title: Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT.
abstract: BACKGROUND
  Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown.
  
  
  METHODS
  We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria.
  
  
  RESULTS
  A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25%) patients in RIC and 125 (32%) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92%; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29%, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94).
  
  
  CONCLUSIONS
  These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL.
authors.affiliation: Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France. mt_rubio@hotmail.com.|INSERM UMR 938, Paris, France. mt_rubio@hotmail.com.|Université Pierre et Marie Curie, Paris, France. mt_rubio@hotmail.com.|Acute Leukemia Working Party of EBMT, Paris, France. mt_rubio@hotmail.com.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Rubio
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France.|Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Acute Leukemia Working Party of EBMT, Paris, France.|EBMT Paris study office/CEREST-TC, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Acute Leukemia Working Party of EBMT, Paris, France.|Ospedale San Raffaele s.r.l., Ematologia, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Piemontese
authors.affiliation: Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Acute Leukemia Working Party of EBMT, Paris, France.|EBMT Paris study office/CEREST-TC, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Polge
authors.affiliation: Ospedale San Raffaele s.r.l., Ematologia, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Department of Haematology II, Ospedale San Martino, Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.affiliation: Rome Transplant Network, Stem Cell Transplant Unit, Tor Vergata University, Rome, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Arcese
authors.affiliation: Stem Cell Transplant Unit, Medical Park Hospitals, Antalya, Turkey.
authors.forename: Yener
authors.initials: Y
authors.lastname: Koc
authors.affiliation: Department of Bone Marrow Transplantation, University Hospital, Essen, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Beelen
authors.affiliation: Bone Marrow Transplantation Department, Anadolu Medical Center Hospital, Kocaeli, Turkey.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Gülbas
authors.affiliation: Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.affiliation: Ospedale Civile BMT Center, Pescara, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Santarone
authors.affiliation: Department of Internal Medicine III, Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Munich, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tischer
authors.affiliation: SPb State I. Pavlov Medical University, St. Petersburg, Russia.
authors.forename: Boris
authors.initials: B
authors.lastname: Afanasyev
authors.affiliation: Klinikum Augsburg, University of Munich, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.affiliation: Department of Bone Marrow Transplantation and Hemato-Oncology, Cancer Center, Gliwice, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.affiliation: Service d'Hématologie et de Thérapie cellulaire, Saint Antoine Hospital, Paris, France.|INSERM UMR 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Acute Leukemia Working Party of EBMT, Paris, France.|EBMT Paris study office/CEREST-TC, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Université Pierre et Marie Curie, Paris, France.|Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007951:Leukemia, Myeloid / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D009364:Neoplasm Recurrence, Local; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D008558:Melphalan
keywords: Acute Leukemia; Allogeneic stem cell transplantation; Anti-leukemic effect; Conditioning regimen; Haplo-identical donor; Toxicity