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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.

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      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.

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      Affiliations
      [1 ] Division of Hematology, Department of Medical Specialties, University Hospital, Geneva, Switzerland yves.chalandon@hcuge.ch.
      [2 ] Hematology Division, University Hospital, Basel, Switzerland.
      [3 ] Universita La Sapienza, II Facolta di Medicina, U.O.C Ematologia A.O.S. Andrea, Rome, Italy.
      [4 ] Centro di Biostatistica e Bioinformatica, Università "Tor Vergata", Rome, Italy.
      [5 ] Imperial College, Department of Haematology, Hammersmith Hospital, London, UK.
      [6 ] Radboud University - Nijmegen Medical Center, Department of Hematology, Nijmegen, The Netherlands.
      [7 ] Dept. of Medicine-Hematology, Oncology, University of Freiburg, Freiburg, Germany.
      [8 ] Dept. of Hematology-BMT, Hopital St. Louis, Paris, France.
      [9 ] Centro Unico Regionale Trapianti, Azienda Ospedaliera, Reggio Calabria, Italy.
      [10 ] Experimental Hematology, Institut Jules Bordet, Brussels, Belgium.
      [11 ] UAM allo-CSH, CHRU Hopital Huriez, Lille, France.
      [12 ] Chronic Malignancies WP Registry, Dept. Medical Statistics and Bioinformatics, Leiden, The Netherlands.
      [13 ] University Hospital Hamburg, Hamburg, Germany.
      [14 ] Complejo Hospitalario de Navarra, Pamplona, Spain.
      Journal
      Haematologica
      Haematologica
      Ferrata Storti Foundation (Haematologica)
      1592-8721
      0390-6078
      Sep 2014
      : 99
      : 9
      24997146 haematol.2013.100198 10.3324/haematol.2013.100198 4562539

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