title: Immunomagnetic CD4+ and CD8+ cell depletion for patients at high risk for severe acute GVHD.
abstract: 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.
authors.affiliation: Bone Marrow Transplantation Program Methodist Hospital of Indiana, Indianapolis 46206-1367, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jansen
authors.forename: S
authors.initials: S
authors.lastname: Hanks
authors.forename: L P
authors.initials: LP
authors.lastname: Akard
authors.forename: J M
authors.initials: JM
authors.lastname: Thompson
authors.forename: S
authors.initials: S
authors.lastname: Burns
authors.forename: Q
authors.initials: Q
authors.lastname: Chang
authors.forename: D
authors.initials: D
authors.lastname: English
authors.forename: P
authors.initials: P
authors.lastname: Garrett
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000209:etiology; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D018189:Immunomagnetic Separation; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013577:Syndrome; D014184:Transplantation, Homologous
chemical_list: D016572:Cyclosporine