RESUMO
Testicular cancer patients refractory or in relapse after primary chemotherapy have < or =25% 5-year progression-free survival with salvage. To improve prognosis, patients entered a phase I/II tandem dose-escalation trial of carboplatin (1500-2100 mg/m(2)) and etoposide (1200-2250 mg/m(2)) with ABMT. Patients were eligible for a second cycle if disease progression was absent and performance status allowed. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. At the time of ABMT, 10 were chemosensitive, four were chemoresistant, and 10 were absolutely refractory to platinum. Disease status (no. patients) at transplant: primary refractory disease (six), first relapse (10), second relapse (eight), third relapse (five). Fifteen (52%) received both transplants. Treatment-related mortality was 10%. Best response after ABMT included: two CR, one CR surgically NED, five PR, three PR surgically NED, seven SD, and eight PD. Eight (28%) patients are continuously progression-free a median 60 months (range, 31-93) from first ABMT. Three seminoma patients remain progression-free. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. Eighteen relapses occurred a median of 4 months after ABMT I (two late relapses at 28 and 44 months). The median PFS and OS for the whole group are 4 and 14 months, respectively. Patients with relapsed/ refractory testicular cancer benefit most from ABMT if they have platinum-sensitive disease in first relapse. Patients who do poorly despite ABMT have a mediastinal primary site, true cisplatin-refractory disease, disease progression prior to ABMT, and/or markedly elevated betaHCG at ABMT. New treatment modalities are needed for the latter group.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Testiculares/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Transplante de Medula Óssea/mortalidade , Carboplatina/administração & dosagem , Carboplatina/toxicidade , Estudos de Coortes , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/toxicidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/terapia , Recidiva , Terapia de Salvação , Neoplasias Testiculares/mortalidade , Transplante Autólogo/mortalidade , Resultado do TratamentoRESUMO
We performed a multicenter comparative analysis of autologous peripheral blood stem cell transplantation (PBSCT) and allogeneic bone marrow transplantation (alloBMT) in multiple myeloma. Forty-eight consecutive patients received either PBSCT (24 patients) or alloBMT (24 patients) at one of three institutions in the study group. Preparatory regimens consisted of melphalan and total body irradiation (TBI) or melphalan alone in the PBSCT group. The alloBMT group received one of four regimens: cyclophosphamide and TBI; cyclophosphamide, VP-16 and 1,3-bis(2-chloroethyl)-1-nitrosourea (CVB); busulfan and cyclophosphamide (BU/CY) and total marrow irradiation (TMI); or melphalan and TBI. Procedure-related mortality was 12.5% for the PBSCT group and 25% for the alloBMT group. With a median follow-up for survivors in the PBSCT and alloBMT groups of 11 months (range, 4-46) and 15 months (range, 2-84 months), respectively, there was no significant difference in median overall survival (33.5 versus 38.6 months, p = 0.7637) or event-free survival (16.7 versus 31 months, p = 0.8450). There was, however, a plateau in survival at 40% in the alloBMT group. No plateau in survival was seen in the PBSCT group. Clinical relapses occurred as late as 39 months posttransplant. Patients have survived up to 28 months postrelapse.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Purging da Medula Óssea , Bussulfano/administração & dosagem , Carmustina/administração & dosagem , Causas de Morte , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Autólogo , Transplante Homólogo , Irradiação Corporal TotalRESUMO
Autoimmune neutropenia (AIN) is characterized by antibody mediated peripheral destruction of neutrophils. Since there is no effective treatment, antibiotics have to be used frequently for recurrent infections. Five selected patients with serologically proven AIN were treated with r-metHuG-CSF at 5-8 micrograms/kg body weight (300-480 micrograms) daily; the dose and frequency of r-metHuG-CSF was reduced after neutrophil counts above 1.0 x 10(9)/l were obtained. R-metHuG-CSF is effective in AIN and causes a sustained rise in ANC which can be maintained on a low dose administered twice or thrice weekly.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neutropenia/imunologia , Adulto , Idoso , Doenças Autoimunes/patologia , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Neutropenia/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Fatores de TempoRESUMO
We conducted a study to evaluate the efficacy of the combination of tacrolimus and short-course methotrexate for the prevention of acute GVHD in patients with hematologic malignancies. Patients received preparative regimens specific for their disease category. Twenty-six out of 28 received HLA-identical sibling transplants and the two remaining patients received one-antigen mismatched transplants from a family member. With a median follow-up of 14 months, the Kaplan-Meier estimate of event-free survival was 50 +/- 9%. The probability of grade II-IV GVHD was 15 +/- 7%. Four patients developed GVHD: two had grade II and one each developed grade III and IV GVHD. Administration of methotrexate was associated with severe mucositis and there was no correlation between the distribution of the GVHD grade and the cumulative dose of methotrexate given. Thirteen patients have died; nine from transplant-related complications and four from relapse. The major toxicity of tacrolimus was renal. Nine out of 28 patients (32%) developed renal dysfunction attributed to tacrolimus. The combination of tacrolimus and methotrexate is an effective regimen for GVHD prophylaxis but associated with significant renal and mucosal toxicity. Further studies of tacrolimus as a single agent or in combination with either steroids or with a lower dose of methotrexate or with other antiproliferative drugs to modify the adverse events may improve the therapeutic index of this useful and promising agent.
Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Imunossupressores/administração & dosagem , Metotrexato/administração & dosagem , Tacrolimo/administração & dosagem , Doença Aguda , Adulto , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/mortalidade , Quimioterapia Combinada , Feminino , Sobrevivência de Enxerto , Neoplasias Hematológicas/mortalidade , Humanos , Hiperbilirrubinemia/etiologia , Imunossupressores/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Recidiva , Insuficiência Renal/etiologia , Tacrolimo/efeitos adversos , Transplante HomólogoRESUMO
A 49-year-old man with t(8; 21) acute myeloid leukemia relapsed 8 months after successful induction chemotherapy with a paraspinal granulocytic sarcoma. There was no evidence of leukemia in the bone marrow at relapse. At initial presentation, the blasts co-expressed CD 15, CD 33, CD 34, CD 45, CD 19, and CD 56 (a neural cell-adhesion molecule). Expression of certain cell-adhesion molecules on leukemic blasts may determine a tendency to develop extramedullary relapse. The co-expression of CD 56 may have a role in the predisposition of t(8; 21) AML to develop GS.
Assuntos
Leucemia Mieloide Aguda/complicações , Leucemia Mieloide/complicações , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Antígeno CD56 , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas , Translocação GenéticaRESUMO
PURPOSE: Detection of occult carcinoma in patients with breast cancer may aid the establishment of prognosis and development of new therapeutic approaches. To improve on existing methods of detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for keratin 19 (K19) transcripts to identify mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. PATIENTS AND METHODS: Peripheral-blood or bone marrow samples obtained from 34 patients with stages I to IV breast cancer and 39 control subjects without breast cancer were screened for K19 mRNA by nested primer PCR. RESULTS: In reconstitution experiments, K19 RT-PCR reliably detected 10 mammary carcinoma cells in 1 million normal peripheral-blood mononuclear (PBMN) cells. Four of 19 patients with stage IV breast cancer had detectable K19 transcript in peripheral blood. Five of six patients with histologically negative bone marrow biopsies following preablative chemotherapy and before autologous bone marrow transplant (BMT) were positive by this assay. Stem-cell apheresis harvests obtained from one of these patients and three additional patients immediately before BMT were all K19-negative. K19 RT-PCR analysis of CSF from a breast cancer patient with known carcinomatous meningitis was also positive. Thirty-eight of 39 non-breast cancer patients had negative K19 RT-PCR assays. The one exception was a patient with chronic myelogenous leukemia. CONCLUSION: RT-PCR of K19 is a sensitive, specific, and rapid method for detection of occult mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. The presence of residual breast cancer cells in histologically normal bone marrow aspirates but not in stem-cell apheresis harvests is a frequent finding. This assay may be useful in diagnosing metastatic disease, as well as in monitoring the effectiveness of systemic therapy.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Queratinas/análise , Sequência de Bases , Medula Óssea/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Queratinas/genética , Dados de Sequência Molecular , Metástase Neoplásica/diagnóstico , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análise , RNA Neoplásico/análise , DNA Polimerase Dirigida por RNA , Sensibilidade e EspecificidadeRESUMO
Significant morbidities are associated with the routine administration of blood products. Although the exact etiology of these complications may be unknown, many are thought to arise from the incidental cotransfusion of "donor" lymphocytes. We have developed an assay to detect small numbers of male white blood cells (WBCs) circulating in female patients who have received multiple blood transfusions using the polymerase chain reaction (PCR). Twenty female patients undergoing major surgical procedures were studied and received an average of 9.3 U of packed red blood cells (4.8 U from male donors) and 11.7 U of platelets (6.1 U from male donors). DNA was extracted from whole blood or peripheral blood buffy coats posttransfusion and PCR performed using oligonucleotides designed to amplify a segment within the repetitive Y-chromosome DYZ1 locus. Posttransfusion, 15 of 20 women showed evidence of circulating male WBCs for an average of 2.0 days (range, 1 to 6). We conclude that (1) DYZ1 PCR analysis is a useful approach for the detection of small numbers of circulating transfused male WBCs in female patients; and (2) circulating donor WBCs persist for a mean of 2.0 days in the majority of women receiving multiple transfusions. Future application of this technique may detect persisting or proliferating WBCs and lead to an improved understanding of common transfusion-related morbidities.