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Introduction Donor lymphocyte infusion (DLI) is a useful therapy for mixed chimerism (MC) and measurable residual disease (MRD) after allogeneic transplantation (HSCT). Multiple DLI products can be obtained through apheresis and cryopreservation, but their costs can be prohibitive in developing countries. T-cells in whole blood units can reach ≥1 × 106/kg in healthy donors and are increased after G-CSF exposure. The ideal CD3+ cell dose remains undefined. Objectives We aim to assess the safety and efficacy of G-CSF-primed whole blood units (WB-DLI) in peripheral blood HLA-matched sibling (MSD) and haploidentical (Haplo) transplant recipients. Methods Adults who received WB-DLI at any time after HSCT due to relapse, MRD, MC or poor graft function were included. Patients with active graft-versus-host disease (GVHD) were excluded. Donors received filgrastim 5 μg/kg QD (days 1-3) followed by a 450 mL whole blood draw on day 4 with crossmatching and lymphocyte quantification. For patients with major/bidirectional ABO mismatch without group switch or a mixed field reaction, a reactive major crossmatch was an absolute contraindication. WB-DLI was infused fresh and unmanipulated in an outpatient basis. Concurrent chemotherapy was allowed. Disease and chimerism were assessed on day 30 and 60, respectively. GVHD prophylaxis included oral cyclosporine/tacrolimus tapered in 60 days. Results Fourteen patients received a single WB-DLI, median age was 32 years (range, 16-67), 50% were women. Most common diagnoses were ALL, (n=5) and AML (n=5), followed by MDS (n=2), NHL (n=1) and CML (n=1). Nine had were Haplo grafts, while 4 were MSD. Indication for WB-DLI was relapse in 6 patients, 3 had MRD, 4 MC and 1 had poor graft function. Median chimerism pre-WB-DLI was 72% (range, 38-100%). Median mononuclear cell count obtained was 32 × 10x6/kg (range, 9-74), while median CD3+ cell count was 6.7 × 106/Kg (range, 5.2-19). No immediate severe adverse effects were observed. Febrile non-hemolytic reaction occurred in n=4. No complications were observed in n=4 ABO mismatch cases. Overall 50% responded; chimerism improved in 50%, with a median increase of 28% (range, 9-53%). Median post-DLI chimerism was 92.5% (range, 20-100). Regarding patients treated for relapse or MRD 4/9 responded (33%). Overall 8/14 patients relapsed (57%) with 12-month progression free survival of 27.5% which was significantly lower in relapsed/MRD patients (log rank test p=0.042). Overall survival at 12 months was estimated at 61.2%. Three developed aGVHD, 2 grade III/IV in a median of 13 days (range, 7-38). Four died due to relapse. Median follow-up was 5 months (0.6-20.1 months). The cost of performing WB-DLI was $350 USD per unit. Conclusions DLI obtained from GCSF-primed whole-blood is safe and affordable. It improves mixed chimerism, while it is less effective for overt relapse, similarly to DLI obtained through standard methods. |
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