Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor-␣ (TNF-␣) is implicated in the pathophysiology of GVHD at several steps in the process. Infliximab is a genetically constructed immunoglobulin G1 (IgG1) murine-human chimeric monoclonal antibody that binds the soluble subunit and the membrane-bound precursor of TNF-␣, blocking its interaction with receptors and causing lysis of cells that produce TNF-␣. In this study we retrospectively evaluated 134 patients who had steroidrefractory acute GVHD. Of these, 21 who received infliximab as a single agent were analyzed. The overall response rate was 67% (n ؍ 14), and 13 patients (62%) experienced complete response (CR).
Our results are comparable to the published data on HDCT in B-cell non-Hodgkin's lymphoma (NHL) patients despite the fact that patients with PTCL are known to have a worse outcome compared with B-cell NHL patients. Considering the dismal outcome of conventional chemotherapy in PTCL patients, these data suggest the hypothesis that the poor prognostic implication of T-cell phenotyping in NHL might be overcome by frontline HDCT and transplantation.
Daclizumab, a humanized monoclonal IgG1 directed against the chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%). Survival on day 120 was 29% (95% CI, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3 + 25+ lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (Blood, 2000; 95:83-89)
Summary:(NHL). 2,3 When recurrences occur after autologous BMT, treatment options are limited, and the prognosis is poor. 4 Allogeneic BMT is also an effective treatment for selecWe evaluated the response to and toxicity of allogeneic or autologous bone marrow transplantation (BMT) for ted categories of patients. for NHL at our institution. It is our practice to offer alloallogeneic bone marrow. Three patients are alive and geneic BMT mainly to patients who do not qualify for autodisease-free at 25, 22 and 7 months after allogeneic logous BMT due to refractory disease or extensive bone BMT. Four patients died of treatment-related causes marrow involvement. 8 Seventy-five patients had disease and one from disease recurrence. All four patients progression or recurrence after autologous BMT; 12 were undergoing autologous BMT had responsive relapses. treated with a second autologous (four patients) or alloThree patients received peripheral blood stem cells and geneic (eight patients) marrow or blood stem cell transone patient bone marrow. Two patients are alive and plant. disease-free at 12 and 30 months after autologous transAllogeneic BMT was offered to patients who had an plants. There were no treatment-related deaths; two HLA-compatible donor (HLA-identical sibling or 1 antigen patients died of disease recurrence. This retrospective mismatched relative), regardless of disease responsiveness. study shows that in selected patients, allogeneic or autoPatients who had chemosensitive recurrences, normocellulogous BMT is an effective salvage therapy for NHL lar marrows without involvement and who lacked an HLA which recurs after autologous BMT. compatible donor, were offered an autologous transplant. Keywords: lymphoma; relapse; BMT Additional eligibility criteria included a left ventricular ejection fraction у50%, adequate pulmonary function as measured by a diffusing capacity of carbon monoxide and Autologous BMT is an effective treatment for patients with a forced expiratory volume in 1 second у50% of the prechemotherapy sensitive recurrences of intermediate-grade dicted capacity, bilirubin р2 mg/dl, creatinine less than 1.5 lymphomas, 1 and is increasingly used for the initial treattimes normal and a performance status р1. ment of poor prognosis non-Hodgkin's lymphoma Induction therapyCorrespondence: Dr K van Besien, Section of Bone Marrow TransplanDifferent induction strategies were used after relapse. induction chemotherapy with cytoxan, etoposide and cis-
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