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Chronic graft-versus-host disease (cGVHD) is an important determinant of long-term morbidity and mortality in allogeneic stem cell transplantation patients. Because cGVHD has clinical, histologic, and laboratory findings of autoimmune diseases and anti–B-cell therapy has shown efficacy in autoimmune diseases, we hypothesized that monoclonal anti-CD20 antibody therapy might improve patients with cGVHD. We treated 5 men and 1 woman with therapy-refractory extensive cGVHD with anti-CD20 monoclonal antibody. Intravenous infusion was given at a weekly dose of 375 mg/m2 for 4 weeks. In case of incomplete clinical response, additional courses of 4 weeks were given. Five patients responded to treatment with marked clinical, biochemical, and histologic improvement. One patient failed to respond. Anti-CD20 monoclonal antibody seems to be effective in cGVHD. A controlled trial is mandatory to confirm these results. The outcome of this study suggests a participating role of B cells in the pathogenesis of cGVHD.

Abstract 4322 Background Single nucleotide polymorphisms (SNPs) in the innate immunity receptor NOD2/CARD15 have been demonstrated to modulate the outcome of allogeneic haematopoietic stem cell transplantation. The effect of the NOD2/CARD15 polymorphism seems to be associated with donor source as well as type of conditioning regimen. Methods We reviewed NOD2/CARD15 mutations in all donor/recipient pairs of 192 consecutive patients who received non-myeloablative allogeneic stem cell transplantation(SCT) at our institution between 2002 and 2006. All patients were treated uniformly with fludarabine 30 mg/m2/day for 3 days followed by 200 cGy TBI (n=154) or TBI alone (n=38) and received grafts from HLA-matched related (n=132) or unrelated (n=60) donors. Results Mutated alleles were observed in 36 of 192 (19%) patients and in 35 of 192 (18%) donors. These SNPs, however, did not have a significant impact on clinical outcome data (P > 0.05, Kaplan Meier and Fine & Gray's test). Acute graft-versus-host disease (GVHD) occurred in 24 of 61 (39%) patients with the polymorphism and in 66 of 131 (50%) patients without the polymorphism. Chronic GVHD developed in 28 of 55 (51%) patients with SNP pairs and in 79 of 121 (65%) patients with the wild type. The incidence of transplant-related mortality was 21% in both groups, 13 of 61 patients in the group with the polymorphism and 27 of 131 without the polymorphism. Relapse was seen in 23 of 61 (38%) patients with the SNP pairs and in 48 of 131 (37%) wild type patients. Finally, overall survival was 43% (26/61) in patients with the polymorphism and 39% (51/131) in patients without the polymorphism. Conclusion These data indicate that mutations in the NOD2/CARD15 genes do not influence the clinical outcome of non-myeloablative allogeneic SCT directly. Since NOD2/CARD15 variants are not recognized as a single significant prognostic factor, screening for NOD2/CARD15 when selecting a donor does not seem to have additional value in patients undergoing non-myeloablative SCT. Disclosures: No relevant conflicts of interest to declare.

Lung injury limits the success of hematopoietic stem cell transplantation (HSCT). The overall incidence varies from 30–50% and noninfectious causes occur in one third to one half of these. We reviewed pulmonary complications in 369 patients who received either allo-BMT or allo-PBSCT at our institution between 1993 and 2003. Control subjects were selected from the same database and matched on sex, underlying diagnosis, age, type of transplantation and cytomegalovirus-serostatus. For all patients the conditioning myeloablative regimen consisted of cyclophosphamide (60 mg/kg/day for 2 days) followed by total body irradiation (total lung dose 850 cGy). The graft was partially T-cell depleted (1–2 x 105 T cells/kg). Sixty-one patients (16.5%) developed pulmonary complications, which were diagnosed at a median of 22 weeks after transplantation (range 2–263). Twenty-one patients (5.7%) developed infectious pneumonia. Non-infectious complications were further subclassified as BO (3.5%), BOOP (0.5%), DAH (0.8%), IPS (5.4%) or mixed etiology (0.5%). Acute GVHD ≥ grade II was significantly more common in patients with pulmonary complications than in the controls (36/61 versus 24/61 patients, P=0.02). There was no significant difference in the incidence of chronic GVHD (in 26/48 pulmonary patients versus 20/55 controls, P=0.1). Median survival was 41 weeks (range 4–583) for the pulmonary patients and 173 weeks (range 8–582) for the control subjects. These data illustrate that the incidence of pulmonary complications is low after T-cell depleted HSCT and demonstrate a clear association with acute GVHD. Improvement of the poor outcome of pulmonary complications is of utmost importance. Current studies at our institution are focused at the detection of early markers so that possible pre-emptive-like therapy can be initiated before symptomatic lung damage arises.