Unrelated Donor Transplant Recipients Given Thymoglobuline Have Superior GRFS When Compared to Matched Related Donor Recipients Undergoing Transplantation without ATG

Abstract

Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors (URDs) and mismatched related donors (MMRDs) typically have a higher incidence of acute and chronic graft-versus-host disease (GVHD) compared with matched related donors (MRDs). Anti-T-cell globulins (ATGs) are often used to reduce GVHD in these recipients. We report the outcomes of 211 adult peripheral blood stem cell transplant recipients with myeloid malignancies who received a standardized transplant protocol, in which ATG (Thymoglobuline 4.5 mg/kg) was administered to recipients of URD and MMRD (n = 147) but not MRD (n = 64) transplant. For all patients, incidence of acute GVHD grades 2 to 4 was 21.4%, and chronic GVHD was 35.0%. Two-year overall survival was 63.2% (95% confidence interval, 55.8% to 71.5%), relapse-free survival was 55.3% (47.4% to 64.6%), and GVHD-free, relapsefree survival (GRFS) was 30.7% (23.2% to 40.8%). There were no differences between recipients of MRDs and other donors in relapse, nonrelapse mortality, and overall and relapse-free survival. However, compared with MRD, recipients from URDs and MMRDs had reduced moderate to severe chronic GVHD (10.4% versus 30.1%, P= .002), less chronic GVHD requiring systemic therapy (19.4% versus 38.9%, P = .006), and superior 2-year GRFS (35.5% versus 20.0%, P = .003). In this retrospective review of nonrandomized transplant groups, outcomes of HSCT performed using an URD with ATG during conditioning were superior to transplant from an MRD without ATG. The addition of Thymoglobuline to conditioning in HSCT from MRD should be further examined in prospective trials.

Epstein–Barr virus posttransplant lymphoproliferative disorder: update on management and outcomes

“…Future management strategies with prophylactic or preemptive EBV-specific or multipathogen cytotoxic T lymphocytes show promising efficacy and safety profiles. recipients with high graft versus host disease (GVHD) risk [13][14][15]. One recent report of using ATG for all MMRD and MURD recipients by Ali et al [15] demonstrated a 71% reactivation of EBV (!1000 IU/ml), however a relatively low rate of PTLD (2.4%) using a preemptive management approach.…”

“…The study demonstrated an overall survival 1 year post diagnosis of PTLD of 53%. Although this risk factor is not a recent development, the use of ATG in HCT practice is changing, with its use becoming more widespread, including in mismatched and matched unrelated donor (MMRD and MURD) recipients as well as increasingly in matched related donor (MRD) recipients with high graft versus host disease (GVHD) risk [13–15]. One recent report of using ATG for all MMRD and MURD recipients by Ali et al [15] demonstrated a 71% reactivation of EBV (≥1000 IU/ml), however a relatively low rate of PTLD (2.4%) using a preemptive management approach.…”

Cytomegalovirus (CMV) management in allogeneic hematopoietic cell transplantation: Pre‐transplant predictors of survival, reactivation, and spontaneous clearance

“…This effect has been previously described. 46 Given that the development of grade II-IV aGVHD would normally be associated with a high risk of CMV reactivation, 38 it may be that the lower than expected rates of aGVHD in URD recipients who received routine corticosteroids or ATG as GVHD prophylaxis in our cohort, explains why we could not demonstrate an impact of ATG or aGVHD on cs-CMVi.…”

“…c vs URD 19%, P = .03), D+/R+ were more likely to spontaneously clear CMV than D−/R+ with CMV viral loads of 56-137 IU/mL (D+/ R+ 45% vs D−/R+ 13%, P < .01). MRD were also more likely to spontaneously clear CMV than URD at any viral load >250 IU/mL (MRD 44% vs URD 23%, P = .04), and likewise D+/R+ were more likely to spontaneously clear CMV than D−/R+ at any viral load >250 IU/mL (D+/R+ 43% vs D−/R+ 13%, P < .01).The median time to first CMV reactivation (>56 IU/mL) was 26 days (95% CI, 24-32; range, 6-179), CMV viral load >250 IU/mL was 39 days (95% CI, 33-40; range, 11-175) and >1000 IU/mL was 41 days (95% CI, 39-46; range 11-195), (See Figure3and TableS2).URD reactivated CMV more quickly, with median time to viral load of >250 IU/mL at 36 days (95% CI, 31-39) vs 43 days (95% CI,[39][40][41][42][43][44][45][46][47][48][49][50] in MRD (P < .01). In patients who did not spontaneously clear CMV (n = 54), the median time between first CMV reactivation (>56 IU/ mL) and viral load >250 IU/mL was 13 days (95% CI, 11-14), while the F I G U R E 2 Rate of spontaneous clearance of CMV by (A) viral load (IU/mL) for all patients to reactivate CMV (n = 84), and (B) by viral load in D+/R+ vs D−/R+ and matched related donor (MRD) vs unrelated donor (URD) time from first viral load >250 IU/mL to reach vial loads >1000 IU/ mL was 4 days (95% CI, 3-4), (See Table…”

Correlative factors of ocular surface lesions after allogeneic hematopoietic stem cell transplantation: A retrospective study

“…While patients with in vivo T-cell depletion using ATG show reduced incidence of acute or chronic GVHD, without increasing mortality and affecting overall survival ( 28 ). Many studies conducted in Europe and Australia have proved that compared with HLA-matched sibling transplantation, the occurrence of chronic GVHD was lower in URD-HSCT with ATG ( 29 , 30 ). Thus, the correlation between the selection of donor and the occurrence and severity of oGVHD needs to be further studied on the premise of controlling precondition before transplantation.…”