Donor Lymphocyte Infusions (DLI) Following Haplo Bone Marrow Transplantation (hBMT) with High-Dose of Cyclophosphamide Post-Transplant As Gvhd Prophylaxis

In the haploidentical setting, the use of donor lymphocyte infusions (DLI) is associated with a significant risk of acute and chronic graft vs host disease (GvHD): in one report, a median T-cell dose of 2.4 × 10^⋀8/kg was administered to recipients of unmanipulated haploidentical stem cell transplants, and a cumulative incidence of chronic GVHD of 50% was reported (Huang X, BBMT 2009). It is possible that patients receiving high dose Cyclophosphamide post-transplant (PT-CY) may be able to receive DLI with a lower risk of GvHD

We tested the feasibility and occurrence of GVHD, following 32 DLI administered in sixteen patients, who relapsed after an unmanipulated haploidentical T-cell replete BMT, and PT-CY.

All sixteen patients were transplanted from haploidentical related donor, after a myeloablative conditioning (n=10) or a non myeloablative conditioning (n=6) with PT-CY as GVHD prophylaxis, in association with CyA and micophenolate. The diagnosis was Hodgkin's lymphoma (n 6), acute lymphoblastic B-cell leukemia (n=3), acute myeloid leukemia (n=5), pro-lymphocytic T-cell leukemia (n=1), chronic myeloid leukemia blast crisis (n=1). The median time of relapse was 211 days from transplant (range 45–697 days); the median time at DLI was 48 days from relapse (range 29–540 days) and 252 days from transplant (range 109–690). Ten patients had hematologic relapse, while six had molecular relapse.

At time of first DLI all patients were off GVHD prophylaxis.

The minimum dose of lymphocytes was 1 × 103̂/kg (n=2); higher doses were as follows: 1 × 104̂/kg (n=13), 1 × 105̂/kg (n=11), 5 × 105̂/kg (n=4), 1 × 106̂/kg (n=2). The median number of DLI/patient, was 1 (range 1–5). In eleven cases DLI followed chemotherapy: gemcitabine or bendamustine in Hodgkin's lymphoma and pro-lymphocytic leukemia; fludarabine, ara-C and antracycline containing regimens in acute leukemia. Median time of DLI was 12 days from chemotherapy (range 10–14 days), during the chemotherapy-induced nadir. Five patients received DLI alone.

The infusions were well tolerated and no major adverse effect was observed.

The cumulative incidence of acute GvHD grade II-III, was 6%, and 0% for chronic GVHD. No aplasia related to haplo-DLI occurred.

Five patients died with progressive disease; 11 patients are surviving (69%), 4 of them are disease-free, seven have active disease; two patients relapsed after 313 and 135 days from DLI, respectively. The median follow-up is 221 days (range 46–559 days).

This study suggests that patients grafted with haplo-mismatched BMT and high dose post-transplant cyclophosphamide, can be treated with DLI at doses up to 1× 106̂/kg, with a very low risk of developing acute or chronic GVHD.

No relevant conflicts of interest to declare.