With advance of genetic methods PID patients with complex phenotype caused by multiple genetic defects are more frequently described. They present a challenge in immediate symptoms treatment as well as in deciding on curative therapy approach.
We describe a 12 month old female patient with ATM gene compound-heterozygous mutations (с.5932G>T; c.1561_1562delGA) and 4p16.3 microduplication.
Patient’s symptoms included dysmorphic facial features, combined immunodeficiency, elevated alpha fetal protein and cytopenia since the age of 6 months (transfusion-dependent anemia and thrombocytopenia, and neutropenia). Based on bone marrow histology she was diagnosed with myelodysplastic syndrome, yet her thrombocytopenia was refractory to transfusions due to autoimmune component. Treatment with IVIG, high-dose methylprednisolone, romiplostim and rituximab was ineffective. The patient received haploidentical hematopoietic stem cell transplantation (HSCT) complicated by primary graft dysfunction. In preparation for the second HSCT the patient was treated with daratumumab 16 mg/kg every 2 weeks # 4 with partial response of her cytopenia. Second haploidentical HSCT with Fludarabine (150 mg/m2 days − 6 to − 2), Thiotepa (10 mg/kg days -5 to -4), Thymoglobulin (5 mg/kg days -5 to -4), Rituximab (100 mg/m2 day -1), Plerixafor (720 mkg/kg days -6 to -4) conditioning and TCR alfa/beta/CD19 depletion was performed. Granulocytes engraftment was recorded on day +17. Right now the patient in the early post-HSCT period, doing well.
We present challenges in combined cytopenia treatment in a patient with complex PID phenotype and demonstrate partial response to daratumumab.