RESUMO
PURPOSE: The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS: Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION: LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Análise Atuarial , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Recidiva , Transplante HomólogoRESUMO
PURPOSE: We analyzed the safety and effectiveness of high-dose etoposide (2 g/m2) followed by granulocyte colony-stimulating factor (G-CSF) as a peripheral-blood progenitor cell (PBPC) mobilization regimen and assessed extent of tumor reduction in patients with breast cancer, non-Hodgkin's lymphoma (NHL), and Hodgkin's disease (HD). PATIENTS AND METHODS: One hundred sixty-nine consecutive patients who eventually underwent PBPC transplantation received treatment with high-dose etoposide (2 g/m2) followed by daily G-CSF (5 microg/kg). RESULTS: This mobilization method was effective in nearly all patients. No patients died of mobilization-related complications. A 50% reduction in tumor size was seen in 19% of assessable patients with breast cancer, 44% of those with NHL, and 38% of those with HD. Hematopoietic recovery (HR) following transplantation occurred in all patients. Patients with > or = 4 x 10(6) CD34+ cells/kg engrafted with neutrophils at a median of 9 days after transplant and patients with at least 1.2 x 10(6) CD34+/CD33- cells/kg achieved platelet recovery at a median of 15 days. CONCLUSION: Etoposide plus G-CSF is an effective and safe method for mobilization of PBPCs. Etoposide is an effective agent in tumor reduction in NHL and HD and is less effective in breast cancer. The substantially lower incidence of prior exposure to this agent compared with cyclophosphamide favors its use.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Etoposídeo/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Doença de Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Coleta de Amostras Sanguíneas , Neoplasias da Mama/terapia , Criopreservação , Etoposídeo/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Humanos , Imunofenotipagem , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.
Assuntos
Antineoplásicos/uso terapêutico , Transplante de Medula Óssea , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Hematopoese , Interleucina-3/uso terapêutico , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Idoso , Superfície Corporal , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Modelos Logísticos , Linfoma não Hodgkin/fisiopatologia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Proteínas Recombinantes de Fusão/uso terapêutico , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasias Meníngeas , Segunda Neoplasia Primária , Sarcoma Mieloide , Neoplasias Cutâneas , Adolescente , Adulto , Idoso , Aloenxertos , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/terapia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/terapia , Sarcoma Mieloide/mortalidade , Sarcoma Mieloide/terapia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapiaRESUMO
Conditioning regimens for transplantation are important in determining transplant outcome. This review focuses on transplantation in aplastic anemia and leukemia using marrow from HLA-identical siblings. Results of conditioning with newer regimens such as busulfan plus cyclophosphamide and etoposide plus total body irradiation are reviewed and compared to results achieved with cyclophosphamide and total body irradiation. The potential for improved results using recent innovations such as dose adjustment of busulfan, agents which may decrease transplant-related toxicity, and directed radiation are discussed.
Assuntos
Purging da Medula Óssea , Transplante de Medula Óssea , Anemia Aplástica/cirurgia , Soro Antilinfocitário , Purging da Medula Óssea/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Humanos , Leucemia/cirurgia , Depleção Linfocítica , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Linfócitos T , Transplante Homólogo , Irradiação Corporal Total/efeitos adversosRESUMO
The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.
Assuntos
Transplante de Medula Óssea/métodos , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Humanos , Leucemia Mieloide Aguda/terapia , Mieloma Múltiplo/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante Homólogo , Resultado do TratamentoRESUMO
We evaluated relapse-free survival and the incidence and type of complications in 17 patients aged 40 or older with chronic myelogenous leukemia, acute myelogenous leukemia, or lymphoma who underwent allogeneic marrow transplantation following busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Nine patients are disease-free survivors 5-38 months (median 26 months) following transplantation. The incidence of grades II-IV acute graft-versus-host disease was 35%. No significant difference was detected in the incidence of GVHD or interstitial pneumonia between patients aged 40 and older and a group of younger patients transplanted over the same time period. These observations should encourage consideration of allogeneic marrow transplantation in older patients and suggest that this busulfan-cyclophosphamide regimen is a promising alternative to regimens containing total-body irradiation in older individuals.
Assuntos
Transplante de Medula Óssea , Irradiação Corporal Total , Análise Atuarial , Doença Aguda , Adolescente , Adulto , Criança , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Contagem de Plaquetas , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidadeRESUMO
Five of 182 recipients of allogeneic bone marrow transplants performed between 2/84 and 6/90 developed seizures while receiving cyclosporine and methylprednisolone to prevent acute graft-versus-host disease. All received a radiation-free regimen of busulfan and cyclophosphamide as preparative therapy. Two patients received HLA-mismatched allografts; and three patients received marrow from HLA-identical sibling donors. Two patients had received extensive intrathecal therapy prior to transplantation. All patients were receiving standard prophylactic doses of CsA and MP at the time of onset (median 31 days posttransplantation) of seizures. Three patients had mild-to-moderate hypertension and varying degrees of morphologic evidence of microangiopathic hemolytic anemia. None had unusually low magnesium levels. Cyclosporine levels were not in the toxic range. Cranial magnetic resonance imaging and computed tomography (CT) showed bilateral abnormalities primarily in the posterior temporal, occipital, and parietal lobes. These abnormalities were shown to be transient on sequential MRI exams in two patients. Seizures as well as radiologic abnormalities resolved on stopping CsA and did not recur in 2 patients who subsequently received CsA in lower doses. These findings confirm and expand previous observations of CsA-associated seizures and demonstrate that they occur in allogeneic bone marrow transplant recipients following a radiation-free preparative regimen of busulfan and cyclophosphamide.
Assuntos
Transplante de Medula Óssea , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclosporinas/efeitos adversos , Convulsões/induzido quimicamente , Adolescente , Adulto , Encéfalo/anatomia & histologia , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Convulsões/patologia , Tomografia Computadorizada por Raios XRESUMO
We report the use of busulfan and cyclophosphamide as conditioning before allogeneic bone marrow transplantation for a 38-year-old man with multiple myeloma. Three months post-transplant the monoclonal IgA band previously present was no longer detectable in the serum and plasma cells were no longer visible in the marrow. The patient died on day 93 with fungal infection. We conclude that the combination of busulfan and cyclophosphamide could be valuable before transplant for other patients with multiple myeloma.
Assuntos
Transplante de Medula Óssea , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Mieloma Múltiplo/cirurgia , Cuidados Pré-Operatórios , Adulto , Humanos , Masculino , Mieloma Múltiplo/tratamento farmacológico , Cuidados Pré-Operatórios/métodos , Indução de RemissãoRESUMO
We report a case of sustained disease-free survival following second autologous marrow transplantation (BMT) in a patient with Hodgkin's lymphoma which had recurred following several conventional chemotherapy regimens as well as a prior autologous transplant. The initial autologous BMT was performed in fourth complete remission and followed high-dose cyclophosphamide, etoposide and thiotepa. The disease recurred 8 months later and the patient underwent a second ABMT following conditioning with busulfan and cyclophosphamide 1 year after his first transplant. Aside from slow engraftment, his course was uncomplicated. This patient remains in complete remission more than 4 years and 6 months following the second transplantation. This case demonstrates that second autologous transplantation can result in sustained disease-free survival in individuals with Hodgkin's disease with recurrence following initial transplantation.
Assuntos
Transplante de Medula Óssea , Doença de Hodgkin/cirurgia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Sobrevivência de Enxerto , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , Reoperação , Fatores de Tempo , Transplante AutólogoRESUMO
Ten patients with AML or CML aged 40-55 years underwent allogeneic marrow transplantation from HLA-identical siblings following a preparation regimen of busulfan 16 mg/kg and cyclophosphamide (CY) 90 mg/kg. The CY dose was substantially lower than has been previously used in combination with busulfan. All 10 individuals engrafted. Cytogenetic analysis of marrow and peripheral blood cells demonstrated similar patterns of chimerism to those previously described using higher CY doses. This study demonstrates that when administered with busulfan 16 mg/kg a dose of 90 mg/kg CY is adequately immunosuppressive to permit consistent engraftment of marrow from HLA-identical sibling donors.
Assuntos
Transplante de Medula Óssea/métodos , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea/efeitos adversos , Terapia Combinada , Citogenética , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Transplante HomólogoRESUMO
Nine individuals between 15 and 43 years of age with non-Hodgkin's lymphoma underwent allogeneic marrow transplantation following busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. These individuals were not considered optimal candidates for autologous transplantation chiefly because of marrow involvement or resistance to chemotherapy. All patients engrafted and eight achieved complete remission. Three patients relapsed; one patient died of transplant-related complications. Five individuals are disease-free survivors between 103 and 1169 days following transplantation. Of three individuals with relapsed Burkitt's lymphoma none experienced a sustained disease-free interval following transplantation. Three of four individuals with large cell or lymphoblastic lymphoma are surviving 585 to 1169 days following transplantation. Allogeneic marrow transplantation following busulfan and cyclophosphamide appears reasonably safe and is effective in selected patients with non-Hodgkin's lymphoma who are not good candidates for autologous marrow transplantation.
Assuntos
Transplante de Medula Óssea , Linfoma não Hodgkin/cirurgia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea/efeitos adversos , Bussulfano/administração & dosagem , Ensaios Clínicos como Assunto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Transplante HomólogoRESUMO
We describe here a patient with accelerated phase Philadelphia chromosome (Ph1) negative chronic myelogenous leukemia without BCR gene rearrangement, who received an allogeneic bone marrow transplant following a conditioning regimen consisting of busulfan (BU) and cyclophosphamide (CY). Hematopoiesis was restored following splenectomy performed 1 month post-transplant. There were no distinguishing cytogenetic differences between donor and host. Five years post-transplant the patient relapsed with the original disease. Restriction fragment length polymorphism (RFLP) studies performed at that time exhibited host specific DNA markers suggesting recurrent leukemia of host origin. RFLP analysis of the cells cryopreserved immediately post-transplant also revealed all cells to be of host origin. This patient experienced 5 years of remission with autologous hematopoietic recovery from an aggressive myeloproliferative disorder after high dose BU and CY without engraftment of donor hematopoietic cells.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Mieloide de Fase Acelerada/cirurgia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/cirurgia , Adulto , Purging da Medula Óssea , Bussulfano/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Marcadores Genéticos , Sobrevivência de Enxerto , Humanos , Hidroxiureia/administração & dosagem , Leucemia Mieloide de Fase Acelerada/tratamento farmacológico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Polimorfismo de Fragmento de Restrição , Indução de Remissão , Esplenectomia , Transplante HomólogoRESUMO
The mechanism by which GVHD augments the graft-versus-leukemia (GVL) effect of marrow transplants has not been ascertained. One possibility involves the secondary activation of natural killer (NK) cells by cytokines released during the GVHD process. To evaluate this possibility we have compared NK activity and lymphokine-activated killer cell precursor (LAKp) frequencies in serially sampled PBMC from recipients of unmanipulated autologous or allogeneic marrow with and without active GVHD. NK activity recovered rapidly after BMT and was elevated during episodes of acute GVHD. However, NK activity did not differ between recipients of autologous or allogeneic marrow without GVHD nor was NK activity increased in association with chronic GVHD. Endogenously-activated NK cells were detected only in recipients of allogeneic marrow but this did not correlate with GVHD status. In contrast to NK activity, LAKp frequencies fell below the control range during the first 8 weeks after BMT. By 9-14 weeks the median LAKp frequency was normal and did not differ between the three groups then or later after transplant. We conclude that acute GVHD may serve to increase the lytic activity of NK cells but does not result in increased LAKp. LAKp frequencies are below normal during the first two months after BMT, a finding not previously recognized from bulk culture LAK studies. The role of LAK effectors in GVL may involve more the degree of cellular activation rather than the number of cells activated.
Assuntos
Transplante de Medula Óssea/imunologia , Doença Enxerto-Hospedeiro/imunologia , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/imunologia , Doença Aguda , Anemia Aplástica/imunologia , Anemia Aplástica/cirurgia , Transplante de Medula Óssea/efeitos adversos , Humanos , Leucemia/imunologia , Leucemia/cirurgia , Linfoma/imunologia , Linfoma/cirurgia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/cirurgia , RecidivaRESUMO
Between May 1987 and September 1989, 72 patients undergoing marrow transplantation at a single institution were randomized to receive 50 mg/kg of a commercial gammaglobulin preparation or placebo daily in four divided doses for 28 days following transplantation. Patients receiving oral gammaglobulin had significantly increased concentrations of stool IgG (p = 0.01) compared with the placebo group. There was no difference in the amount of diarrhea, frequency of GVHD, duration of hospitalization or survival in the two groups. The present study demonstrates that orally administered IgG can survive passage through the gastrointestinal tract of bone marrow transplantation recipients but there was no effect of oral administration of immunoglobulin on morbidity or mortality following bone marrow transplantation.
Assuntos
Transplante de Medula Óssea/efeitos adversos , gama-Globulinas/administração & dosagem , Administração Oral , Anemia Aplástica/cirurgia , Transplante de Medula Óssea/imunologia , Método Duplo-Cego , Fezes/química , Gastroenteropatias/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunoglobulina G/análise , Controle de Infecções , Leucemia/cirurgia , Linfoma/cirurgiaRESUMO
Long-term outcome was analyzed in 28 patients transplanted between 1989 and 1992 following busulfan and cyclophosphamide and who had busulfan levels studied. While there was no significant correlation of busulfan levels with diagnosis, patients who had received extensive prior chemotherapy had a significantly higher area under the curve (AUC; P = 0.02) and maximum busulfan levels (Cmax; P = 0.03). High AUC was associated with the development of hepatic veno-occlusive disease (P = 0.03) and with early transplant-related mortality (P = 0.06). No significant correlation of busulfan levels with relapse, late non-relapse death, late complications, nor event-free survival was detected.
Assuntos
Antineoplásicos Alquilantes/toxicidade , Bussulfano/toxicidade , Hepatopatia Veno-Oclusiva/induzido quimicamente , Adolescente , Adulto , Antineoplásicos Alquilantes/sangue , Antineoplásicos Alquilantes/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Área Sob a Curva , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/mortalidade , Bussulfano/sangue , Bussulfano/farmacocinética , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Estudos Longitudinais , Condicionamento Pré-Transplante/efeitos adversos , Resultado do TratamentoRESUMO
Prognostic factors in 42 patients aged 11 to 62 (median 46) years, with myelodysplastic syndrome (MDS) or after leukemic transformation, who underwent allogeneic marrow transplantation between 1984 and 1999 were analyzed. Thirty-six had advanced disease morphology; 19 had leukemic transformation. Twenty-nine received a preparative regimen of BuCy2 and 13 busulfan 14 mg/kg, etoposide 50 mg/kg and cyclophosphamide 120 mg/kg. Severe hepatic veno-occlusive disease (VOD) occurred in three patients all of whom received anti-leukemic chemotherapy prior to transplantation. Fifteen patients (36%) died from early transplant-related complications; nine patients relapsed. The estimated 4 year disease-free survival (DFS) was 35% (95% CI 26-44%). Older age was the most significant adverse prognostic factor. Patients with leukemic transformation who underwent early transplantation had significantly better DFS than those treated first with chemotherapy (P = 0.002). Delayed toxicity was rare in these patients; no late relapses occurred. Bone Marrow Transplantation (2000) 25, 1219-1222.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Transplante de Medula Óssea , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Adulto , Criança , Terapia Combinada , Humanos , Leucemia/fisiopatologia , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/fisiopatologia , Prognóstico , Transplante HomólogoRESUMO
Therapeutic options for patients with Hodgkin's disease who relapse after high-dose chemotherapy with autologous stem cell support are limited. Salvage chemotherapy is not curative, and allogeneic stem cell transplantation in this setting is associated with mortality rates of 40-65%. We report our institution's experience with second autologous transplants in this patient population. Five patients (median age 36) with relapsed Hodgkin's disease underwent a second autologous stem cell transplant at a median of 66 months after first transplant. Four patients received CBV, and one patient received BuCy as conditioning. Neutrophil and platelet engraftment occurred by days +10 and +16, respectively. All patients achieved a complete response, and no relapses have occurred after a median follow-up of 42 months. All four patients who received CBV developed interstitial pneumonitis, and two patients died of pulmonary complications 37 and 48 months following second transplant. Three patients remain alive and disease-free 41, 42 and 155 months after second transplant. These data indicate that second autologous transplantation should be considered for selected patients who relapse after a prolonged response to first autologous transplant. However, BCNU pneumonitis is the major toxicity in patients who have undergone previous mantle radiation and received busulfan with first transplant.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Causas de Morte , Feminino , Seguimentos , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/mortalidade , Humanos , Cinética , Masculino , Recidiva , Indução de Remissão , Terapia de Salvação , Transplante Autólogo/métodosRESUMO
The results of autologous and allogeneic BMT in 44 patients with Hodgkin's or non-Hodgkin's lymphomas who received preparative therapy consisting of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg are presented. Sixteen patients are surviving free of disease between 8 months and 6 years after transplantation. Thirteen patients either did not attain complete remission or experienced a recurrence of their disease. Fifteen patients died from treatment-related complications. Karnofsky score < or = 70, lactate dehydrogenase greater than twice normal and the development of hepatic veno-occlusive disease were associated with failure to achieve lymphoma-free survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Bussulfano/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/radioterapia , Doença de Hodgkin/cirurgia , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/radioterapia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Two major problems of unrelated donor transplantation have been an increased incidence of GVHD and graft failure. Even with HLA identity by microlymphocytotoxicity assay and non-reactive MLC, URD marrow transplant recipients have a higher incidence of graft rejection and GVHD. The preparative regimen busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BuCy2) has been shown to be at least as effective in preparation of recipients with CML of HLA-identical sibling grafts as cyclophosphamide and total body irradiation (Cy/TBI). However, concern about a high rejection rate in URD transplants has prevented most centers from using BuCy2 in this setting. From March 1990 to March 1994, 26 patients underwent URD transplantation following preparation with BuCy2. Patients received either standard cyclosporine and methotrexate or cyclosporine and methylprednisolone for GVHD prophylaxis. Two patients died on day 16 and 20 without evidence of hematopoietic engraftment. Of the 24 patients evaluable for engraftment, 23 (96%) had evidence of donor engraftment defined as an ANC > 0.5 x 10(9)/1. No patient who had initial engraftment had late graft failure. Within our study group the risk of graft rejection or graft failure does not appear to be higher than that reported for URD transplants utilizing TBI-containing regimens.