Page 115 - Haematologica Vol. 109 - July 2024

ARTICLE - MUD versus haplo PT-CY stem cell transplantation in children with AML A. Ruggeri et al.
in pediatric AML. Importantly, in our cohort haplo HCT was associated with higher incidence of grade 3-4 aGVHD and this could be related to the graft source itself, namely the content of CD3+ cells in the poeripheral blood stem cells as well to the differences in the overall GVHD prophylax- is in the two group. Importantly MUD recipients received ATG which is a key factor associated with reduced risk of GVHD. Whenever the combination of ATG and PTCY could be considered in the pediatric setting deserves further investigation. Overall, no differences in pivotal outcome parameters were found between haplo PT-CY and MUD. The results were consistent across the different disease sta- tus when we checked for interaction between the disease status and the donor type. We are aware of the limitations of this study, namely the retrospective nature, the short follow-up, due to the recent use of PT-CY in this setting and the limited data on infection and immune reconstitution due to the registry based analysis. However, we believe that our results are important and highlight the feasibility of this approach also in children. How the PTCY approach could be adopted also in the unrelated donor setting in the pediatric HCT deserves further investigation.
Eligibility criteria for HCT for each cooperative group are be- yond the purpose of this multinational retrospective study. Nevertheless, eligibility for haplo-HCT may be either the same as for MUD or more restricted to higher risk patients only. Therefore, in case any unknown prognostic feature could not be adjusted within the matched pair analysis, the worst risk distribution would affect the outcome of the haplo PT-CY more than the MUD cohort. In the pair match analysis, the year of transplant was not considered as ex- act matching but using a propensity score. This resulted in a median year of transplant of 2017 and 2018 for MUD and haplo respectively. Consequently, the median follow-up
References
1. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
2. Segerink WH, de Haas V, Kaspers GJL. Measurable residual disease in pediatric acute myeloid leukemia: a systematic review. Expert Rev Anticancer Ther. 2021;21(4):451-459.
3. Egan G, Chopra Y, Mourad S, Chiang KY, Hitzler J. Treatment of acute myeloid leukemia in children: a practical perspective. Pediatr Blood Cancer. 2021;68(7):e28979.
4. Reinhardt D, Antoniou E, Waack K. Pediatric acute myeloid leukemia - past, present, and future. J Clin Med. 2022;1(3):504.
5. Rubnitz JE, Kaspers GJL. How I treat pediatric acute myeloid leukemia. Blood.2021;138(12):1009-1018.
6. Horan JT, Alonzo TA, Lyman GH, et al. Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children’s Oncology Group. J Clin Oncol. 2008;26(35):5797-5801.
7. Gragert L, Eapen M, Williams E, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. Registry. N Engl J
was different in the two groups. In order to solve this issue and make the groups more comparable, we censored the outcomes at 2 years preventing us to provide results at a longer period to avoid imbalance between the groups. Such a haplo platform may enlarge access to HCT to virtually all eligible pediatric patients with AML. Furthermore, the prompt availability and the flexibility of a family member may be crucial in the challenging HCT scheduling of rapidly evolving pediatric malignancies, such as high-risk AML. Albeit MUD HCT remains the standard of care, our study confirmed in a large international analysis the comparable results of haplo-HCT with PT-CY and MD HCT, so that pediatric patients with AML who either lack a MD or cannot afford a MUD HCT, can be safely transplanted without delay.
Disclosures
No conflicts of interest to disclose.
Contributions
AR and SC designed the study. NS and AR wrote the man- uscript. JEG performed the statistical analysis. KK, MA, LZ, KC, ES, PS, CB, AB, YB, JP, FG, MI, JG, CP, BV, AB, AP, MF, IG, IB, OA, AD, and VR provided cases for the study. All authors edited and approved the manuscript.
Acknowledgments
We thank the clinical staff and investigators of the EBMT centers involved in this research and especially thank the patients who participated in the study.
Data-sharing statement
Data cannot be shared unless a specific request is sent to the EBMT.
Med. 2014;371(4):339-348.
8. Luznik L, O’Donnell PV, Symons HJ, et al. HLA-haploidentical
bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-iose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641-650.
9. Di Bartolomeo P, Santarone S, De Angelis G, et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121(5):849-857.
10. Locatelli F, Merli P, Pagliara D, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after ab T-cell and B-cell depletion. Blood. 2017;130(5):677-685.
11. Massei MS, Capolsini I, Perruccio K, et al. HLA-haploidentical transplantation with regulatory and conventional T-cells adoptive immunotherapy in pediatric patients with high-risk acute leukemia. Transplant Cell Ther. 2021;58(5):526-533.
12. Bertaina A, Zecca M, Buldini B, et al. Unrelated donor vs HLA- haploidentical a/b T-cell- and B-cell-depleted HSCT in children
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