Page 91 - Haematologica August 2018

Haplo versus MSD in AML in CR1
Table 4. Propensity score analysis for main outcomes after allo-HSCT according to donor type in patients with intermediate (a) and high risk (b) AML.
a) Outcome
A) Outcome
Haplo
MSD
HR (95% CI) P
B) Outcome
Haplo
MSD
HR (95% CI)
P
RI %
RI % ±s.d.
18±6
21±5
1.04 (0.65-1.66) 0.86
RI % ±s.d.
22±11
39±10
0.53 (0.28-1.00)
0.05
NRM
NRM % % ±s.d.
26±8
10±4
2.59 (1.59-4.20) <0.01
NRM % ±s.d.
17±10
13±7
1.07 (0.45-2.51)
0.87
LFS %
LFS % ±s.d.
56±8
69±6
1.60 (1.15-2.22) <0.01
LFS % ±s.d.
61±13
48±10
0.68 (0.40-1.13)
0.14
OS %
OS % ±s.d.
Gr.II-IV aGvHD %
Gr. II-IV aGvHD % ±s.d.
cGvHD%
cGvHD% ±s.d.
GRFS%
GRFS% ±s.d.
68±9 29±7 30±9 45±10
79±5 21±5 35±6 53±7
1.60 (1.12-2.29) <0.01
OS % ±s.d.
67±13
57±9
0.68 (0.39-1.19)
0.18
1.49 (0.95-2.31) 0.07
Gr. II-IV aGvHD % ±s.d.
37±12
21±7
2.06 (1.13-3.74)
0.01
0.82 (0.54-1.24) 0.37
cGvHD% ±s.d.
37±13
31±10
0.98 (0.54-1.77)
0.95
1.27 (0.94-1.71) 0.11
GRFS% ±s.d.
51±13
41±10
0.82 (0.52-1.28)
0.39
RI: relapse incidence; NRM: non-relapse mortality; LFS: leukemia-free survival; OS: overall survival; GRFS: refined graft-versus-host-free relapse free survival; Gr. II-IV aGvHD: grade II- IV acute graft-versus-host disease; cGvHD: chronic graft-versus-host disease; HAPLO: haploidentical donor; MSD: matched sibling donor; HR: hazard ratio; CI: confidence interval.
reconstitution in Haplo setting, also favored by the use of additional high doses of immunosuppressive agents as compared to MSD. However, as ours is a registry-based study, details on type of infections were not available.
Importantly, the type of donor did not influence the risk of relapse in intermediate AML. Recently, Ringden et al.37 published no difference in leukemic relapse between MSD and Haplo. On the other hand, in high-risk AML, we found a trend for higher RI in MSD recipients; this could reflect a lower immunogenicity of MSD transplant in AML with more biological aggressive characteristics. Our results should be taken with caution as there are impor- tant factors that we were not able to take into account, such as molecular biology data, important for disease stratification. Risk group was, indeed, defined according to cytogenetics at diagnosis.
In intermediate AML, a RIC regimen was associated to higher risk of relapse as previously described,35 while in high-risk AML, the type of conditioning regimen affected neither relapse nor GvHD incidence In this setting, CMV serology and incremental age were the only factors affect- ing risk of relapse, while the type of donor was the only related to risk of GvHD.
The probability of LFS was lower in Haplo, in line with previous reports.37
In a retrospective study from a single center, Bashey et al.17 reported outcomes of 475 patients receiving unmanip- ulated Haplo transplant using PT-CY in comparison to MSD or 10/10 matched unrelated donors. This series on patients with lymphoid and myeloid malignancies includ- ed 170 patients with AML. In line with our results, OS was superior in MSD as compared to Haplo recipients. Of
note, they also found higher incidence of grade II-IV aGvHD, without differences in cGvHD, and higher NRM in the Haplo setting. In our study, as in Bashey population, the time from diagnosis to transplant was longer for Haplo than MSD and this could have negatively affected out- comes of transplant. In multivariate analysis, incremental age produced effects on LFS and OS, regardless of cytoge- netics, in line with others.40
Our data were analyzed using the propensity score analysis in order to balance characteristics of the two pop- ulations. The matched pair analysis confirmed the results of higher aGvHD incidence in Haplo compared to MSD, and confirmed the main outcome results that we found in standard analysis, for both intermediate and high risk AML.
Given the main finding of our study, outcomes of trans- plantation from Haplo versus MSD depend on the leukemic cytogenetics risk. Intermediate AML outcomes were better in the MSD setting as compared to Haplo with no significant differences in RI among the two types of donor. Whilst in high-risk AML, there were no signifi- cant differences in the main transplantation outcomes between Haplo and MSD, except for the lower risk of relapse in the Haplo group. However, we acknowledge that the number of patients with high risk cytogenetics in our study was low and, consequently, the statistical power was too.
In conclusion, our results underline that matched sibling donor remain the first donor choice for AML patients in first CR when available. It should be of interest to further investigate the role of Haplo in this setting with well- designed prospective studies.
References
1. Kanakry CG, de Lima MJ, Luznik L. Alternative donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Semin Hematol. 2015; 52(3):232- 242.
2. Clift RA, Hansen JA, Thomas ED, et al. Marrow transplantation from donors other
than HLA-identical siblings. Transplantation.
1979;28(3):235-242.
3. Powles RL, Morgenstern GR, Kay HE, et al.
Mismatched family donors for bone-mar- row transplantation as treatment for acute leukaemia. Lancet. 1983;1(8325):612-615.
4. Gragert L, Eapen M, Williams E, et al. HLA match likelihoods for hematopoietic stem- cell grafts in the U.S. Registry. N Engl J Med. 2014;371(4):339-348.
5. Lown RN, Shaw BE. Beating the odds: fac- tors implicated in the speed and availability of unrelated haematopoietic cell donor pro- vision. Bone Marrow Transplant. 2013; 48(2):210-219.
6. Scaradavou A, Brunstein CG, Eapen M, et al. Double-unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia. Blood. 2013;121(5):752-758.
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