Aim:To establish the safety and feasibility of rapidly infusing rituximab over 90 min in patients with primary CNS lymphoma (PCNSL).Patients & methods:We retrospectively reviewed all patients with PCNSL who received rapid rituximab infusions (RRI) from January 2016 to January 2017. Primary end point was incidence of infusion reactions.Results & conclusion:11 patients received a total of 44 RRIs. Rituximab was dosed at 500 or 750 mg/m2. Premedication included acetaminophen and diphenhydramine. No infusion reactions occurred during any RRI. Two infusions were administered with steroids for neurologic symptoms at baseline (4.5%). Rapid administration of rituximab was safe and feasible for patients with PCNSL and at the higher doses received.
BackgroundAllogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.MethodsWe studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1−/− T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25hi, CD62Llo). Additionally, Ceacam1−/− CD8 T cells had greater expression of the gut-trafficking integrin α4β7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1−/− recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1−/− mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1+ lymphoma model was improved in animals receiving Ceacam1−/− vs. control T cells.ConclusionsWe conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation.
CharacteristicsDay 4 (n = 45) Day 5 (n = 42) P value Donor age at donation (years) a 38 (16-66) 40 (18-63) 0.623 Donor males b 22 (48.9%) 16 (38.1%) 0.223 Ratio weight donor/ recipient a 1.1 (0.6-4) 1.4 (0.5-15.2) 0.387 Donor body mass index (kg/m 2 ) a 25.1 (19-41.6) 24.6 (19.7-34.1) 0.587 PBSC CD34+/ml pre-apheresis a 86 (29-254) 96 (26.3-229.4) 0.316 Apheresis sample CD34+ x 10 6 /kg recipient BW a 9.4 (1.9-30) 9.5 (1.9-44) 0.331 Target HSC count reached on first apheresis b 38 (84.4%) 36 (85.7%) 0.868 a Values expressed as median (range). b Values expressed as number of donors (%). Summary/Conclusion:Our results suggest that apheresis on the 4 th day of low-dose G-CSF-induced mobilization in allogeneic stem cell donors is as feasible and effective as collection on Day 5, reducing G-CSF exposure to healthy donors and global costs.
Biology of Blood and Marrow Transplantation 15 (2009) 1-1. doi:10.1016/j.bbmt.2008.12.007Received by publisher: 0000-01-01Harvest Date: 2016-01-04 12:23:27DOI: 10.1016/j.bbmt.2008.12.007Page Range: 1-
Thymic graft-versus-host-disease (tGVHD) is an important contributor to impaired T cell reconstitution in patients with GVHD. We analyzed molecules relevant for T cell trafficking and cytolytic function in tGVHD. Thymic output and cellularity were inversely proportional to numbers of mature donor T cells in the allograft, suggesting that tGVHD severity was inversely associated with thymic function. Upon adoptive transfer of CFSE-labeled donor T cells, we noted that thymus-infiltrating alloreactive donor T cells were largely fast-proliferating and highly activated. These T cells infiltrated the thymus within one week after allogeneic bone marrow transplantation. We analyzed T cells in tGVHD with mice deficient for certain molecules, and found that the trafficking molecules CCR9, β7 integrin, and PSGL-1 were all partially required for tGVHD, while L-selectin and αE integrin subunit may be dispensable. Similarly, we examined the role of T cell cytolytic pathways for tGVHD, and found that FasL and tumor necrosis factor associated apoptosis inducing ligand (TRAIL) were required for tGVHD, but that perforin and TNF were dispensable. As host thymic stroma may be an important target for donor alloreactive T cells, we assessed the expression of the death receptors Fas and DR5 in thymic stroma from normal and irradiated mice, and found that endothelium and fibroblasts, as well as epithelial cells upregulated the expression of both Fas and DR5 after irradiation. FLIP, which is a negative regulator of Fas ligand and TRAIL mediated apoptosis, was also downregulated after irradiation. Our study suggests that TRAIL, which has previously been shown to be important in graft-versus-tumor activity, may also be important for mediating GVHD.
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