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CD34 positive selection as prophylaxis against graft versus host disease in allogeneic peripheral blood stem cell
Nauman M Butt1, Noreen McGinnity, Richard E Clark
1Jose Carreras Bone Marrow Transplant Unit, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK. nbutt@liv.ac.uk
Insights
CD34 positive selection effectively depletes T-cells in Peripheral Blood Stem Cell (PBSC) allografts, significantly reducing graft-versus-host disease (GVHD) while maintaining prompt engraftment and acceptable relapse rates.
Area of Science:
- Hematology
- Immunology
- Transplantation
Background:
- Graft-versus-host disease (GVHD) is a major complication of allogeneic stem cell transplantation.
- T-cell depletion (TCD) is a strategy to mitigate GVHD.
- Peripheral Blood Stem Cells (PBSC) are increasingly used for allografts.
Purpose of the Study:
- To evaluate the efficacy of CD34 positive selection for T-cell depletion in HLA-identical PBSC allografts.
- To assess the impact of this method on GVHD prophylaxis.
- To determine the effects on engraftment and disease relapse.
Main Methods:
- CD34 positive selection using immunomagnetic separation was performed on 14 consecutive HLA-identical PBSC allografts.
- Graft T-cell dose and CD34+ cell dose were quantified.
- Engraftment times (neutrophils and platelets) and incidence/severity of acute GVHD were monitored.
- Disease relapse and survival outcomes were assessed.
Main Results:
- Achieved a median T-cell dose of 1.89 x 10^4/kg, representing a 4-log depletion.
- Median neutrophil engraftment at 15 days and platelet engraftment at 20 days.
- Only four patients developed mild, grade I cutaneous acute GVHD.
- Four patients (all with AML) relapsed or progressed; 10 patients remain alive and well.
- Median progression-free survival was 69% at 686 days.
Conclusions:
- CD34 positive selection via immunomagnetic separation is an effective method for TCD in HLA-identical PBSC allografting.
- This approach leads to clinically insignificant acute GVHD and prompt engraftment.
- The method offers an acceptable risk of disease relapse, making it a viable strategy.
Abstract:
We report our experience of CD34 positive selection as a means of graft T-cell depletion (TCD) in 14 consecutive HLA-identical Peripheral blood stem cells (PBSC) allografts as prophylaxis against graft versus host disease (GVHDp). CD34 positive selection was performed by immunomagnetic separation achieving a median CD34 and T-cell dose of 4.17 (range 1.4-8.50) x 10(6)/kg and 1.89 (range 0.92-13.18) x 10(4)/kg, respectively, in the graft. This represents 4-log depletion of T-cells. The median time to achieve a neutrophil count of 0.5 x 10(9)/l was 15 days and to achieve a platelet count of 50 x 10(9)/l was 20 days. Only four patients developed acute GVHD at a median of 41 days but this was exclusively mild grade I cutaneous disease and settled with oral steroids. Four patients, all of whom had AML, relapsed or progressed after transplant at a median of 161 (range 109-311) days. One of these had been transplanted in early relapse (9% blasts) whilst another was in second remission. The remaining 10 patients are alive and well. The median progression free survival for the whole population is 69% at 686 days. We conclude that CD34 positive selection by immunomagnetic separation in HLA-identical PBSC allografting achieves significant TCD with clinically trivial acute GVHD, prompt engraftment and an acceptable disease relapse risk.
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