Autografting in chronic myeloid leukemia with cultured marrow: update of the Vancouver Study.
When chronic myeloid leukemia (CML) marrow is set up in long-term culture (LTC), Philadelphia chromosome (Ph)-positive (Ph+) cells typically decline and Ph-negative (Ph-) hematopoietic cells often become detectable. In 1987, we initiated a study to evaluate the feasibility of using 10-day cultured marrow autografts to allow intensive treatment of CML. Patients were selected on the basis of a previous assessment of the frequencies of normal and leukemic LTC-initiating cells (LTC-IC) remaining in their marrow after 10 days of LTC. Of the 87 patients evaluated, 36 (41%) were considered eligible, and 22 (15 in first chronic phase [CP], Group 1; and 7 with more advanced disease, Group 2) were autografted with 10-day cultured marrow after intensive therapy. Satisfactory hematological recovery occurred in 16 patients, and of these, only Ph- cells were detected in 13 (nine in Group 1), with 76-94% Ph- cells in the other three (two in Group 1). Ph+ cells reappeared between 4 and 36 months post-autograft in all but one of the 13 patients in whom complete (morphological and cytogenetic) remission had been achieved; the remaining patient died in remission. Nine of these twelve patients were then treated with alpha-interferon (IFN-alpha) 1-3 x 10(6) units/m2, 3-7 days/week; four returned to complete remission, three developed increasing numbers of Ph+ cells, and two are still too early to evaluate. Fifteen patients (12 in Group 1) remain alive and well, nine in hematological remission (eight in Group 1), 9 to 64 months (median 28) post-autograft.(ABSTRACT TRUNCATED AT 250 WORDS)
Barnett
M J
MJ
Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver General Hospital, Canada.
Eaves
C J
CJ
Phillips
G L
GL
Hogge
D E
DE
Klingemann
H G
HG
Lansdorp
P M
PM
Nantel
S H
SH
Reece
D E
DE
Shepherd
J D
JD
Sutherland
H J
HJ
D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D001955:British Columbia / Q000453:epidemiology; D003131:Combined Modality Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000453:epidemiology / Q000628:therapy*; D008875:Middle Aged; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured