RESUMO
We evaluated ABO associated outcomes in 1737 patients who underwent allogeneic hematopoietic cell transplantation (allo-HCT) at Stanford University between January 1986 and July 2011. Grafts were 61% ABO matched, 18% major mismatched (MM), 17% minor MM, and 4% bidirectional MM. Median follow-up was 6 years. In multivariate analysis, overall survival (OS) was inferior in minor MM hematopoietic cell transplantations (median 2.1 versus 6.3 years; hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.19 to 2.05; P = .001) in comparison with ABO-matched grafts. ABO minor MM was associated with an increase in early nonrelapse mortality (NRM) (18% versus 13%; HR, 1.48; 95% CI, 1.06 to 2.06; P = .02). In an independent Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 435 lymphoma patients receiving mobilized peripheral blood grafts, impairment of OS (HR, 1.55; 95% CI, 1.07 to 2.25; P = .021) and increased NRM (HR, 1.72; 95% CI, 1.11 to 2.68; P = .03) were observed in recipients of ABO minor-MM grafts. A second independent analysis of a CIBMTR data set including 5179 patients with acute myeloid leukemia and myelodysplastic syndrome identified a nonsignificant trend toward decreased OS in recipients of ABO minor-MM grafts and also found ABO major MM to be significantly associated with decreased OS (HR, 1.19; 95% CI, 1.08 to 1.31; P < .001) and increased NRM (HR, 1.23; 95% CI, 1.08 to 1.4; P = .002). ABO minor and major MM are risk factors for worse transplantation outcomes, although the associated hazards may not be uniform across different transplantation populations. Further study is warranted to determine which patient populations are at greatest risk, and whether this risk can be modified by anti-B cell therapy or other peri-transplantation treatments.
Assuntos
Sistema ABO de Grupos Sanguíneos , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
AIM: The influence of non-surgical periodontal therapy on oral health-related quality of life (OHQoL) was investigated. MATERIALS AND METHODS: Sixty-five Chinese adults (25 men, mean 47.4 years) with moderate-to-advanced chronic periodontitis were recruited. All received oral hygiene instructions (OHI) and non-surgical periodontal treatment in a quadrant-wise approach, followed by recalls at 1, 3, 6, 9 and 12 months post treatment, when OHI and prophylaxis were repeated. Clinical parameters were recorded, and oral health impact profile short-form (OHIP-14S) was administered at all time points. RESULTS: Moderate-to-deep sites (≥4 mm) decreased from 31.0% to 3.0% at 12 months post treatment (p < 0.005) which corresponded well with reductions in plaque, 72.8% to 25.4% (p < 0.005) and bleeding on probing, 86.3% to 32.0% (p < 0.005). Median OHIP-14S scores gradually reduced from 17 at baseline to 14 over the first 6 months and remained plateaued at 12-month post treatment (p < 0.005). Improvements in subdomains of physical pain, psychological discomfort and psychological disability accounted for the changes. CONCLUSION: This study demonstrates that OHQoL, in particular, pain and psychological subdomains, improvement was associated with non-surgical periodontal therapy responses. Clinicians could capitalize upon the positive psychological OHQoL impacts of mechanical periodontal treatment for subsequent patient-centred motivation during maintenance therapy.
Assuntos
Periodontite Crônica/terapia , Profilaxia Dentária/métodos , Saúde Bucal , Qualidade de Vida , Adulto , Periodontite Crônica/prevenção & controle , Periodontite Crônica/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Higiene Bucal , Cooperação do Paciente/psicologia , Estudos Prospectivos , Perfil de Impacto da Doença , Resultado do TratamentoRESUMO
The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naïve donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control.
Assuntos
Soro Antilinfocitário/efeitos adversos , Infecções por Citomegalovirus/virologia , Imunossupressores/efeitos adversos , Irradiação Linfática/efeitos adversos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Antígenos Virais/sangue , Antígenos Virais/imunologia , Soro Antilinfocitário/imunologia , Soro Antilinfocitário/uso terapêutico , Antivirais/imunologia , Antivirais/uso terapêutico , Citomegalovirus/imunologia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/imunologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Transplante , Transplante Homólogo , Carga Viral , Viremia/tratamento farmacológico , Viremia/imunologia , Adulto JovemRESUMO
Donor leukocyte infusions induce remissions in some patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (HCT); however, graft-versus-host disease (GVHD) remains the major complication of this strategy. Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes that express the CD3(+)CD56(+) phenotype and show marked up-regulation of the natural killer cell receptor NKG2D (CD314). CIK cells are non-major histocompatibility complex-restricted and NKG2D-dependent in target recognition and cytotoxicity. We explored the feasibility of ex vivo expansion of allogeneic CIK cells in patients with relapsed hematologic malignancies after allogeneic HCT. Eighteen patients (median age, 53 years; range, 20-69 years) received CIK cell infusions at escalating doses of 1 × 10(7) CD3(+) cells/kg (n = 4), 5 × 10(7) CD3(+) cells/kg (n = 6), and 1 × 10(8) CD3(+) cells/kg (n = 8). The median expansion of CD3(+) cells was 12-fold (range, 4- to 91-fold). CD3(+)CD56(+) cells represented a median of 11% (range, 4%-44%) of the harvested cells, with a median 31-fold (range, 7- to 515-fold) expansion. Median CD3(+)CD314(+) cell expression was 53% (range, 32%-78%) of harvested cells. Significant cytotoxicity was demonstrated in vitro against a panel of human tumor cell lines. Acute GVHD grade I-II was seen in 2 patients, and 1 patient had limited chronic GVHD. After a median follow-up of 20 months (range, 1-69 months) from CIK infusion, the median overall survival was 28 months, and the median event-free survival was 4 months. All deaths were due to relapsed disease; however, 5 patients had longer remissions after infusion of CIK cells than from allogeneic HCT to relapse. Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD, supporting further investigation as an upfront modality to enhance graft-versus-tumor responses in high-risk patient populations.
Assuntos
Células Matadoras Induzidas por Citocinas/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunoterapia Adotiva/métodos , Adulto , Idoso , Quimerismo , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/etiologia , Neoplasias Hematológicas/imunologia , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Recidiva , Transplante Homólogo/efeitos adversos , Adulto JovemRESUMO
Autologous hematopoietic cell transplantation with augmented BCNU regimens is effective treatment for recurrent or refractory Hodgkin lymphoma (HL); however, BCNU-related toxicity and disease recurrence remain challenges. We designed a conditioning regimen with gemcitabine in combination with vinorelbine in an effort to reduce the BCNU dose and toxicity without compromising efficacy. In this phase I/II dose escalation study, the gemcitabine maximum tolerated dose (MTD) was determined at 1250 mg/m(2), and a total of 92 patients were treated at this dose to establish safety and efficacy. The primary endpoint was the incidence of BCNU-related toxicity. Secondary endpoints included 2-year freedom from progression (FFP), event-free survival (EFS), and overall survival (OS). Sixty-eight patients (74%) had 1 or more previously defined adverse risk factors for transplant (stage IV at relapse, B symptoms at relapse, greater than minimal disease pretransplant). The incidence of BCNU-related toxicity was 15% (95% confidence interval, 9%-24%). Only 2% of patients had a documented reduction in diffusing capacity of 20% or greater. With a median follow-up of 29 months, the FFP at 2 years was 71% and the OS at 2 years was 83%. Two-year FFP was 96%, 72%, 67%, and 14% for patients with 0 (n = 24), 1 (n = 37), 2 (n = 23), or 3 (n = 8) risk factors, respectively. Regression analysis identified PET status pretransplant and B symptoms at relapse as significant prognostic factors for FFP. This new transplant regimen for HL resulted in decreased BCNU toxicity with encouraging FFP and OS. A prospective, risk-modeled comparison of this new combination with other conditioning regimens is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/terapia , Estudos Prospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina , Adulto Jovem , GencitabinaRESUMO
Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 x 10(9)/L vs > 30 x 10(9)/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph(+) ALL patients and that disease status at the time of HCT is an important predictor of outcome.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas , Criança , Pré-Escolar , Terapia Combinada , Fracionamento da Dose de Radiação , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Pirimidinas/uso terapêutico , Indução de Remissão/métodos , Fatores de Risco , Irmãos , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Irradiação Corporal TotalRESUMO
AIM: To investigate the factors predicting non-surgical periodontal treatment responses using multilevel multiple regression. MATERIAL AND METHODS: Forty men (mean 45.6 years) were recruited; 20 were smokers. A 12-month reduction in probing pocket depth (PPD) and gain in probing attachment level (PAL) of 5814 sites were analysed, with 594 being initially diseased sites (initial PPD> or =5 mm). RESULTS: Variance Component models showed that site-level variations contributed about 70-90% of the total variance. About a 10% reduction of the total variations of PPD reduction in initially diseased sites was achieved with the inclusion of the 10 predictors in the multilevel multiple regression. Multilevel multiple regression showed that three predictors, subject level: non-smokers; tooth-level: anterior teeth; and site level: sites without plaque at baseline, were significantly associated with a greater reduction in PPD in initially diseased sites over the 12-month study period (p<0.05). No consistent predictor was found for PAL gain. CONCLUSION: Multilevel analysis was applied on periodontal treatment response data. Smokers showed less favourable PPD reduction at deep sites after non-surgical periodontal therapy.
Assuntos
Perda da Inserção Periodontal/terapia , Bolsa Periodontal/terapia , Fumar/efeitos adversos , Cicatrização , Adulto , Análise de Variância , Estudos de Casos e Controles , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multinível , Perda da Inserção Periodontal/patologia , Bolsa Periodontal/patologia , Aplainamento Radicular , Resultado do TratamentoRESUMO
Allogeneic hematopoietic cell transplantation (HCT) is the only curative strategy for patients with myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPD). We report the results of 148 patients (median age = 59 years old) with de novo MDS (n = 40), acute myelogenous leukemia (AML) after antecedent MDS/MPD (n = 49), treatment-related MDS (t-MDS) (n = 25), MPD (n = 27), and chronic myelomonocytic leukemia (CMML) (n = 7) who underwent allogeneic HCT using a conditioning regimen of low-dose total body irradiation (TBI) alone (200 cGy) on day 0 (n = 5) or with the addition of fludarabine (Flu) 30 mg/m(2)/day on days -4 to -2 (n = 143). Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil (MMF). Seventy-five patients (51%) received an allograft from a matched related donor (MRD), and 73 patients (49%) were recipients of unrelated donor (URD) grafts. There was no significant difference in the incidence of acute (gr II-IV) and chronic extensive graft-versus-host disease (aGVHD, cGVHD) between the recipients of related and unrelated donor grafts. By day +28, 75% of patients demonstrated mixed T cell chimerism. Graft rejection was seen in 15% of patients. With a median follow-up of 47 (range: 6-89) months, the 3-year relapse-free survival (RFS) and overall survival (OS) are both 27% for all patients, with a relapse incidence of 41%. The 3-year RFS for the patients with de novo MDS, AML after antecedent MDS/MPD, t-MDS, MPD, and CMML were 22%, 20%, 29%, 37%, and 43%, respectively, and the 3-year OS was 20%, 23%, 27%, 43%, and 43%, respectively. The 3-year nonrelapse mortality (NRM) was 32%. Factors associated with a lower risk of relapse were the development of extensive cGVHD and having a low risk or intermediate-1 risk International Prognostic Score for the de novo MDS patients. Nonmyeloablative HCT confers remissions in patients who otherwise were not eligible for conventional HCT but for whom relapse is the leading cause of treatment failure.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mielomonocítica Crônica/terapia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Irradiação Corporal TotalRESUMO
BACKGROUND: The reactivation of varicella-zoster virus from latency causes zoster and is common among recipients of hematopoietic-cell transplants. METHODS: We randomly assigned patients who were scheduled to undergo autologous hematopoietic-cell transplantation for non-Hodgkin's or Hodgkin's lymphoma to receive varicella vaccine or no vaccine. Heat-inactivated, live attenuated varicella vaccine was given within 30 days before transplantation and 30, 60, and 90 days after transplantation. The patients were monitored for zoster and for immunity against varicella-zoster virus for 12 months. RESULTS: Of the 119 patients enrolled, 111 received a transplant. Zoster developed in 7 of 53 vaccinated patients (13 percent) and in 19 of 58 unvaccinated patients (33 percent) (P=0.01). After two patients in whom zoster developed before transplantation were excluded, the respective rates were 13 percent and 30 percent (P=0.02). In vitro CD4 T-cell proliferation in response to varicella-zoster virus (expressed as the mean stimulation index) was greater in patients who received the vaccine than in those who did not at 90 days, after three doses (P=0.04); at 120 days, after all four doses (P<0.001); at 6 months (P=0.004); and at 12 months (P=0.02). The risk of zoster was reduced for each unit increase in the stimulation index above 1.6; a stimulation index above 5.0 correlated with greater than 93 percent protection. Induration, erythema, or local pain at the injection site was observed in association with 10 percent of the doses. CONCLUSIONS: Inactivated varicella vaccine given before hematopoietic-cell transplantation and during the first 90 days thereafter reduces the risk of zoster. The protection correlates with reconstitution of CD4 T-cell immunity against varicella-zoster virus.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Vacina contra Varicela/imunologia , Transplante de Células-Tronco Hematopoéticas , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/imunologia , Vacinas de Produtos Inativados/imunologia , Adulto , Anticorpos Antivirais/imunologia , Contagem de Linfócito CD4 , Vacina contra Varicela/administração & dosagem , Feminino , Herpes Zoster/epidemiologia , Herpes Zoster/imunologia , Humanos , Imunoglobulina G/imunologia , Interferon gama/imunologia , Linfoma/imunologia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Transplante Autólogo/imunologia , Fator de Necrose Tumoral alfa/imunologia , Vacinas de Produtos Inativados/administração & dosagemRESUMO
OBJECTIVES: Optimal granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cell (G-PBMC) graft compositions for myeloablative allogeneic hematopoietic cell transplantation (AHCT) have not been identified. G-PBMC cell contents were analyzed for influence on outcomes. PATIENTS AND METHODS: Human leukocyte antigen(HLA)-identical related donor AHCT was used to treat 101 patients with hematologic malignancies at a single institution between 1995 and 2002. CD34+, CD3+, CD4+, and CD8+ cell doses were enumerated by flow cytometry and evaluated by univariate analysis. RESULTS: Categorized by the median of cell doses infused, no G-PBMC cell dose significantly correlated with neutrophil and platelet engraftment. Incidence of grade II to IV acute graft-versus-host disease (GVHD) was 24.6% (95% confidence interval [CI]: 15.9-33.3) and was not significantly influenced by evaluated G-PBMC cell doses. With a median follow-up time of 18 months for surviving patients, estimates for extensive chronic GVHD was 43.8% (95% CI: 31.4-56.2), for freedom from progression was 69.5% (95% CI: 58.1-80.9), and for overall survival was 46.9% (95% CI: 35.5-58.3). CD34+, CD3+, CD4+, and CD8+ cell doses were not significantly predictive of extensive chronic GVHD, freedom from progression or overall survival. Additionally, comparing patients receiving the upper versus lower 33rd percentiles of CD34+ cell dose, associations with extensive chronic GVHD remained insignificant (p=0.21; relative risk (RR)=1.7; 95% CI: 0.7-3.9). CONCLUSIONS: G-PBMC graft content does not influence outcomes after myeloablative AHCT. In particular, no significant association between extensive chronic GVHD was identified with any G-PBMC cell dose, including CD34.
Assuntos
Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Antígenos de Superfície , Feminino , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
PURPOSE: To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT). PATIENTS AND METHODS: From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS). RESULTS: At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation). CONCLUSION: More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Criança , Progressão da Doença , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Análise Multivariada , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante AutólogoRESUMO
OBJECTIVE: The rationale for this retrospective study was to identify the long-term overall and event-free survival, relapse, and treatment-related mortality rates of high-risk pediatric and adult first (CR1) and second remission (CR2) patients with acute lymphoblastic leukemia (ALL) who were treated with a single preparatory regimen consisting of fractionated total-body irradiation (FTBI) and high-dose etoposide (VP-16) prior to allogeneic hematopoietic cell transplantation. PATIENTS AND METHODS: Over a 15-year period at Stanford University Medical Center, 85 consecutive high-risk pediatric (up to age 17 years; n=41) and adult (age 18-55 years; n=44); patients with leukemia (ALL) in CR1 (n=55) and CR2 (n=30) received HLA-matched sibling allogeneic bone marrow or peripheral blood progenitor grafts after being treated with FTBI (1320 cGy) and high-dose VP-16 (60 mg/kg) as their preparatory regimen. The majority of patients transplanted in CR1 (n=45) had high-risk features, including age above 30 years, white blood cell count at presentation exceeding 25000/microL, extramedullary disease, need for more than 4 weeks of induction chemotherapy to achieve CR, or high-risk chromosomal translocations. Most patients transplanted in CR1 were adults (n=39), whereas patients in CR2 were primarily children or adolescents (n=25). RESULTS: The 10-year Kaplan-Meier estimates of relapse were significantly (p=0.05) lower in CR1 patients (15%+/-10%) than in CR2 patients (33%+/-20%). Relapse was the most common cause of treatment failure in patients transplanted in CR2. There was a significantly (p=0.05) higher rate of chronic graft-vs-host disease in CR1 (32%+/-14%) compared with CR2 (9%+/-11%) patients; however, overall survival for patients transplanted in CR1 (66%+/-14%) was comparable (p=0.67) to that of patients transplanted in CR2 (62%+/-19%). Event-free survival rates also were similar (p=0.53) between CR1 (64%+/-14%) and CR2 (61%+/-18%) patients. Treatment-related mortality rates were equivalent (p=0.51) between CR1 and CR2, as well as between Philadelphia chromosome (Ph) positive (Ph(+))and Ph(-) (p=0.23) ALL patients. CONCLUSION: Overall, FTBI/VP-16 is a highly effective preparatory regimen that provides durable remissions for patients receiving allogeneic hematopoietic cell transplantation for high-risk ALL in CR1 or CR2.
Assuntos
Etoposídeo/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irradiação Corporal Total , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Falha de TratamentoRESUMO
Allogeneic hematopoietic cell transplantation (HCT) has been shown to be curative in a group of patients with aggressive non-Hodgkin lymphoma (NHL). A previous study has demonstrated equivalent outcomes with a conditioning regimen based on total body irradiation and another not based on total body irradiation with preparative therapy using cyclophosphamide, carmustine, and etoposide (CBV) in autologous HCT. We investigated the safety and efficacy of using CBV in an allogeneic setting. Patients were required to have relapsed or be at high risk for subsequent relapse of NHL. All patients had a fully HLA-matched sibling donor. Patients received carmustine (15 mg/kg), etoposide (60 mg/kg), and cyclophosphamide (100 mg/kg) on days -6, -4, and -2, respectively, followed by allogeneic HCT. All patients were treated with cyclosporine and methylprednisolone as prophylaxis for graft-versus-host disease (GVHD). Thirty-one patients (median age, 46 years) who were felt to be inappropriate candidates for autologous transplantation were enrolled. Each subject had a median of 3 previous chemotherapy regimens. All patients engrafted. Fifteen of 31 patients are alive. Median follow-up time was 11.5 months (range, .4-126). There were 8 deaths due to relapse. Nonrelapse mortality (n = 8) included infection (n = 3), GVHD (n = 2), diffuse alveolar hemorrhage (n = 1), veno-occlusive disease in the setting of concurrent acute GVHD of the liver (n = 1), and leukoencephalopathy (n = 1). Probabilities of event-free survival and overall survival were, respectively, 44% (95% confidence interval, 26%-62%) and 51% (33%-69%) at 1 year and 44% (26%-62%) and 47% (29%-65%) at 5 years. Probability of relapse was 33% (15%-51%) at 1 year and 5 years. Probability of nonrelapse mortality was 31% (13%-49%) at 1 year and 5 years. Incidences were 29% for acute GVHD and 39% for chronic GVHD. None of the 12 patients who developed chronic GVHD has disease recurrence. Patients who had required >3 previous chemotherapy regimens before HCT had an increased probability of relapse. CBV is an effective preparative regimen for patients with aggressive NHL who undergo allogeneic HCT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Causas de Morte , Terapia Combinada/métodos , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Teste de Histocompatibilidade , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
The influence of graft composition on clinical outcomes after reduced-intensity conditioning is not well-characterized. In this report we prospectively enumerated CD34+, CD3+, CD4+, and CD8+ cell doses in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) allografts in 63 patients who received transplants following non-myeloablative conditioning with total body irradiation 200 cGy plus fludarabine as treatment for malignant diseases. Donors were HLA-identical siblings (n = 38) or HLA-matched unrelated individuals (n = 25). By univariate analyses G-PBMC CD8+ T-cell dose in at least the 50th percentile favorably correlated with full donor blood T-cell chimerism (P = .03), freedom from progression (P = .001), and overall survival (P = .01). No G-PBMC cell dose influenced grade II to IV acute or extensive chronic graft-versus-host disease. In multivariate analysis only G-PBMC CD8+ T-cell dose (P = .003; RR = 0.2, 95% CI = 0.1-0.6) was associated with improved freedom from progression. Infusion of low G-PBMC CD8+ T-cell dose for reduced-intensity allografting may adversely affect T-cell engraftment and survival outcome.
Assuntos
Linfócitos T CD8-Positivos/transplante , Sobrevivência de Enxerto , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Condicionamento Pré-Transplante , Adulto , Idoso , Antígenos CD , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto/efeitos da radiação , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Neoplasias Hematológicas/terapia , Mobilização de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos , Proteínas Recombinantes , Taxa de Sobrevida , Quimeras de Transplante , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Irradiação Corporal TotalRESUMO
Based on the favorable safety profile and the independent activity of rituximab in B-cell lymphoma, we evaluated its efficacy and toxicity after high-dose therapy (HDT) and autologous hematopoietic cell transplantation (HCT). Thirty-five patients with diffuse large cell (25 patients), mantle cell (3 patients), transformed (3 patients), or other (4 patients) subtypes of B-cell lymphoma received HDT followed by a purged autologous graft. The rituximab schedule was 4 weekly infusions (375 mg/m(2)) starting at day 42 after HCT and, for patients 5 to 35, a second 4-week course 6 months after HCT. All planned therapy was completed in 29 patients. With 30 months' median follow-up, the 2-year event-free survival (EFS) rate was 83% and the overall survival (OS) rate was 88%. For 21 patients with relapsed or refractory large cell lymphoma, the EFS rate was 81% and the OS rate was 85%. Grades 3 to 4 neutropenia occurred in 19 (54%) patients. A prospective study of immune reconstitution included measurements of lymphocyte subsets, immunoglobulins, and response to vaccination. Serious infections were not observed despite delayed B-cell recovery in all patients and suppressed immunoglobulin G (IgG) levels and low pneumococcus antibody titers in a subset. Rituximab after HDT and HCT is feasible, and these phase 2 data support the current US Intergroup phase 3 trial in recurrent/refractory diffuse large cell lymphoma.