Abstract

Imatinib has remarkable activity in CML in all phases, with high rates of hematologic and cytogenetic response. However, in AP and BP responses are frequently less than complete hematologic remission (CHR), including partial hematologic remission (PHR) and return to chronic phase (second CP). The objective of this study was to investigate whether different responses to imatinib conferred a survival advantage in pts with CML in AP and BP. We evaluated 214 pts in AP and 76 pts in BP (11 lymphoid, 63 myeloid, 2 unclassified) treated with imatinib. Median age for AP pts was 49 yrs (range: 22–82 yrs) and for BP, 54 yrs (19–75 yrs). With a median follow-up of 49 months (1.9–67.5 months), 82 (38%) AP and 66 (87%) BP pts have died. A CHR and major cytogenetic (CG) response (MCR) have been achieved in 87% and 53% of AP pts, and 37% and 14% of BP pts, respectively. For AP pts the median overall survival (OS) and progression free survival (PFS) were 65 and 49 months, respectively. In BP pts, median OS and PFS were 7 and 3 months. The OS by best response to imatinib was as follows:

Response No. (%) Median OS (months) p value Median PFS (months) p value 
CG CR=complete CG response (Ph=0%), CG PR=partial CG response (Ph<35%), CG minor=minor CG response (Ph=35–95%), Marrow CR/PR=marrow complete/partial response 
Accelerated phase 
CG CR 96 (45) Not reached <0.0001 Not reached <0.0001 
CG PR 13 (6) 43  28  
CG minor 13 (6) 48  31  
CHR 57 (27) 34  22  
PHR 16 (7) 14   
Resistant 11 (5)   
Blast Phase 
CG CR 6 (8) Not reached <0.0001 Not reached <0.0001 
CG PR + minor 8 (11) 12   
CHR + PHR 12 (16) 13  11  
Second CP 6 (8)   
Marrow CR/PR 9 (12)   
Resistant 25 (33)   
Response No. (%) Median OS (months) p value Median PFS (months) p value 
CG CR=complete CG response (Ph=0%), CG PR=partial CG response (Ph<35%), CG minor=minor CG response (Ph=35–95%), Marrow CR/PR=marrow complete/partial response 
Accelerated phase 
CG CR 96 (45) Not reached <0.0001 Not reached <0.0001 
CG PR 13 (6) 43  28  
CG minor 13 (6) 48  31  
CHR 57 (27) 34  22  
PHR 16 (7) 14   
Resistant 11 (5)   
Blast Phase 
CG CR 6 (8) Not reached <0.0001 Not reached <0.0001 
CG PR + minor 8 (11) 12   
CHR + PHR 12 (16) 13  11  
Second CP 6 (8)   
Marrow CR/PR 9 (12)   
Resistant 25 (33)   

We conclude that although cytogenetic responses confer the most survival advantage in AP and BP after imatinib therapy, hematologic responses are associated with a survival benefit.

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