Abstract

Introduction and Methods: RIC HSCT has become a therapeutic option for elderly patients (pts) with AML and MDS in 1st CR (CR1). However the overall applicability of this procedure in such pts has not been assessed. To do so we wrote a protocol stipulating that all pts age > 50 with AML would be seen by a transplant service consult at first MDACC presentation. A donor search would be initiated and all pts with a matched sibling, or unrelated donor would receive RIC HSCT in 1st CR using a Fludarabine/Melphalan conditioning regimen.

Results: 99 of 257 pts undergoing induction therapy from 2001–2003 achieved a CR (39%). BMT consulted on 62 of the 99 (63%), and 25 of the 62 (40%) had a potential donor (20 sibling, 5 unrelated). 14 pts received a HSCT in CR1 (14% of CR1 pts, 5 % of all pts; 13 sibling, 1 unrelated). Survival (OS) and relapse-free survival (RFS) were each worse in non-consulted pts (group A) than in consulted pts (p =0.009 for S, medians of 28 and 66 weeks; p =0.019 for RFS, with medians of 20 vs. 36 weeks). This may have reflected the worse performance status of Group A pts (ECOG-PS 3,4 in 19% vs. 5%). Consulted pts without a donor (group B) did worse than consulted pts with donor (groups C+D [OS 49 vs. 124 wks (p=0.03); RFS 23 vs. 52 wks (p=0.016)]. Transplanted pts in CR1 (group C) did better than the remainder of consulted pts (groups B+D) and OS (p=0.023) and RFS (p<0.001) were not reached at 86 wks median f/u. Median time to HSCT was 17 weeks and transplant-related mortality zero. Among pts with donors in CR1 transplanted pts did better [RFS: p=0.001; OS: p=0.156]. The primary reason for not receiving a HSCT in CR1 pts with potential donor (Group D) was disease relapse in 81%. Significant group differences included: younger age of consulted pts (p=0.01); younger age of consulted pts with donor (p=0.03); younger age of transplanted pts (p =.01), less frequent −5/−7 (p=0.02) but more frequent 11Q abnormalities (p =0.007) in the donor and transplant group.

GroupABCDE
OverallCR/no ConsultCR/consult/no donorCR/consult/donor/HSCTCR/consult/donor/no HSCTNo CR
*median in wks; #miscellaneous/complex karyotype/insufficient metaphases, nr=not reached 
 N= 37 37 14 11 158 
RFS* 28 20 23 nr 24 na 
OS* 24 28 49 nr 100 13 
Follow up* 66 59 66 86 73 60 
Median Age 65 68 65 57 60 67 
%AHD 49 46 54 43 36 65 
AML/MDS 216/41 30/7 28/9 12/2 9/2 137/21 
cyto:+8, −5,−7 162 20 26 108 
cyto:# 79 16 10 42 
cyto:11q 16 
GroupABCDE
OverallCR/no ConsultCR/consult/no donorCR/consult/donor/HSCTCR/consult/donor/no HSCTNo CR
*median in wks; #miscellaneous/complex karyotype/insufficient metaphases, nr=not reached 
 N= 37 37 14 11 158 
RFS* 28 20 23 nr 24 na 
OS* 24 28 49 nr 100 13 
Follow up* 66 59 66 86 73 60 
Median Age 65 68 65 57 60 67 
%AHD 49 46 54 43 36 65 
AML/MDS 216/41 30/7 28/9 12/2 9/2 137/21 
cyto:+8, −5,−7 162 20 26 108 
cyto:# 79 16 10 42 
cyto:11q 16 

To adjust for selection and time to transplant biases, transplanted pts were matched with controls from the consult no-donor group (B) with each control having an RFS time at least as long as the interval from CR date to transplant date in their transplanted pairmate. The improved RFS in the transplant group persisted but was no longer statistically significant (p=0.197).

Conclusion: RIC HSCT in selected elderly CR1 pts improved OS and RFS, likely due to the graft-versus-leukemia effect. However, transplant efficacy could also be due to younger age, better cytogenetics, less comorbidity, lead-time bias or unknown selection factors. The performance of RIC HSCT in only 14% of elderly pts in CR1 and only 5% of elderly pts raises questions about the general applicability of this procedure, since most pts die before receiving a HSCT or do not enter CR1.

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