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Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation for high-risk AML

Bone Marrow Transplantation volume 52, pages 620–621 (2017)Cite this article

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients suffering from AML. During the past 20 years, the development of reduced intensity conditioning (RIC) regimens and the use of alternative donors overcame in part the main limitations of allo-HSCT: procedure-related toxicities and donor availability.1, 2, 3 Thus, more patients presenting with older age, comorbidities and/or more advanced diseases can now be considered for allo-HSCT. Overall, disease recurrence became the major issue after Allo-HSCT, especially in patients with refractory or high-risk AML.4 In this context, developing post-allo-HSCT strategies to prevent AML recurrence is now one of the most important challenges in the setting of Allo-HSCT for AML. Many strategies may be used, including cellular support and/or pharmacological agents. However, there is no standard of care in this area. Donor lymphocyte infusion (DLI) is one of the most commonly used post-allo-HSCT interventions.5 However, most of DLI experiences were reported in the setting of AML relapses after allo-HSCT.6, 7, 8 In these situations, efficacy remains limited with overall survival (OS) ranging from 20–30%. We and others previously reported that OS may be improved (to 50–80%), when DLI is performed in a preemptive manner, guided by chimerism and/or molecular residual disease results.9, 10, 11 Thus, we hypothesized that the use of prophylactic DLI (pDLI) may be considered as an interesting way to prevent AML recurrence. However, the anticipated risk of pDLI-induced GvHD may counterbalance its potential benefit. To date, few experiences of pDLI for AML are available, making that both efficacy and safety remain unclear.

Thus, we report here the outcome of AML patients transplanted at the Paoli-Calmettes Institute and who received pDLI. We started the use of pDLI in patients transplanted for refractory AML and progressively proposed this strategy also in CR patients with high risk of relapse, based on cytogenetic and/or molecular disease characteristics. In our experience, 22 patients with high-risk AML received pDLI from 2006 to 2015 (details in Table 1). AML patients were at high risk because of refractory disease at the time of allo-HSCT (n=10), relapse AML (n=4, 2 after a first allo-HSCT), CR1 AML with unfavorable cytogenetics (n=6), CR1 AML with high FLT3–internal tandem duplication/FLT3–wild type ratio at 0.75 (n=1) or CR1 AML with numerous induction chemotherapy courses needed to obtain CR (n=1). All patients received a fludarabine/busulfan-based conditioning regimen, with reduced (2 days at 130 mg/m2 per day) or myeloablative doses (3 or 4 days at 130 mg/m2 per day) of IV busulfan. Patients who underwent allo-HSCT from haploidentical donor were given additional thiotepa in the conditioning regimen and post-transplantation cyclophosphamide. Eight of the 10 patients with refractory AML at the time of allo-HSCT received the RIC regimen during the aplasia, following a debulking intensive chemotherapy course as a so-called sequential approach. pDLI was performed in a median time of 130 days post allo-HSCT (range: 85–242). At the time of pDLI, all patients were in CR with a T-cell donor chimerism of at least 90%, and 13 (59%) were still receiving immunosuppressive treatment (IST). The CD3+ cell doses of the first pDLI ranged from 0.1 to 10x106 CD3-positive cells per kg. Nine patients received more than one pDLI (two pDLI, n=7; three pDLI, n=2), with increased CD3-positive cell doses.

Table 1 Patient characteristics
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Author notes

  1. F Legrand, A-C Le Floch, D Blaise and R Devillier: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Institut Paoli-Calmettes, Marseille, France

    F Legrand, A-C Le Floch, A Granata, S Fürst, C Faucher, S Harbi, J El-Cheikh, P-J Weiller, N Vey, D Blaise & R Devillier

  2. Cell therapy facility, Institut Paoli-Calmettes, Marseille, France

    C Lemarie, B Calmels & C Chabannon

  3. CIC biothérapies: Inserm CBT-1409, Marseille, France

    C Lemarie, B Calmels & C Chabannon

  4. Departement of Hematology, Humanitas Cancer Center, Rozzano, Italy

    S Bramanti

  5. Centre de Recherche en Cancérologie de Marseille, Inserm, U1068, Institut Paoli-Calmettes, Marseille, France

    B Calmels, C Chabannon, N Vey, D Blaise & R Devillier

  6. Bone marrow transplantation program, American University of Beirut, Beirut, Lebanon

    J El-Cheikh & L Castagna

  7. Aix-Marseille Université UM 105, Marseille, France

    C Chabannon, P-J Weiller, N Vey, D Blaise & R Devillier

  8. CNRS UMR 7258, Marseille, France

    N Vey, D Blaise & R Devillier

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  1. F Legrand
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Correspondence to R Devillier.

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Legrand, F., Le Floch, AC., Granata, A. et al. Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation for high-risk AML. Bone Marrow Transplant 52, 620–621 (2017). https://doi.org/10.1038/bmt.2016.326

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