A comparative study of GVHD prophylaxis using low dose ATG versus PTCy for PBSCT based on two independent prospective cohorts

Abstract

Both anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) have shown prophylactic effects on graft-versus-host disease (GVHD) in multiple phase III studies. We conducted a comparative study of for low dose ATG (thymoglobulin) versus PTCy for GVHD prophylaxis in peripheral blood stem cell transplantation (PBSCT). The ATG (n = 67) and PTCy (n = 40) groups included patients enrolled in multicenter phase II studies (JSCT-ATG15 and JSCT-PTCY19, respectively). The probability of GVHD-free and relapse-free survival at 2 years as the primary endpoint was not significantly different between these two groups (57.9% for ATG vs. 67.8% for PTCy, P = 0.49). Both neutrophil and platelet engraftments were both significantly shorter in the ATG group than in the PTCy group (neutrophils: median 13 days vs. 15 days, P = 0.007; platelets: median 20 days vs. 27 days, P = 0.007). The cumulative incidences of acute and chronic GVHD, relapse, non-relapse mortality, and off-immunosuppressant use were similar between these two groups. The probabilities of overall and progression-free survival were 83.4% and 70.0% in the ATG group and 76.5% and 75.2% in the PTCy group, respectively, with no significant differences. These data indicate that low dose ATG and PTCy are equivalent for GVHD prophylaxis for PBSCT.

Fig. 1

Incidence of engraftment in the ATG and PTCy groups. The cumulative incidence of neutrophil engraftment in the ATG (solid lines) and PTCy (dashed lines) groups (a), and the median neutrophil engraftment days from the day of HSCT in the ATG and PTCy groups (b). The cumulative incidence of platelet engraftment in the ATG (solid lines) and PTCy (dashed lines) groups (c), and the median platelet engraftment days from the day of HSCT in the ATG and PTCy groups (d). The ends of the center box indicate the upper and lower quartile of the data, the line inside the rectangle indicates the median, the whiskers indicate the maximum and minimum values, and the dots outside the rectangle indicate outliers.

Fig. 2

Incidence of GVHD in the ATG and PTCy groups. The cumulative incidences of grade II-IV (a) and grade III-IV (b) acute GVHD, and overall cGVHD (c) and moderate to severe chronic GVHD (d) in the ATG (solid lines) and non-ATG (dashed lines) groups.

Fig. 3

Incidences of relapse, NRM, and off-immunosuppressants, and probabilities of OS, PFS and GRFS in the ATG and PTCy groups. The cumulative incidences of relapse (a), NRM (b), and off-immunosuppressants (c), and the probabilities of OS (d), PFS (e), and GRFS (f) in the ATG (solid lines) and non-ATG (dashed lines) groups.

Fig. 4

Probability of OS in the ATG and PTCy groups according to donor, HLA compatibility, and conditioning intensity. The probability of OS in the ATG and non-ATG groups according to donor (a), HLA compatibility (b), and conditioning intensity (c). (a); related donor (black line) and unrelated donor (red line) in the ATG group, and related donor (green line) and unrelated donor (blue line) in the PTCy group, (b); HLA-matched donor (black line) in the ATG group, and HLA-matched donor (red line) and HLA-mismatched donor (green line) in the PTCy group, (c); MAC (black line) in the ATG group, and MAC (red line) and RIC (green line) in the PTCy group.