Comparative analysis of autografting in chronic myelogenous leukemia: effects of priming regimen and marrow or blood origin of stem cells.
The aims of this study were (1) to evaluate the effect of intermediate (cyclophosphamide alone) or intensive (mitoxantrone, cytosine arabinoside, cyclophosphamide) priming on the cytogenetic response in mobilized bone marrow (BM) or peripheral blood (PB) progenitors in patients with chronic myelogenous leukemia (CML), (2) to determine the incidence of cytogenetic remissions after mobilized progenitor transplantation in CML, and (3) to determine the effect of in vivo priming on the ability to select Philadelphia chromosome-negative (Ph-negative) CD34(+)HLA-DR- cells from mobilized BM or PB in quantities sufficient for transplantation. Between February 1994 and March 1997, 44 patients were enrolled in three sequential protocols. Although the duration of neutropenia after only cyclophosphamide mobilization was shorter, clinical morbidity for the intermediate and intensive priming protocols was similar. Cytogenetic responses in mobilized PB progenitors were similar after mobilization with either intermediate or intensive chemotherapy. The degree of Ph negativity in the mobilized product correlated with disease stage at the time of mobilization (early chronic phase [ECP] > late CP > accelerated phase). Cytogenetic responses after transplantation with mobilized progenitors obtained after the different regimens were similar. The cytogenetic status of the graft predicted the cytogenetic status of marrow obtained 3 weeks after transplantation whereas cytogenetic responses 3, 6, and 12 months after transplantation correlated with the number of BCR/ABL-negative CD34(+)HLA-DR- cells, but not the number of Ph-negative metaphases in the graft. In patients with ECP CML, mobilized PB collections yielded significantly more CD34(+)HLA-DR- cells than from steady state or mobilized BM. CD34(+)HLA-DR- cells were Ph negative and polyclonal (X-chromosome inactivation) in the majority of ECP CML patients, before and after mobilization and irrespective of the mobilization regimen. Because infusion of large numbers of Ph-negative CD34(+)HLA-DR- cells predicted superior outcome after transplantation, approaches in which CD34(+)HLA-DR- cells are selected from mobilized PB may result in longer lasting and clinically significant cytogenetic responses after transplantation.
Verfaillie
C M
CM
Department of Medicine, Stem Cell Biology Program, Bone Marrow Transplantation Program, and Department of Laboratory Medicine at the University of Minnesota, Minneapolis, MN, USA. verfa001@maroon.tc.umn.edu
Bhatia
R
R
Steinbuch
M
M
DeFor
T
T
Hirsch
B
B
Miller
J S
JS
Weisdorf
D
D
McGlave
P B
PB
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous
D018952:Antigens, CD34; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D003561:Cytarabine; D003520:Cyclophosphamide; D008942:Mitoxantrone