{"doi":"10.1111/bjh.19289","title":"Donor‐specific antibody desensitization with daratumumab prior to haematopoietic cell transplant for sickle cell disease: A case report","abstract":"Allogeneic haematopoietic cell transplant (alloHCT) is the only widely available cure for sickle cell disease (SCD), with 3-year event-free survival (EFS) of 89% and 3-year overall survival (OS) of 96% in children receiving a myeloablative matched sibling donor (MSD) transplant. Donor paucity of MSD and matched unrelated donors (MUD) limits alloHCT with the latter available for <20% non-Caucasian patients. Although alternative donors have a lower EFS than MSD, there is no significant difference in EFS among non-sibling donors.1 Approximately 23% of patients have detectable HLA antibodies, that when specific to the donor (DSA), increase the risk of primary graft failure (GF) resulting in worse OS.2-4 Desensitization strategies to reduce DSA levels include antibody adsorption, therapeutic plasmapheresis, intravenous immunoglobulin (IVIg), immunosuppressive chemotherapy (e.g. cyclophosphamide, fludarabine) and antibody depletion (e.g. rituximab or bortezomib).2, 3, 5 We present a single case report for a pretransplant immune suppression (PTIS) approach, novel to sickle cell disease, with suboptimal response to traditional PTIS and desensitization with subsequent successful haploidentical donor engraftment. Our patient is a 23-year-old female with severe sickle-beta thalassaemia (HbS/B0) characterized by multiple disease-specific complications and frequent, prolonged and progressive vaso-occlusive episodes necessitating multiple hospital admissions annually, chronic pain and poor quality of life. Hydroxycarbamide (hydroxyurea), crizanlizumab and voxelotor were unsuccessful. The patient had a history of red cell antibodies (anti-E, anti-K, anti-Fya, anti-N and anti-s), and additionally, anti-C and anti-Leb were detected serologically (Bio-Rad IH-1000 System) during our evaluation. Human Erythrocyte Antigen genotyping (Immucor PreciseType Human Erythrocyte Antigen 1.2 BeadChip DNA array) revealed C-, E-, K-, Fya-, N-, s- and Leb-confirming risk of forming all of the alloantibodies previously detected. The patient received phenotypically matched red cells, nevertheless she developed acute haemolysis following first red cell exchange (RCE) prior to apheresis with a significant decrease in her haemoglobin of 3.6 g/dL. No additional antibodies were detected at this time. Safe phenotypically matched RCEs for multiple expected apheresis cycles for gene therapy protocol became challenging. Given this risk, the patient was removed from the protocol and alloHCT options were explored. In the absence of suitable donors, paternal haploidentical transplantation was her only curative option. HLA class I DSA against A33, B78 and Cw2 at baseline were >10 000 MFI (16 557, 10 720 and 11 163 MFI respectively, detected using solid phase immunoassays, including single antigen bead assays for antibody identification). PTIS included rituximab, bortezomib, dexamethasone, fludarabine, cyclophosphamide and IVIg, followed by 11 therapeutic plasma exchange (TPE) sessions with persistent high DSA levels (Figure 1; Table S1). Outside an IRB protocol, the patient then received in a compassionate approach, eight doses of daratumumab (Darzalex®, Janssen Biotech, Inc.) with no adverse infusion reactions, followed by six additional TPE sessions and a dose of rituximab given B-cell recovery. This regimen, led to undetectable Cw2 antibody, along with substantial reductions in A33 and B78 (2500 and 600 MFI respectively). She received myeloablative conditioning with model-based dosing rabbit anti-thymocyte globulin (rATG),6 busulfan (cumulative exposure of 90 mg*h/L) and fludarabine (160 mg/m2) from Days −6 to −2 and haploidentical graft with unmodified peripheral blood stem cells (PBSC) (CD34+ count of 7.09 × 106 cells/kg) followed by post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis. Neutrophils recovered on Day +19 with 100% donor chimerism (CD33, CD3 and CD56 lineages) at Day +28. Given persistent severe thromboc","journal":"British Journal of Haematology","year":2024,"id":467052,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1154488,"name":"Gloria Contreras Yametti","orcid":"0000-0002-8464-035X","position":1,"is_corresponding":false},{"id":916442,"name":"Amanda G. Blouin","orcid":"0000-0003-2238-4837","position":2,"is_corresponding":false},{"id":637550,"name":"Grace Linder","orcid":null,"position":3,"is_corresponding":false},{"id":1299545,"name":"P. Dayand Borge","orcid":"0000-0002-2823-2685","position":4,"is_corresponding":false},{"id":1299546,"name":"Elena Maryamchik","orcid":"0000-0002-4719-4629","position":5,"is_corresponding":false},{"id":1299944,"name":"Alexandra Budhai","orcid":null,"position":6,"is_corresponding":false},{"id":439620,"name":"Gaurav K. Gupta","orcid":"0000-0002-2951-0034","position":7,"is_corresponding":false},{"id":327024,"name":"Andromachi Scaradavou","orcid":"0000-0003-2425-1069","position":8,"is_corresponding":false},{"id":108808,"name":"Barbara Spitzer","orcid":"0000-0003-1603-1381","position":9,"is_corresponding":false},{"id":327026,"name":"Kevin J. Curran","orcid":"0000-0002-3337-9956","position":10,"is_corresponding":false},{"id":260639,"name":"Joseph H. Oved","orcid":"0000-0002-1129-5129","position":11,"is_corresponding":false},{"id":312103,"name":"Andrew C. Harris","orcid":"0000-0002-4538-8817","position":12,"is_corresponding":false},{"id":313730,"name":"Akshay Sharma","orcid":"0000-0003-3281-2081","position":13,"is_corresponding":false},{"id":297903,"name":"Jaap Jan Boelens","orcid":"0000-0003-2232-6952","position":14,"is_corresponding":false},{"id":327028,"name":"Maria Cancio","orcid":"0000-0003-4430-6290","position":15,"is_corresponding":false},{"id":890700,"name":"Binni Kunvarjee","orcid":"0000-0002-8255-7982","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:05:10.907983Z","pmid":"38212144","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}