title: Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies.
abstract: Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.
authors.affiliation: 1] Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden [2] Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
authors.forename: R F
authors.initials: RF
authors.lastname: Olsson
authors.affiliation: 1] CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA [2] Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Logan
authors.affiliation: Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chaudhury
authors.affiliation: CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Section of Hematology/Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
authors.forename: G
authors.initials: G
authors.lastname: Akpek
authors.affiliation: Department of Hematology and Oncology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Bolwell
authors.affiliation: The Ottawa Hospital Blood and Marrow Transplant Program and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: C N
authors.initials: CN
authors.lastname: Bredeson
authors.affiliation: Department of Pediatrics, University of California San Francisco Medical Center, San Francisco, CA, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Dvorak
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Center for Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: V T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Pediatric Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, UK.
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: 1] Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden [2] Centre for Allogeneic Stem Cell Transplantation, Stockholm, Sweden.
authors.forename: O T H
authors.initials: OT
authors.lastname: Ringdén
authors.affiliation: CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Pasquini
authors.affiliation: 1] Cancer Transplant Institute, Virginia G Piper Cancer Center, Scottsdale, AZ, USA [2] Arizona Oncology, Scottsdale, AZ, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Schriber
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Cooke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000009:adverse effects; D009367:Neoplasm Staging; D055031:Primary Graft Dysfunction / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists