Originally published as JCO Early Release 10.1200/JCO.2007.11.6053 on October 1 2007

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Donor Lymphocyte Infusion in the Treatment of First Hematological Relapse After Allogeneic Stem-Cell Transplantation in Adults With Acute Myeloid Leukemia: A Retrospective Risk Factors Analysis and Comparison With Other Strategies by the EBMT Acute Leukemia Working Party

Christoph Schmid, Myriam Labopin, Arnon Nagler, Martin Bornhäuser, Jürgen Finke, Athanasios Fassas, Liisa Volin, Günham Gürman, Johan Maertens, Pierre Bordigoni, Ernst Holler, Gerhard Ehninger, Emmanuelle Polge, Norbert-Claude Gorin, Hans-Jochem Kolb, Vanderson Rocha

From the Department of Medicine II, Klinikum Augsburg, Ludwig Maximilians University of Munich; Jos; Carrears Unit for Hematopoietic Transplantation, Department of Medicine III, Ludwig Maximilians University of Munich; Department of Hematology and Oncology, University of Dresden; Department of Medicine-Hematology, Oncology, University of Freiburg; Department of Hematology and Oncology, University Regensburg, Germany; Acute Leukemia Working Party-European Group of Blood and Marrow Transplantation; Hôpital Saint-Antoine AP-HP et Université Pierre et Marie Curie; Bone Marrow Transplant Unit, Hôpital Saint Louis, Université de Paris 7, Paris; Unité de transplantation médullaire, Hôpital d'enfants de Brabois-Médecine Infantile II, Vandoeuvre Les Nancy, France; Chaim Sheba Medical Center, Tel-Aviv University, Tel-Hashomer, Israel; George Papanicolaou General Hospital, Thessaloniki, Greece; Department of Medicine, Helsinki University Central Hospital, HUS Helsinki, Finland; Adult Stem Cell Transplantation Unit, Ankara University, Faculty of Medicine, Ankara, Turkey; and the Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium

Address reprint requests to Christoph Schmid, MD, Department of Medicine II, SCT Unit, Klinikum Augsburg, Ludwig-Maximilians-Universität München, PO Box 101920, 86009 Augsburg, Germany; e-mail: christoph.schmid{at}2med.zk.augsburg-med.de

Purpose To evaluate the role of donor lymphocyte infusion (DLI) in the treatment of relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT).

Patients and Methods We retrospectively analyzed the data of 399 patients with AML in first hematological relapse after HSCT whose treatment did (n = 171) or did not (n = 228) include DLI. After correction for imbalances and established risk factors, the two groups were compared with respect to overall survival. Further, a detailed analysis of risk factors for survival among DLI recipients was performed.

Results Median follow-up was 27 and 40 months, respectively. Estimated survival at 2 years (± standard deviation) was 21% ± 3% for patients receiving DLI and 9% ± 2% for patients not receiving DLI. After adjustment for differences between the groups, better outcome was associated with age younger than 37 years (P = .008), relapse occurring more than 5 months after HSCT (P < .0001), and use of DLI (P = .04). Among DLI recipients, a lower tumor burden at relapse (< 35% of bone marrow blasts; P = .006), female sex (P = .02), favorable cytogenetics (P = .004), and remission at time of DLI (P < .0001) were predictive for survival in a multivariate analysis. Two-year survival was 56% ± 10%, if DLI was performed in remission or with favorable karyotype, and 15% ± 3% if DLI was given in aplasia or with active disease.

Conclusion Although further evidence for a graft-versus-leukemia effect by DLI is provided, our results confirm, that the clinical benefit is limited to a minority of patients. Strategies to reduce tumor burden before DLI, as well as alternative treatment options should be investigated in adults with relapsed AML after HSCT.

published online ahead of print at www.jco.org on October 1, 2007.

Presented in part at the meeting of the American Society of Hematology, San Diego, CA, December 4-7, 2004, and at the European Group for Blood and Marrow Transplantation, Prague, Czech Republic, March 20-23, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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