CD8+ T-cell-depleted, matched unrelated donor, allogeneic bone marrow transplantation for advanced AML using busulfan-based preparative regimens

Abstract

Summary:The role of T-cell depletion (TCD) to prevent graftversus-host disease (GVHD) after matched unrelated donor allogeneic bone marrow transplant (MUD BMT) remains undefined. Most studies employ total body irradiation and pan TCD. Between March 1993 and June 2002, we treated 33 relapsed acute myelogenous leukemia (AML) patients with busulfan-based preparative regimens and selective TCD. The preparative regimen consisted of busulfan 14 mg/kg, cyclophosphamide 120 mg/kg and VP-16 50 mg/kg in all but one patient who only received busulfan and cyclophosphamide. Donor marrow was depleted of CD8 þ T cells by immunomagnetic bead separation. The patients were also treated with cyclosporine and methylprednisolone or FK-506 and mini-dose methotrexate. Four (15%) of 33 patients developed graft failure or rejection. However, three of these patients were serologically mismatched at HLA-Cw. Although 67% of evaluable patients developed acute GVHD, severe grade III-IV acute GVHD only developed in 19%. The severity of acute GVHD correlated with the degree of CD8 þ TCD. Median relapse-free survival was 5 months among 20 patients treated with active AML, and 28 months among 13 patients treated in complete remission. Our results confirm that MUD BMT with CD8 þ TCD for AML is a potentially curative treatment option.

T Cell–Depleted Unrelated Donor Stem Cell Transplantation Provides Favorable Disease-Free Survival for Adults with Hematologic Malignancies

“…Limited reports of TCD unrelated BM or PBSC grafts following myeloablation have been published7,23-26 Most studies utilized partial TCD together with immune suppressive medications25 post transplant. They reported slower immune recovery, a higher incidence of infectious complications, 18,27,28 and relapse in certain diseases compared with T-cell replete transplantation 29-31.…”

A Comprehensive Model to Predict Severe Acute Graft-Versus-Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation

“…CD8+ T cells were more abundant than CD4+ T cells in the blood of mice after aGVHD induction, and the severity of aGVHD was associated with the in ltration of CD8+ T cells in target tissues [44]. Several studies reported that CD8+ T cells count in the graft could predict the aGVHD in patient receiving ISD HSCT [16], URD HSCT [45], and umbilical cord blood transplantation [46].…”

T-cell therapy after hematopoietic stem cell transplantation

“…Depletion of all CD8 þ T cells has also been attempted, based on data supporting their critical role in human GvHD [30][31][32]. The hope is that the spared CD4 þ subset will be sufficient to allow immune recovery.…”