VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

AUTOGRAFTING IN CHRONIC MYELOID LEUKEMIA WITH CULTURED
MARROW: RESULTS OF A PILOT STUDY.
Michael J Barnett, Connie J Eaves, Gordon L Phillips, Donna E Hogge,
Hans-G Klingemann, Peter M Lansdorp, Stephen H Nantel, Donna E Reece,
John D Shepherd, Heather J Sutherland, Allen C Eaves.
Leukemia/Bone Marrow Transplantation Program of British Columbia:
Division of Hematology, British Columbia Cancer Agency, Vancouver General
Hospital and the University of British Columbia,
Vancouver, British Columbia, Canada.
INTRODUCTION I ON
In 1987, we initiated a study to evaluate the feasibility of using 10-day cultured
marrow autografts to allow intensive treatment of patients with chronic
myeloid leukemia (CML). 1
The rationale for this approach is based on evidence
that leukemic stem cells (operationally defined as Philadelphia chromosome
[ph']-positive long-term culture initiating cells [LTC-IC]) are, on average, present
in CML marrow at levels 10-fold lower than their normal counterparts and can
be selectively "purged" (by a factor of 30-fold) following incubation for 10 days
in LTC. 2
" 4
Patients were selected for this pilot study on the basis of a previous
laboratory assessment of the frequencies of normal and leukemic LTC-IC remaining
in their marrow at the end of 10 days of incubation in vitro under LTC
conditions. The purpose of this was to establish whether a subsequently harvested
and similarly treated autograft would be likely to have sufficient normal
stem cells to allow engraftment and no detectable leukemic stem cells. 1
METHODS
Between April 1987 and February 1992,88 candidate patients (aged < 60
years, in morphological chronic phase of CML and ineligible for allogeneic bone
marrow transplantation [BMT]) had their marrow assessed after 10 days of LTC
for normal and leukemic LTC-IC numbers using previously described procedures.
1,5
In 36 patients (41%), normal LTC-IC in these cultured samples were
present at > 2% of normal marrow values and leukemic LTC-IC were not detectable.
Only patients meeting these criteria were considered eligible for
autografting.
Twenty-two patients (aged 22 to 59 years, median 43), 15 in first chronic
phase (Group 1) and 7 in accelerated or > first chronic phase (Group 2), were
autografted with 10-day cultured marrow after either a total body irradiationbased
(3 patients) or a busulfan-based (19 patients) regimen. The methods employed
for manipulating the autograft were as previously described. 1
Briefly, ~2
x 10 10
nucleated cells were set up in culture, and 10 days later all cells present
(range 1.0 to 4.4 x 108/kg, median 1.7) were collected and infused.
SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 209