title: Early administration of donor lymphocyte infusions upon molecular relapse after allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia: a study by the Chronic Malignancies Working Party of the EBMT.
abstract: Patients with chronic myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation may be treated by tyrosine kinase inhibitors and/or by donor lymphocyte infusions. The best strategies and timing of administration of lymphocytes are unclear. We analyzed 155 patients who relapsed after allogeneic stem cell transplantation with disease detectable only by molecular methods and who subsequently received lymphocytes. Transplants were performed in first chronic phase (n=125) or in advanced disease (n=29) from identical siblings (n=84) or unrelated donors (n=71) between 1986 and 2003. They received lymphocytes either during molecular relapse (n=85) or upon progression to more advanced disease (1993 to 2004). The median interval from relapse to lymphocyte infusion was 210 (0-1673) days. The median follow up after it was 46 (3-135) months. Overall survival was 76±4% at five years after lymphocyte infusions (89±8% with sibling donors and 63±13% with unrelated donors (P=0.003)). Survival was 69±14% when lymphocytes were given within six months of the detection of molecular relapse and 81±10% (P=0.061) when given later; 81±11% if given at molecular relapse versus 71±12% (P=0.26) with more advanced disease. In multivariate analysis survival was worse if the donor was unrelated (HR 2.54 (95% CI: 1.15-5.53), P=0.021) and better with lymphocyte infusions beyond six months from molecular relapse (HR 0.4 (95%CI: 0.19-0.84), P=0.018). These data confirm the remarkable efficacy of lymphocyte infusions for this disease. There appears to be no advantage from administering it early upon detection of molecular relapse in patients who received allogeneic stem cell transplantation for chronic myeloid leukemia.
authors.affiliation: Division of Hematology, Department of Medical Specialties, University Hospital, Geneva, Switzerland yves.chalandon@hcuge.ch.
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.affiliation: Hematology Division, University Hospital, Basel, Switzerland.
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Passweg
authors.affiliation: Universita La Sapienza, II Facolta di Medicina, U.O.C Ematologia A.O.S. Andrea, Rome, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Guglielmi
authors.affiliation: Centro di Biostatistica e Bioinformatica, Università "Tor Vergata", Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Iacobelli
authors.affiliation: Imperial College, Department of Haematology, Hammersmith Hospital, London, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Apperley
authors.affiliation: Radboud University - Nijmegen Medical Center, Department of Hematology, Nijmegen, The Netherlands.
authors.forename: Nicolaas P M
authors.initials: NP
authors.lastname: Schaap
authors.affiliation: Dept. of Medicine-Hematology, Oncology, University of Freiburg, Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.affiliation: Dept. of Hematology-BMT, Hopital St. Louis, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.affiliation: Centro Unico Regionale Trapianti, Azienda Ospedaliera, Reggio Calabria, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fedele
authors.affiliation: Experimental Hematology, Institut Jules Bordet, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.affiliation: UAM allo-CSH, CHRU Hopital Huriez, Lille, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Chronic Malignancies WP Registry, Dept. Medical Statistics and Bioinformatics, Leiden, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: van Biezen
authors.affiliation: Radboud University - Nijmegen Medical Center, Department of Hematology, Nijmegen, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.affiliation: University Hospital Hamburg, Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.affiliation: Complejo Hospitalario de Navarra, Pamplona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarria
mesh_terms: D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D018365:Neoplasm, Residual / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012008:Recurrence; D035781:Siblings; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous; D061349:Unrelated Donors