Novel Therapy with Interferon-α in Combination with Donor Lymphocyte Infusion for High Risk Acute Leukemia Patients Who Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation

Relapse remains a major cause of failure for allogeneic stem cell transplantation (allo-HSCT). Donor lymphocyte infusion (DLI) is routinely employed as salvage for patients who relapsed after allo-HSCT. In order to improve the graft versus leukemia (GVL) effect of DLI, we investigated the efficacy and safety of combining interferon-α with DLI (aDLI) in patients with high risk acute leukemia who relapsed after allo-HSCT, and compared the efficacy, toxicity and leukemia free survival (LFS) of aDLI and traditional donor lymphocyte infusion(tDLI)in our transplantation center.

Sixteen acute leukemia patients were enrolled in this study. All patients were treated with interferon-α-2b therapy at a dose of 3×10⁶U/day subcutaneously for 5 days followed by G-CSF mobilized donor peripheral stem cell infusion. IFN-α treatment continued until complete remission or development of graft-versus-host disease (GVHD). We coined the term “aDLI” for this novel treatment protocol. The median duration of interferon-α treatment was 17 (range, 5–50) days, and the median CD3⁺ cells dose was 9.25×10⁷/kg(range, 4–20×10⁷/kg)of recipient weight. Bone marrow smear, real-time PCR, STR-PCR,FISH,cytogenetic analysis and flow cytometry were used to monitor engraftment and minimal residual disease. In parallel, we retrospectively analyzed the results of tDLI for 14 acute leukemia patients with hematological relapse post allo-HSCT treated in the same period in our transplantation center, and compared the efficacy, toxicity and LFS of tDLI with aDLI.

Patients treated on the aDLI protocol included 9 ALL and 7 AML, with a median age of 26.5 years. Fourteen of 16 patients had high risk acute leukemia: 3 patients with Ph+ ALL, 6 patients relapsed after CR1, 4 patients had complicated chromosome abnormality, and 1 patient had testicular leukemia. The median relapse time was 5.5 (range, 1–25) months post transplant. Salvage chemotherapy was administrated in 7 patients before aDLI, with only 3 patients achieved CR. The overall complete remission (CR) rate for aDLI protocol was 75% (12/16), with CR rate of aDLI alone without chemotherapy at 66.7% (6/9). The median time from aDLI to bone marrow CR was 7(range, 6–14)days, and the median time to molecular complete remission (MCR) and full donor chemerism (median level was 96.3%) in responsive patients was 2 weeks post DLI. With a median follow-up of 5.5 (range, 1–34) months, 7 patients were alive with durable MCR. Two-year LFS was 50%. Treatment related toxicities included reversible episode of fever, GVHD and myelosuppression. The tDLI group had similar demographic characteristics with respect to age, disease subtypes, transplant and relapse history. Compared to tDLI, the aDLI protocol had higher CR rate (75.0% vs 14.3%, p =0.001), faster response (median time to obtain BM CR and full donor chimerism were 7 days vs 23 days, and 30 days vs 60 days respectively), higher incidence of acute GVHD (56.3 % vs 27.3%, p=0.05), and significant better 2-year LFS(50.0% vs 7.1%,p=0.05. Importantly, there was no significant difference between the two groups with respect to the incidence of pancytopenia (53.8% vs 75%, p>0.05) and treatment related mortality(18.8% vs 7.1%, p>0.05).

Interferon-α-2b in combination with donor lymphocyte infusion appears to induce rapid and durable remissions in high risk acute leukemia patients who relapsed following allo-HSCT, with acceptable treatment-related toxicity. This novel adoptive immunotherapeutic strategy warrants additional studies in allo-HSCT settings

No relevant conflicts of interest to declare.