Page 90 - Haematologica August 2018

D. Salvatore et al.
Patient CMV seropositivity
Donor CMV seropositivity
Time from diagn to allo-HSCT > median
cGvHD
Haplo versus MSD
Age (incremental age of 10 years)
Year of allo-HSCT
RIC versus MAC
PBSC versus BM
Female to male recipient versus other Patient CMV seropositivity
Donor CMV seropositivity
Time from diagnosis to allo-HSCT > median
0.95 (0.65-1.39) 0.80 0.94 (0.66-1.33) 0.72 0.95 (0.87-1.04) 0.24
1.02 (0.58-1.78) 0.95 1.07 (0.94-1.21) 0.33 1.00 (0.94-1.06) 0.96 0.96 (0.68-1.36) 0.83 1.03 (0.68-1.56) 0.89 1.23 (0.88-1.72) 0.23 0.87 (0.62-1.20) 0.39 1.04 (0.76-1.42) 0.79 0.94 (0.87-1.03) 0.18
1326
HR: hazard ratio; CI: confidence interval; RI: relapse incidence; NRM: non-relapse mortality; LFS: leukemia free survival; OS: overall survival; GRFS: refined graft-versus-host dis- ease/relapse-free survival; aGvHD: acute graft-versus-host disease; cGvHD: chronic graft-versus-host disease; Haplo: haploidentical donor; MSD: matched sibling donor; allo- HSCT: allogeneic hematopoietic stem cell transplantation; RIC: reduced intensity conditioning regimen; MAC: myeloablative conditioning regimen; PBSC: peripheral blood stem cells; BM: bone marrow; CMV: cytomegalovirus.
Propensity score matching analysis
We were able to pair-match 183 Haplo with 364 MSD. The results of propensity score analysis are summarized in Table 4.
In the group of patients presenting an intermediate risk cytogenetics, Haplo was associated with a higher risk of NRM (HR 2.59. 95% CI: 1.59-4.20. P<0.01), lower LFS (HR 1.60; 95% CI: 1.15- 2.22; P<0.01) and OS (HR 1.61; 95% CI: 1.12-2.30; P<0.01). There was no significant association between Haplo grade II-IV aGvHD, cGvHD and GRFS.
In the group of patients presenting cytogenetics classi- fied as high risk, Haplo was associated to higher risk of acute GvHD grade II-IV (HR 2.06; 95% CI: 1.14-3.75; P=0.02) and a trend for a lower risk of relapse (HR 0.53; 95% CI: 0.28-1.01; P=0.053). There was no significant association between Haplo and other main outcomes. Survival curves according to the results of pair-matched analysis in each cytogenetic group are shown in Figure 1 and 2.
Discussion
Allogeneic HSCT might be a curative option in patients diagnosed with AML and achieving CR, especially in those with unfavorable cytogenetics for which prognosis is very poor with chemotherapy alone. Use of HSCT in patients with intermediate risk cytogenetics is sometimes debated, according to the different transplant center poli- cies. Subsequently, for these two cytogenetic risk cate- gories, a donor search might be immediately launched at time of diagnosis.32 In the absence of a MSD, Haplo may represent a valid alternative, despite initial concerns being raised due to the high risk of graft failure and NRM in this setting.9
The aim of the current study was to compare the out- comes of patients transplanted either from a MSD or Haplo donor in patients with AML in first CR. According to cytogenetic at time of diagnosis, AML was classified as intermediate or high risk. Moreover, due to a significant interaction according to cytogenetic risk, intermediate and high-risk AML were then analyzed separately. According to donor type, higher risk of grade II-IV aGvHD was reported in Haplo recipients. Furthermore, donor CMV
positive serology was found as a risk factor for aGvHD, as already shown by others.33,34
In agreement with previous reports,35,36 among AML with intermediate cytogenetic risk, the intensity of the conditioning regimen was associated with higher risk of aGvHD, as well as female to male donor, while in AML with high cytogenetic risk, the only factor associated with higher risk of aGvHD was the type of donor. Furthermore, stem cell sources were not influential for acute GvHD, as previously described.20
No significant differences in the CI of cGvHD were found according to donor type. This could also be related to the higher proportion of BM in the Haplo group.
Our results are in some part different to those reported by Luznik et al.12 Importantly, the experience reported by the Baltimore group is mainly in non myeloablative condi- tioning regimen and BM as stem cell source and this could in part explain the difference among our results. Also, being a registry study, we reported data from several transplant centers including different immunosuppressive protocols according to different Centers and as compared to previous reports19 and therefore no direct comparison could be performed.
Compared with MSD recipients, Haplo recipients had a longer time to neutrophils recovery with a median time to engraftment of 2 days longer than MSD, in line with pre- vious studies;17,18 this is probably due to the higher propor- tion of patients receiving bone marrow graft among Haplos and the myelosuppression from PT-CY.
NRM was worse in the Haplo recipients in univariate and multivariate analysis. When looking at cytogenetics groups, this result was confirmed in intermediate risk, but not in high risk, where Haplo and MSD had similar NRM, in line with previous reports.17,19,20 Furthermore, female donor to male recipient was associated to a higher NRM in intermediate AML and not in high risk AML. Therefore, one can speculate that the impact of female to male mis- match could depend on the risk of the underlying disease, as previously shown.36 However, a possible explanation to the results in the high-risk group might be related to the low number of patients, preventing us to make definitive conclusions.
Death from infections was more common in Haplo transplants than MSD maybe due to a slower immune
haematologica | 2018; 103(8)