Outcomes of Donor Lymphocyte Infusion for Treatment of Mixed Donor Chimerism after a Reduced-Intensity Preparative Regimen for Pediatric Patients with Nonmalignant Diseases

Abstract

Mixed donor chimerism is increasingly common in the pediatric hematopoietic stem cell transplantation (HSCT) setting because of the increased use of reduced-intensity preparative regimens for nonmalignant diseases. Donor lymphocyte infusion (DLI) is potentially useful in the treatment of mixed donor chimerism, but little are data available on the use of DLI in this setting. We conducted a retrospective review of 27 pediatric patients who received DLI for mixed donor chimerism between January 2006 and December 2010 after receiving a preparative regimen of alemtuzumab, fludarabine, and melphalan. Twenty-one patients (78%) were alive at a median of 35 months post-transplant. Seven patients (26%) sustained full donor chimerism after DLI only at a median of 35 months post-HSCT. Nine patients (33%) continued with mixed donor chimerism (median, 38% [range, 18% to 70%]) at a median of 37 months after DLI only. Five patients underwent unconditioned stem cell boosts or second conditioned transplants after no improvement in donor chimerism was seen following DLI. Donor source appeared to contribute to outcomes after DLI; patients with mismatched unrelated donors had earlier first decline in chimerism and timing of first DLI, a higher response rate to DLI, and an increased rate of graft-versus-host disease (GVHD). There was no response to DLI in patients with matched sibling donors. Ten patients, all with improvement in chimerism after DLI, developed acute GVHD after DLI, with 3 having grade III GVHD. Three patients developed chronic GVHD after DLI. These data illustrate the potential efficacy of DLI in the treatment of mixed donor chimerism after a reduced-intensity preparative regimen.

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

“…54 Currently, preemptive and prophylactic DLI (pDLI) is widely used to minimize the risk of post-transplant relapse for patients receiving T-cell depletion 55 and having diseases at advanced stage. 55,56 pDLI is also often administered for promoting FDC, enhancing immune reconstitution, 27,57,58 as well as treating virus infection after HSCT and preventing viral reactivation. 59 G-CSF-primed pDLI To explore the relationship between pDLI and risk stratificationdirected interventions for MRD, Yan et al 60 executed a clinical study in which a total of 709 patients were divided into three groups (group A: MRD − after transplantation; group B: MRD + receiving low-dose IL-2; group C: MRD + receiving G-CSF-primed modified DLI with or without low-dose IL-2).…”

Interleukin-15-activated cytokine-induced killer cells may sustain remission in leukemia patients after allogeneic stem cell transplantation: feasibility, safety and first insights on efficacy

“…Regarding toxicity, some studies of pre-emptive IT including withdrawal of immunosuppression and DLI report GvHD rates as high as 70% in adult patients, 7 but these were less frequent in pediatric patients: 8 GvHD developed in 19% of pediatric patients, and toxic deaths due to GvHD occurred in 4%. The limited published data on haploidentical DLI report that 25% of the 40 patients who received haploidentical DLI developed aGvHD, of whom 15% had severe aGvHD and 2 severe aGvHDpatients died.…”

HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity

“…HCT-CI score 0 25 (35) 78 (40) HCT-CI score 1 16 (22) 44 (23) HCT-CI score 2 14 (19) 28 (15) HCT-CI score $3 17 (24) 43 (22) …”