Positive selection and transplantation of autologous highly purified CD133(+) stem cells in resistant/relapsed chronic lymphocytic leukemia patients results in rapid hematopoietic reconstitution without an adequate leukemic cell purging.
We assessed the capacity of positively selected autologous CD133(+) hematopoietic stem cells (HSCs) to reconstitute lymphomyelopoiesis in chronic lymphocytic leukemia (CLL) patients receiving myeloablative chemotherapy. Ten resistant/relapsed CLL patients underwent HSC mobilization with chemotherapy and granulocyte-colony stimulating factor (G-CSF). Positive selection of circulating CD133(+) HSCs was performed by immunomagnetic technique. Highly purified HSCs were reinfused after busulphan/melphalan myeloablative treatment. A median number of 4.2 x 10(6) CD34(+) cells/kg and of 3.14 x 10(6) CD133(+) cells/kg were collected. Immunomagnetic selection resulted in the reinfusion of a median number of 2.45 x 10(6) CD133(+) cells/kg (median purity: 94.8%; median recovery: 84%) and 2.4 x 10(6) CD34(+) cells/kg (median purity: 93%; median recovery: 71%). HSC selection resulted in a median T cell and CD19(+)/CD5(+) cell depletion of 3.85 log and 2.8 log, respectively. At the molecular level, however, 7 of 8 valuable purified HSC fractions were contaminated by leukemic cells. All CLL patients showed rapid and sustained myeloid engraftment after reinfusion of purified CD133(+) cells. Immunologic reconstitution was comparable to that routinely observed in patients reinfused with unmanipulated leukapheresis products and no late infectious complications were observed. With a median follow-up of 28 months for transplanted patients, 5 patients are in clinical complete remission, 3 are in partial remission, and 1 is in progression. In conclusion, the reinfusion of highly purified CD133(+) HSCs allowed the rapid and sustained recovery of hematopoiesis after myeloablative treatment in resistant/relapsed CLL patients. However, the purging potential of positive selection of CD133(+) cells is not adequate to achieve tumor-free autografts.
Isidori
Alessandro
A
Institute of Hematology and Medical Oncology, "L. & A. Seràgnoli," University of Bologna, Bologna, Italy. a.isidori@ospedalesansalvatore.it
Motta
Maria Rosa
MR
Tani
Monica
M
Terragna
Carolina
C
Zinzani
Pierluigi
P
Curti
Antonio
A
Rizzi
Simonetta
S
Taioli
Simona
S
Giudice
Valeria
V
D'Addio
Alessandra
A
Gugliotta
Gabriele
G
Conte
Roberto
R
Baccarani
Michele
M
Lemoli
Roberto M
RM
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000097:blood*; D016465:Bone Marrow Purging; D002469:Cell Separation; D002908:Chronic Disease; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006085:Graft Survival; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D010455:Peptides / Q000097:blood*; D010865:Pilot Projects; D039904:Pluripotent Stem Cells / Q000637:transplantation*; D016879:Salvage Therapy / Q000379:methods; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous / Q000379:methods*
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides