autologous blood and marrow transplantation - Blog Science ...

484 Chapter 9: Long-Term Effects
posttransplant 6
" 7
; at the higher end of this range, posttransplant myelodysplastic
syndromes become a significant limiting factor in the successful application of
dose-intensive therapies. It remains to be determined, however, whether the
development of posttransplant MDS is the result of the high-dose chemoradiotherapy
or events occurring in association with the transplant process itself, or
whether it stems from the use of the conventional-dose chemotherapy that most
patients receive in the months or years preceding the transplant process. The
answer to this question has significant implications for the use and methodology of
autologous marrow and stem cell transplantation, and for the application of this
therapy to newer, nonmalignant indications such as autoimmune disorders.
In 30 to 50% of MDS cases, nonrandom cytogenetic abnormalities are apparent
in karyotypic analyses of bone marrow cells; this proportion may reach 80% in
patients with chemotherapy-induced (secondary) MDS. 8
The most common
abnormalities are deletions of 5q, 7q, or 20q, monosomies of 7 or Y, and trisomy
8. These abnormalities, once identified, can be used as markers to study the
appearance and progression of the MDS clone(s). Here we summarize the results
of two investigations of myelodysplastic syndromes using fluorescence in situ
hybridization (FISH) to study the origin and clonality of MDS progenitors in de
novo and posttransplant MDS. We then discuss their implications with respect to
HDC/autologous marrow or stem cell transplantation.
MATERIALS AND METHODS
Study 1 : FISH analysis of pretransplant progenitor cells
from patients with posttransplant MDS
In this study, we identified patients from three institutions with posttransplant MDS.
Twelve patients with clonal, MDS-related cytogenetic abnormalities for whom a FISH
probe was available and from whom pretransplant marrow or stem cell specimens were
available were selected for further analysis. Patient characteristics are shown in Table 1.
FISH probes corresponding to each patient's karyotypic abnormality were used
to analyze cryopreserved pretransplant marrow or peripheral blood stem cell
specimens (n=8) or archival bone marrow smears obtained immediately before
transplantation (n=4). Two hundred cells were examined on each slide by two
independent observers, and the mean of these determinations is reported.
Study 2: FISH analysis of immunomagnetically sorted CD34-positive
progenitors in patients with MDS
In this study, marrow aliquots in heparin were obtained from patients with
known or suspected MDS. If a diagnosis of MDS was confirmed histologically, and