In the field of solid organ transplantation, daratumumab has also been used in solid organ transplant candidates to decrease allosensitization, to counteract antibody-mediated rejection (AMR), and to allow solid organ transplantation21C24. transplantation (allo-HSCT), especially the human leukocyte antigen (HLA)-matched sibling donors (MSDs) and matched unrelated donors (MUDs), is an important option for the prevention of ALL recurrence4. The limited availability of MSDs and MUDs limits the acceptance of allo-HSCT for ALL patients5. Haploidentical stem cell transplantation (haplo-SCT) has become an important alternative approach for such patients6,7. However, the donor-specific JAG1 anti-HLA antibodies (DSA) are considered an important barrier for the successful engraftment of donor stem cell. Identification of DSA is one of the important causes of primary graft failure (PGF) in haplo-SCT and other types of HLA-mismatched donor transplantation8C10. These antibodies are considered to have a weak to low level of mean fluorescence intensity (MFI) if the values range from 1,000 to 3,000; moderate-level MFI, values from 3,000 to 5,000; and strong-level MFI, values >5,00011. Several desensitization strategies have been used to decrease the total antibody load of DSA to reduce the risk of PGF: plasmapheresis or immunoabsorption, monoclonal antibody to CD20+ B lymphocytes (rituximab), inhibitors against antibody-producing plasma cells (bortezomib), intravenous immunoglobulins, donor HLA antigen CL-387785 (EKI-785) (platelet or white blood cell) infusions, and inhibition of complement cascade12. These desensitization strategies have been used in solid organ transplantation and allo-HSCT13C15. They improved the risk of PGF and the survival rate of patients in transplantation of partially mismatched hematopoietic stem cell donors. Here we present a patient with refractory B-cell ALL, with strongly positive DSA levels, directed against donor HLA antigens. Before her haplo-SCT, we chose daratumumab combined with chemotherapy for this patient, and she achieved a significant decrease in DSA levels and complete remission (CR). Medical History Presentation A 36-year-old female patient was diagnosed with common B-cell ALL. After one course of VDCLP (vincristine, daunorubicin, cyclophosphamide, l-asparaginase, and prednisolone), two cycles of CAM (cyclophosphamide, cytarabine, and 6-mercaptopurine), and two courses of high-dose methotrexate combined with venetoclax chemotherapy, her disease did not achieve CR with 30.36% leukemia cells in the bone marrow (BM) by flow cytometry (FCM) (Fig. 1A). Except for a daughter haploid donor, she had no sibling donor and HLA-matched or HLA-mismatched unrelated donor for her allo-HSCT. Unfortunately, strong MFI level values were found in her DSA test (immunomagnetic beads liquid chip technology) (Table 1). In addition, her ABO blood group could not be detected because of the loss of erythrocyte antigen expression. Open in a separate window Figure 1. Immunophenotype of leukemia cells by FCM before and after combination therapy with daratumumab. (A) Before daratumumab: Malignant B lymphocytes characterized as CD19+CD22+CD34+CD10dim and CD20?CD38? by FCM. (B) After daratumumab: She achieved CR with CD19?CD22?CD34+CD10?CD20?CD38? by FCM. FCM: flow cytometry; CR: complete remission. Table 1. Change in DSA Levels After Daratumumab Therapy.
Patient (mother)3601:01,02:0108:01,35:0107:02,03:0315:02,15:0105:01,06:02Donor (daughter)1301:01,32:0108:01,52:0107:02,12:0215:02,04:0505:01,04:01Molecular specificitySpecificityBefore therapyAfter first therapyAfter second therapyDay 0 (immunoglobulin)Day 7HLA-I (MFI)?A*32:01A3219,138.8910,256.3810,640.2112,144.49Negative?B*52:01B5216,160.918,482.327,455.168,721.4NegativeHLA-II (MFI)?DRB 1*04:04DR419,606.2512,341.139,289.788,258.89Negative?DRB 1*04:01DR419,131.5111,638.189,386.648,682.2Negative?DRB 1*04:03DR416,333.149,105.77,601.777,239.81Negative?DRB 1*04:05DR415,719.318,961.46,366.446,141.03Negative?DRB 1*04:02DR414,776.567,920.727,103.396,332.34Negative Open in a separate window DSA: donor-specific anti-HLA antibodies; HLA: human leukocyte antigen; Immunoglobulin: intravenous immunoglobulin, 1g/kg; MFI: mean fluorescence intensity of microbead reaction. The bold-faced indicates a different match between the patient and the donor. Although CD38 expression on leukemia cells was negative, daratumumab (16 mg/kg) combined with etoposide and venetoclax therapy was chosen for her. After one cycle of combination therapy, she achieved CR with a significant decrease in DSA levels (Fig. 1B, Table 1). At the same time, her erythrocyte antigen expression recovered, and her ABO blood group could be detected. After a second course of the same combination therapy, the DSA levels remained low and stable CL-387785 (EKI-785) (Table 1); consequently, she was prepared to receive haplo-SCT from her daughter as a donor. To further reduce DSA levels, she received corticosteroids (40 mg/day, from day -7 to day 0) and high-dose immunoglobulin CL-387785 (EKI-785) (0.5 g/kg, on day ?2, ?1) before allo-HSCT. She did not receive plasmapheresis prior to haplo-SCT because.