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).
SummaryChronic graft‐versus‐host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid‐resistant cGVHD. Thirty‐five patients who developed GVHD after day 100 post‐transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count ≥100 × 109/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD‐free survival are warranted.
We report 2 cases of serotonin syndrome and myelosuppression in bone marrow transplant recipients who received linezolid in combination with a selective serotonin reuptake inhibitor (SSRI). Given the risks to patients in this high-risk group, we recommend that this combination of medications be avoided if alternative antibiotic therapy is possible. If no alternative therapy is possible, prescribers should discontinue SSRI therapy and monitor these patients closely for evidence of serotonin syndrome or the development of hematological toxicity.
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