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2.
J Infect ; 52(6): e173-6, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16246422

RESUMO

Hypersensitivity to mosquito bite (HMB) can occur in association with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukaemia/lymphoma, which was named 'Tokura-Ishihara disease'. This disease is very rare and most previous reports have been documented in Japan. We present a patient who suffered from of pustules on skin, high fever, myalgia and multiple lymph node enlargements after mosquito bite from childhood. Recently, multiple lymph nodes were palpable on his both inguinal area. Peripheral blood smear (PBS) revealed many large granular lymphocytes and the skin lesion showed a dense dermal and subcutaneous infiltrate of lymphocytes. The lymph nodes and perinodal adipose tissue were infiltrated by atypical lymphoid cells in which EBER-positive signals were identified by in situ hybridization using EBV encoded RNA-1 probe. He was diagnosed as having Tokura-Ishihara disease and receives chemotherapy now. Here, we report a case of this disease with a precise pathological description on the lymph node biopsy.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Hipersensibilidade/complicações , Mordeduras e Picadas de Insetos/imunologia , Células Matadoras Naturais/patologia , Linfoma/etiologia , Adulto , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia , Culicidae , Infecções por Vírus Epstein-Barr/patologia , Etoposídeo/administração & dosagem , Glioxal/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Mordeduras e Picadas de Insetos/patologia , Células Matadoras Naturais/virologia , Linfonodos/patologia , Linfócitos/patologia , Linfoma/tratamento farmacológico , Linfoma/patologia , Linfoma/virologia , Masculino , Prednimustina/administração & dosagem , Pele/patologia
3.
Ann Hematol ; 83(3): 176-82, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15064867

RESUMO

Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and metabolic heterogeneity. We hypothesized that low hematotoxicity might correlate with reduced systemic dose and thus reduced disease control. A total of 266 patients with advanced HD treated with cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD) were analyzed (HD6 trial of the German Hodgkin's Lymphoma Study Group). The reported WHO grade of leukocytopenia was averaged over chemotherapy cycles given and weighted with the reciprocal dose intensity of the corresponding cycle. The low and high toxicity groups were defined in retrospect as having had an averaged WHO grade of leukocytopenia 2.1, respectively. The independent impact of low hematological toxicity on freedom from treatment failure (FFTF) was assessed multivariately adjusting for the international prognostic score for advanced HD. The results were validated in two independent cohorts [181 patients treated with COPP-ABVD (HD9-trial) and 250 patients treated with COPP-ABV-ifosfamide, methotrexate, etoposide, and prednisone (IMEP) (HD6 trial)]. The 5-year FFTF rates were 68% for patients with high toxicity vs 47% for patients with low toxicity [multivariate relative risk (RR) 2.0, 95% confidence interval (CI) 1.4-3.0, p=0.0002]. Patients with low toxicity received significantly higher nominal dose ( p=0.02) and dose intensity ( p<0.0001). This finding was confirmed in both validation cohorts (multivariate RR 2.1, 95% CI 1.2-3.8, p=0.01 and RR 1.5, 95% CI 1.01-2.26, p=0.04, respectively). Patients with low hematotoxicity have significantly higher failure rates despite higher doses and dose intensity. Hematotoxicity is an independent prognostic factor for treatment outcome. This observation suggests a strategy of individualized dosing adapted to hematotoxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/efeitos dos fármacos , Doenças Hematológicas/induzido quimicamente , Doença de Hodgkin/tratamento farmacológico , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Glioxal/administração & dosagem , Glioxal/efeitos adversos , Doença de Hodgkin/patologia , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Masculino , Prednimustina/administração & dosagem , Prednimustina/efeitos adversos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos
4.
Ann Oncol ; 15(2): 276-82, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14760122

RESUMO

BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Glioxal/administração & dosagem , Doença de Hodgkin/patologia , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prednimustina/administração & dosagem , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Fatores Sexuais , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagem
5.
Vestn Ross Akad Med Nauk ; (1): 42-5, 2002.
Artigo em Russo | MEDLINE | ID: mdl-11882971

RESUMO

To improve the action and selectivity of new drugs on tumor cells and the use of currently available pharmaceutical technologies to develop the systems of controlled transport of well-known antitumor compounds is one of the ways of enhancing the efficiency of drug therapy for tumors. The tropicity of steroid hormones to definite organs and tissues makes it possible to use them as specific messengers of alkylating groups to target tissues and tumors. Hormone cytostatics synthesized by this principle have a double mechanism of hormonal and cytotoxic actions. The original Russian water-insoluble hormone cytostatistics testifenon, kortifen, and cytestrol acetate demonstrated local tissue irritation together with high antitumor activity. No rational dosage forms make it possible to conduct clinical trials by parenteral administration. The aim of this paper is to summarize the authors' results of designing hydrophobic antitumor hormone cytostatics. The advantages and disadvantages of different approaches to designing traditional dosage forms and to applying colloid liposomal systems for intravenous administration of water-insoluble agents are shown.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacologia , Corticosterona/análogos & derivados , Corticosterona/administração & dosagem , Corticosterona/farmacologia , Lipossomos/metabolismo , Compostos de Mostarda Nitrogenada/administração & dosagem , Compostos de Mostarda Nitrogenada/farmacologia , Prednimustina/administração & dosagem , Prednimustina/farmacologia , Biomarcadores Tumorais , Feminino , Humanos , Injeções Intravenosas
6.
Eur J Haematol ; 66(1): 11-7, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11168502

RESUMO

Few studies have been performed regarding multiple myeloma (MM) in elderly patients. We report a retrospective series of 130 unselected patients with MM aged 75 yr or more at diagnosis. Presenting features were identical to those reported in younger patients, except for a higher rate of infection. Heavy comorbidity was characteristic of unselected geriatric patients. Ninety-four patients received conventional chemotherapy. The response rate was 62%. Treatment toxicity was mild. Median survival was 22 months. Durie-Salmon (DS) clinical stages II and III MM were severe and often led to death, while significantly more patients with DS stage I MM died from unrelated causes (p<0.0001). Univariate analysis showed that age > or = 85 yr, performance status > or = 2, creatinine level > or = 120 micromol/l, beta 2 microglobulin level > 4 mg/l, C-reactive protein level > 6 mg/l, platelet count < 100 x 10(9)/l, presence of infection and lack of response to chemotherapy were adverse prognostic factors for survival. In Cox multivariate regression analysis, age > or = 85 yr (p<0.0001), performance status > or = 2 (p<0.0001) and creatinine level > or = 120 micromol/l (p<0.0001) were independent factors in predicting short survival. This study provides evidence that in patients with symptomatic MM age should not be considered as a major obstacle to active treatment. Prospective clinical trials are needed in this population of patients and should include an assessment of quality of life.


Assuntos
Mieloma Múltiplo/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Comorbidade , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , França/epidemiologia , Humanos , Interferon-alfa/administração & dosagem , Tábuas de Vida , Lomustina/administração & dosagem , Masculino , Melfalan/administração & dosagem , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Proteínas do Mieloma/análise , Estadiamento de Neoplasias , Síndromes Paraneoplásicas/epidemiologia , Prednimustina/administração & dosagem , Prednisona/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem
7.
Anticancer Res ; 21(5): 3701-6, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11848547

RESUMO

The purpose of this study was to investigate the effect of long-term administration of G-CSF with regard to its impact on overall survival of patients with ovarian cancer. We report the results of a non-randomized trial on 64 patients with advanced ovarian cancer treated with 6 cycles of conventional chemotherapy. Chemotherapy comprised carboplatin 400 mg/m2 and epirubicin 70 mg/m2 on day 1 of each cycle and prednimustine 100 mg/m2 on days 3 to 7, every 28 days. Thirty-three patients received CEP chemotherapy with G-CSF support whereas 31 women received CEP chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day subcutanously on days 8 to 21 of each cycle. The severity of reduction in white cells and neutrophil count was significantly different in the two treatment groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users had a non significant 0.88-fold lower risk of dying from ovarian cancer (95% CI, 0.48-1.60, p=0.678). In a survival analysis using a Cox proportional hazards model, residual tumor remained as an independent prognostic factor. The increasing amount of residual tumor resulted in a 1.767-fold higher risk (95% CI, 1.23-2.53, p=0.002) of death secondary to the underlying disease. In conclusion, this trial has failed to demonstrate any negative impact on patients' overall survival for the additional use of G-CSF with platinum-based chemotherapy; our results were consistent with the beneficial effects of G-CSF treatment on cytotoxic chemotherapy-induced myelosuppression.


Assuntos
Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Esquema de Medicação , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Pessoa de Meia-Idade , Prednimustina/administração & dosagem , Prednimustina/efeitos adversos , Taxa de Sobrevida
8.
Clin Cancer Res ; 6(9): 3417-23, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10999723

RESUMO

Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug resistance protein (MRP1). To determine the clinical relevance of these multidrug resistance factors in previously untreated diffuse large B-cell lymphomas (n = 48), we studied LRP and MRP1 expression in lymphoma cells and their impact on clinical outcome. LRP and MRP1 expression were immunohistochemically assessed by means of the monoclonal antibodies LRP-56 and MRPr1, respectively. LRP was positive in 23% and MRP1 in 44% of the samples. LRP expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.01), and the International Prognostic Index (P = 0.0001). LRP-positive patients had a lower complete response rate to polychemotherapy than LRP-negative patients (18 versus 65%; P = 0.006). Patients with LRP expression had a shorter overall survival than those without LRP expression (median of 0.9 years versus median not reached; P = 0.001). MRP1 expression was independent of clinical and laboratory parameters and had no impact on the outcome of chemotherapy or survival of the patients. These data suggest that LRP expression but not MRP1 expression is an important mechanism of drug resistance associated with worse clinical outcome in previously untreated diffuse large B-cell lymphomas. Thus, the reversal of LRP-mediated drug resistance may improve clinical outcome in diffuse large B-cell lymphoma in the future.


Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas de Neoplasias/biossíntese , Partículas de Ribonucleoproteínas em Forma de Abóbada/biossíntese , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Doxorrubicina/administração & dosagem , Resistência a Múltiplos Medicamentos , Etoposídeo/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Lomustina/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Prednimustina/administração & dosagem , Prednisona/administração & dosagem , Análise de Regressão , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem
9.
Crit Rev Oncol Hematol ; 35(2): 95-100, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10936466

RESUMO

In elderly patients age-specific comorbidity often reduces the possibility of administering intensive chemotherapy and of obtaining response to treatment. Therefore, chemotherapy must differ from that for non-elderly patients, while maintaining the primary goal of a complete clinical response. We treated 19 patients over the age of 70 years (median age 75 years, range 70-86) with stage II-IV high-grade non-Hodgkin's lymphoma (NHL) with a combination regimen including idarubicin plus etoposide and prednimustine (or chlorambucil+prednisone), all administered orally on an outpatient basis. The therapeutic schedule included six 5-day courses of idarubicin 20 mg/sqm on day 1 (or 10 mg/sqm on days 1 and 3 in the nine patients last treated), etoposide 60 mg/sqm/12 h days 2-5, prednimustine 60 mg/sqm days 2-5, G-CSF 300 microg/day from day+7 until PMN>1000/microl. In ten patients prednimustine was replaced by chlorambucil 10 mg/sqm, days 2-5, and prednisone 50 mg days 2-5, because of non-availability of the drug. Of the 19 patients submitted to this regimen 15 (79%) obtained a clinical response: eight reached a complete response (CR), and seven a partial response (PR). Hematologic toxicity was generally mild. Only three patients had to be hospitalised for infection. Except alopecia, non-hematologic toxicities were negligible. At a median follow-up of 16 months, five of eight patients who obtained CR relapsed (median CR duration 7 months). The actuarial median survival is 34 months (range 6-46). This study demonstrates the feasibility and efficacy of an all-oral regimen including idarubicin, plus etoposide and prednimustine (or chlorambucil+prednisone) in NHL patients aged over 70 years.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Administração Oral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Agranulocitose/induzido quimicamente , Alquilantes/administração & dosagem , Alquilantes/efeitos adversos , Intervalo Livre de Doença , Avaliação de Medicamentos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Prednimustina/administração & dosagem , Prednimustina/efeitos adversos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
10.
Gynecol Oncol ; 72(2): 215-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10021304

RESUMO

OBJECTIVE: The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced ovarian cancer. METHODS: Between 1985 and 1992 64 patients with radically operated ovarian cancers (4 stage IC, 2 stage II, 54 stage III, and 4 stage IV) were enrolled in a randomized study. Radical surgery comprised total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and pelvic and paraaortic lymphadenectomy. All patients received adjuvant chemotherapy with carboplatin IV 400 mg/m2, epirubicin IV 70 mg/m2 on day 1 and prednimustine orally 100 mg/m2 on days 3 to 7 at 1-month intervals. Thirty-two patients without residual disease were randomized to whole abdominal radiation (30 Gy, administered over 4 weeks). An additional 21.6 Gy were delivered to the pelvis and 12 Gy to the paraaortic region up to the diaphragm for total doses of 51.6 and 42 Gy, respectively. Cancer-related survival was calculated with the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The relapse-free and overall survival rates of patients who received adjuvant chemoradiotherapy were significantly higher than those of patients who received adjuvant chemotherapy only (68% vs 56% at 2 years and 49% vs 26% at 5 years, P = 0.013, and 87% vs 61% at 2 years and 59% vs 33% at 5 years, P = 0.029). The differences were most pronounced in patients with stage III disease (77% vs 54% at 2 years and 45% vs 19% at 5 years, P = 0. 0061, and 88% vs 58% at 2 years and 59% vs 26% at 5 years, P = 0. 012). Toxicities were acceptable. CONCLUSION: Sequential combination of platinum-based chemotherapy with open-field abdominal radiotherapy is a promising adjuvant regimen for patients with advanced ovarian cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/radioterapia , Carboplatina/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Prednimustina/administração & dosagem , Radioterapia Adjuvante , Taxa de Sobrevida
11.
Am J Hematol ; 59(2): 156-60, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9766801

RESUMO

Elderly patients with intermediate- or high-grade non-Hodgkin's lymphoma have a worse outcome than those who are younger than 60 years. It has been shown that aggressive combination chemotherapy is poorly tolerated in older patients resulting in a subsequent decrease in dose intensity. A phase II trial was conducted with mitoxantrone, prednimustine, and vincristine (NSO) in this group of patients. NSO consists of mitoxantrone 12 mg/M2 intravenously on day one, vincristine 1.4 mg/M2 intravenously on day 1 (maximum dose of two mg), and prednimustine 100 mg/M2 orally once a day for four days. NSO was repeated every 21 days. Thirty-six patients were able to be evaluated. There were 18 males and 18 females with the median age of 71 (range 60-85). NSO was well tolerated and nonhematological toxicities were uncommon. More than 80% of the patients received 90% or greater of the intended dose. The complete response rate was 60.6% and partial response was 21.8%. At 60 months the Kaplan-Meier estimate of progression-free survival was 47.9% (standard error 8.6%) and actual survival was 40.6% (standard error 8.8%). There were no differences in outcome between those with performance status (PS) of zero or one and those with PS > 1. NSO is well tolerated by elderly patients including those with PS > 1. These results compare favorably with other combinations in elderly patients with aggressive non-Hodgkin's lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Mitoxantrona/administração & dosagem , Prednimustina/administração & dosagem , Vincristina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Mitoxantrona/toxicidade , Prednimustina/toxicidade , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/toxicidade
12.
J Clin Oncol ; 16(5): 1922-30, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9586911

RESUMO

PURPOSE: To compare mantle-cell lymphomas (MCLs) and follicle-center lymphomas (FCLs) for their features of clinical presentation, response to chemotherapy, and prognosis on the basis of a prospective randomized clinical trial. PATIENTS AND METHODS: Patients with MCL and FCL who entered onto the prospective randomized comparison of cyclophosphamide, vincristine, and prednisone (COP) versus prednimustine and mitoxantrone (PmM) followed by a second randomization for interferon (IFN) maintenance versus observation only. RESULTS: One hundred sixty-five of 234 patients had FCL and 45 of 234 patients had MCL. With FCL, both sexes were equally affected (men, 47%); patients with MCL were predominantly men (78%; P < .0004) and had a higher median age (64 v 53 years; P < .0001). Patients with MCL also had more widespread disease, reflected by the proportion of patients with two or greater extranodal manifestations (43% v 21%; P < .005) and nine or greater involved nodal areas (64% v 45%; nonsignificant [NS]). Response to chemotherapy was significantly lower in patients with MCL (complete remission [CR] + partial remission [PR], 69% v 88%; P < .05) and occurred at a slower pace. Patients with MCL also had a shorter event-free interval (median, 8 v 24 months; P < .0001) and overall survival (median, 28 v 77 months; P < .0001). In both subtypes, however, patients with less than two residual lymphoma manifestations in remission experienced a relatively good prognosis with an estimated 5-year survival of greater than 60% for MCL and greater than 75% for FCL. CONCLUSION: MCL and FCL differ substantially in their features of presentation, response to chemotherapy, and long-term prognosis. The extent of residual disease after completion of chemotherapy discriminates patients with different prognosis and may be used for the stratification of postremission strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Prednimustina/administração & dosagem , Prednisona/administração & dosagem , Estudos Prospectivos , Taxa de Sobrevida , Vincristina/administração & dosagem
13.
J Clin Oncol ; 16(1): 27-34, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9440719

RESUMO

PURPOSE: We report the results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group, which compared a chemotherapy regimen specifically devised for elderly patients, ie, etoposide, mitoxantrone, and prednimustine (VMP), versus the standard regimen of cyclophosphamide, doxorobucin, vincristine, and prednisone (CHOP) in patients older than 70 years of age with intermediate- and high-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients older than 70 years of age with stage II, III, or IV intermediate- and high-grade NHL, with an Eastern Cooperative Oncology Group (ECOG) performance status less than 4 and acceptable cardiac, renal, and liver function were randomized to receive six courses of VMP or six courses of CHOP. Between February 1989 and June 1994, 130 patients aged 70 to 93 years (median, 75) were enrolled and 120 were assessable for response, 60 patients in each arm. RESULTS: Overall objective response rates were 50% and 77% in VMP- and CHOP-treated patients, respectively (P = .01), while complete response (CR) rates were borderline significant (27% v 45%; P = .06). At 2 years, the progression-free survival (PFS) rate was 25% with VMP versus 55% with CHOP (P = .002) and the overall survival (OS) rate was 30% with VMP versus 65% with CHOP (P = .004). Statistically significant more alopecia and neurologic and gastrointestinal toxicities were reported with CHOP. CONCLUSION: CHOP is the standard regimen for patients > or = 70 years of age with stage II to IV intermediate- and high-grade NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Mitoxantrona/administração & dosagem , Prednimustina/administração & dosagem , Prednisona/administração & dosagem , Vincristina/administração & dosagem
14.
Leukemia ; 11 Suppl 2: S52-4, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9178841

RESUMO

We evaluated 1179 consecutive patients with low-grade B-NHL diagnosed according to criteria of the Kiel classification and presenting with initial bone marrow involvement. Therapeutic approaches were not changed during the observation period 1975-1995. CLL (n=895) and IC (n=169) were treated palliatively with chlorambucil/prednisone or prednimustine. In CBCC (n=65) and CC (n=50) remission was induced with COP or CHOP. The overall response rate was 67%, but only 35% of CBCC and 23% of CC patients achieved complete remission. Median survival was 64 months in CBCC and 28 months in CC. As the median age of our patient population was 68 years (range: 23-93) it seems doubtful whether overall prognosis can be improved by aggressive therapeutic measures. One exception might be CBCC patients who were younger (median age 56 years) and who were usually in good general condition so that they might qualify for high dosage chemotherapy and stem cell support. Whether the prognosis of IC and CLL (median survival 74 months and 107 months, respectively) can be improved by treatment with drugs such as purine analogs will depend on the long-term outcome of clinical studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Clorambucila/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Linfoma de Células B/mortalidade , Cuidados Paliativos , Prednimustina/administração & dosagem , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Vincristina/administração & dosagem
15.
Eur J Cancer ; 33(2): 312-5, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9135508

RESUMO

The aim of this study was to assess the efficacy and toxicity of an idarubicin-prednimustine combination in advanced breast cancer. 19 patients received idarubicin 35 mg/m2 day 1 and prednimustine 100 mg/m2 days 2-6, every 21 days. Three objective responses with a median duration of 7 months were observed. Tolerance was good. A further 23 patients were given idarubicin administered at 15 mg/m2 days 1, 2 and 3 and prednimustine at the aforementioned dosage. 8 (35%) showed an objective response (4 CRs, 4 PRs) with a median duration of 6 months. No severe toxicity was observed. Results suggest activity of idarubicin-prednimustine combinations in advanced breast cancer, and further studies are indicated since this regimen is easily administered, especially to elderly patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Administração Oral , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Esquema de Medicação , Feminino , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , Pessoa de Meia-Idade , Prednimustina/administração & dosagem , Prednimustina/efeitos adversos , Resultado do Tratamento
16.
Haematologica ; 82(1): 57-63, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9107084

RESUMO

BACKGROUND AND OBJECTIVE: This study examines the occurrence of solid tumor (ST) in relation to the different types of therapy (radiotherapy, chemotherapy and radiochemotherapy; splenectomy or splenic irradiation vs no splenectomy-no splenic irradiation) received by patients treated for Hodgkin's disease (HD). METHODS: The study included 1,045 HD patients treated at the Department of Radiation Oncology, the Institute of Radiology and the Department of Human Biopathology, Hematology Section, University of Rome, "La Sapienza", from 1972 to 1992. For 23% of the patients the follow-up period was longer than 10 years. The average follow-up period was 72 months. For a more accurate calculation of the risk of ST occurrence, the patients were first divided into 3 subgroups according to initial treatment and then according to the total treatment they had received. Moreover, to establish a probable connection between solid tumor and splenic treatment the patients were also divided into 3 subgroups (splenectomy, splenic irradiation and no splenectomy/no splenic irradiation). RESULTS: We recorded twenty-four cases of ST after initial treatment. Secondary solid tumor showed a cumulative risk of 0.2% and 13.4% at 5 and 20 years, respectively. After initial treatment with radiotherapy (RT) alone, the cumulative risk was 1.7% and 5.2% at 10 and 20 years, respectively; in the chemotherapy (CT) group, it was 2.4% and 18.1%; in the CT(+)RT group, it was 1.7% and 9%. No statistically significant differences were observed among the different types of treatment (splenectomy, splenic irradiation or no splenectomy/no splenic irradiation) as regards the occurrence of ST. According to multivariate analysis, the most important factor in the risk of ST was age (> 40). Relative risk was 5.2, p = 0.0001. INTERPRETATION AND CONCLUSIONS: We conclude that an age of over 40 at diagnosis and treatment with CT alone greatly increase the risk of solid tumor occurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Antineoplásicos/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Criança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Glioxal/administração & dosagem , Glioxal/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Doença de Hodgkin/cirurgia , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Itália/epidemiologia , Masculino , Mecloretamina/administração & dosagem , Mecloretamina/efeitos adversos , Pessoa de Meia-Idade , Análise Multivariada , Segunda Neoplasia Primária/etiologia , Prednimustina/administração & dosagem , Prednimustina/efeitos adversos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Radioterapia/efeitos adversos , Risco , Baço/efeitos da radiação , Esplenectomia/efeitos adversos , Análise de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos
17.
Oncology (Williston Park) ; 11(9 Suppl 10): 74-81, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9348574

RESUMO

Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a mean follow-up of 5.09 +/- 1.1 years (range, 2.9 to 7.1 years). The aim of the first trial was to demonstrate the activity of UFT 400 mg/day for 6 months plus prednimustine 60 mg/m2 for 7 consecutive days, every 28 days in 6 cycles given orally (arm B). This scheme was compared with 6 cycles of cyclophosphamide 600 mg/m2, plus methotrexate 40 mg/m2, plus fluorouracil 600 mg/m2, every 4 weeks (arm A). In this study, 187 premenopausal women were evaluable, 96 in arm A and 91 in arm B, all of whom had positive axillary nodes. Although there were more younger patients in arm A than in arm B, prognostic factors were similar in both groups. Disease-free survival and overall survival were similar in both arms. However, some concern is raised by the low disease-free survival rate. The toxicity was mild (mainly nausea and vomiting and alopecia) and slightly worse in arm A. We believe that oral administration could be a useful alternative to the parenteral route. In the second trial, 222 evaluable patients received 20 mg/day of tamoxifen (Nolvadex) for 1 year (arm A), or the same dose of tamoxifen plus UFT 400 mg/day for 6 months. All patients were postmenopausal, and the characteristics of the tumors were the same as those in patients in the first trial. In arm A there were 109 patients and in arm B, 113. The groups were well balanced. The overall survival and the disease-free survival rates were equal in both arms, but were longer in arm B in the subset of patients with five or more axillary-involved nodes. The toxicity was negligible in both arms. We conclude that UFT/tamoxifen might be useful in postmenopausal patients with five or more involved nodes who are unable to follow a more aggressive schedule because of their age or low performance status.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tegafur/uso terapêutico , Uracila/uso terapêutico , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Pós-Menopausa , Prednimustina/administração & dosagem , Pré-Menopausa , Espanha , Análise de Sobrevida , Tamoxifeno/administração & dosagem
18.
Leukemia ; 10(5): 836-43, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8656680

RESUMO

The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) in patients with advanced low-grade non-Hodgkin's lymphomas in way of a prospective randomized multicenter trial. Two hundred and forty-six patients with stage III or IV centroblastic-centrocytic (CB-CC (Kiel-classification)) or follicle center lymphoma (FCL (REAL classification)) and centrocytic (CC) or mantle-cell-lymphoma (MCL) were randomized for therapy with either PmM or COP and are fully evaluable for response and toxicity. PmM consisted of prednimustine 100 mg/m2/day on days 1-5 and mitoxantrone 8 mg/m2 /day days 1 and 2, while COP comprised cyclophosphamide 400 mg/m2/day on days 1-5, vincristine 1.4 mg/m2/day on day 1 and prednisone 100 mg/m2/day on days 1-5. Both regimens were repeated for a total of six cycles followed by an additional two courses for consolidation in responding cases and a subsequent second randomization for interferon alpha maintenance vs observation only. Overall response rates were comparable with 83% complete and partial remissions after COP and 84% remissions after PmM. PmM revealed a significantly higher rate of complete remissions (36 vs 18%, P < 0.006), the majority being achieved after four courses. The more rapid and possibly also more effective reduction of the lymphoma cell mass by PmM resulted in a tendency to a longer event-free interval for patients achieving remissions after PmM as compared to COP with estimated median event-free intervals of 31 vs 14 months, respectively (P=0.04). Separate analysis of lymphoma subtypes showed a tendency to a lower rate of complete remission in CC or MCL as compared to CB-CC or FCL (16 vs 30%, P=0.12, NS) while overall response rates were in a similar range (81 vs 85%). In both subtypes, PmM induced a higher rate of complete remission while overall response rates were comparable after PmM or COP. Treatment associated side-effects comprised predominantly myelosuppression and granulocytopenia in particular which was more frequently observed after PmM than COP (43 vs 31 %, P < 0.0001). This difference was clinically irrelevant, however, since serious infectious complications were encountered in less than 3% of cycles after both regimens. COP therapy was associated with a significantly higher incidence and degree of hair loss and complete alopecia (31 vs 2%) as well as of peripheral neurotoxicity (23 vs 2%). These data show that both PmM and COP reveal a high anti-lymphoma activity in patients with advanced stage non-Hodgkin's lymphoma. PmM appears advantageous with a higher rate of complete remissions and a better tolerability with regard to secondary side-effects. A longer follow-up is needed to assess the long-term effects of initial treatment on disease-free and overall survival and the impact on additional maintenance therapy with interferon alpha.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Prednimustina/administração & dosagem , Prednimustina/efeitos adversos , Indução de Remissão , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
19.
Cancer ; 77(10): 2127-31, 1996 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-8640681

RESUMO

BACKGROUND: There is very little experience reported in the literature on the treatment of patients with relapsed or resistant human immunodeficiency virus-related non-Hodgkin's lymphoma (HIV-NHL). We performed a prospective study to evaluate the feasibility and activity of a second-line chemotherapy regimen consisting of etoposide, mitoxantrone, and prednimustine (VMP) in this setting. METHODS: Twenty-one patients were consecutively treated. Thirteen patients were resistant to primary chemotherapy and 8 patients had relapsed after their first complete remission (CR). Etoposide and prednimustine were both given orally at doses of 80 mg/m2 daily for 5 days, and mitoxantrone was given intravenously at a dose of 10 mg/m2 on Day 1; the cycles were repeated every 3 weeks. RESULTS: Nineteen of 21 patients were evaluable for response. The median number of cycles administered was 2 (range, 1-5). A CR occurred in 5 of 19 patients (26%; exact 95% confidence interval; 9-51%). Four of these CRs were observed in the 7 evaluable relapsed patients. Of 45 cycles evaluable for toxicity, severe neutropenia (< 500/microL) occurred in 19 (42%) cycles and severe thrombocytopenia (< 25,000/microL) in 6 (13%) cycles. One toxic death occurred due to sepsis during neutropenia. The overall median survival was 2 months (range, < 1-13 months); the median survival time for the 5 patients with CR (13 months; range, 6-13 months) was statistically significantly longer than that observed in patients without CR (2 months; range, < 1-7 months). CONCLUSIONS: Although the overall prognosis of patients with resistant or relapsed HIV-NHL is very poor, palliative therapy with VMP can be effective and relatively safe in the latter group. Prolonged survival has been observed in some patients who had relapsed after initial chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por HIV/complicações , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Prednimustina/administração & dosagem , Prognóstico , Estudos Prospectivos , Recidiva , Taxa de Sobrevida
20.
Blood ; 86(10): 3970-8, 1995 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-7579368

RESUMO

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy. PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea , Medula Óssea/efeitos dos fármacos , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Células Sanguíneas , Medula Óssea/efeitos da radiação , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Carmustina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Citarabina/farmacologia , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/farmacologia , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Glioxal/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Células-Tronco Hematopoéticas/efeitos da radiação , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Humanos , Ifosfamida/administração & dosagem , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Melfalan/farmacologia , Pessoa de Meia-Idade , Análise Multivariada , Prednimustina/administração & dosagem , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Radioterapia/efeitos adversos , Estudos Retrospectivos , Terapia de Salvação , Vimblastina/administração & dosagem , Vincristina/administração & dosagem
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