Objective. Graft-vs-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) causing significant morbidity and transplant-associated mortality. Acute GVHD (aGVHD) has been observed in approximately 60% of HLA-identical sibling transplants and up to 80% of unrelated donor grafts. Chronic GVHD (cGVHD) occurs in 5070% of patients and frequently requires long-term systemic immunosuppressive treatment. Corticosteroids are considered to be the gold standard of first-line therapy for GVHD. Patients not responding to steroids have a dismal prognosis, being at risk of lifethreatening infections and severe organ toxicities. Extracorporeal photopheresis (ECP) has objective activity in the treatment of both acute and chronic steroid-refractory GVHD patients. Methods. The study included 82 patients (pts) after allo-HSCT, 34 with aGVHD and 48 with cGVHD. The age was from 2 to 55 y.o. (median 22 y.o.). Treatment aGVHD included tacrolimus or cyclosporine A basic immunosuppressive therapy with steroids (2 mg/kg) as a first line Â± MAB. ECP combined with first line or used as third line, after MAB. Therapy cGVHD also included steroids (1 mg/kg) as a first line, imatinib or MMF used as a second line. ECP combined with first or second line therapy. Group aGVHD included: unrelated-HSCT 20 pts, related-HSCT 7 pts, haplo-HSCT 7 pts; grade of aGVHD: II 16 pts, III 6 pts, IV 12 pts; organs involvement: skin 31 pts, GIT 14 pts, liver 7 pts. Group cGVHD included: unrelated-HCT 26 pts, related-HCT 12 pts, haplo-HCT 10 pts; steroid-depended forms 26 pts, steroid-refractory 12 pts, steroid-intolerance 10 pts; severity of cGVHD: moderate cGVHD 15 pts, severe cGVHD 33 pts; organs involvement: skin 44 pts, mucosa 27 pts, GIT 11 pts, liver 9 pts, lungs 10pts. Infection complications (IC): for aGVHD group total frequency - 73%, n=25 (bacterial 53%, n=18, reactivation CMV 61%, n=21, invasive fungal infection 29%, n=10), the most frequent lung infection and urinary tract infection. For cGVHD group: total frequency 73%, n=35 (bacterial 60%, n=29, reactivation CMV 41%, n=20, invasive fungal infection 56%, n=20), the most frequent invasive pulmonary aspergillosis. Results. Response to therapy was observed in 23 pts (67%) with aGVHD and in 36 cases with cGVHD (75%). Factors affecting the achievement of response were severity of GVHD: II grade aGVHD vs III, IV 93% vs 44%, (p=0,015); Â«moderate GVHDÂ» vs Â«severe chronicÂ» - 94% vs 77%, (p=0,024) and confirmed infection in pts with cGVHD (69% vs 93% in pts without infection, p=0,045). Probability of overall survival (OS) at 3 years was 54% for aGVHD, and 71% for cGVHD. Factors affecting to OS were achievement of response (70% vs 16 for aGVHD, p=0,001; 88% vs 33% for cGVHD, p=0,000), severity of aGVHD (77% for II grade vs 37% for III, IV). Evaluating the effectiveness of various schemes of immunosuppressive therapy for aGVHD we did not reveal significant differences for achievement response or OS between combination of ECP and first line therapy and using ECP after MAB, but IC were more common in last group (60% vs 100%, p=0,078). For group with cGVHD, pts treated only by combination steroid and ECP had a worse response then scheme including ECP and imatinib or MMF: 82% vs 65%, p=0,088%, OS pts receiving imatinib was better (85% vs 61%, p=0,041); frequency of IC was similar. Conclusion. ECP is effective for steroid-resistance forms of GVHD. It shows the best results in cases of II grade aGVHD and moderate cGVHD. The use of MAB doesn’t influence frequency of treatment response or OS, but it increases incindence of IC. As concerns cGVHD, better results are documented in combination of ECP and imatinib or MMF. Disclosures: No relevant conflicts of interest to declare.
Full conference title:
American Society of Hematology 2012
- ASH 54th (2012)