Achieving Hematologic Remission with Combination Chemotherapy and Donor Leukocyte Infusions for Relapse of Acute Myeloid Leukemia Six Years After Human Leukocyte Antigen-Mismatched Transplantation: A Case Report

Abstract 4476

Hematopoietic Stem Cell Transplantation (HSCT) from partially HLA-matched (haploidentical) family donors represents a promising therapy for high-risk acute myeloid leukemia (AML). However, for patients with AML relapsed after HSCT from an HLA-mismatched familial donor, there is no standard therapy. They may receive conventional chemotherapy, cyclosporine withdrawal, second HSCT, and donor leukocyte infusion (DLI) with or without prior mobilization. Recently, combination chemotherapy and DLI showed achieving hematologic remission.

We report a case of successful combination chemotherapy and donor leukocyte infusions from original donor in a patient with AML relapsing 6 years after HSCT from an HLA-Mismatched Familial Donor.

A 37-year-old male presented with fever in June 2003.Bone marrow aspirate confirmed the diagnosis of AML(M5 subtype according to FAB classification). The patient initially received intensive chemotherapy. However, the patient with AML that was refractory to conventional therapy. He received HSCT in first CR from his mother 1-loci HLA-mismatched (HLA-A) using BuCY- Conditioning regimen on June 11, 2004. He showed a medullary relapse 6 years after HSCT. His bone marrow blast counts exceeded 80% with 8.25% of donor karyotypes (46 XX FISH). We decided to try to use his mother as the donor for DLI. Cytoreductive chemotherapy was commenced prior to DLI. He was treated twice with DLI on August 02, 2010 and September 23, 2011. He was treated chemotherapy before in first DLI, chemotherapy regimens; FLAG-ida [fludarabine 30 mg/m²/d from day-6 to-2 of cell infusion, cytosine arabinoside 2 g/m²/d from day-6 to-2 of cell infusion, idarubicine 20 mg/d day-1 and G-CSF 300μ g/day from day-7 to +30]. The donors received G-CSF 10μ g/kg subcutaneously daily starting day-3 of cell infusion for 5 days. Donor peripheral blood mononuclear cells were collected by CS-3000 Plus cell separator (Baxter Corp.) on the fifth days of G-CSF administration and infused through a central venous catheter into the patients on the same day. 8.33×10⁷/kg mononuclear cells, 6×10⁷/kg CD3+ cells were reinfused without manipulation. Cyclosporine at the dose of 3 mg/kg were administered for the prevention of GVHD. On days 36 Bone marrow blast counts exceeded 45% with 44% of donor karyotypes (46 XX FISH) after first Chemo-DLI. He received cyclosporine withdrawal. He was treated chemotherapy by low-dose Ara-C and aclarubicin with concomitant use of G-CSF before in second DLI.,chemotherapy regimens;CAG[ Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m² every 12 hours on days-14 to-1. Aclarubicin was administered intravenously at a dosage of 7 mg/m² on days-14 to-7. Recombinant G-CSF was given subcutaneously at a dosage of 200μ g/m2 per day on days-14 to-1]. On day 0,1.4×10⁸/kg mononuclear cells,1×10⁸/kg CD3+ cells were reinfused. On days 25 bone marrow examination showed CR with 89% of donor karyotypes (46 XX FISH). He was treated consolidation chemotherapy by regimens; CAG.On days 62 bone marrow examination showed CR with 100% of donor karyotypes (46 XX FISH). He developed chronic GVHD with limited disease at day 123 of DLI. In the patient whose cGVHD resolved with the use of steroid, cyclosporine plus methotrexate. The patient died from pneumonia without evidence of recurrent leukemia on day +230.

From the cases reported, combination chemotherapy and subsequent mobilized DLI produced a CR with AML in relapse six years after HLA-Mismatched transplantation. We demonstrate that of the patient who relapsed after 6 years, treatment with chemotherapy followed by intensive chemotherapy followed by DLI, can effectively salvage a patient with attainment of durable remissions. Although limited by the small number of one patient, AML in relapse six years after HLA-Mismatched transplantation requires particular attention in future studies, as well as in designing future treatment programs. Clearly a large number of patients is required to confirm the real efficacy of this treatment.