Transplantation with selected autologous peripheral blood CD34(+)Thy1(+) hematopoietic stem cells (HSCs) in multiple myeloma: Impact of HSC dose on engraftment, safety, and immune reconstitution

Objective. The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, t o assess the safety and efficacy of de-escalating cell dose cohorts of CD34 (+)Thy1(+) hematopoietic stern cells (HSCs) as autologous grafts hi deter-m ining engraftment, and to assess the residual tumor cell contamination usin g polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myel oma cells. Materials and Methods. The clinical trial was performed in 31 multiple myel oma patients, using purified human CD34(+)Thy1(+) HSCs mobilized from perip heral blood with cyclosphosphamide and granulocyte-macrophage colony-stimul ating factor to support a single transplant after high-dose melphalan 140 m g/m(2) alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalatian/escalation design. Results. Twenty-three patients were transplanted. Engraftment data in the m elphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 X 10(6) CD34(+)Thy1(+) HSCs/kg provided prompt engraftment (absolute n eutrophil count >0.5 X 10(9)/L day 10; platelet count >50 X 10(9)/L day 13) . A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34(+) selected or unselected autologou s transplantation, which did not correlate with the CD34(+)Thy1(+) HSC dose infused. Successful PCR for CDR III could only be performed in five patien ts on initial apheresis product and final CD34(+)Thy1(+) HSC product and sh owed a median tumor log reduction >3.12. Conclusions. CD34(+)Thy1(+) HSCs are markedly depleted or free of detectabl e tumor cells in multiple myeloma and are capable of producing fast and dur able hematopoietic reconstitution at cell doses >0.8 X 10(6) CD34(+)Thy1(+) HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous hone marrow and peripheral blood mo nonucleated cells transplants in multiple myeloma and may be corrected by a ddition of T cells either to the graft or to the patient in the posttranspl ant phase. (C) 2000 International Society for Experimental Hematology, Publ ished by Elsevier Science Inc.