Patterns and kinetics of T-cell chimerism after allo transplant with alemtuzumab-based conditioning: mixed chimerism protects from GVHD, but does not portend disease recurrence

Abstract

We analyzed the kinetics of CD3 chimerism in 120 consecutive allogeneic hematopoietic cell transplantation (HCT) recipients receiving alemtuzumab-based conditioning. Fifty-two received fludarabine/melphalan, 44 received fludarabine/busulfan, and 24 received clofarabine/melphalan in addition to alemtuzumab. Post-transplant GVHD prophylaxis consisted of tacrolimus. No prophylactic donor lymphocyte infusion or other interventions were used for mixed donor chimerism (MDC). Bone marrow (BM) and/or peripheral blood (PB) samples were obtained at 30 days, 100 days, 180 days, and 1 year following HCT. On Day 30, 15% of assessable patients had MDC in the CD3 compartment. This had increased to 50% by Day 100, and to 63% by Day 180. MDC predicted for a lower risk of acute (p = 0.08) and particularly of chronic GVHD (p = 0.01). MDC was not associated with subsequent relapse or TRM (p = 0.67 and 0.72, respectively). A decline of more than 15% in CD3 chimerism between Day 30 and Day 180 predicted for a 40% risk of subsequent disease recurrence. The observation of MDC after alemtuzumab conditioning does not by itself constitute a risk factor for relapse and should not be used to guide therapeutic intervention. By contrast, declining donor chimerism between Day 30 and Day 180 is associated with a somewhat increased risk of disease recurrence. The high incidence of MDC after alemtuzumab containing conditioning contributes to the low risk of acute and chronic GVHD.

Keywords:

• Allogeneic transplant
• chimerism
• GVHD
• alemtuzumab

Acknowledgments

Koen van Besien: designed research, performed research, analyzed data, wrote manuscript. Alexander Dew: analyzed data, wrote manuscript. Shang Lin: analyzed data, wrote manuscript. Loren Joseph: performed engraftment analysis, reviewed manuscript. Lucy A. Godley: performed research, reviewed manuscript. Richard A. Larson:performed research, reviewed manuscript. Toyosi Odenike: performed research, reviewed manuscript. Elizabeth Rich:performed research, reviewed manuscript. Wendy Stock:performed research, reviewed manuscript. Amittha Wickrema:performed research, reviewed manuscript. Andrew S. Artz:performed research, reviewed manuscript. Koen van Besien is supported by NCI grant K24 CA 116471.

Declaration of interest: Koen van Besien is supported by NCI grant K24 CA 116471.