Donor Lymphocyte Infusion for Relapsed Hematological Malignancies after Unrelated Allogeneic Bone Marrow Transplantation Facilitated by the Japan Marrow Donor Program

Abstract

To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n = 184), myelodysplastic syndrome (n = 69), acute lymphocytic leukemia (n = 57), chronic myelogenous leukemia (CML, n = 36), lymphoid neoplasms (n = 38), adult T cell leukemia/lymphoma (n = 18), and multiple myeloma (n = 12). Sixty-five patients (16%) were in cytogenetic/molecular relapse and 349 (84%) were in hematological relapse after BMT. In total, 266 out of 414 (64%) patients received chemotherapy and/or molecular-targeted agents in combination with UDLI. The median time from BMT to UDLI was 244 days. The median number of infused CD3 cells was 3.51 × 10/kg. Response and survival rates were evaluated at 100 days after UDLI. Complete response was obtained in 37 (57%) of 65 patients with cytogenetic/molecular relapse and in 69 (20%) of 349 patients with hematological relapse (P < .001). Two hundred forty-seven patients (60%) were alive, whereas 110 (26%) had died because of disease progression, 26 (6%) because of infections, 12 (3%) because of graft-versus-host disease (GVHD), and 13 (3%) because of organ failure. Multivariate analysis identified molecular/cytogenetic relapse, GVHD after UDLI, and CML but not combination with chemotherapy as significant prognostic factors. These results indicate that UDLI may have efficacy in relapsed patients with CML, low tumor burden, or occurrence of GVHD after UDLI.

Additional Cytogenetic Abnormalities with Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia on Allogeneic Stem Cell Transplantation in the Tyrosine Kinase Inhibitor Era

“…Prophylactic TKI or MRD-triggered TKI maintenance has been applied in many institutions when tolerable [12,27,35], and, moreover, new-generation TKI, which exhibits potent activity in patients who have developed BCR-ABL mutations resistant to imatinib, has become available [36][37][38]. Donor lymphocyte infusion [39][40][41][42] and second allogenic HSCT [43][44][45] were other feasible options for patients relapsing after HSCT. It is possible that current advances in salvage strategies with the early detection of MRD contributed to overcome the relatively small difference in the risk of relapse.…”

What is the outcome in patients with acute leukaemia who survive severe acute graft‐versus‐host disease?

“…DLI had no significant effect on the probability of relapse, while it increased NRM (Table ). This contrasts with the effect of DLI in patients with chronic myeloid leukaemia, where the probability of relapse is reduced and LFS is increased .…”

G‐CSF administration prior to donor lymphocyte apheresis promotes anti‐leukaemic effects in allogeneic HCT patients

“…In addition, occurrence of chronic GVHD after DLI was associated with a significantly improved survival. We and others found in previous studies that limited forms of GVHD were associated with favourable graft-versus-tumour effects and improved survival, whereas severe GVHD outweighed such benefits by higher GVHDrelated morbidity and mortality (Introna et al, 2017;Miyamoto et al, 2017;Tan et al, 2017;Saillard et al, 2018;Schneidawind et al, 2018). immature myeloid precursor cells with distinct immunoregulatory properties.…”