Prognostic factor 
Studies indicating an association and quality 
Strength of association with tumor response 
Molecular response as a marker of tumor response 
Paschka, 2003^{10}
(Quality = 4/6) CPIFNr 
Best individual molecular ratios in patients who achieved a
MCR and subsequently relapsed were significantly higher than that of patients
who remained in CCR, median f/u 13 mo
(p=0.0017)
BCRABL/ABL Median
All pts = 0.086 (03.9)
Relapse = 1.4 (0.0137.8)
Continuous CCR = 0.071 (03.9)
All pt who achieved median ratio <0.1% are in CCR 
Müller, 2003^{104}
(Quality 5/6) CPnew diagnosis 
Median BCRABL/ABL ratio at start of I (N=98) was 51% (1210%)
Median for CR pts (N=85): 0.067% (05.7%)
Median for PR pts (N=5): 1.4% (0.1811%)
Median for MinorR pts (N=7): 27% (669%)
Median for pts in NR (N=2): 42% (3845%) 
Hughes, 2003^{11}
(Quality 6/6) CP new diagnosis 
Relationship between CCR and reduction in level of transcripts:
Itreated in CCR (N=333): 2.5 log reduction
IFN+cytarabine in CCR (N=37): 2.2 log reduction
p=0.036 
Merx, 2002^{105}
(Quality = 5/5) CPIFNr 
Median BCRABL/ABL ratio at start of I (N=120) was 67% (0.01100%)
Median for CR pts (N=50): 0.85% (0.01821%)
Median for PR pts (N=42): 6.7% (0.594%)
Median for Minor R pts (N=33): 45% (6100%)
Median for NR pts (N=50): 46% (6100%)
CR to PR (p < 0.0001)
PR and MinorR (p < 0.0001),
MinorR and NR (p NS) 
Rosti, 2004^{8}
(Quality 4/5) CPIFNr 
>2 log reduction in the BCRABL/B_{2} microglobulin transcript ratio in 76/85 (89%) pt in CCR with I and 0/23 (0%) pt in PCR 
Stentoft, 2001^{7}
(Quality 4/5) AP & CP 
Longitudinal plots of BCRABL transcripts derived from blood and bone marrow samples correlate (i.e. peripheral blood assessments are adequate)
On plots, 1 log reduction in BCRABL transcript levels correlate with CCR (strength of association not given) 
Wu, 2002^{6}
(Quality 3/5) CP, AP & BC 
Longitudinal plots of BCRABL transcript copy numbers correlate with cytogenetic response 
*Cortes, Talpaz, O'Brien, Giles, et al., 2004^{5}
(Quality*) CPnew diagnosis 
Relationship between increasing transcript levels and relapse at 24 mos: <0.05 increase0/44 (0%) loss of CCR 0.051 increase6/33 (18%) >15/11 (45%) p=0.0001 
Moravcova, 2004^{9}
(Quality 3/6) CPIFNr 
6/11 CP pts achieved CCR with rapid decrease in transcript
182600 fold at 6 mo, and 3712500 fold at 12 mo; no BP or AP pt (0/8)
showed this trend 
Karntarjian, Talpaz, et al., 2004^{12}
(Quality = 5/5) CPIFNr 
If BCRABL/ABL is <0.05%, then all pt (N=71) had a CCR and none relapsed
by 10 mo median f/u 
Prognostic value of baseline transcript levels 
Müller, 2003^{104}
(Quality 5/6) CPnew diagnosis 
Median BCRABL/ABL ratio at start of I (n=98) was 51% (1210%)
Response to I was independent of BCRABL level at start of therapy 
Hochhaus, 2002^{55}
(Quality = 3/6) CP 
Relationship between presence of higher ratio and resistance expressed
as the ration of BCRABL/G6PD:
Prior to Imatinib  4.6 %
With Imatinib resistance  6.0% p=NS

Wu, 2002^{6}
(Quality 3/5) CP, AP & BC 
BCRABL copy number at baseline was not significantly different among I treated patients who ultimately did or did not have cytogenetic response) (p=0.09) 
Prognostic value of transcript trends while on imatinib treatment 
Branford, 2003^{33} (Quality = 5/6) CPnew diagnosis 
Among Itreated pts (n=28), median log reduction is associated with MMR at 24 mo
 Med log reduction > 2 versus < 2 at 3mo (100% vs. 54%; p<0.001 by KM).
 Med log reduction > 2 versus < 2 at 6 mo (86% vs. 0%; p<0.001 by KM)
and incidence of progression.
 Med log reduction <2 versus > 2 at 6 mo (56% vs 4%; p=0.002 by KM).

Hughes, 2003^{35} (Quality = 6/6) 11 CPnew diagnosis 
Relationship between >3 log reduction@ 12 mo & being progression free @ 24 mo: >3 log reduction @ 12 mo: 100%
< 3 log reduction: 95%
no CCR: 85% p=<0.001
Relationship between >3 log reduction and CCR: >3 log reduction at 6 months:
Itreated in CCR:
42%
IFN+cytarabine in CCR:
13% p=0.03
>3 log reduction at 12 months:
Itreated in CCR: 57%
IFN+cytarabine in CCR: 24% p=0.003 
Rosti, 2004^{8}
(Quality 4/5) CPIFNr 
Median transcript level in pt who reached CCR in <6 mo after
start of I:
Baseline 0.2330
3 mo 0.0039
6 mo 0.0003
12 mo 0.0005
24 mo 0.0001
Median transcript level in pt who reached CCR in 912 mo after start of
I:
Baseline 0.2490
3 mo 0.0213
6 mo 0.0046
12 mo 0.0034
24 mo 0.0002 
Müller, 2003^{104}
(Quality 5/6) CPnew diagnosis 
After 3 mo, CCR within the first year could be predicted using the ratio BCRABL/ABL (p=0.0026) or BCRABL/G6PD (p=0.0074).
Empirically derived statistical cutoff point for best prediction of CCR
after 12 mo was a ratio BCRABL/ABL of 10% at 3 months with a positive predictive
value of 71% and a negative predictive value of 82%.
Empirically derived statistical cutoff point for best prediction of CCR
after 12 mo was a reduction of the ratio BCRABL/G6PD of 0.3 log after 3
mo with
a positive predictive value of 76% and a negative predictive value of 80%,
respectively. 
*Müller, 2004^{106}
(Quality*) CP, AP & BC 
BCRABL/ABL ratios after 12mo were lower in I pts in CCR
than I pts with subsequent relapse (0.180.60%, p=0.04)
In n=132 pt from the IRIS study, no pt with BCRABL/ABL <0.12% (>3 log reduction)
after 12 mo relapsed 
*Branford, 2004^{32}
(Quality*) CP 
BCRABL levels do not appear to decrease substantially after 24 mo on I (see efficacy table, IRIS trial) 
*Cortes, Talpaz, O'Brien, Giles, et al., 2004^{5}
(Quality*) CPnew diagnosis 
Relationship between 1 log reduction in transcript levels after 3 mo and 3 log reduction at 24 mo: >1 log: 90% <1 log: 55% p=0.0002

*Press, 2004^{107}
(Quality*) CP 
Relationship between >2 log reduction in transcripts at time of CCR and relapse over 29 mo median f/u
>2 log reduction  3/10 (10%) relapsed <2 log reduction  22/49 (45%) relapsed
OR 7.1 (CI 1.926)

Wang, 2003^{48}
(Quality 2/5)
All phases and relapse states including after allogeneic SCT

Relationship to PFS at 500 days estimated from KM:
BCRABL/ABL ratio @ 4 wk <50%  100%
BCRABL/ABL ratio @ 4 wk >50%  45% p=0.01
BCRABL/ABL ratio @ 3 mo <10%  100%
BCRABL/ABL ratio @ 3 mo >10%  38% p=0.003 
Wu, 2002^{6}
(Quality 3/5) CP, AP & BC
Merx, 2002^{105}
(Quality = 5/5) CPIFNr

BCRABL copy number at 3mos was significantly reduced among I treated patients who had a cytogenetic response (p=0.02) and this trend increased with time (p=0.04 at 6 mo, p=0.005 at 9 mo, and p=0.0008 at 12 mo)
Median BCRABL/ABL ratio at start of I (n=120) was 67% (0.01100%)
Median for CR pts (n=50): 0.85% (0.01821%)
Median for PR pts (n=42): 6.7% (0.594%)
Median for Minor R pts (n=33): 45% (6100%)
Median for NR pts (n=50): 46% (6100%)
CR to PR (p < 0.0001)
PR and MinorR (p < 0.0001),
MinorR and NR (p NS)
Probability of MCR after 6 mo was higher when ratio <20% at 2 mo (p=0.007) 