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Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning-a matched pair analysis.
Ann Hematol. 2019 Mar; 98(3):753-762.AH

Abstract

In acute myeloid leukemia (AML), primary refractory or relapsed disease, secondary AML, and leukemia with unfavorable genetics are considered high-risk AML (hrAML), with allogeneic stem cell transplantation (SCT) representing the standard treatment. Sequential conditioning has been successfully used for SCT in hrAML in HLA-matched transplants, and found its way into HLA-haploidentical SCT (haplo-SCT) later on. Hence, sequential conditioning had become standard for all patients with hrAML in our two centers, regardless of donor type. Thereby, HLA-matched family or unrelated transplants were first/second choice, post-transplant cyclophosphamide (PTCY)-based haplo-SCT was chosen in patients missing matched donors or requiring urgent transplantation. To compare the outcome after HLA-matched and haplo-SCT for hrAML following sequential conditioning, we performed a retrospective, matched-pair comparison, using disease stage, genetic subgroups and age as matching criteria. Thirty-four well-matched pairs were identified. At SCT, patients (median age 54 years) were untreated (9%), had remission (13%), or active disease (78%). Three-year overall and leukemia-free survival (OS/LFS) of the entire cohort was 56 ± 7%/49 ± 7%, without significant differences between donor types (OS after HLA-matched/haplo-SCT 62 ± 10%/52 ± 9% (p = 0.21), LFS 53 ± 10%/46 ± 9% (p = 0.26)). Similarly, the cumulative incidence of relapse, non-relapse-mortality and chronic GvHD, as well as GvHD-free, relapse-free survival (GRFS), and chronic GvHD-free, relapse-free survival (cGRFS), were comparable. However, a higher incidence of acute GvHD ≥ II° was observed after HLA-matched SCT (15 ± 1% versus 50 ± 2%, p = 0.001). In conclusion, sequential conditioning SCT achieved remarkable results in hrAML, independently from donor type. PTCY-based haplo-SCT produced results that were comparable to HLA-matched SCT and can be used as an alternative option.

Authors+Show Affiliations

Department of Medicine II, Stem Cell Transplantation Unit, Klinikum Augsburg, Ludwig-Maximilians University Munich, Stenglinstr.2, 86156 Augsburg, Munich, Germany. maximilian.doppelhammer@klinikum-augsburg.de.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany. Praxis für Hämatologie und Onkologie, Herrsching, Germany.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany. Department of Hematology and Oncology, Klinikum Schwabing, Munich, Germany.Department of Medicine II, Stem Cell Transplantation Unit, Klinikum Augsburg, Ludwig-Maximilians University Munich, Stenglinstr.2, 86156 Augsburg, Munich, Germany.Department of Medicine II, Stem Cell Transplantation Unit, Klinikum Augsburg, Ludwig-Maximilians University Munich, Stenglinstr.2, 86156 Augsburg, Munich, Germany.Department of Medicine II, Stem Cell Transplantation Unit, Klinikum Augsburg, Ludwig-Maximilians University Munich, Stenglinstr.2, 86156 Augsburg, Munich, Germany.Department of Medicine III, Stem Cell Transplantation Unit, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

30617644

Citation

Doppelhammer, Maximilian, et al. "Comparable Outcome After Haploidentical and HLA-matched Allogeneic Stem Cell Transplantation for High-risk Acute Myeloid Leukemia Following Sequential Conditioning-a Matched Pair Analysis." Annals of Hematology, vol. 98, no. 3, 2019, pp. 753-762.
Doppelhammer M, Fraccaroli A, Prevalsek D, et al. Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning-a matched pair analysis. Ann Hematol. 2019;98(3):753-762.
Doppelhammer, M., Fraccaroli, A., Prevalsek, D., Bücklein, V., Häbe, S., Schulz, C., Hubmann, M., Hausmann, A., Claus, R., Rank, A., Schmid, C., & Tischer, J. (2019). Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning-a matched pair analysis. Annals of Hematology, 98(3), 753-762. https://doi.org/10.1007/s00277-019-03593-2
Doppelhammer M, et al. Comparable Outcome After Haploidentical and HLA-matched Allogeneic Stem Cell Transplantation for High-risk Acute Myeloid Leukemia Following Sequential Conditioning-a Matched Pair Analysis. Ann Hematol. 2019;98(3):753-762. PubMed PMID: 30617644.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequential conditioning-a matched pair analysis. AU - Doppelhammer,Maximilian, AU - Fraccaroli,Alessia, AU - Prevalsek,Dusan, AU - Bücklein,Veit, AU - Häbe,Sarah, AU - Schulz,Christoph, AU - Hubmann,Max, AU - Hausmann,Andreas, AU - Claus,Rainer, AU - Rank,Andreas, AU - Schmid,Christoph, AU - Tischer,Johanna, Y1 - 2019/01/08/ PY - 2018/10/13/received PY - 2019/01/01/accepted PY - 2019/1/9/pubmed PY - 2019/2/26/medline PY - 2019/1/9/entrez KW - AML KW - FLAMSA-RIC KW - Haploidentical stem cell transplantation KW - High-risk AML KW - Sequential conditioning SP - 753 EP - 762 JF - Annals of hematology JO - Ann Hematol VL - 98 IS - 3 N2 - In acute myeloid leukemia (AML), primary refractory or relapsed disease, secondary AML, and leukemia with unfavorable genetics are considered high-risk AML (hrAML), with allogeneic stem cell transplantation (SCT) representing the standard treatment. Sequential conditioning has been successfully used for SCT in hrAML in HLA-matched transplants, and found its way into HLA-haploidentical SCT (haplo-SCT) later on. Hence, sequential conditioning had become standard for all patients with hrAML in our two centers, regardless of donor type. Thereby, HLA-matched family or unrelated transplants were first/second choice, post-transplant cyclophosphamide (PTCY)-based haplo-SCT was chosen in patients missing matched donors or requiring urgent transplantation. To compare the outcome after HLA-matched and haplo-SCT for hrAML following sequential conditioning, we performed a retrospective, matched-pair comparison, using disease stage, genetic subgroups and age as matching criteria. Thirty-four well-matched pairs were identified. At SCT, patients (median age 54 years) were untreated (9%), had remission (13%), or active disease (78%). Three-year overall and leukemia-free survival (OS/LFS) of the entire cohort was 56 ± 7%/49 ± 7%, without significant differences between donor types (OS after HLA-matched/haplo-SCT 62 ± 10%/52 ± 9% (p = 0.21), LFS 53 ± 10%/46 ± 9% (p = 0.26)). Similarly, the cumulative incidence of relapse, non-relapse-mortality and chronic GvHD, as well as GvHD-free, relapse-free survival (GRFS), and chronic GvHD-free, relapse-free survival (cGRFS), were comparable. However, a higher incidence of acute GvHD ≥ II° was observed after HLA-matched SCT (15 ± 1% versus 50 ± 2%, p = 0.001). In conclusion, sequential conditioning SCT achieved remarkable results in hrAML, independently from donor type. PTCY-based haplo-SCT produced results that were comparable to HLA-matched SCT and can be used as an alternative option. SN - 1432-0584 UR - https://www.unboundmedicine.com/medline/citation/30617644/Comparable_outcome_after_haploidentical_and_HLA_matched_allogeneic_stem_cell_transplantation_for_high_risk_acute_myeloid_leukemia_following_sequential_conditioning_a_matched_pair_analysis_ L2 - https://dx.doi.org/10.1007/s00277-019-03593-2 DB - PRIME DP - Unbound Medicine ER -