Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for hematological malignancies. While many procedures have strongly improved outcome after Allo-HSCT by reducing procedure-related toxicity and mortality, disease recurrence remains the major concern. Prophylactic donor lymphocyte infusion (pDLI) is more and more used after Allo-HSCT, with the goal to reduce relapse incidence but may be limited by the risk of developing Graft versus Host Disease (GVHD). The risk of haploidentical DLI-associated GVHD might be increased as compared to HLA-matched DLI. While curative DLI has been assessed for the treatment of hematological relapse after Haplo-SCT, outcomes related to prophylactic DLI has not been evaluated in the setting of Haplo-SCT using post-transplant Cyclophosphomide.

We analyzed all consecutive patients who received pDLI after Haplo-SCT for hematological malignancies with intermediate or high risk of relapse at 2 collaborative centers. pDLI was defined by the infusion of donor lymphocytes in the absence of evidence of hematological relapse or positive minimal residual disease (MRD), the presence of a full donor T-cell chimerism (> 98%) and the absence of previous G 2-4 acute GVHD or chronic GVHD. An escalating dose (CD3+ cells/kg) schedule was used as follow: DLI n°1 = 1x10^5/kg, DLI n°2 = 5x10^5/kg and DLI n°3 = 2.5x10^6/kg.

We retrospectively analyzed 36 patients with a median age of 58 years (range 25-75). Patients were mostly transplanted for acute leukemia or myelodysplastic syndrome (75%) or lymphoma (17%); 7 patients (19%) had active disease at the time of Haplo-SCT. Disease risk index was high or very high in 10 patients (28%). Most patients received peripheral blood stem cells as graft source (n=31; 86%), and a conditioning regiment including thiotepa, busulfan, and fludarabine (n = 24; 67%). All patients received post transplantation cyclophosphamide as part of GVHD prophylaxis. Patients received 1 (n = 19; 53%), 2 (n = 13; 36%) or 3 (n = 4; 11%) pDLI at a median time of 109 days (range 70 to 227) between Haplo-SCT and the first prophylactic DLI. Median follow-up after pDLI was 9 months (range 2-56).

One-year cumulative incidence of requiring-systemic steroids GVHD was 34%. There were 9 chronic GVHD (6 moderate + 3 severe forms according to NIH classification), and 2 acute GVHD (both grade II according to Glucksberg classification). Only 1 patient relapsed despite the occurrence of acute GVHD. Non-relapse mortality at 1 year after pDLI was 9%. Causes of non-relapse death were GVHD (n=2) and sepsis without GVHD (n=1). The cumulative incidence of relapse at 1 year after pDLI was 14%. One-year overall survival and progression-free survival were 82% and 77%, respectively.

We conclude that pDLI is feasible after Haplo-SCT. As previously described in the setting of HLA-matched Allo-HSCT, GVHD after pDLI is frequent, but severe forms are observed only in few patients, leading to very low GVHD-related death. Taking into account the high disease risk of the population, relapse rate and survivals after pDLI are promising, justifying the prospective evaluation of pDLI in further randomized prospective studies.

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Disclosures

No relevant conflicts of interest to declare.

Topics:
donors, hematologic neoplasms, hematopoietic stem cell transplantation, lymphocytes, graft-versus-host disease, allopurinol, graft-versus-host disease, acute, graft-versus-host disease, chronic, human leukocyte antigens, transplantation

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2017 by The American Society of Hematology
2017
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