Elena Deripapa, Russian Federation
Dmitriy Rogachev National Center for Pediatric Hematology, Oncology, and Immunology ImmunologyPresenter of 2 Presentations
CHARACTERIZATION OF ONCOLOGICAL MANIFESTATIONS IN PATIENTS WITH DNA-BREAKAGE SYNDROMES: SINGLE CENTER EXPERIENCE.
Abstract
Background and Aims
Malignancies are known manifestation of primary immunodeficiencies, with highest rate being in the DNA-repair disorders (DNA-RD). There is no universal opinion on tumor treatment regiments in DNA-RDT, treatment protocols vary between centers.
Methods
We analyzed DNA-RD patients (42 with Nijmegen breakage syndrome (NBS), 33 with ataxia-telangiectasia (AT) treated in our Center in 2014-2019.
| Diagnosis/ signs | Patients, (n) | Tumors (n) | Age of tumor diagnosis, y. (M) | Limphoma (n) | OLL (n) | Solid tumors (n) | Second tumors (n) | Alive (n, %) |
| NBS | 42 | 26 | 2-18y. (M-6) | 20 | 9 | 1 | 4 | 12/29 |
| AT | 33 | 11 | 1-28y. (M-8) | 8 | 3 | 1 | 1 | 8/24 |
Results
Malignancies were diagnosed in 26 NBS (62%) and in 11 AT (33%) patients (table). 4 NBS and 1 AT patient developed second tumors. Majority of NBS patients received chemotherapy without dose reduction, and no major toxicity or complications. 15 NBS patients underwent hematopoietic stem cell transplantation (HSCT), 12 are alive. All AT patients received reduced doses of chemotherapy due to toxicity and infectious complication, 8 are currently alive.
Conclusions
In our experience, malignancies in DNA-RD group require variable therapeutic approach: while reduced chemotherapy doses are needed for AT, patients with NBS benefit from full dose chemotherapy protocols with supportive IVIG treatment in all cases, followed by HSCT.
A CASE OF SEVERE CYTOPENIA IN A PATIENT WITH COMPOUND-HETEROZYGOUS MUTATIONS IN ATM GENE AND ADDITIONAL GERM-LINE 4P16.3 MICRODUPLICATION
Abstract
Background and Aims
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.
Methods
We describe a 12 month old female patient with ATM gene compound-heterozygous mutations (с.5932G>T; c.1561_1562delGA) and 4p16.3 microduplication.
Results
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.
Conclusions
We present challenges in combined cytopenia treatment in a patient with complex PID phenotype and demonstrate partial response to daratumumab.