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, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells.


METHODS
The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design.


RESULTS
Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment (absolute neutrophil 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 autologous transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log reduction >3.12.


CONCLUSIONS
CD34+Thy1+ HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable 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 bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.
Michallet
M
M
Service d'Hématologie de l'Hôpital Edouard Herriot, Lyon, France. mauricette.michallet@chu-lyon.fr
Philip
T
T
Philip
I
I
Godinot
H
H
Sebban
C
C
Salles
G
G
Thiebaut
A
A
Biron
P
P
Lopez
F
F
Mazars
P
P
Roubi
N
N
Leemhuis
T
T
Hanania
E
E
Reading
C
C
Fine
G
G
Atkinson
K
K
Juttner
C
C
Coiffier
B
B
Fière
D
D
Archimbaud
E
E
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D002469:Cell Separation / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D016133:Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000032:analysis*
D018952:Antigens, CD34; D018800:Thy-1 Antigens