Abstract 494

The introduction of tyrosine kinase inhibitors (TKI) and advent of RIC and non-myeloablative (NMA) conditioning hematopoietic cell transplants (HCT) have changed and the therapeutic strategy for patients with CML. We analyzed the post HCT outcomes of CML patients aged 40 and older undergoing RIC/NMA HCT in 2001–2007. Detailed information regarding pre HCT TKI use or rationale for timing of transplant was not available; however, the analysis time period captures the entry of TKIs into clinical practice. Outcomes were compared between age cohorts of 40–49, 50–59, and ≥ 60 years. Overall survival (OS), Day +100 acute graft versus host disease (aGVHD) grades II-IV, chronic (cGVHD), transplant-related mortality (TRM), relapse, and disease-free survival (DFS) were analyzed with multivariate analysis testing the impact of age, gender, disease status at HCT (CP1vs. CP2/accelerated phase (AP) vs. blast phase (BP), sex match, HLA match, GVHD prophylaxis, and conditioning intensity (RIC versus NMA as described by Bacigalupo et all 2009) on outcomes. A total of 306 CML patients underwent HCT at 125 centers: 117 (38%) aged 40–49; 119 (39%) aged 50–59; and 70 (23%) aged ≥ 60. At HCT most patients in the 40–49 age cohort were in CP1 (72%), while only 44% of patients aged 50–59 and 31% aged ≤ 60 were in CP1. Interval from diagnosis to HCT for CP1 patients was similar across age groups with a large percentage of each age cohort undergoing HCT ≥ 2 years (32%, 40%, and 45%, respectively). Sibling donors were the stem cell source for 56% of those aged 40–49; older cohorts had a higher percentage of unrelated donors (58 and 60%, respectively). Primarily peripheral blood grafts (78%, 80% and 90%) and RIC (78%, 76% and 70%) were used across age groups, respectively. GVHD prophylaxis was similar. Three year OS and cGVHD, Day +100 grade II-IV acute GVHD, and 1 year TRM were similar in all age cohorts. Three year relapse incidence increased and DFS decreased with age. Importantly in analysis of CP1 patients only, relapse and DFS were similar in each age cohort.

Table 1:

Univariate Analysis

OutcomeAge 40–49 Probability (95% CI)Age 50–59 Probability (95% CI)Age ≥ 60 Probability (95% CI)P-value
Entire Cohort     
OSA 54% (44–64) 52% (42–61) 41% (30–54) 0.26 
aGVHDB II-IV 26% (18–34) 32% (24–40) 32% (21–43) 0.53 
cGVHDA 58% (47–68) 51% (41–61) 43% (33–55) 0.19 
TRMC 18% (11–26) 20% (13–27) 13% (6–22) 0.43 
RelapseA 36% (27–46) 43% (34–52) 66% (53–77) 0.001 
DFSA 35% (26–45) 32% (24–41) 16% (7–27) 0.01 
CP1 Only     
RelapseA 34% (23–46) 42% (28–56) 51% (29–72) 0.40 
DFSA 43% (31–55) 36% (23–51) 39% (19–61) 0.81 
OutcomeAge 40–49 Probability (95% CI)Age 50–59 Probability (95% CI)Age ≥ 60 Probability (95% CI)P-value
Entire Cohort     
OSA 54% (44–64) 52% (42–61) 41% (30–54) 0.26 
aGVHDB II-IV 26% (18–34) 32% (24–40) 32% (21–43) 0.53 
cGVHDA 58% (47–68) 51% (41–61) 43% (33–55) 0.19 
TRMC 18% (11–26) 20% (13–27) 13% (6–22) 0.43 
RelapseA 36% (27–46) 43% (34–52) 66% (53–77) 0.001 
DFSA 35% (26–45) 32% (24–41) 16% (7–27) 0.01 
CP1 Only     
RelapseA 34% (23–46) 42% (28–56) 51% (29–72) 0.40 
DFSA 43% (31–55) 36% (23–51) 39% (19–61) 0.81 

A=3 year; B=Day +100; C=1 year

View Large

Multivariate analysis confirmed the significant adverse impact of advanced CML (AP/CP2+ and BP) at HCT, NMA conditioning intensity, male gender, and older age on relapse and DFS. Overall survival was not impacted by age, but was significantly worse with advanced CML at HCT. (Table 2)

Table 2:

Multivariate Analysis

OutcomeRR95% CIP value
Relapse:    
Age: 1 0.69–1.642 0.0003 
40–49 1.064 1.441–3.607  
50–59 2.28   
≥60    
Disease Status: 1 0.1319–0.917 0.01 
CP1 1.335 0.0036–1.403  
AP/CP2+ 2.823   
BP    
Conditioning Intensity 1 0.222–0.469 <0.0001 
NMA 0.323   
RIC   
Gender 1 0.397–0.83 0.0032 
Male 0.574   
Female    
Overall Survival    
Age: 1 0.55–1.226 0.42 
40–49 0.821 0.683–1.618  
50–59 1.051   
≥60    
Disease Status: 1 1.206–2.47 <0.0001 
CP1 1.726 3.199–10.074 0.42 
AP/CP2+ 5.677   
BP    
Gender: 1 0.0189–0.481 0.019 
Male 0.671   
Female    
OutcomeRR95% CIP value
Relapse:    
Age: 1 0.69–1.642 0.0003 
40–49 1.064 1.441–3.607  
50–59 2.28   
≥60    
Disease Status: 1 0.1319–0.917 0.01 
CP1 1.335 0.0036–1.403  
AP/CP2+ 2.823   
BP    
Conditioning Intensity 1 0.222–0.469 <0.0001 
NMA 0.323   
RIC   
Gender 1 0.397–0.83 0.0032 
Male 0.574   
Female    
Overall Survival    
Age: 1 0.55–1.226 0.42 
40–49 0.821 0.683–1.618  
50–59 1.051   
≥60    
Disease Status: 1 1.206–2.47 <0.0001 
CP1 1.726 3.199–10.074 0.42 
AP/CP2+ 5.677   
BP    
Gender: 1 0.0189–0.481 0.019 
Male 0.671   
Female    
View Large

These data indicate that HCT is safe in older patients with CML with equivalent acute and chronic GVHD, TRM, and OS across age cohorts. Relapse increased in patients receiving NMA conditioning and in those aged 60 and above; most of whom had advanced disease. However, for HCT during CP1 relapse risks and DFS were similar, regardless of age. Allogeneic HCT using RIC conditioning for older patients with CP1 CML can control relapse with acceptable toxicity and survival. Comparison of outcomes with second line TKI versus HCT are as yet unreported but these favorable findings indicate appropriate consideration of HCT for older patients with CML.

Disclosures:

Gupta:Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Topics:
conditioning (psychology), donors, hematopoietic stem cell transplantation, leukemia, myelocytic, chronic, older adult, protein-tyrosine kinase inhibitor, relationship - sibling, transplantation, graft-versus-host disease, chronic, graft-versus-host disease

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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