autologous blood and marrow transplantation - Blog Science ...

120 Chapter 3: CML
Table 5. Normal stem cells in CML
• Cytogenetic mosaics after busulfan treatment (Finney et al., 1972 30
; etc.)
• Ph-negative precursors in long term culture (Coulombel et al., 1983 31
; Verfaillie et al.,
1992 32
; Barnettetal, 1994 33
)
• Partial and complete cytogenetic remissions after intensive CHT (Cunningham et al.,
1979 27
; Sharp et al., 1979 28
; Goto et al., 1982 34
)
• Cytogenetic remissions after IFN-a (Talpaz et al., 19 8 6 35
; Kantarjian et al., 1991 36
; and
others)
• Ph-negativity after autografting with and without mobilization (Butturini et al., 1990 37
;
Carella et al., 1993 17
; Simonsson et al, 1994 38
)
dose chemotherapy and autografting has been shown, 28
and several randomized
studies use this new intensive approach. The study scheme of CML Study III A is
shown in Fig. 4. It involves one stratification and two randomization steps:
1. Determination of suitability for, and consent to, allogeneic BMT.
2. Genetic randomization according to donor availability between BMT vs.
no BMT.
3. Randomization of IFN-based standard therapy vs. high-dose chemotherapy
followed by autografting for non-BMT patients.
By December 1998, 138 patients had been recruited for CML Study III A, 34
were included in the second randomization step, and 16 were randomized for highdose
chemotherapy and autografting. Since treatment in CML appears to be the
more effective the earlier during the course of the disease it is carried out (Table 7),
high-dose chemotherapy and autografting are applied up-front as soon as it is clear
that no donor is available and stem cells have been collected. The preferred
mobilization treatment consists of idarubicin, Ara-C, and etoposide (mini-ICE). 29
How do BMT and drug treatment compare with regard to survival?
Until recently, the only potentially curative treatment option in CML was
allogeneic BMT. Since IFN can also change the natural course of CML and
prolong survival, the risks and limitations of BMT have to be critically considered.
Transplantation-related early morbidity and mortality are serious problems. BMT-
Table 6. Favorable survival results with autografting
• Unmanipulated marrow (Goldman et al., 1981 16
; Hoyle et al, 1994 39
)
• Ph-negative marrow induced with IFN and intensive CHT (Simonsson et al., 1993 15
)
• Ph-negative peripheral stem cells mobilized with CHT (Carella et al., 1993 17
)
• EBMT experience (Reiffers et al., 1994 40
)
» 8-center study (McGlave et al., 1994 18
; update: Bhatia et al„ 1997 41
)