Cytogenetic analysis of chimerism and leukemia relapse in chronic
myelogenous leukemia patients after T cell-depleted bone marrow
transplantation
K Offit, JP Burns, I Cunningham, SC Jhanwar, P Black, NA Kernan, RJ O'Reilly and RS Chaganti
Laboratory of Cancer Genetics and Cytogenetics, Sloan Kettering Institute,
New York, NY 10021.
Serial cytogenetic studies were performed on 64 patients with chronic
myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow
transplantation (BMT). Forty patients with CML in chronic phase (CP)
received cytoreduction followed by BMT with HLA-matched T cell-depleted
allogeneic marrow. The remaining 24 patients were transplanted in second
chronic, accelerated, or blastic phase, or received T cell- depleted grafts
with a dose of T cells added back. The Y chromosome and autosomal
heteromorphisms were used to distinguish between donor and host cells.
Mixed hematopoietic chimerism (presence of donor and host cells) was
identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome
reappeared in 16 of the 40 first CP CML patients. As expected, patients who
had detectable Ph chromosome positive cells at any time during the
posttransplant period had a high likelihood of subsequent clinical relapse.
Transient disappearance of the Ph positive clone was rarely observed, and
was followed by reappearance of the Ph chromosome or clinical relapse. A
subset of engrafted patients with greater than 25% host cells within 3
months post-BMT had a significantly shorter survival time free of
cytogenetic or clinical relapse compared with other patients. In patients
who had received donor T cells added to the T cell-depleted graft, there
was a higher proportion of complete chimerism. Clonal progression of Ph
positive as well as negative cells was observed and may be the result of
radiation induced breakage. Serial cytogenetic studies of patients post-BMT
can provide useful information regarding the biologic and clinical behavior
of CML.
Volume 75,
Issue 6,
pp. 1346-1355,
03/15/1990
Copyright © 1990 by The American Society of Hematology