RESUMO
We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m2 i.v. (days -3 and -2) plus melphalan 70 mg/m2 i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/terapia , Terapia de Salvação/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma de Células B/mortalidade , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Radioimunoterapia/métodos , Radioimunoterapia/mortalidade , Terapia de Salvação/mortalidade , Análise de Sobrevida , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Radioisótopos de Ítrio/uso terapêuticoRESUMO
PURPOSE: To evaluate the differences in the outcomes of patients with stage II and IIIa non-small cell lung cancer (NSCLC) treated with either 131I-labeled mouse/human chimeric monoclonal antibody against intracellular DNA exposed in necrotic and degenerating regions of tumors (131I-chTNT-mediated radioimmunotherapy) combined with percutaneous microwave coagulation therapy (PMCT) guided by computed tomography (CT) or with postoperative adjuvant chemoradiation. METHODS: Ninety-six patients with stage II and IIIa NSCLC were randomized into two groups. Group A included 49 patients who were treated with chemotherapy with docetaxel and cisplatin and three-dimensional conformal radiotherapy 3-4 weeks after surgery. Group B included 47 patients treated with 131I-chTNT and PMCT sequentially, with follow-up chemotherapy. RESULTS: The survival rates of patients in group A for the first and second years were 79.59% and 48.98%, respectively. The median survival was 23.0 months. Survival rates at 1 and 2 years for group B were 82.98% and 53.19%, respectively and the median survival was 29.1 months. The survival rate of group B patients for the first and second years was better compared with group A, and the difference in median survival between the groups was statistically significant (p<0.05). However, median survival and the incidence of adverse events were not significantly different between the two groups. CONCLUSIONS: 131I-chTNT radioimmunotherapy with PMCT has a complementary effect in NSCLC, which can effectively improve therapeutic ratio and survival of patients effectively and has the same effect as that of post-operative adjuvant chemoradiation.
Assuntos
Técnicas de Ablação , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia Adjuvante , Neoplasias Pulmonares/terapia , Micro-Ondas/uso terapêutico , Radioimunoterapia , Radioterapia Conformacional , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/mortalidade , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , China , Cisplatino , Docetaxel , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Micro-Ondas/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioimunoterapia/efeitos adversos , Radioimunoterapia/mortalidade , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Radioterapia Conformacional/mortalidade , Análise de Sobrevida , Taxoides/administração & dosagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
PURPOSE: To investigate how induced tumor heterogeneity influences immune responses to radiotherapy with different proportions of mixed immune-responsive and unresponsive tumor cells in a triple-negative breast cancer model. It is hypothesized that studying the immune environment of mixed tumors and responses to radiotherapy could nominate immune active therapies to enhance immune responses after radiotherapy. EXPERIMENTAL DESIGN: Evaluate efficacy and immune responses generated by radiotherapy in tumors with different proportions of immunologically responsive and unresponsive tumor cells. Then study the cellular responses and transcriptomic differences between the tumors to nominate immunotherapy combinations with radiotherapy and evaluate the combination. RESULTS: The addition of the responsive cells to unresponsive tumors led to a greater than expected therapeutic response to radiotherapy with both innate and adaptive immune components. There was a distinct change in myeloid cells, greater inflammatory macrophage activity, and enhanced antigen presentation with responsive cells after radiotherapy. Because differences in matrix components, cell adhesion biology, and innate immune signaling correlated with myeloid cell response and phenotype, we hypothesized that radiotherapy combined with CD40 agonist antibody would sensitize unresponsive tumors. The combination therapy resulted in improved innate and adaptive immune response. Importantly, CD40 treatment increased tumor response to radiotherapy and protected against metastatic spread in a metastatic model. CONCLUSIONS: These data combined with transcriptomics from human patients support radiotherapy and myeloid cell targeting for immunologically cold tumors. The established study model presents opportunities to investigate the complex overlapping biologic mechanisms that limit immunotherapy and to implement radiotherapy with different immunotherapy combinations.
Assuntos
Neoplasias da Mama/patologia , Imunoterapia/mortalidade , Radioimunoterapia/mortalidade , Radioterapia/mortalidade , Animais , Apoptose , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity. METHODS: Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy. RESULTS: Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes. CONCLUSION: To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioimunoterapia , Compostos Radiofarmacêuticos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Tomada de Decisão Clínica , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Progressão da Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Valor Preditivo dos Testes , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Radioimunoterapia/efeitos adversos , Radioimunoterapia/mortalidade , Compostos Radiofarmacêuticos/efeitos adversos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto JovemRESUMO
Polish Lymphoma Research Group performed a phase-II trial to test whether 90Y ibritumomab tiuxetan radioimmunotherapy (Y90) may constitute an alternative consolidation for mantle cell lymphoma patients unfit for high-dose therapy. Forty-six patients were consolidated with Y90 following response to the 1st (n = 34) or 2nd line (n = 12) (immuno)chemotherapy. Majority of the patients had advanced disease (stage IV and presence of B-symptoms in 85% and 70%, respectively) and high MIPI (5.8, range 4-7). Consolidation with Y90 increased the complete remission (CR) rate obtained by the 1st line therapy from 41% to 91% and allowed for median PFS of 3.3 and OS of 6.5 years. In the first relapse, CR rate increased from 16% to 75%, while median PFS and OS totaled 2.2 and 6.5 years, respectively. At 8 years, 30% of patients, consolidated in the 1st line CR were alive, without relapse. Toxicity associated with Y90 is manageable, more severe after fludarabine-based regimens.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfoma de Célula do Manto/terapia , Recidiva Local de Neoplasia/terapia , Radioimunoterapia/mortalidade , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Linfoma de Célula do Manto/imunologia , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Polônia , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
Prospective randomized studies have demonstrated a survival benefit of immunotherapy in stage IV cutaneous melanoma. Some retrospective studies have hypothesized a synergistic effect of radiation and immunotherapy. Our objective was to identify whether there is a survival benefit for patients treated with radiation and immunotherapy in stage IV cutaneous melanoma of the head and neck (CMHN). The National Cancer Database was used to identify patients with stage IV CMHN between 2012 and 2014. These patients were stratified based on receipt of radiation and immunotherapy. Adjusted Cox regression was used to analyze overall survival. A total of 542 patients were identified with stage IV CMHN, of whom 153 (28%) patients received immunotherapy. Receipt of immunotherapy (hazard ratio [HR] 0.69, P = 0.02) and negative LNs (HR 0.50, P = 0.002) were independently associated with improved survival, whereas radiation conferred no survival benefit (HR 1.17, P = 0.26). Patients who received immunotherapy without radiation were associated with significantly improved survival compared with those who received immunotherapy with radiation (P < 0.0001). However, of patients who received radiation, the addition of immunotherapy did not seem to improve survival (P = 0.979). In stage IV CMHN, immunotherapy confers a 32 per cent survival benefit. The use of immunotherapy in patients who require radiation, however, is not associated with improved survival.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/mortalidade , Ipilimumab/uso terapêutico , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Análise de Variância , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Imunoterapia/métodos , Linfonodos/patologia , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/radioterapia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radioimunoterapia/métodos , Radioimunoterapia/mortalidade , Radioterapia/mortalidade , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia , Análise de Sobrevida , Fatores de TempoRESUMO
PURPOSE: One-year monitoring of patients receiving intraperitoneal (IP) Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. METHODS: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome. RESULTS: Six dose levels (7.4, 9.6, 12.6, 16.3, 21.1, 27.4 MBq/m) were well tolerated with early possibly agent-related adverse events being mild, transient, and not dose dependent. These included asymptomatic, abnormal laboratory values. No late renal, liver, cardiac, or other toxicity was noted up to 1 year. There were no clinical signs or symptoms of an immune response to Pb-TCMC-trastuzumab, and assays to detect an immune response to this conjugate were negative for all tested. Tumor marker studies in ovarian cancer patients showed a trend of decreasing Cancer antigen 72-4 (CA 72-4) aka tumor-associated glycoprotein 72 (TAG-72) and tumor growth with increasing administered radioactivity. Other tumor markers, including carbohydrate antigen (CA125), human epididymis protein 4 (HE-4), serum amyloid A (SAA), mesothelin, interleukin-6 (IL-6), and carcinoembryonic antigen (CEA) did not correlate with imaging outcome. CONCLUSIONS: IP Pb-TCMC-trastuzumab up to 27 MBq/m seems safe for patients with peritoneal carcinomatosis who have failed standard therapies. Serum TAG-72 levels better correlated to imaging changes in ovarian cancer patients than the more common tumor marker, CA125.
Assuntos
Isotiocianatos/química , Radioisótopos de Chumbo/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Radioimunoterapia/mortalidade , Trastuzumab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Ibritumomab is an (90)Yttrium ((90)Y) labelled radioimmunoconjugate registered to treat follicular lymphoma relapsing or refractory after Rituximab therapy. Combining the specificity of anti CD20 monoclonal antibodies with the efficacy of radiotherapy, it is particularly effective in patients with advanced stages of disease with generalized lymphadenopathy. MATERIAL AND METHODS: Twenty-one patients with follicular lymphoma, after failing 2-5 lines of previous treatment, were subjected to radioimmunotherapy in three Polish Lymphoma Research Group (PLRG) centres. Ibritumomab infusion was followed by 2 doses of Rituximab (250 mg/m(2) at day -7 and 0) to enhance its biodistribution. Radioimmunoconjugate was prepared in the Nuclear Medicine Departments of participating centres based on patient weight and full blood count results (14.8 MBq/kg, max 1200 MBq, reduced to 11.1 MBq/kg in cases with blood platelet 100,000-150,000 or leukocytes 1500-2000). 14.8 MBq/kg (0.4 mCi/kg) 100 thousand to 149 thousand/mm(3) platelets 11.1 MBq/kg (0.3 mCi/kg) RESULTS: The primary endpoint of the study was the assessment of response rate and haematological toxicity. Objective responses were observed in all patients, with 10 partial and 12 complete regressions. Cytopenia, starting 3-4 weeks after radioimmunotherapy, reflected haematological toxicity - the only important side effect. Thrombocytopenia was more pronounced, with platelet counts of < 50,000/ul in every second patient. One patient developed myelodysplastic syndrome 21 months after the procedure. After the medium time of follow up over 2 years, 2 patients died. Median progression free survival (secondary study endpoint) was 15 months. CONCLUSIONS: Ibritumomab radioimmunotherapy is an efficient method of palliation treatment of heavily pre-treated follicular lymphoma patients, failing numerous previous treatment lines. Earlier application increases the number of complete responses and prolongs progression free survival.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfoma Folicular/mortalidade , Linfoma Folicular/radioterapia , Lesões por Radiação/mortalidade , Radioimunoterapia/mortalidade , Medição de Risco/métodos , Trombocitopenia/mortalidade , Adulto , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Prognóstico , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed population including patients who have far more extensive and bulky disease than others. Management of these patients continue to be a challenge; frequently, patients have both local recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall survival estimated between 3% and 7% for inoperable disease. The standard treatment for these patients is concurrent chemo-radiotherapy (CRT) improving survival when compared to sequential combination as shown in several metanalysis. Recently, immune-therapies, including checkpoint inhibitor, such as monoclonal antibodies against programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), have shown to enhance survival compared to chemotherapy in patients with advanced NSCLC. The integration of radiotherapy with immunotherapy is a conceptually promising strategy and several preclinical experiments have further developed the rationale for combining them. Radiotherapy has the capacity to overcome a lot of tumor immune escape mechanisms through the liberation of immunogenic private antigens showing a better local control and augmenting the immune response of systemic agents. This manuscript discusses the potential clinical interest for the combination of radiation and immunotherapy in locally advanced NSCLC.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Doses de Radiação , Radioimunoterapia/métodos , Animais , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Radioimunoterapia/efeitos adversos , Radioimunoterapia/mortalidade , Resultado do Tratamento , Evasão Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering (90)Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. METHODS: Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. RESULTS: Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year. CONCLUSIONS: Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.
Assuntos
Adenocarcinoma/terapia , Anticorpos Monoclonais/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/terapia , Radioimunoterapia/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mucinas/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Radioimunoterapia/efeitos adversos , Radioimunoterapia/mortalidade , Compostos Radiofarmacêuticos/efeitos adversos , Indução de Remissão , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Radioisótopos de Ítrio/efeitos adversos , GencitabinaRESUMO
We have intensified the conditioning regimen prior to stem cell transplantation in 57 patients with high-risk AML and MDS by treating patients with a 188Re-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.5 Gy of additional radiation to the marrow, the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy): Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) (n = 30) or busulfan (n = 27) and high-dose cyclophosphamide +/- thiotepa. Patients subsequently received a T cell depleted allogeneic graft from a HLA-compatible family donor (n = 24), a matched unrelated donor (n = 23) or a haploidentical family donor (n = 6). In four patients, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day +30 and day +100 mortalities were 3 and 7%, respectively, and after a median follow-up of 26 months treatment-related mortality was 30%. Late renal toxicity was observed in 14% of patients. The disease-free survival rate for 44 patients in 1 or 2 CR or in very good PR (< 15% blasts in the marrow at transplant) is 64% with only 8% disease-free survival for those with > 15% blasts in the marrow at transplant.
Assuntos
Antígenos CD/imunologia , Antígenos de Diferenciação/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunoconjugados/uso terapêutico , Leucemia Mieloide/terapia , Radioimunoterapia/métodos , Radioisótopos/uso terapêutico , Rênio/uso terapêutico , Doença Aguda , Adolescente , Adulto , Anticorpos Monoclonais , Células da Medula Óssea/imunologia , Moléculas de Adesão Celular , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunoconjugados/farmacocinética , Imunoconjugados/toxicidade , Leucemia Mieloide/complicações , Leucemia Mieloide/mortalidade , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Radioimunoterapia/efeitos adversos , Radioimunoterapia/mortalidade , Radioisótopos/toxicidade , Rênio/toxicidade , Terapia de Salvação/métodos , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Resultado do TratamentoAssuntos
Anticorpos Monoclonais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Célula do Manto/terapia , Condicionamento Pré-Transplante/métodos , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Antígenos CD20/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/uso terapêutico , Citarabina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Seguimentos , França , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/radioterapia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Radioimunoterapia/métodos , Radioimunoterapia/mortalidade , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). METHODS: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); one patient in the non-CSI cohort received IO-RIT. RESULTS: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. CONCLUSIONS: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.