Transplantation of a combination of CD133⁺ and CD34⁺ selected progenitor cells from alternative donors

Abstract

Summary Positive selected haematopoietic stem cells are increasingly used for allogeneic transplantation with the CD34 antigen employed in most separation techniques. However, the recently described pentaspan molecule CD133 appears to be a marker of more primitive haematopoietic progenitors. Here we report our experience with a new CD133‐based selection method in 10 paediatric patients with matched unrelated (n = 2) or mismatched‐related donors (n = 8). These patients received a combination of stem cells (median = 29·3 × 106/kg), selected with either anti‐CD34 or anti‐CD133 coated microbeads. The proportion of CD133+ selected cells was gradually increased from patient to patient from 10% to 100%. Comparison of CD133+ and CD34+ separation procedures revealed similar purity and recovery of target populations but a lower depletion of T cells by CD133+ selection (3·7 log vs. 4·1 log, P < 0·001). Both separation procedures produced >90% CD34+/CD133+ double positive target cells. Engraftment occurred in all patients (sustained primary, n = 8; after reconditioning, n = 2). No primary acute graft versus host disease (GvHD) ≥ grade II or chronic GvHD was observed. The patients showed a rapid platelet recovery (median time to independence from substitution = 13·5 d), whereas T cell regeneration was variable. Five patients are alive with a median follow‐up of 10 months. Our data demonstrates the feasibility of CD133+ selection for transplantation from alternative donors and encourages further trials with total CD133+ separated grafts.

Rapid reconstitution of dendritic cells after allogeneic transplantation of CD133+ selected hematopoietic stem cells

“…The absolute numbers of myeloid and plasmacytoid DCs measured in the blood until day þ 112 after transplantation are given as boxes and whiskers plots (Figure 2c and d). Extending a recent study in which significantly higher numbers of CD34 þ and CD133 þ selected PBSC were coinfused in pediatric patients, 4 this trial formally proves for the first time that allogeneic CD133 þ purified PBSC derived from one or two large-volume leukaphereses are sufficient as the only source of hematopoietic progenitor cells in adult recipients. Purity and recovery of CD133 þ cells as well as the efficacy of T-cell depletion were comparable with the results achieved after CD34 þ selection.…”

“…3 Differences in outcome between patients with the balanced and unbalanced form have been reported in some studies, 4 but not in others. 5 However, intensified chemotherapy has been shown to improve outcome and may mitigate or nullify the adverse prognostic impact of t(1;19).…”

“…Thus, event-free survival (EFS) of 75-85% is reported with modern treatment protocols for ALL. 1,4,6,7 The improved outcome has been accomplished by reinforced early therapy and extended combination therapy. It is not known, however, whether addition or dose escalation of any specific drug was the critical factor, or if improved outcome was the result of a general increase in treatment intensity.…”

Cell tracking velocimetry as a tool for defining saturation binding of magnetically conjugated antibodies

“…Recent magnetic separation technology development has led to such diverse applications as cancer progression monitoring by separation of circulating tumor cells (1)(2)(3)(4)(5)(6) and reconstitution of hematopoiesis in patients having undergone chemotherapy (7)(8)(9)(10)(11).…”

Immunologic Purging of Autologous Peripheral Blood Stem Cell Products Based on CD34 and CD133 Expression Can Be Effectively and Safely Applied in Half of the Acute Myeloid Leukemia Patients

“…CD133 selected cells successfully engrafted in a fetal sheep transplantation model (8). Also, in the clinical setting, transplantation with CD133-positive cells, like CD34-positive cells, resulted in a fast recovery of mature blood cells (9,10). Because AML is considered to be a CD34-and CD133-positive malignancy, positive selection for CD34 and CD133 has thus far not been applied.…”