Contributions
Abstract: EP1267
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a curative therapy for several hematological malignancies. However, a major cause of alloHSCT therapeutic failure is represented by the underlying disease relapse. Donor lymphocyte infusion (DLI) is a powerful adoptive immunotherapy that can be used after alloHSCT in patients with high-risk disease (prophylaxis), mixed donor chimerism or minimal residual disease (preemptive), and relapse (therapeutic). DLI exploits donor derived graft versus tumor effects to induce a durable remission.
Aims
To evaluate DLI characteristics, outcomes and adverse events in a series of patients treated in three Bone Marrow Transplant Units of Northern Italy between January 2010 and June 2020.
Methods
Among 938 alloHSCT patients, 119 (12.7%) underwent DLI. Median age was 48.7 years (18-70). Patients were affected by acute myeloid leukemia (AML) (n=56), acute lymphoblastic leukemia (n=18), multiple myeloma (n=10), chronic myeloproliferative disease (n=10), Hodgkin lymphoma (n=7), myelodysplastic syndrome (n=6), non-Hodgkin lymphoma (n=5), chronic lymphocytic leukemia (n=4), mixed phenotype leukemia (n=1), severe aplastic anemia (n=1), and large granular lymphocytic leukemia (n=1). Conditioning was myeloablative in 57 (47.9%) patients, reduced-intensity in 62 (52.1%). Thirty-six (30%) donors were HLA-matched, 13 (11%) haploidentical, 70 (59%) HLA-matched unrelated. DLIs were prophylactic in 18 (15%) patients, preemptive in 43 (36%). Fifty-eight patients (49%) underwent therapeutic DLIs, 35 (60%) in combination with other drugs. DLI was administered in escalated schedule, from 1x105 to 1x107 CD3+ cells/Kg. Disease free survival (DFS) was calculated from the first DLI to relapse or last follow-up.
Results
The median number of DLIs was 4.6 (1-49), the median dose of total CD3+ cells infused was 2.9x107/Kg (0.03-19.7). The median time elapsed between alloHSCT and the first DLI was 19 months (2-122). Complete remission (CR) was maintained in 13/18 (72%) patients undergoing prophylactic DLIs. Patients who received preemptive and therapeutic DLIs achieved CR in 30/43 (70%) and 22/58 (38%) cases, respectively. The median DFS was undefined in patients undergoing prophylactic or preemptive DLIs, 0.5 months (0-187) in those receiving therapeutic DLIs (p=<0.001). In the largest group of patients (i.e., AML), prophylactic, preemptive and therapeutic DLIs maintained or induced CR in 6/8 (75%), 12/20 (60%), and 10/28 (36%) cases, respectively.
Overall, 27/119 patients (23%) developed graft-versus-host-disease (GVHD). No significant differences were observed in terms of number of DLIs and donor type between patients with and without GVHD. Patients with GVHD received a slightly higher total number of CD3+ cells/Kg than those without (3.31x107 vs 2.74x107, p=ns), though in a lower time frame (4.8 vs 5.2 months). GVHD was associated to a significantly higher CR rate (78% vs 48%, p=0.006), however, 3/27 (11.1%) patients died of GVHD. None of patients experienced bone-marrow aplasia following DLI.
Overall, with a median follow-up of 38 months (0.3-189), 56/119 (47%) patients are currently alive in CR.
Conclusion
Although with the limits of a relatively small and heterogeneous series, our study indicates that DLI is an effective prophylactic and preemptive treatment option in alloHSCT patients. Prospective studies on homogeneous patient cohorts in terms of disease type and drug combination are awaited in order to address and ameliorate the effectiveness of DLI in therapeutic settings.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Donor lymphocyte infusion, Relapse
Abstract: EP1267
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a curative therapy for several hematological malignancies. However, a major cause of alloHSCT therapeutic failure is represented by the underlying disease relapse. Donor lymphocyte infusion (DLI) is a powerful adoptive immunotherapy that can be used after alloHSCT in patients with high-risk disease (prophylaxis), mixed donor chimerism or minimal residual disease (preemptive), and relapse (therapeutic). DLI exploits donor derived graft versus tumor effects to induce a durable remission.
Aims
To evaluate DLI characteristics, outcomes and adverse events in a series of patients treated in three Bone Marrow Transplant Units of Northern Italy between January 2010 and June 2020.
Methods
Among 938 alloHSCT patients, 119 (12.7%) underwent DLI. Median age was 48.7 years (18-70). Patients were affected by acute myeloid leukemia (AML) (n=56), acute lymphoblastic leukemia (n=18), multiple myeloma (n=10), chronic myeloproliferative disease (n=10), Hodgkin lymphoma (n=7), myelodysplastic syndrome (n=6), non-Hodgkin lymphoma (n=5), chronic lymphocytic leukemia (n=4), mixed phenotype leukemia (n=1), severe aplastic anemia (n=1), and large granular lymphocytic leukemia (n=1). Conditioning was myeloablative in 57 (47.9%) patients, reduced-intensity in 62 (52.1%). Thirty-six (30%) donors were HLA-matched, 13 (11%) haploidentical, 70 (59%) HLA-matched unrelated. DLIs were prophylactic in 18 (15%) patients, preemptive in 43 (36%). Fifty-eight patients (49%) underwent therapeutic DLIs, 35 (60%) in combination with other drugs. DLI was administered in escalated schedule, from 1x105 to 1x107 CD3+ cells/Kg. Disease free survival (DFS) was calculated from the first DLI to relapse or last follow-up.
Results
The median number of DLIs was 4.6 (1-49), the median dose of total CD3+ cells infused was 2.9x107/Kg (0.03-19.7). The median time elapsed between alloHSCT and the first DLI was 19 months (2-122). Complete remission (CR) was maintained in 13/18 (72%) patients undergoing prophylactic DLIs. Patients who received preemptive and therapeutic DLIs achieved CR in 30/43 (70%) and 22/58 (38%) cases, respectively. The median DFS was undefined in patients undergoing prophylactic or preemptive DLIs, 0.5 months (0-187) in those receiving therapeutic DLIs (p=<0.001). In the largest group of patients (i.e., AML), prophylactic, preemptive and therapeutic DLIs maintained or induced CR in 6/8 (75%), 12/20 (60%), and 10/28 (36%) cases, respectively.
Overall, 27/119 patients (23%) developed graft-versus-host-disease (GVHD). No significant differences were observed in terms of number of DLIs and donor type between patients with and without GVHD. Patients with GVHD received a slightly higher total number of CD3+ cells/Kg than those without (3.31x107 vs 2.74x107, p=ns), though in a lower time frame (4.8 vs 5.2 months). GVHD was associated to a significantly higher CR rate (78% vs 48%, p=0.006), however, 3/27 (11.1%) patients died of GVHD. None of patients experienced bone-marrow aplasia following DLI.
Overall, with a median follow-up of 38 months (0.3-189), 56/119 (47%) patients are currently alive in CR.
Conclusion
Although with the limits of a relatively small and heterogeneous series, our study indicates that DLI is an effective prophylactic and preemptive treatment option in alloHSCT patients. Prospective studies on homogeneous patient cohorts in terms of disease type and drug combination are awaited in order to address and ameliorate the effectiveness of DLI in therapeutic settings.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Donor lymphocyte infusion, Relapse