Immunomagnetic CD4⁺ and CDS⁺ cell depletion for patients at high risk for severe acute GVHD

Acute GVHD remains a major problem in allogeneic BMT, in particular when donors other than HLA-identical siblings are used. To determine the efficacy of an immunomagnetic method for depletion of CD4⁺ and CD8⁺ lymphocytes from the marrow graft, a series of 15 patients was studied. Thirteen patients had matched unrelated donors, and two patients had related donors. Cyclosporine was used as GVHD prophylaxis in combination with CD4⁺ and CD8⁺ depletion, which removed 94.1 ± 3.2%, 97.0 ± 5.1%, and 96.7 ± 3.1% of CD3⁺, CD4⁺ and CD8⁺ cells, respectively. All patients engrafted promptly with AGC >500/mm³ after a median of 16 days post-BMT. Acute GVHD grade II-IV developed in 0/2 related transplants and 4/13 MUD transplants; only one patient had grade III-IV acute GVHD. No late graft failure was observed. Three patients relapsed; two had advanced disease at the time of BMT. Seven patients are alive and in CCR after a median of 497 days; actuarial survival is 39% at 24 months. The fever syndrome observed with selective CD8⁺ cell depletion was not seen with the combined CD4⁺ and CD8⁺ cell depletion. Immunomagnetic CD4⁺ and CD8⁺ cell depletion of marrow grafts, in combination with in vivo cyclosporine, is a simple, reproducible and effective method to decrease the incidence and severity of acute GVHD in patients at high risk for this complication after allogeneic BMT.