Myeloablative conditioning is well tolerated by older patients receiving T-cell-depleted grafts

Abstract

Summary:Older age has been linked to increased transplant-related mortality from graft-versus-host disease (GvHD). Depletion of T cells from stem cell grafts seems to protect from complications of GvHD particularly in older patients. After myeloablative conditioning, patients with haematological malignancies received allogeneic grafts from HLA identical siblings. For GvHD prophylaxis, PBPC grafts were treated ex vivo with anti-CD52, and therapeutic doses of cyclosporin until day þ 90. Survival of patients younger or older than the population age median was analysed. In all, 62 consecutive patients with a median age of 42.5 years were studied. Death was procedure related in 17% and from relapse of malignancy in five. At a median, follow-up is 662 (7-2316) days, 74% survive disease free. The rate of haematopoietic recovery and treatmentrelated mortality was similar in both groups. A total of 73% of 30 individuals in the younger group and 75% (P ¼ 0.8) in the older cohort survive at a median follow-up of 444 and 806 days (P ¼ 0.4). GvHD occurred in 13% and was the only adverse factor for survival (Po0.04). Myeloablative conditioning is well tolerated up to the age of 59 in patients receiving T-cell-depleted grafts. This information is useful to more precisely select patients who would benefit most from reduced intensity conditioning schedules. Bone Marrow Transplantation (2005) 36, 675-682.

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

“…Several studies have demonstrated the efficacy of TCD allogeneic bone marrow (BM)1-3 and TCD peripheral blood stem cell transplants (PBSCT)4,5 from matched related donors (MRD) in patients with hematologic malignancies. In these reports, reduction in the incidence and severity of acute and chronic GVHD, compared with T-cell replete transplantation, has not compromised the anti-tumor effect of the allograft.…”

Reduced-intensity conditioning for severe aplasia using fludarabine and CY followed by infusion of ex vivo T-cell-depleted grafts leads to excellent engraftment and absence of GVHD

“…24 Stem-cell-rich products were incubated at a concentration of 1 mg alemtuzumab/10 10 mononuclear cells 'in the bag' and allowed to react at 20 1C for 30 min. 12,13 Without further manipulation the cell suspension containing the Ab was then infused i.v. in sets devoid of any filters.…”

“…11,12 Indeed, experience has revealed that with this approach the reduced incidence and severity of GVHD has been associated with improvement in the early outcome after transplantation. However, in AA this strategy has been associated with higher incidence of graft failure, but it could be overcome by more powerful immunosuppression during conditioning and by restricting the transfusion of blood products to prevent allosensitization.…”

Conditioning with Purine Analogs Leads to Good Engraftment Rates of Immunodepleted Grafts for Aplastic Anemia

“…Although 1 of these patients required DLI for delayed rise of chimerism, the remainder experienced no significant posttransplantation problems, with no GVHD and a low rate of CMV reactivation (4 of 30), and all patients survived with normal blood parameters. We have previously shown that in the absence of GVHD, older age has little detrimental effect on SCT outcomes, including patients receiving myeloablative therapy for hematologic malignancies [20].…”