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The last two decades have seen Donor Lymphocyte Infusion (DLI) emerge as a treatment option for disease relapse following allogeneic stem cell transplant. Reviewing the literature reveals a great degree of variability in how DLI is performed. One trend is to use G-CSF-mobilized stem cells instead of conventionally collected stem cells. It is also unclear whether the type of cells utilized, fresh versus cryopreserved, impacts the DLI efficacy.
We identified all patients who underwent DLI for persistent or relapsed disease at the Temple BMT Unit between 7/1993 and 12/2013. We determined response to DLI per standard criteria to calculate event free survival (EFS) and overall survival (OS), post-DLI. Correlative calculations were conducted between DLI and pre-transplant conditioning regimen [Myeloablative vs. Non-Myeloablative], DLI conditioning regimen [if any], # of CD3+ cells infused, absence or presence of post-DLI GVHD and interval between original transplant and disease progression with respect to EFS and OS.
We identified 63 patients who received DLI for persistent or relapsed disease. Median F/U was 5.4 years (range 0.03-11.88). The OS was similar between the cryopreserved and fresh cells groups [median OS for cryopreserved=0.39 yrs, median OS for fresh=0.32 yrs; p=0.79] [Fig 1A]. Type of pre-transplant conditioning [myeloablative versus non-myeloablative] had no impact on OS [for myeloablative, p=0.52; for non-myeloablative, p=0.12]. The EFS was similar between the two groups [median EFS for cryopreserved=0.41 yrs, median EFS for fresh=0.42 yrs; p=0.43] [Fig 1B]. Analysis based upon pre-transplant conditioning resulted in similar EFS values [for myeloablative, p=0.98; for non-myeloablative, p=0.14]. Presence or absence of GVHD post-DLI had no impact on OS or EFS [n=55, p=0.5]. The dose of CD3+ cells infused for each DLI [median dose =5.00E7cells, range=2.00E6-5.20E8] had no correlation with OS [p=0.13] or EFS [p=0.3]. The interval between original transplant and disease progression [n=63, median time=0.36 yrs, range=0.09-9.01yrs] had a significant impact on OS [p <0.01] and EFS [p<0.01]. Notably, treatment with any chemotherapy prior to receiving a DLI did not significantly impact OS [p=0.22] or EFS [p=0.54].
Our analysis reveals no difference in OS or EFS between the use of fresh or cryopreserved cells for DLI. There is a trend to favor fresh cell DLI in patients who have undergone a non-myeloablative transplant. Our study confirmed previous observations that a greater interval between original transplant and relapse correlates with greater DLI success. We also highlight that in the setting of relapsed disease, pretreatment with chemotherapy did not impact post-DLI OS or EFS. In conclusion, selected patients can achieve long term survival with DLI for post-transplant relapse though the overall outcomes remain dismal.
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Fig 1: A. Post-DLI OS; B. Post-DLI EFS