It Is Better to Do RIC Without ATG

Mojtaba Akhtari, MD

Acute and chronic graft-versus-host diseases (GVHD) are considered major contributors to transplant-related morbidity and mortality, and their incidence and severity are increased with unrelated donors in comparison with matched sibling donor hematopoietic stem cell transplant (HSCT).

GVHD is a major limiting factor for wider use of allogeneic HSCT as a therapeutic modality for malignant and nonmalignant disorders. Different GVHD prophylactic strategies including ex vivo and in vivo T-cell depletion have been developed. In vivo depletion of T-cells by using antithymocyte globulin (ATG) preparations has shown promising results, and incorporating ATG as part of the conditioning regimen in the setting of myeloablative allogeneic HSCT has archived an established position; and the evidence supporting its use in that context is quite convincing, since the data is from a prospective randomized multicenter phase III trial. [1]

ATG is associated with reduced risk of acute and chronic GVHD without increasing the risk of relapse in myeloablative donor transplants. However, there has been an ongoing debate about the role of ATG in reduced intensity conditioning (RIC) HSCT, and there are still bone marrow transplant centers that use ATG in the RIC setting, and their main argument is that ATG could help with engraftment and reducing the risk of GVHD. Different types and doses of ATG have been used in the RIC setting.

The recent article by Soiffer et al, which was published in Blood evaluated the risk of GVHD, relapse, and death in a cohort of 1,676 patients undergoing RIC HSCT between 2000 and 2007, and of those 584 received ATG, 213 received alemtuzumab, and 879 did not undergo any T-cell depletion. [2] The data was gathered and analyzed through the Center for International Blood and Marrow Transplant Research (CIBMTR) retrospectively.

The ATG and alemtuzumab groups had lower rates of acute GHVD (38%, 19%, and 40%, respectively, P < .0001) and chronic GHVD (40%, 24%, and 52%, respectively, P < .0001) in comparison with T-cell replete group. However, ATG and alemtuzumab groups had higher relapse rates than the T-cell replete group (51%, 49%, and 38% respectively, P < .001). The ATG and alemtuzumab groups had lower disease-free survival than the T-cell replete group (25%, 30%, and 39%, respectively, P < .001). Corresponding survival probabilities were 38%, 50%, and 46%, respectively.

The data is quite important, since it is suggestive of increased relapse and reduced disease-free survival with in vivo T-cell depletion in RIC setting. Those results should be incorporated into the decision making plans for patients undergoing RIC in our day-to-day practice, and to start with it is better to do RIC without ATG.

References:

1. Finke J, Bethge WA, Schmoor C, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–864.

2. Soiffer RJ, LeRademacher J, Ho V, et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117:6963–6970.