International Journal of Cell Cloning, Vol 4, 250-262, Copyright © 1986 by AlphaMed Press
Failure of bone marrow cryopreservation in chronic granulocytic leukemia: relation to excessive granulo-macrophagic progenitor pool
L Douay, M Lopez, NC Gorin, A Nauman, MC Giarratana, JP Laporte, J Stachowiak, C Salmon and G Duhamel
Autologous bone marrow transplantation (ABMT) in chronic granulocytic
leukemia (CGL) aims at reversing the acute or acceleration phases by
injection of stem cells collected during the chronic phase. This study was
designed to explain an unusual rate of delayed engraftment (50%) in our
experience of ABMT in CGL patients. We investigated all the factors
possibly responsible for abnormal perpetuation of aplasia following
infusion of cryopreserved marrow stem cells. The study of CFU-gm recovery
in 41 bags of frozen marrow from 25 patients revealed an overall deficiency
with a mean CFU-gm recovery of 55 +/- 38% in CGL patients versus 73 +/- 15%
in the control group (p less than 0.001). Our data also showed an inverse
linear relation (r = -0.40, p less than 0.05) between CFU-gm concentration
and recovery after freezing. A good CFU-gm recovery (greater than or equal
to = 50%) was observed in 70% of cases when the concentration was less than
3700 CFU-gm/ml as compared to 30% of cases when the concentration was over
3700 CFU-gm/ml (p less than 0.001). The lack of improvement by diluting
rich CFU-gm marrows to reduce CFU-gm concentration/ml, as well as the
absence of relationship between CFU-gm recovery after freezing and
nucleated cells concentration, suggest a particular fragility of CGL stem
cells to freezing, probably related to their excessive amplification. At
the present time, we strongly recommend that the highest possible dose of
progenitor cells be cryopreserved, preferably at a low concentration, in
patients with CGL, and particular attention devoted to the freezing
procedure in each individual patient, with numerous appropriate efficiency
tests.
