Efficacy and safety of CD34-selected and CD19-depleted autografting in multiple myeloma patients: a pilot study

OBJECTIVE: If multiple myeloma patients are to be cured after high-dose treatment supported by autologous stem cell transplantation, grafts must be purged of circulating myeloma cells. Myeloma cells are present in all grafts and have been identified as CD38(++)CD45(-) plasma cells, plasma blasts, and CD19(+) B cells.

MATERIALS AND METHODS: In an attempt to improve the purging strategy, we studied a two-step procedure consisting of CD34(+) enrichment followed by CD19 depletion. This article describes the evaluation of this sequential magnetic microbead selection after 18 procedures in 14 patients.

RESULTS: The processed autografts contained a median CD34 purity of 81% (range 21-99%) and a recovery of 47% (range 15-82%). Flow cytometric analysis documented the expected reduction of CD34(-) B cells and plasma cells, in most cases to a level below the sensitivity of flow cytometry. Real-time reverse transcriptase polymerase chain reaction documented a CD19 mRNA relative reduction to 0.042 (range 0.01-0.21). Allele-specific oligonucleotide IgH primers were designed for five patients. All products were positive for clonal myeloma cells before processing, but only 1 of 5 was negative after the procedure. The clinical outcome after reinfusion of the processed autografts was evaluated by blood cell recovery and found to be within the range expected from engraftment of unmanipulated autografts. One patient who had delayed platelet recovery associated with cytomegalovirus infection recovered after anti-cytomegalovirus treatment.

CONCLUSIONS: This pilot study documented engraftment after reinfusion of CD34-selected and CD19-depleted autografts. However, one patient suffered from unexpected prolonged thrombocytopenia. The efficacy of the procedure was evaluated and reduction of myeloma cells was indicated, with only one autograft free of clonal cells.