We evaluated the cytomegalovirus (CMV) serostatus as a risk factor for survival and treatment‐related mortality (TRM) in 125 patients allografted from an unrelated donor between 1994 and 1999. All patients received pretransplant in vivo T‐cell depletion using rabbit anti‐thymocyte globulin (ATG). Only one patient had primary graft failure and severe grade III/IV graft‐versus‐host disease occurred in 14% of the patients. The overall survival (OS) at 3 years was 70% for CMV‐negative patients (n = 76) and 29% in the seropositive cohort (n = 49) (P > 0·001). In multivariate analyses, CMV seropositivity remained an independent negative prognostic factor for OS (RR: 2·1; CI: 1·2–3·8; P = 0·014), apart from age > 20 years (RR: 2·74; CI: 1·2–3·8; P = 0·004) and late leucocyte engraftment (RR: 2·4; CI: 1·2–4·9; P = 0·015). The TRM for all patients was 27%. Despite monitoring for CMV antigenaemia and preemptive therapy with ganciclovir when reactivation occurred, seropositive patients had a three times higher risk of fatal treatment‐related complications than seronegative patients. In multivariate analyses, CMV seropositivity remained the strongest independent negative factor for TRM (RR: 5·3; CI: 1·9–14·6; P = 0·002), followed by age > 20 years (RR: 4·8; CI: 1·3–18·1; P = 0·02) and delayed leucocyte engraftment (RR: 3·6; CI: 1·2–11; P = 0·02). The TRM was identical in seropositive patients with (n = 27) or without (n = 22) CMV reactivation (44% versus 50%). We conclude that CMV seropositivity, despite preemptive ganciclovir therapy and even without reactivation, is a major negative prognostic factor for survival as well as for TRM in unrelated stem cell transplantation using pretransplant in vivo T‐cell depletion with ATG.
Summary:One-hundred and two patients with good risk myeloid leukemia (CML first chronic phase or AML first CR) were transplanted from HLA-related donors after conditioning with (n ؍ 45) or without anti-thymocyte globulin (ATG) (n ؍ 57). One graft failure was observed in the non-ATG and none in the ATG group. The median time to leukocyte engraftment (Ͼ1 ؋ 10 9 /l) was 16 (range 12-33) in the ATG group and 17 days (range 11-29) in the non-ATG group (NS) and for platelet engraftment (Ͼ20 ؋ 10 9 /l) 24 and 19 days (P ؍ 0.002), respectively. Acute GVHD grade II-IV was observed in 47% of the non-ATG and in 20% of the ATG group (P ؍ 0.004). Grade III/IV GVHD occurred in 7% of the ATG and in 32% of the non-ATG group (P ؍ 0.002). Chronic GVHD was seen in 36% and 67% (P ؍ 0.005), respectively. After a median follow-up of 48 months (range 2-128), the 5-year estimated OS is 66% (95% KI: 51-81%) for the ATG group and 59% (95% KI: 46-72%) for the non-ATG group (NS). The 5-year estimated DFS is 64% (95% KI: 50-78%) for ATG and 55% (95% KI: 43-67%) for the non-ATG regimen (NS). The 5-year probability of relapse was 5% in the ATG and 15% in the non-ATG group (NS). ATG as part of the conditioning regimen leads to a significant reduction in GVHD without increase of relapse in patients with myeloid leukemia after stem cell transplantation from HLA-related donors. Allogeneic stem cell transplantation from HLA-identical siblings for patients suffering from acute or chronic myeloid leukemia has become a curative treatment option. Transplant-related mortality as the cause of death is approximately 30%, and most deaths are related directly or indirectly to acute or chronic graft-versus-host disease (GVHD). Allogeneic stem cell transplantation from HLAidentical siblings with an unmanipulated graft resulted in an incidence of acute GVHD of approximately 30 to 60%. 1 Several investigators have shown that removal of T cells from the graft by ex vivo T cell depletion resulted in a dramatic decrease in GVHD. However, it became rapidly apparent that T cell depletion resulted in a high incidence of graft failure and an increased risk of leukemia relapse. [2][3][4][5][6] Partial or selective depletion of different subpopulations of T cells, or T cell depletion with T cell add-back has been investigated and resulted either in enhanced graft failure or increased risk of GVHD after T cell add-back. [7][8][9] Other forms of T cell depletion including T cell depletion with monoclonal antibodies either in vivo or ex vivo have been investigated extensively, resulting in a decrease of GVHD, but a relatively high incidence of graft failure has been observed. 10,11 By adding monoclonal anti-52 antibodies to the conditioning regimen to deplete residual host T cells, the problem of graft failure has been partly overcome. 12 Another strategy of in vivo T cell depletion is the use of anti-thymocyte globulin as part of the conditioning regimen. We and others have recently shown that ATG as part of the preparative regimen in unrelated stem cell tran...
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