Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/cirurgia , Adolescente , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Criança , Terapia Combinada , Ciclofosfamida/uso terapêutico , Seguimentos , Doença Enxerto-Hospedeiro , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/radioterapia , Recidiva , Indução de Remissão , SobreviventesRESUMO
In a series of five 17-d replicate trials, a total of 54 cannulated and 12 noncannulated pigs were used to determine the effects of weaning age (17 d or 24 d) on pH, dry matter percentage, aerobic and anaerobic microflora, lactate, and volatile fatty acid (VFA) concentrations in the jejunum, ileum, and cecum of weanling pigs. At -14 d of age, cannulated pigs were surgically fitted with T-cannulas in the jejunum (n = 20), ileum (n = 18), or cecum (n = 16). Upon weaning, cannulated pigs were individually caged in an environmentally controlled room with ad libitum access to a phase starter diet and water. Noncannulated pigs were killed at weaning and samples were collected from the jejunum, ileum, and cecum. Digesta and fecal swabs from cannulated pigs were collected twice weekly. The pH of cecal contents was lower (P < 0.05) and dry matter percentage was greater (P < 0.05) than those ofjejunal or ileal contents. Pigs weaned at 24 d of age had increased (P < 0.05) E. coli populations 3 d postweaning compared to preweaning populations, regardless of site of collection, whereas this increase was not observed in pigs weaned at 17 d of age. Unweaned pigs maintained higher (P < 0.05) lactobacilli populations compared to weaned pigs; however, populations declined (P < 0.05) in both groups by 3 d postweaning, with pigs weaned at 24 d of age having lactobacilli populations greater than pigs weaned at 17 d of age. Fecal populations of E. coli and lactobacilli declined (P < 0.05), whereas fecal bifidobacteria populations increased (P < 0.05) postweaning, regardless of weaning age. Concentrations of total fecal anaerobes declined (P < 0.05) in pigs weaned at 17 d of age but were maintained in pigs weaned at 24 d of age. Volatile fatty acid concentrations were greater (P < 0.05) in the cecum than in the jejunum or ileum, and acetic acid concentrations decreased (P < 0.05) postweaning regardless of weaning age. A tendency for L+ lactate concentrations to be greater (P < 0.07) in the ileum and jejunum vs the cecum was observed. Results indicate that weaning and weaning age have significant effects on microbial populations and VFA concentrations.
Assuntos
Ácidos Graxos Voláteis/análise , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Suínos/fisiologia , Desmame , Fatores Etários , Ração Animal , Animais , Bactérias Anaeróbias/crescimento & desenvolvimento , Bactérias Anaeróbias/isolamento & purificação , Ceco/metabolismo , Ceco/microbiologia , Contagem de Colônia Microbiana/veterinária , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/isolamento & purificação , Fezes/química , Fezes/microbiologia , Feminino , Conteúdo Gastrointestinal/química , Conteúdo Gastrointestinal/microbiologia , Hidrocortisona/sangue , Concentração de Íons de Hidrogênio , Íleo/metabolismo , Íleo/microbiologia , Jejuno/metabolismo , Jejuno/microbiologia , Lactatos/metabolismo , Lactobacillaceae/crescimento & desenvolvimento , Lactobacillaceae/isolamento & purificação , Masculino , Suínos/microbiologiaRESUMO
In the early 1990s, 4 randomized studies compared conditioning regimens before transplantation for leukemia with either cyclophosphamide (CY) and total-body irradiation (TBI), or busulfan (Bu) and CY. This study analyzed the long-term outcomes for 316 patients with chronic myeloid leukemia (CML) and 172 patients with acute myeloid leukemia (AML) who participated in these 4 trials, now with a mean follow-up of more than 7 years. Among patients with CML, no statistically significant difference in survival or disease-free survival emerged from testing the 2 regimens. The projected 10-year survival estimates were 65% and 63% with Bu-CY versus CY-TBI, respectively. Among patients with AML, the projected 10-year survival estimates were 51% and 63% (95% CI, 52%-74%) with Bu-CY versus CY-TBI, respectively. At last follow-up, most surviving patients had unimpaired health and had returned to work, regardless of the conditioning regimen. Late complications were analyzed after adjustment for patient age and for acute and chronic graft-versus-host disease (GVHD). CML patients who received CY-TBI had an increased risk of cataract formation, and patients treated with Bu-CY had an increased risk of irreversible alopecia. Chronic GVHD was the primary risk factor for late pulmonary disease and avascular osteonecrosis. Thus, Bu-CY and CY-TBI provided similar probabilities of cure for patients with CML. In patients with AML, a nonsignificant 10% lower survival rate was observed after Bu-CY. Late complications occurred equally after both conditioning regimens (except for increased risk of cataract after CY-TBI and of alopecia with Bu-CY).
Assuntos
Transplante de Medula Óssea , Imunossupressores/administração & dosagem , Leucemia Mieloide/terapia , Condicionamento Pré-Transplante/métodos , Irradiação Corporal Total , Adolescente , Adulto , Alopecia/epidemiologia , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Hipotireoidismo/epidemiologia , Imunossupressores/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Pneumopatias/epidemiologia , Metástase Neoplásica , Osteonecrose/epidemiologia , Estudos RetrospectivosAssuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/uso terapêutico , Transplante de Medula Óssea , Terapia Combinada , Humanos , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Monitorização Fisiológica , Recidiva , Transplante Homólogo , Estados UnidosRESUMO
One hundred seven adult patients with thalassemia aged from 17 through 35 years and transplanted from HLA-identical siblings between November 1988 and September 1996 were evaluated on December 31, 1997. The outcome experience of 20 consecutive patients transplanted between November 13, 1988 and January 10, 1991 and reported in September 1992 is updated after 5 additional years. The experience on 87 patients transplanted between May 1991 and September 1996 is described and evaluated as of the end of December 1997. Of 107 patients, 69 survive between 1.5 and 9 years after transplantation. Sixty-six of these patients do not have thalassemia and are identified as ex-thalassemic after bone marrow transplantation. The youngest survivor is 20 years old, 6 are older than 30 years, and the oldest is 37 years of age. Patients with chronic active hepatitis at the time of transplant were significantly more likely to die than patients without (P =.05; relative risk, 2.05). Marrow transplantation is a valid treatment option for older patients with thalassemia who have suitable donors and show deterioration with conventional therapy.
Assuntos
Transplante de Medula Óssea , Talassemia/terapia , Adolescente , Adulto , Feminino , Rejeição de Enxerto , Humanos , Masculino , Análise de Regressão , Análise de Sobrevida , Transplante HomólogoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Bussulfano/uso terapêutico , Terapia Combinada , Ciclofosfamida/uso terapêutico , Seguimentos , Humanos , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo , Irradiação Corporal TotalAssuntos
Transplante de Medula Óssea , Leucemia Mieloide/terapia , Condicionamento Pré-Transplante/métodos , Irradiação Corporal Total/métodos , Doença Aguda , Transplante de Medula Óssea/efeitos adversos , Bronquiolite Obliterante/etiologia , Carcinoma Broncogênico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Leucemia Mieloide/mortalidade , Tábuas de Vida , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Segunda Neoplasia Primária , Dosagem Radioterapêutica , Indução de Remissão , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Resultado do Tratamento , Irradiação Corporal Total/efeitos adversosRESUMO
Allogeneic marrow transplantation is curative therapy for thalassemia, but fewer than 30% of patients have an HLA-identical sibling marrow donor. Selection of alternative donors of hematopoietic stem cells (unrelated individuals or HLA-nonidentical family members) has been aided by establishment of world-wide donor registries now exceeding 3.6 million volunteers and by DNA-based HLA typing to more closely match potential donors. Coupled with improved methods to control graft-versus-host disease and prevent fungal and cytomegalovirus infection, remarkable progress has been made in alternative donor transplantation. For patients 50 years of age or younger, with recently diagnosed chronic myelogenous leukemia (CML) in chronic phase, 1- and 5-year survivals after HLA-A, B, DRB1 identical unrelated marrow transplantation in Seattle are 82% and 74%, respectively. These results are essentially identical to outcome in similar patients given HLA-matched sibling allografts. However, the world-wide number of alternative donor transplants for thalassemia remains limited to date: 4 unrelated and 60 HLA-nonidentical related transplants have been reported to the IBMTR since 1969 with actuarial overall survival of 75%. Using the paradigm of CML, it is likely that access to curative therapy of thalassemia will improve with optimal HLA typing and donor selection early in the course of disease.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Sistema de Registros , Talassemia/terapia , Obtenção de Tecidos e Órgãos/organização & administração , Teste de Histocompatibilidade , Humanos , Agências Internacionais , Leucemia/mortalidade , Doadores Vivos , Taxa de Sobrevida , Talassemia/mortalidade , Doadores de Tecidos , WashingtonRESUMO
BACKGROUND: Chronic myeloid leukemia can be cured by marrow transplantation from an HLA-identical sibling donor. The use of transplants from unrelated donors is an option for the 70 percent of patients without an HLA-identical sibling, but the morbidity and mortality associated with such transplants have been cause for concern. We analyzed the safety and efficacy of transplants from unrelated donors for the treatment of chronic myeloid leukemia and identified variables that predict a favorable outcome. METHODS: Between May 1985 and December 1994, 196 patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase received marrow transplants from unrelated donors. RESULTS: The median follow-up was 5 years (range, 1.2 to 10.1). Graft failure occurred in 5 percent of patients who could be evaluated. Acute graft-versus-host disease of grade III or IV severity was observed in 35 percent of patients who received HLA-matched transplants, and the estimated cumulative incidence of relapse at five years was 10 percent. The Kaplan-Meier estimate of survival at five years was 57 percent. Survival was adversely affected by an interval from diagnosis to transplantation of one year or more, an HLA-DRB1 mismatch, a high body-weight index, and an age of more than 50 years. Survival was improved by the prophylactic use of fluconazole and ganciclovir. The Kaplan-Meier estimate of survival at five years was 74 percent (95 percent confidence interval, 62 to 86 percent) for patients who were 50 years of age or younger who received a transplant from an HLA-matched donor within one year after diagnosis. CONCLUSIONS: Transplantation of marrow from an HLA-matched, unrelated donor is safe and effective therapy for selected patients with chronic myeloid leukemia.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide de Fase Crônica/terapia , Doadores de Tecidos , Adolescente , Adulto , Transplante de Medula Óssea/imunologia , Criança , Feminino , Seguimentos , Doença Enxerto-Hospedeiro , Teste de Histocompatibilidade , Humanos , Leucemia Mieloide de Fase Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Análise de Sobrevida , Fatores de TempoAssuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Sangue Fetal , Antígenos HLA , Humanos , Imunoterapia , Pessoa de Meia-Idade , Análise de Sobrevida , Fatores de Tempo , Transplante Autólogo , Transplante HomólogoRESUMO
Marrow transplantation from human leukocyte antigen (HLA) matched related donors offers a high probability of prolonged treatment-free survival for patients with chronic myeloid leukaemia in chronic phase. Delay, patient and donor gender, patient age and previous palliation with busulphan predict outcome in this setting. Because of the median age at diagnosis and the genetics of the HLA system, transplants from HLA-matched related donors are available to less than 15% of newly diagnosed patients. Alternative donors include relatives with minor degrees of incompatibility and HLA-compatible unrelated volunteers. The probability of finding suitable unrelated donors has increased with the development of a network of registries now containing more than 3.6 million donors worldwide. Survival prospects will be improved by transplantation earlier in the course of the disease, better-matched donors and the discovery of new approaches for the prevention of graft-versus-host disease and opportunistic infections.
Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Feminino , Teste de Histocompatibilidade , Humanos , Masculino , Doadores de Tecidos , Transplante Homólogo , Resultado do TratamentoAssuntos
Alquilantes , Anemia Aplástica/terapia , Soro Antilinfocitário , Transplante de Medula Óssea , Ciclofosfamida , Imunossupressores , Linfócitos T/imunologia , Condicionamento Pré-Transplante , Adolescente , Adulto , Alquilantes/efeitos adversos , Anemia Aplástica/mortalidade , Soro Antilinfocitário/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/efeitos adversos , Feminino , Seguimentos , Rejeição de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/efeitos adversos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Resultado do TratamentoRESUMO
The purpose of this report is to describe the results of stem cell transplantation as initial treatment for secondary acute myeloid leukemia (AML). Forty-six patients (median age 42 years) with secondary AML (17 therapy-related, 29 myelodysplasia-related) who had not received remission induction chemotherapy underwent allogeneic (n = 43) or syngeneic (n = 3) transplantation. The 5-year actuarial disease-free survival was 24.4%, and the cumulative incidences of relapse and nonrelapse mortality were 31.3% and 44.3%, respectively. Lower peripheral blood blast count was associated with a lower risk of relapse (P = .05) and shorter time from AML diagnosis to transplant was associated with a lower risk of nonrelapse mortality (P = .02) and improved disease-free survival (P = .026). Patients with therapy-related secondary AML tended to have lower disease-free survival (P = .16) and a higher relapse rate (P = .16) than patients whose leukemia was not therapy-related. The results of these 46 previously untreated patients were compared to 20 patients (median age 36 years, 12 therapy-related, 8 myelodysplasia-related) transplanted with chemotherapy-sensitive disease after induction chemotherapy (first complete remission [n = 6], second complete remission [n = 3], first untreated relapse [n = 11]). We found no statistically significant difference in outcome between these 2 groups of patients. These results suggest that prompt transplantation should be considered after diagnosis of secondary AML or, if possible, high-risk myelodysplasia, particularly in patients with low peripheral blast counts. Innovative transplant strategies are needed to reduce the high risks of relapse and nonrelapse mortality seen in this patient population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/terapia , Segunda Neoplasia Primária/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/etiologia , Leucemia Mieloide/mortalidade , Leucemia Induzida por Radiação/tratamento farmacológico , Leucemia Induzida por Radiação/mortalidade , Leucemia Induzida por Radiação/terapia , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/mortalidade , Modelos de Riscos Proporcionais , Radioterapia/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
The influence of busulfan (BU) plasma concentration on outcome of transplantation from HLA identical family members for the treatment of chronic myelogenous leukemia (CML) was examined in 45 patients transplanted in chronic phase (CP) (n = 39) or accelerated phase (AP) (n = 6). All patients received the same regimen of BU, 16 mg/kg orally and cyclophosphamide (CY), 120 mg/kg intravenously. Plasma concentrations of BU at steady state (C(SS)BU) during the dosing interval were measured for each patient. The mean C(SS)BU was 917 ng/mL (range, 642 to 1,749; median, 917; standard deviation, 213). Of patients with C(SS)BU below the median, seven (five of 18 in CP and two of four in AP) developed persistent cytogenetic relapse and three of these patients died. There were no relapses in patients with C(SS)BU above the median. The difference in the cumulative incidence of relapse between the two groups was statistically significant (P = .0003). C(SS)BU was the only statistically significant determinant of relapse in univariable or multivariable analysis. The 3-year survival estimates were 0.82 and 0.64 for patients with C(SS)BU above and below the median (P = .33). There was no statistically significant association of C(SS)BU with survival or nonrelapse mortality, although the power to detect a difference in survival between 0.82 and 0.64 was only 0.24, similarly C(SS)BU above the median was not associated with an increased risk of severe regimen-related toxicity. We conclude that low BU plasma levels are associated with an increased risk of relapse.
Assuntos
Transplante de Medula Óssea , Bussulfano/sangue , Leucemia Mieloide de Fase Acelerada/terapia , Leucemia Mieloide de Fase Crônica/terapia , Condicionamento Pré-Transplante , Adulto , Transplante de Medula Óssea/mortalidade , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Causas de Morte , Ciclofosfamida/administração & dosagem , Feminino , Rejeição de Enxerto/epidemiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Infecções/etiologia , Infecções/mortalidade , Leucemia Mieloide de Fase Acelerada/sangue , Leucemia Mieloide de Fase Acelerada/mortalidade , Leucemia Mieloide de Fase Acelerada/patologia , Leucemia Mieloide de Fase Crônica/sangue , Leucemia Mieloide de Fase Crônica/mortalidade , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Qualidade de Vida , Recidiva , Indução de Remissão , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Resultado do TratamentoRESUMO
Consecutive patients with non-Hodgkin's lymphoma (NHL, n = 133) or Hodgkin's disease (HD, n = 20) were treated with 12.0 Gy of fractionated total body irradiation, etoposide 60 mg/kg, and CY 100 mg/kg followed by infusion of autologous hematopoietic stem cells. Seventy-nine patients received purged (n = 62) or unpurged BM (n = 17), and 74 received unpurged PBSCs alone (n = 56) or with BM (n = 18). The median day for achieving a sustained granulocyte count of 0.5 x 10(9)/I was 14 range (7-66) for BM recipients and 10 (7-30) for PBSC +/- BM recipients (P = 0.03). A platelet count of 20 x 10(9)/I was achieved at a median of day 24 (6-145) in BM recipients and day 11 (range, 7-56) in PBSC +/- BM recipients (P = 0.007). The median number of platelet units transfused was 86 (0-1432) for BM recipients and 30 (6-786) for PBSC +/- BM recipients (P = 0.001). The median number of hospital days was 36 (10-88) for BM recipients and 27 (14-76) for PBSC +/- BM recipients (P = 0.0001). The unadjusted Kaplan-Meier (KM) estimates of survival, event-free survival (EFS) and relapse at 2 years were 0.57, 0.45 and 0.43 for patients receiving BM and 0.55, 0.36 and 0.59 for patients receiving PBSC +/- BM. After adjusting for confounding variables, the estimated relative risk (RR) of death from any cause was 0.92 (P = 0.75), of relapse was 1.25 (P = 0.39), of non-relapse mortality was 0.71 (P = 0.42) and of mortality and/or relapse was 1.17 (P = 0.48) for patients receiving PBSC +/- BM as compared to BM. For 46 patients with NHL receiving unpurged PBSC alone, the unadjusted KM estimate of relapse was 0.61 compared with 0.48 for 52 comparable patients receiving purged BM, while the RR for relapse for patients receiving unpurged PBSCs was 1.37 (P = 0.33) after adjusting for other significant covariates. These data confirm previous observations that patients who receive PBSC +/- BM have faster engraftment, fewer transfusions and shorter hospital stays than patients who receive only BM. There were no statistically significant differences between the two groups in survival, relapse, death from causes other than relapse and event-free survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Irradiação Corporal Total , Adolescente , Adulto , Purging da Medula Óssea , Transplante de Medula Óssea/mortalidade , Transplante de Medula Óssea/estatística & dados numéricos , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Sobrevivência de Enxerto , Fatores de Crescimento de Células Hematopoéticas/farmacologia , Fatores de Crescimento de Células Hematopoéticas/uso terapêutico , Humanos , Tábuas de Vida , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Linfoma/radioterapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Transplante Autólogo , Resultado do TratamentoRESUMO
The purpose of this study was to determine the toxicities and potential effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) followed by autologous peripheral blood stem cell (PBSC) infusion in patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC infusion in 104 patients with breast cancer (n = 48), malignant lymphoma (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and other malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Grade 3-4 regimen-related toxicities occurred in 14% of patients, causing regimen-related mortality in six (6%) patients with an overall transplant-related mortality of 9%. Transplant-related deaths occurred in 6/62 patients (10%) treated in an academic medical center and in 3/42 (7%) treated in a community cancer center. Complete remissions (CR) were achieved in 1/17 (6%) patients with refractory stage IV breast cancer, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) with more-advanced lymphoma and 4/4 with less-advanced lymphoma. These patients are alive and disease-free a median of 712, 279, 461 and 404 days after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 days after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regimen followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in patients with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have significant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Neoplasias/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/terapia , Bussulfano/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfoma/terapia , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias Ovarianas/terapia , Tiotepa/administração & dosagem , Transplante AutólogoRESUMO
PURPOSE: To evaluate the outcome of patients with multiple myeloma (MM) who received high-dose therapy followed by autologous bone marrow (BM) or peripheral-blood stem-cell (PBSC) infusion. PATIENTS AND METHODS: Sixty-three consecutive patients with MM received autologous BM (n = 13) or PBSC with or without BM (n = 50) following regimens that contained busulfan (Bu) and cyclophosphamide (Cy) (n = 18), modified total-body irradiation (TBI) followed by Bu and Cy (n = 36), or Bu, melphalan, and thiotepa (n = 9). Two thirds of the patients had resistant disease and 69% had received more than 6 months of previous chemotherapy. RESULTS AND CONCLUSION: Recovery of peripheral-blood cell counts was more rapid in patients who received PBSC with or without BM than in patients who received BM alone. Sixteen of 63 patients (25%) died of complications of treatment within 100 days. Nineteen (40%) of 48 assessable patients achieved a complete response (CR), 23 (48%) had a partial response (PR), and six (12%) had no response. The probabilities of survival and survival without relapse or progression for all 63 patients at 3.0 years were .43 and .21, respectively. The probability of relapse or progression at 3 years was .69, and 17 patients (27%) have died of progressive MM. The probabilities of survival and relapse-free survival at 3 years for the 19 patients who achieved a CR were .42 and .17, respectively. In the multivariate analysis, beta2-microglobulin levels more than 2.5 micrograms/mL, more than two regimens of prior therapy and eight cycles of treatment, time to transplant longer than 3 years from diagnosis, and prior radiation were associated with adverse outcomes. Additional strategies, such as intervention earlier in the disease course, improved treatment regimens, sequential high-dose treatments, and posttransplant therapies may improve outcome of selected patients with MM.
Assuntos
Antineoplásicos/uso terapêutico , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Idoso , Bussulfano/uso terapêutico , Causas de Morte , Terapia Combinada , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/radioterapia , Avaliação de Resultados em Cuidados de Saúde , Análise de SobrevidaAssuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transplante de Medula Óssea/imunologia , Antígenos HLA , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Taxa de Sobrevida , Fatores de Tempo , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Washington/epidemiologiaRESUMO
Thalassemia patients can be categorized as class 1 (minimal liver damage and iron overload), class 3 (extensive liver damage from iron overload), and class 2 (intermediate). These categories are prognostic for treatment outcome after marrow transplantation. Class 3 patients have more transplant-related mortality than other patients. This study examines transplantation outcome for class 3 patients. Records were reviewed of 215 patients in class 3 who received transplants in Pesaro from HLA-identical related donors between May 1, 1984 and May 1, 1994. The influence of pretransplant, peritransplant, and posttransplant variables on survival, relapse, and transplant-related mortality was examined by product-limit and proportional-hazards multivariate analysis. Age and conditioning regimen were influential on survival, and regimens with less than 200 mg/kg cyclosporine (CY) were associated with 5-year survival probabilities of .74 and .63 patients younger than 17 years and older patients, respectively. Transfusion history and regimen were influential on rejection with 5 year probabilities of .53 and .24 in patients who received less than or greater than 100 red blood cell transfusions before transplantation and regimens containing less than 200 mg/kg CY. Results of transplantation for patients with advanced thalassemia treatment have improved with the introduction of conditioning regimens with less CY. This has been associated with an increase in rejection (particularly in patients who have received < 100 red blood cell transfusions before transplant). Efforts at reducing the rejection rate by modifying the conditioning regimen should be concentrated on younger patients who have received a small number of transfusions. Patients with thalassemia who have HLA-identical family members should be transplanted before they are in class 3.