ; 22(5-6): 483-93, 1996 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8882962

RESUMEN

The results of a prospective trial of an 8 week treatment for elderly patients with advanced intermediate-high grade NHL are reported. Our aim was to reduce general toxicity without losing an antilymphoma effect. For this reason the use of growth factor was studied. We also analysed the behavior of different histological groups (E + F vs G + H). From November 1991 to November 1993 100 patients older than 65 years with combination intermediate-high grade advanced stage NHL were treated with the P-VEBEC regimen, an original including epirubicin 50 mg/sqm, cyclophosphamide 300 mg/sqm and etoposide 100 mg/sqm on weeks 1, 3, 5, 7; vinblastine 5 mg/sqm and bleomycin 5 mg/sqm on weeks 2, 4, 6, 8; prednisone 50 mg/sqm/day per os in the first two weeks and thereafter every other day .46 pts received rG-CSF 5 micrograms/Kg/day throughout the treatment starting on day 2 of every week for 4 consecutive days. Twenty eight pts had B symptoms, 41 had bulky disease, 37 LDH levels above normal, 50 stage IV patients and 30 had bone marrow involvement. Sixty two percent achieved a complete remission (CR). Adverse prognostic factors for CR were E and F histology, stage IV disease, bone marrow infiltration, serum LDH levels above normal, international Prognostic Index (I.I.) intermediate-high and high risk categories and relative dose intensity (RDI) less than 0.80. Severe toxicity was rarely recorded and only one toxic death was observed. With a median follow-up of 33 months OS, DFS and EFS were 44%, 60% and 30% respectively. EFS was influenced by stage, BM involvement, level of LDH and I.I. intermediate-high and high risks. The 52 patients with DLCL (diffuse large cell lymphomas--G + H according to WF) did better with a higher CR, OS, DFS and EFS rates, than the other WF subtypes. In conclusion P-VEBEC is a feasible combination to use in elderly patients, mainly in DLCL. The use of rG-CSF improves the RDI. A RDI > 0.80 could play a role in improving the outcome, especially in patients with adverse prognostic factors. For other subgroups another schedule is probably justified.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Anciano , Antiinfecciosos/uso terapéutico , Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Infecciones Bacterianas/prevención & control , Bleomicina/administración & dosificación , Médula Ósea/patología , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Esquema de Medicación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Cetoconazol/uso terapéutico , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Masculino , Micosis/prevención & control , Estadificación de Neoplasias , Ofloxacino/uso terapéutico , Prednisona/administración & dosificación , Pronóstico , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Tasa de Supervivencia , Vinblastina/administración & dosificación
14.
Ann Oncol ; 5(10): 895-900, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7535080

RESUMEN

BACKGROUND: Chemotherapy regimens devised for elderly patients with intermediate-high grade NHL are a matter of discussion. The aim is to reduce general toxicity without loosing an antilymphoma effect. The most important limiting factor of chemotherapy is myelotoxicity; for this reason the use of growth factor may be useful in these patients. PATIENTS AND METHODS: From November '91 to November '92, 67 pts older than 65 years with intermediate-and high-grade advanced-stage NHL were treated with the P-VEBEC regimen, an original scheme with epirubicin 50 mg/m2, cyclophosphamide 350 mg/m2 and etoposide 100 mg/m2 on weeks 1, 3, 5, 7; vinblastine 5 mg/m2 and bleomycin 5 mg/m2 on weeks 2, 4, 6, 8, prednisone 50 mg/m2/day p. os in the first 2 weeks and thereafter every other day. Twenty-eight pts received r-GSF 5 micrograms/kg/day throughout the treatment starting on day 2 of every week for 4 consecutive days. Their median age was 71 years (65-80), 31 pts were male and 36 female, histology according W.F. was D 6; E 17; F 16; G 19; H 9. Twenty-five percent of pts had B symptoms, 35% had bulky disease, 41% LDH level > normal, 44% stage IV and 26% had B.M. involvement. RESULTS: C.R. was achieved by 66% of pts. Adverse prognostic factors for CR were E histology, stage IV, bone marrow infiltration and LDH above normal. Severe toxicity was never recorded, no toxic death was observed. With a median follow-up of 24 months OS, DFS and EFS were 55%, 52%, and 33%, respectively. EFS was influenced by stage, BM involvement and level of LDH. The relative dose intensity (RDI) was calculated by the method of Hryniuk and Bush. Patients who received rG-CSF had a significantly higher median RDI (94% vs 79%) and lower myelotoxicity (neutrophil nadir < 500 18% vs 56%). The rate of CR was influenced by RDI > 80% (89% vs 56%). EFS was also better in pts who received a RDI higher than 80% (50% vs 18% p = 0.05). CONCLUSION: P-VEBEC is a feasible cycle in elderly patients; the use of rG-CSF improves RDI. In patients with adverse prognostic factors (BM involvement, poor performance status) a RDI > 0.80 could play a role in improving the outcome.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Linfoma no Hodgkin/mortalidad , Masculino , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Prednisona/administración & dosificación , Prednisona/efectos adversos , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Vinblastina/administración & dosificación , Vinblastina/efectos adversos
15.
Haematologica ; 79(1): 46-54, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-15378948

RESUMEN

BACKGROUND: Elderly Hodgkin's disease patients have a poor prognosis. The question arises whether these patients need aggressive treatment or a palliative strategy. So far, as a consequence of the scarcity of trials designed for them, useful information can be obtained only by retrospective analyses. METHODS: We retrospectively studied clinical data from 567 patients recorded from 1982 to 1989 in the Piemonte Hodgkin's Disease Register (PHDR). The 65 patients over 65 years of age were compared to younger ones. We analyzed the role of disease independently of confounding variables, mainly inadequacy of staging and/or treatment, comorbidity and toxicity. RESULTS: In the elderly comorbidity was as high as 35%. Forty elderly patients (60%) entered a suboptimal plan with a low degree of aggressivity, which was different from the usual PHDR protocol. Elderly patients also had a high proportion of subsequent protocol interruptions (25%). Chemotherapy dose intensity was negatively affected by advanced age (p < 0.01 after both 3 and 6 courses of chemotherapy). Toxic deaths were significantly higher in elderly patients than in younger ones (14% vs 1%; p < 0.05). CR rates, overall survival (OS), disease-specific survival (DSS) and event free survival (EFS) were all significantly influenced by age (p < 0.01). Relapse-free survival (RFS) in patients achieving CR did not differ according to age class (77% vs 60%; p = ns). RFS was better in elderly patients entering the PHDR protocols than in those following an alternative plan (75% vs 54%; p = 0.04); however, elderly patients treated according to PHDR guidelines showed a higher incidence of toxic deaths than those treated less aggressively (23% vs 8%). The two groups had similar EFS (36% vs 24%; p = ns). CONCLUSIONS: Elderly patients who achieve CR can have good RFS and cure is possible, but the toxic cost of conventional strategies is unacceptable and selected strategies still must be found.


Asunto(s)
Enfermedad de Hodgkin/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Comorbilidad , Supervivencia sin Enfermedad , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Italia/epidemiología , Tablas de Vida , Masculino , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia
16.
Radiol Med ; 83(3): 230-6, 1992 Mar.
Artículo en Italiano | MEDLINE | ID: mdl-1579671

RESUMEN

Forty-five patients with mediastinal spread of malignant, Hodgkin's and non-Hodgkin's lymphomas were examined with MR Imaging at 0.5 T. Ninety-two examinations were performed at diagnosis and/or during and after treatment to investigate MR capabilities in distinguishing fibrous tissue from active disease in the masses residuing after therapy--which cannot be done by means of CT. MR results indicated T2-weighted sequences to be the most useful. MR results were compared with the data collected from follow-up, clinics, and biology. MR Imaging had high accuracy (92.1%). The number of false negatives was very low, thanks to the low intensity of fibrous tissue, while a relatively high number of false positives was observed, probably due to the difficulties in discriminating inflammatory from neoplastic tissue.


Asunto(s)
Enfermedad de Hodgkin/radioterapia , Linfoma no Hodgkin/radioterapia , Imagen por Resonancia Magnética , Neoplasias del Mediastino/radioterapia , Recurrencia Local de Neoplasia/diagnóstico , Estudios de Seguimiento , Enfermedad de Hodgkin/diagnóstico , Humanos , Linfoma no Hodgkin/diagnóstico , Neoplasias del Mediastino/diagnóstico , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
17.
Ann Oncol ; 2(10): 733-7, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1724908

RESUMEN

In a series of 193 patients with advanced stage diffuse large-cell lymphoma (DLCL) treated with MACOP-B, 18 (11%) were defined as having a stage II large B-cell lymphoma with sclerosis of the mediastinum. This type of lymphoma has been reported to have a highly aggressive behaviour and special histological and clinical features. In our series young women were more commonly affected and the most striking clinical feature was the presence of a bulky mediastinal mass in 81%. A comparison was made between stage II patients with DLCL with and without sclerosis. The group of patients with sclerosis had prognostic parameters significantly worse than those of the patients without sclerosis, namely, elevated LDH level and bulky disease. The complete remission rates (89% vs 76%) were similar in the two groups and, with a median follow-up of 23 months, survival and disease-free survival rates were also superimposable. MACOP-B chemotherapy has been proven effective in this subgroup of lymphoma patients with sclerosis that had thus far been reported to have a poor prognosis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , L-Lactato Deshidrogenasa/metabolismo , Leucovorina/administración & dosificación , Linfoma de Células B/enzimología , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/enzimología , Linfoma de Células B Grandes Difuso/patología , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Esclerosis , Vincristina/administración & dosificación
18.
Haematologica ; 76(1): 43-6, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-2055560

RESUMEN

BACKGROUND: An effective second-line treatment for intermediate and high grade non-Hodgkin's lymphoma is greatly needed since 30% of patients do not achieved complete remission (CR) and another 20% to 30% of the CRs will eventually relapse. METHODS: A four-drug combination with Mitoxantrone, Etoposide, Cisplatin and Dexamethasone (MEPD) was devised for the treatment of patients with relapsing or refractory non-Hodgkin's lymphoma (NHL). So far 22 patients with intermediate or high grade NHL have entered the study. All patients were previously treated with doxorubicin based regimens. RESULTS: Seven patients obtained a complete remission (CR), 3 a partial remission (PR), 4 a minor response (MR) and 8 were treatment failures (F). Thus, an overall response rate of 45% has been achieved. To date three of the complete responders have relapsed at 3, 6 and 15 months. Four patients are still in CR at +2, +4, +9 and +17 months, respectively. Patients with relapsing lymphoma responded better than those with primary refractory disease. Myelosuppression was the most frequent side effect, nevertheless there were no severe infections. CONCLUSIONS: These preliminary results suggest the effectiveness of MEPD as salvage chemotherapy in resistant NHL and warrant further clinical studies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Anciano , Cisplatino/administración & dosificación , Dexametasona/administración & dosificación , Evaluación de Medicamentos , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Inducción de Remisión/métodos
19.
Haematologica ; 75(1): 64-8, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2338289

RESUMEN

Conventional chest X-rays and CT scans, performed at the time of the initial staging in 67 patients affected by Hodgkin's disease, were reviewed and compared. CT scans provided evidence of disease not shown by concomitant conventional chest X-rays in 10 patients (15%). The impact on patient management of the additional CT data was evident in 8 cases (11.9%), either changing the whole treatment plan (4 patients) or enlarging radiation ports (4 patients). Traditional prognostic features did not influence the outcome, and only hilar adenopathy adversely affected event-free survival, without however reaching statistical relevance (p greater than 0.05). Our data suggest that thoracic CT scan is helpful in drawing up the treatment plan, while its role in identifying new prognostic factors is still uncertain.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico por imagen , Neoplasias Torácicas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Antineoplásicos/uso terapéutico , Terapia Combinada , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Neoplasias Torácicas/patología , Neoplasias Torácicas/terapia
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