title: Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?
abstract: Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: aleksandar.radujkovic@med.uni-heidelberg.de.
authors: Aleksandar
authors: A
authors: Radujkovic
authors: Dipartimento di Medicina Clinica e Molecolare, Università "Sapienza", Rome, Italy.
authors: Cesare
authors: C
authors: Guglielmi
authors: Dipartimento di Medicina Clinica e Molecolare, Università "Sapienza", Rome, Italy.
authors: Stefania
authors: S
authors: Bergantini
authors: University of Rome Tor Vergata, Centro Interdipartimentale di Biostatistica e Bioinformatica (CIBB), Rome, Italy.
authors: Simona
authors: S
authors: Iacobelli
authors: Department of Medical Statistics and Bioinformatics, Leiden University, Leiden, The Netherlands.
authors: Anja
authors: A
authors: van Biezen
authors: Department of Haematology, Hammersmith Hospitals Trust, Imperial College London, London, United Kingdom.
authors: Dragana
authors: D
authors: Milojkovic
authors: Department of Hematology, University Hospital Basel, Basel, Switzerland.
authors: Alois
authors: A
authors: Gratwohl
authors: Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Antonius V M B
authors: AV
authors: Schattenberg
authors: Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Leo F
authors: LF
authors: Verdonck
authors: Department of Hematology/Oncology, University of Leipzig, Leipzig, Germany.
authors: Dietger W
authors: DW
authors: Niederwieser
authors: Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Theo
authors: T
authors: de Witte
authors: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Nicolaus
authors: N
authors: Kröger
authors: Complejo Hospitalario de Navarra, Pamplona, Spain.
authors: Eduardo
authors: E
authors: Olavarria
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012737:Sex Factors; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists
keywords: Allogeneic stem cell transplantation; Chronic myeloid leukemia; Donor lymphocyte infusions; Graft-versus-host disease; Graft-versus-leukemia; Relapse