Evaluating the Impact of Antithymocyte Globulin on Lung Function at 1 Year after Allogeneic Stem Cell Transplantation

Abstract

Background The use of antithymocyte globuline (ATG) in hematopoietic stem cell transplant (HSCT) conditioning regimens has reduced the incidence of graft versus host disease, particularly in its chronic form; the impact of this approach on the prevention of lung dysfunction is not well characterized. Methods We performed a retrospective analysis of pulmonary function among patients transplanted following conditioning with oral busulfan followed by either cyclophosphamide or fludarabine with or without the addition of ATG. Results Three hundred ninety-three patients were included; 75 patients received ATG, and 318 did not. No differences between the 2 groups were seen in the mean percentage of the predicted values for FEV1, FVC, TLC and DLco at 80 days or 1 year after transplantation. However, the mean value of FEV1/VC ratio at 1 year was higher for ATG patients. The mean change in PFT parameters from baseline to 1 year after HSCT did not show a statistically significant difference for any PFT parameters except for the FEV1/VC ratio, which showed a lesser decline in the ATG group. The risk of developing severe airflow obstruction or a restrictive pattern was similar between the 2 treatment groups at 1 year after HSCT. Conclusions Incorporation of ATG into the HSCT conditioning regimen provided protection against FEV1/VC ratio decline but did not decrease the risk of other pulmonary events that we evaluated within the first year after HSCT. However, further evaluations in larger numbers of patients are needed to better clarify the role of ATG in the development of delayed pulmonary complications.

Identification of risk factors for bronchiolitis obliterans syndrome after reduced toxicity conditioning before hematopoietic cell transplantation

“…28 In a retrospective study in 82 patients undergoing allo-HCT using T-cell depletion (in vivo by administration of the monoclonal anti-CD52 Ab alemtuzumab or ex vivo by CD34-positive selection) of related donor grafts, no patient developed BOS, whereas 8.1% of patients in the control group did. 29 The effect of in-vivo T-cell depletion on lung function is consistent with recently published data by Milano et al 27 , who showed a protective effect of GVHD prophylaxis with ATG on FEV1/FVC ratio at 1 year after allo-HCT. The protective effect of ATG on chronic lung dysfunction has been demonstrated in prospective randomized trials.…”

“…7,26 In contrast, the T-cell mediation of cGVHD, including BOS, is more controversial. Nevertheless, in multicentre, randomized trials, the use of ATG as GVHD prophylaxis for allo-HCT from matched, unrelated donors reduced significantly the incidence of cGVHD 13 and BOS, 27 while ex vivo T-cell depletion of stem cell grafts failed to lower the incidence of cGVHD. 28 In a retrospective study in 82 patients undergoing allo-HCT using T-cell depletion (in vivo by administration of the monoclonal anti-CD52 Ab alemtuzumab or ex vivo by CD34-positive selection) of related donor grafts, no patient developed BOS, whereas 8.1% of patients in the control group did.…”

Rabbit Anti–T Cell Globulin in Allogeneic Hematopoietic Cell Transplantation

“…Consistent with the increase in viral infection rate in Hoegh-Petersen's study [51], there was a trend toward increased percentage of patients with !1 herpes simplex virus, varicella zoster virus, or cytomegalovirus (CMV) infection among patients treated with 10 versus 4 to 8 mg/kg Thymoglobulin in Remberger's study [47], an increased percentage of patients who died because of a viral infection among those treated with 10 versus 6 mg/kg Thymoglobulin in Wang's study (despite death due to any infection not being different) [46], and an increased percentage of patients with lower respiratory tract viral infection (that did not increase transplantation-related mortality) in patients treated with 4.5 to 6.0 mg/kg versus no Thymoglobulin in Milano's study [52]. The cumulative incidence of Epstein-Barr virus (EBV)e induced post-transplantation lymphoproliferative disorder (PTLD) has been conspicuously increased with ATG in some studies (Table 3).…”

Nonmalignant Late Effects in Survivors of Partially Matched Donor Hematopoietic Stem Cell Transplantation

“…Third, several studies have demonstrated that the addition of ATG to GVHD prophylaxis can significantly reduce the cumulative incidence and severity of chronic GVHD after HSCT [32][33][34][35][36]. Furthermore, Bacigalupo et al [35] and Milano et al [37] observed that ATG could reduce the occurrence of chronic lung disease after HSCT. In our multivariate analysis, we found that ATG remained independently associated with ocular and dental late effects when adjusted for other parameters, such as age, gender, HLA disparity, duration of IST, and chronic GVHD.…”