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R. Ram et al.
able, considering the fact that 61% of the patients had an unrelated donor (12% were only 9/10-HLA identical). Nonetheless, there were several cases of late acute GvHD. This may suggest a more cautious approach than the stan- dard post 3-month cyclosporine-tapering schedule. Another important finding in our analysis is the fact that the administration of ATG was found to be associated with a lower incidence of acute GvHD. The impact of ATG on acute GvHD, although still controversial, was demonstrated also by others.17,18 Although the three differ- ent protocols used different doses of ATG (15-60 mg/kg), it would appear that there was no significant difference between the various doses, as has been shown previously.19 Interestingly, in our study, the use of ATG was not found to correlate with a lower incidence of chronic GvHD and was not associated with a higher relapse rate.
Non-relapse mortality at three months was low (6%) and probably reflects the low incidence of early complica- tions (i.e. severe mucositis and SOS) and of grade 3-4 acute GvHD. The fact that patients with primary refracto- ry AML experience a prolonged and profound neutropenia suggest that this group may benefit from fungal and bac- terial prophylaxis, as well as a weekly surveillance testing.
This protocol had significant anti-leukemia efficacy
AB
with 98% of the patients responding. Considering that, for the same population, response to salvage chemothera- py is only 30-50%,20 (and is approaching 64% in patients receiving a direct allogeneic HCT3), our results suggest that, for selected patients, the sequential therapy approach is superior. When focusing on durable response and OS, in our cohort that received sequential therapy the 3-year overall survival was 61%. These results are superior to previous reports of patients who had primary refractory disease, achieved complete remission after salvage chemotherapy and proceeded to allogeneic HCT (OS of 48%), to those who were transplanted directly with a refractory disease (OS of 36%), and those with refractory disease who never received a transplant (OS of 25%).3 Yet, although limited by the small sample size, among those patients who had post-transplant relapse, high-risk dis- ease features were common. In addition, patients with a higher Duval score had a shorter OS compared to those with a lower score, and thus our study further validates the original Duval paper.16
In our study, the only factor that was associated with prolonged survival was prior chronic GvHD, suggesting that, although associated with significant morbidity, and sometimes also with increased mortality, in this cohort of high-risk patients, graft-versus-leukemia effect is essential.
CD
Figure 2. Transplantation outcome. (A) Relapse rate, (B) non-relapse mortality, (C) overall survival (OS), and (D) OS by time to hematopoietic cell transplantation (HCT).
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haematologica | 2019; 104(9)