Regular Prophylactic Donor Lymphocyte Infusion Is Effective and Safe to Prevent Relapse after Hematopoietic Cell Transplantation in High-Risk Patients

Background

Donor lymphocyte infusion (DLI) is the mainstream therapy for the prevention and treatment of relapse following hematopoietic cell transplantation (HCT). The efficacy of DLI for patients with acute leukemia, however, is limited in previous studies. This may be due to the more rapid proliferative capacity of malignant cells in acute leukemia, since a full response to DLI often requires months. Moreover, DLI is more effective when there is less disease burden to eradicate. Therefore, patients with high risk of relapse may take advantage of an early DLI after HCT. In this study, we applied an early prophylactic DLI in high relapse-risk patients with negative MRD (MRD-) after HCT.

Patients and Methods

From July 2013 to December 2015, 56 adult patients with high relapse-risk in our center were admitted in this study. High relapse-risk was defined as failure to attain a complete remission (CR) after two cycles of induction therapy (primary induction failure), more than second complete remission (¡ÝCR2), no complete remission before HCT, or increasing MRD before HCT detected by flow cytometry (FCM) or real-time quantitative PCR (RQ-PCR). All patients received modified busulfan/cyclophosphamide¨Cbased myeloablative conditioning regimen. Rabbit antithymocyte globulin was administered for patients receiving unrelated donor HCT or haploidentical HCT. All patients received graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine A, methotrexate and low-dose mycophenolate mofetil. Post-HCT MRD was monitored at regular intervals with FCM or RQ-PCR. All patients achieved negative MRD post-HCT in our study.

Results

In total, 56 patients (median age, 36, range, 17-46; 66.1% male) with high relapse risk were included in our study. 15 patients had acute lymphoblastic leukemia; 25 had acute myeloid leukemia; 5 had chronic myelogenous leukemia blast phase; the rest hadT-cell lymphoblastic lymphoma, myelodysplastic syndromes with refractory anemia with excess blasts-2, and peripheral T-cell lymphoma. Among them, 37 (66.1%) received haploidentical-HCT, 16 (28.6%) received matched sibling donor-HCT, and three (5.4%) received unrelated donor-HCT. The median time from HCT to DLI was 82 days (range, 47-160). After a median follow-up of 21 months (range, 7-34), the overall survival (OS) at two years was 78.4%; the disease-free survival (DFS) at two years was 75.4%, with relapse rate of 13.3%. Clinical characteristics were subjected into univariate Cox analysis for OS or relapse rate to find prognostic factors. Neither donor type nor disease type had significant impact on OS or relapse rate in our study. Of note, four patients relapsed after the first DLI underwent chemotherapy combined with a second DLI. Unfortunately, this strategy failed to treat relapse in all of the four patients.

The main concern following DLI is the emergence of GVHD. In our study, 19 of the 56 patients (33.9%) developed aGVHD after DLI, mostly Grade I to Grade II (n = 15, 78.9%). cGVHD was observed in 25 of the 56 patients (44.6%), mostly with limited manifestations (n = 20, 80%). Among the deceased 11 patients, only one patient died secondary to GVHD complications due to bronchiolitis obliterans.

Conclusions

For patients with high risk of relapse following HCT, this study indicates that early administration of DLI is effective and safe to prevent relapse. Regular application of DLI for negative MRD patients post-HCT with high relapse risk may be a feasible strategy to prevent future relapse.

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