RESUMO
Whether chemosensitivity, as determined by positron emission tomography using fluorine-18-deoxyglucose (FDG-PET), is a requirement for successful allogeneic hematopoietic stem cell transplantation (allo-SCT) has yet to be established. We analyzed 88 patients with B cell non-Hodgkin lymphoma (B-NHL) for event-free (EFS) and overall survival (OS) according to computed tomography (CT) and FDG-PET criteria before uniform nonmyeloablative (NMA) allo-SCT. Patients who were chemosensitive, according to CT criteria, experienced significantly greater EFS (P < .001) and OS (P < .03) compared with those who were chemorefractory at the time of allo-SCT. Of 58 patients within this cohort who were chemosensitive by CT criteria, there was no difference in EFS (P = .85) or OS (P = .96) between FDG-PET-positive (Deauville 4 to 5, n = 24) and FDG-PET-negative (Deauville 1 to 3, n = 34) patients. There was no difference in survival according to age < or ≥ 60 years, prior autologous-stem cell transplantation, allograft characteristics, or histology. FDG-PET adds no prognostic value in chemosensitive B-NHL before NMA-allo-SCT.
Assuntos
Fluordesoxiglucose F18 , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Transplante HomólogoRESUMO
The aim of this prospective phase II trial was to determine the safety and efficacy of a nonmyeloablative conditioning program incorporating peritransplant rituximab in patients with CD20+ B cell non-Hodgkin lymphoma (B-NHL) receiving an allogeneic stem cell transplant (allo-SCT). Fifty-one adult B-NHL patients, with a median age of 54 years, were treated with cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. Rituximab 375 mg/m(2) was given on day -8 and in 4 weekly doses beginning day +21. Equine antithymocyte globulin was given to recipients of volunteer unrelated donor grafts. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil and tacrolimus, sirolimus, and methotrexate in 8 and 43 patients, respectively. Thirty-three patients received grafts from unrelated donors, and 18 received grafts from matched related donors. All patients engrafted. Full donor chimerism in bone marrow and peripheral T cells was seen in 92% and 89% of patients, respectively, at 3 months after allo-SCT. The cumulative incidence of grades II to IV acute GVHD at 6 months was 25% (95% confidence interval [CI], 13% to 38%) and grades III to IV was 11% (95% CI, 2% to 20%). The 2-year cumulative incidence of chronic GVHD was 29% (95% CI, 15% to 44%). The 2-year event-free and overall survival for all patients was 72% (95% CI, 59% to 85%) and 78% (95% CI, 66% to 90%), respectively. The 2-year event-free survival for chemosensitive patients was 84% (95% CI, 72% to 96%) compared with 30% (95% CI, 2% to 58%) for chemorefractory patients before allo-SCT (P < .001). This nonmyeloablative regimen, with peritransplant rituximab, is safe and effective in patients with B-NHL.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Linfoma de Células B/imunologia , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rituximab , Análise de Sobrevida , Quimeras de Transplante , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Irradiação Corporal TotalRESUMO
Delays in immune recovery after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and relapse. IL-7 has a central role in T-cell development and survival and enhances immune recovery in murine models of allo-HSCT. We performed a phase 1 trial of r-hIL-7 (CYT107) in recipients of T-cell depleted allo-HSCTs. Twelve patients were treated with escalating doses of r-hIL-7 administered weekly for 3 weeks. The study drug was well tolerated with only one patient developing acute skin GVHD. At baseline, patients were profoundly lymphopenic. CYT107 induced a doubling in CD4(+) and CD8(+) T cells. The main effect of IL-7 was an expansion of effector memory T cells, the predominant subset identified in our patients. There was no significant effect on CD4(+)CD25(+)FoxP3(+) T cells, NK, or B cells. Importantly, we not only saw quantitative increases in T cells after a short course of IL-7 but also demonstrated an increase in functional T cells, including viral-specific T cells that recognize CMV. Enhanced TCR diversity was also observed after treatment. Our results indicate that r-hIL-7 can enhance immune recovery after a T cell-depleted allo-HSCT without causing significant GVHD or other serious toxicity (www.clinicaltrials.gov; NCT00684008).
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Interleucina-7/uso terapêutico , Linfócitos T/efeitos dos fármacos , Adulto , Idoso , Área Sob a Curva , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Rearranjo Gênico do Linfócito T , Doença Enxerto-Hospedeiro/induzido quimicamente , Neoplasias Hematológicas/imunologia , Humanos , Interleucina-7/genética , Interleucina-7/farmacocinética , Subunidade alfa de Receptor de Interleucina-7/imunologia , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Homólogo , Resultado do TratamentoRESUMO
Encouraging results have been reported with sirolimus, tacrolimus and low-dose methotrexate after non-myeloablative allogeneic hematopoietic cell transplant. We conducted a retrospective analysis of 71 patients with lymphoid malignancies treated with this prophylaxis regimen after non-myeloablative or reduced intensity allogeneic hematopoietic cell transplant. Grafts were human leukocyte antigen (HLA)-matched related in 29 (41%), matched unrelated in 36 (51%) and 9/10 HLA-matched unrelated in six (8%) patients. The regimen was well tolerated and over 90% of patients completed the planned treatment. The cumulative incidences of 1-year grade B-D and C-D acute graft-versus-host disease (GVHD) were 0.28 (95% confidence interval [CI], 0.18-0.39) and 0.07 (95% CI, 0.03-0.15), respectively, and of 1- and 2-year chronic GVHD (National Institutes of Health criteria) in 70 evaluable patients were 0.15 (95% CI, 0.08-0.24) and 0.33 (95% CI, 0.22-0.44), respectively. The median day of onset of acute GVHD was 123 days (range, 17-268 days). Peri-transplant rituximab or anti-thymocyte globulin did not affect GVHD. The cumulative incidence of 1-year non-relapse mortality and relapse were 4% and 20%, respectively. With a median follow-up of 3.5 (range: 0.18-5.1) years, overall survival and progression-free survival at 2 years were 82% and 66%, respectively. This GVHD regimen results in a low incidence and severity of acute and chronic GVHD after reduced intensity and non-myeloablative allogeneic hematopoietic cell transplant for lymphoid malignancies. The study also highlights the incidence of late onset acute GVHD in non-myeloablative/reduced intensity conditioning, and the contribution of the new GVHD staging system that more accurately reflects clinical outcomes.
Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodos , Doadores não Relacionados , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo/métodos , Adulto JovemRESUMO
Researchers and regulatory bodies tend to focus on non-essential toxic elements when testing for inorganic chemical pollutants in food. Both toxic and essential elements are increasingly getting into the food chain from the extensive use agrochemicals and the use of contaminated water, raw sewage and untreated industrial effluent to irrigate crops. A holistic testing protocol for chemical contaminants in food should be the norm in order to protect human health, especially considering that the essential elements are as a matter of fact essential poisons. They are essential but are toxic above certain thresholds. Eating contaminated foods that are not considered to be dietary sources of the essential poisons may result in an inadvertent overdose, especially considering that consumers may be taking food supplements that recommended as sources of the essential elements. We measured the levels of manganese and zinc in rice and calculated the daily bioaccessible levels of the two elements. The daily bioaccessible levels were significantly higher than the recommended daily intakes in most of the samples. It has to be noted that exposure from various sources is additive, therefore, lower levels than recommended limits in one source may not guarantee safety from a particular chemical toxicant.