Amelioration of Late Complications Following Unrelated Donor Bone Marrow Transplantation When Anti-Thymocyte Globulin Is Used as a Part of Conditioning.
Journal - ASH Annual Meeting Abstracts
Polyclonal anti-thymocyte globulin (ATG) reduces the risk forprimary graft rejection as well as acute graft-versus-host disease(GVHD) by depleting T cells in both the host and the infusedallograft. However, the impact of ATG on late outcomes is lesscertain. We report the results of a retrospective landmark analysisof consecutive patients who underwent an unrelated donor bonemarrow transplant at our center between January 2001 and October2005 (n=45) and survived at least 90 days following transplant.We compared late outcomes in patients who either recieved ATG(n=25) or did not (n=20) as a part of their conditioning regimen.Conditioning was with either busulfan and cyclophosphamide (n=28; 17 without ATG) or BCNU, etoposide, cytarabine, and melphalan(n=18; 3 without ATG). Most patients (20) received rabbit ATGat a median dose of 3 mg/kg (range: 1.5–9 mg/kg) on day-4 and -3. Others were given equine ATG. GVHD prophylaxis consistedof tacrolimus + methotrexate in both groups. Median age was42 years (range 18–65; 14 female). Bone marrow from unrelateddonors matched at HLA-A, B, C, and DRB1 (7/8 and 8/8 matches)was used as the stem cell source. Diseases treated were CML(11), HD (9), AML (8), MDS (6), NHL (3), MM (3), and other (5).A median of 3 prior therapies had been given before transplant(range 1–5). There was no significant difference (Pearson2) in the number of patients beyond CR1/CP1 (n=25) and thosehaving failed a prior autograft (n=17) between the two groups.The median overall survival in the recipients of ATG was 1382days (95% CI: 373– 2391 days) as opposed to 364 days (95%CI: 0–851) in those not receiving ATG (P=0.125 by Log-Ranktest); with a 1-year overall survival of 76% (59%–93%)vs. 50% (28–72) in the ATG vs. no ATG cohorts respectively,and 69% (49–89) vs. 44% (22–66) at 2-years. The1-year progression free survival was 84% (69–98) vs.90%(77–100) in the ATG vs. no ATG cohorts, and 84% (69–98)vs. 67% (37–97) at 2 years. Chronic GVHD developed in15/20 (75%) patients not receiving ATG (45% extensive), andin 12/25 (48%) in those recieving ATG (16% extensive) (P=0.06Pearson 2). Graft rejection was seen in 2/20 patients in thenon-ATG arm and 1/25 patients in the ATG arm. Despite a lowerincidence of chronic GVHD, the relapse rate was similar in thetwo groups (16% in the ATG group vs. 20% in the non-ATG group;P=0.73). Lymphoid recovery was similar in the two groups. Theabsolute lymphocyte counts at day-90 and day-180 post transplantwere 680 vs 800/microL and 1100 vs. 1500/microL in the no ATGvs. ATG cohorts (P=0.275 repeated measures ANOVA). Serious lateinfections requiring parenteral antimicrobial treatment occuredin 8 patients (32%) receiving ATG, and in 9 patients (45%) inthe non-ATG arm ((P=0.248). CMV reactivation was seen in 8 patients(32%) receiving ATG, and 7 (35%) in the non-ATG arm. Elevenpatients (55%) have died in the no ATG cohort from either relapse(2), GVHD (4) or infection (5); whereas in the ATG cohort 9(36%) have died of either relapse (4), GVHD (3) or infection(2). In conclusion, ATG appears to reduce delayed transplantrelated complications, such as chronic GVHD and infections,in patients receiving bone marrow from unrelated donors. Thismay lead to a favorable trend towards improved survival in patientsrecieving ATG as a part of non-total body irradiation basedconditioning.Footnotes* Corresponding authorDisclosure: No relevant conflicts of interest to declare.