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Haploidentical versus unrelated donor HSCT for active AML
Table 5. Weighted Cox model for leukemia-free survival, overall survival, relapse incidence, non-relapse mortality, graft-versus-host disease-free, relapse-free survival and graft-versus-host disease.
Leukemia-free survival
Overall survival Relapse incidence Non-relapse mortality GRFS
Acute GvHD II-IV Acute GvHD III-IV Chronic GvHD
Extensive chronic GvHD
Haplo PTCy
22.8% (17.1-30.2)
29.3% (22.9-37.5) 52% (43.9-58.8) 25.3% (18.7-31.3) 16.2% (11.5-22.9) 28.2% (21.3-34.5) 8.9% (4.6-13) 19.3% (13-25.1)
11.3% (6.2-16.1)
UD 10/10
25.6% (19.4-33.7)
32.2% (25.4-40.8) 48.2% (43.6-52.5) 26.2% (22.3-29.9) 17.1% (11.9-24.4) 31.3% (27-35.3) 14.5% (11.4-17.4) 22.9% (19.1-26.6)
11.2% (8.5-13.8)
UD 9/10
21.6% (15-30.9)
25.4% (18.3-35.4)
53.2% (45.6-59.7)
25.2% (19.3-30.6)
16.1% (10.5-24.7)
40.4% (32.8-47.2)
20.1% (13.5-26.2)
25.5% (19.1-31.4)
11.1% (6.6-15.3)
P value Haplo PTCy versus UD 10/10
NS
NS
NS
NS
NS
NS
0.04
NS
NS
P value Haplo PTCy versus UD 9/10
NS
NS
NS
NS
NS
0.01
0.005
0.04
NS
Data are presented as percentages with 95% confidence intervals in brackets; GvHD: graft-versus-host disease; GRFS: graft-versus-host disease-free, relapse-free survival; Haplo: haploidentical; not significant; PTCy: post-transplant cyclophosphamide; UD: unrelated donors.
urgent need to search for a donor for AML patients with active disease who lack a matched sibling donor. Haploidentical donors are available for the majority of patients, providing access to further stem cell donations or donor lymphocyte infusions as needed.35 Furthermore, it is a factor on which the physicians can have an influence, unlike many other factors. In accordance, Wattad et al. showed that patients transplanted during refractory dis- ease after salvage therapy had a significantly poorer out- come compared to that of patients who proceeded direct- ly to transplantation, and those transplanted in CR after salvage therapy.12 Thus, we could recommend not to try additional lines of chemotherapy to achieve CR in patients with active disease, but to take advantage of the first available donor in order to proceed to transplantation.
The cytogenetic characterization of the leukemia repre- sents a major prognostic factor for LFS, RI, OS, and GRFS.36,37 We previously reported that poor-risk cytogenet- ics was an adverse pre-HSCT variable in patients with pri- mary refractory AML who underwent HSCT with a graft from a matched sibling or matched UD.13 Accordingly, in the present study, primary refractory AML with poor cytogenetic characteristics was associated, at 2 years, with a significant decrease in LFS and OS, and increase in RI. These data pave the road for investigating additional approaches relying on sequential conditioning regimens and/or post-transplant treatments.38-42
Being retrospective and registry-based, this study has some limitations: several of the patients’ characteristics differed between the groups. We addressed this limita- tion, at least in part, by using the propensity score tech- nique. In addition, there was a relative inherent selection process for HSCT in our study and a relative lack of infor-
mation on the reasons for an EBMT center allocating patients to HSCT from a haploidentical donor versus UD, so that distinguishing the choice of the donor from the role of a potential center effect is difficult. Finally, the counts of circulating and bone marrow blasts at the time of HSCT were missing for a substantial number of patients. However, the aim of this analysis was to com- pare the two types of donors using EBMT registry data. The design of the study and inclusion criteria were intend- ed to answer this clinical question and were not, therefore, adapted for developing a prognostic score. There are ongoing trials aiming to compare outcomes after Haplo PTCy versus UD in hematologic malignancies, but they do not focus specifically on the setting of active AML disease (NCT02623309). Therefore, in the absence of any prospect of such comparative studies, our data suggest that haploidentical donors are equally effective as 10/10 matched and 9/10 mismatched UD for allogeneic trans- plantation in patients with active AML.
In conclusion, our results indicate that, when an HLA- identical sibling donor is not available for an AML patient with active disease who is, otherwise, a candidate for HSCT, a haploidentical donor may be used with the expectation of similar rates of NRM, LFS, OS, and GRFS at 2 years, compared with those achieved with 10/10 matched and 9/10 mismatched UD.
Acknowledgments
We thank all the European Society for Blood and Marrow Transplantation (EBMT) participating centers and national reg- istries for providing patients’ data for the study, and data man- agers for their valuable contribution (Online Supplementary Data). Further information is available at the EBMT web site.
References
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2. Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood. 2015;126 (3):319-327.
3. Schlenk RF, Frech P, Weber D, et al. Impact of pretreatment characteristics and salvage strategy on outcome in patients with relapsed acute myeloid leukemia. Leukemia. 2017;31(5):1217-1220.
4. Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53-61.
5. Revesz D, Chelghoum Y, Le QH, Elhamri M, Michallet M, Thomas X. Salvage by timed sequential chemotherapy in primary resistant acute myeloid leukemia: analysis of prognostic factors. Ann Hematol. 2003;82 (11):684-690.
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