Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study

Annalisa Ruggeri; Giorgia Battipaglia; Myriam Labopin; Gerhard Ehninger; Dietrich Beelen; Johanna Tischer; Arnold Ganser; Rainer Schwerdtfeger; Bertram Glass; Jurgen Finke; Mauricette Michallet; Matthias Stelljes; Pavel Jindra; Renate Arnold; Nicolaus Kröger; Mohamad Mohty; Arnon Nagler

doi:10.1186/s13045-016-0321-y

Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study

J Hematol Oncol. 2016 Sep 17;9(1):89. doi: 10.1186/s13045-016-0321-y.

Authors

Annalisa Ruggeri¹, Giorgia Battipaglia^{2

3}, Myriam Labopin², Gerhard Ehninger⁴, Dietrich Beelen⁵, Johanna Tischer⁶, Arnold Ganser⁷, Rainer Schwerdtfeger⁸, Bertram Glass⁹, Jurgen Finke¹⁰, Mauricette Michallet¹¹, Matthias Stelljes¹², Pavel Jindra¹³, Renate Arnold¹⁴, Nicolaus Kröger¹⁵, Mohamad Mohty^{2

16

17}, Arnon Nagler^{17

18

19}

Affiliations

¹ Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, 184 Rue du Faubourg Saint Antoine, 75012, Paris, France. annalisaruggeri80@hotmail.com.
² Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, 184 Rue du Faubourg Saint Antoine, 75012, Paris, France.
³ Department of Hematology and Marrow Transplantation, University Federico II of Naples, Naples, Italy.
⁴ Medical Clinic and Polyclinic, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
⁵ Department of Bone Marrow Transplantation, University Hospital Essen, Essen, Germany.
⁶ Department of Internal Medicine III, UH of Munich (LMU), Munich, Germany.
⁷ Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
⁸ Department of Haematology, Oncology Helios-Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125, Berlin, Germany.
⁹ Department of Hematology, Oncology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Hamburg, Germany.
¹⁰ Department of Hematology/Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, Germany.
¹¹ Department of Hematology, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Bénite, France.
¹² Department of Medicine A, University of Muenster, Munster, Germany.
¹³ Departments of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic.
¹⁴ Charité Universitatsmedizin, 10117, Berlin, Germany.
¹⁵ University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁶ Hôpital Saint-Antoine, Paris University UPMC, INSERM U938, Paris, France.
¹⁷ Université Pierre and Marie Curie, Paris, France.
¹⁸ Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
¹⁹ ALWP Office, Hôpital Saint Antoine, AP-HP, Paris, France.

Abstract

Background: Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated.

Methods: We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3-157) months.

Results: Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II-IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p < 0.001) and LFS (HR 0.67, p < 0.001)).

Conclusions: Transplantation using UD was associated with better LFS and lower RI compared to MSD for high-risk patients with AML transplanted in first relapse.

Keywords: Acute myeloid leukemia; Matched sibling donor; Relapse; Unrelated donor.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Blood Donors*
Disease-Free Survival
Female
Graft Survival
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation / adverse effects
Hematopoietic Stem Cell Transplantation / methods*
Humans
Leukemia, Myeloid, Acute / complications
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / therapy*
Male
Middle Aged
Recurrence
Registries
Retrospective Studies
Siblings
Survival Rate
Unrelated Donors
Young Adult