Browsing by Subject "Allogeneic"

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    Addition of Infliximab to Standard Acute Graft-versus-Host Disease Prophylaxis following Allogeneic Peripheral Blood Cell Transplantation
    (Elsevier, 2008-07-01) Hamadani, Mehdi; Hofmeister, Craig C.; Jansak, Buffy; Phillips, Gary; Elder, Patrick; Blum, William; Penza, Sam; Lin, Thomas S.; Klisovic, Rebecca; Marcucci, Guido; Farag, Sherif S.; Devine, Steven M.; Medicine, School of Medicine
    Infliximab, a chimeric monoclonal antibody (mAb) against tumor necrosis factor (TNF)-α, has shown activity against steroid refractory acute graft-versus-host disease (aGVHD). We conducted a prospective trial of infliximab for the prophylaxis of aGVHD. Patients older than 20 years undergoing myeloablative allogeneic stem cell transplantation (SCT) for hematologic malignancies were eligible. GVHD prophylaxis consisted of infliximab given 1 day prior to conditioning and then on days 0, +7, +14, +28, and +42, together with standard cyclosporine (CSA) and methotrexate (MTX). Nineteen patients with a median age of 53 years were enrolled. All patients received peripheral blood allografts from matched sibling (n = 14) or unrelated donors (n = 5). Results were compared with a matched historic control group (n = 30) treated contemporaneously at our institution. The cumulative incidences of grades II-IV aGVHD in the infliximab and control groups were 36.8% and 36.6%, respectively (P = .77). Rates of chronic GVHD were 78% and 61%, respectively (P = .22). Significantly more bacterial and invasive fungal infections were observed in the infliximab group (P = .01 and P = .02, respectively). Kaplan-Meier estimates of 2-year overall survival (OS) and progression free survival (PFS) for patients receiving infliximab were 42% and 36%, respectively. The corresponding numbers for patients in the control group were 46% and 43%, respectively. The addition of infliximab to standard GVHD prophylaxis did not lower the risk of GVHD and was associated with an increased risk of bacterial and invasive fungal infections.
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    Adoptive Immunotherapy by Allogeneic Stem Cell Transplantation for Metastatic Renal Cell Carcinoma: A CALGB Intergroup Phase II Study
    (Elsevier, 2006-07-01) Rini, Brian I.; Halabi, Susan; Barrier, Robert; Margolin, Kim A.; Avigan, David; Logan, Theodore; Stadler, Walter M.; McCarthy, Philip L.; Linker, Charles A.; Small, Eric J.; Medicine, School of Medicine
    A graft-versus-tumor effect through nonmyeloablative allogeneic stem cell transplantation (N-SCT) in metastatic renal cell carcinoma (RCC) has been reported. An Intergroup phase II trial was undertaken to define further the feasibility, toxicity and efficacy of this approach in a multi-institutional setting, Patients with cytokine-refractory, metastatic RCC were treated with N-SCT. The conditioning regimen was fludarabine 30 mg · m−2 · d−1 on day (d) −7 through d −3 and cyclophosphamide 60 mg · kg−1 · d−1 on d −4 and d −3. Patients received 2-8 × 106 CD34+ cells/kg of granulocyte colony-stimulating factor mobilized stem cells from a 6/6 HLA-matched sibling donor. Immunosuppression after transplantation included tacrolimus and methotrexate. Twenty-two patients were enrolled at 14 institutions. Greater than 90% donor T-cell chimerism was observed in 17 of 19 evaluable patients (89%) by d +120. No objective response was observed. Acute graft-versus-host disease (GVHD) was observed in 11 patients (50%). Chronic GVHD was reported in 5 patients (23%). There was 1 patient death from liver failure secondary to chronic GVHD. Regimen-related mortality was 2 of 22 (9%; liver failure, sepsis). Median survival time was 5.5 months (95% confidence interval, 3.9-12.0 months) and the median time to progression was 3.0 months (95% confidence interval, 2.3-4.2 months). N-SCT for metastatic RCC is feasible in a multi-institutional setting. Adequate donor T-cell engraftment was achieved in most patients before disease progression. A graft-versus-tumor effect was not observed in this study despite acute and chronic GVHD, thus highlighting the need for further understanding of this approach. Allogeneic SCT remains investigational in RCC.