P180 Moving onto plan C: Finding detours when DSA creates a roadblock to bone marrow transplantation

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Aim This case study illustrates potential avenues to consider when identifying hematopoietic stem cell donor options for HLA sensitized patients. Methods HLA typing was performed using reverse sequence specific oligonucleotide probe hybridization assays (One Lambda, Inc.) and Sanger sequence base typing assays (local and commercial kits). HLA-specific antibody was assessed using class I and class II phenotypes (Lifecodes®, Immucor) and single antigen panels (One Lambda Inc.). Results The presence of donor specific antibody (DSA) can adversely impact the likelihood of bone marrow engraftment depending on the specificity and strength of the DSA. DSA assessment and monitoring is becoming crucial as centers are utilizing HLA mismatched donors. In the last 5 years, 60–70% of the overall allogeneic bone marrow transplants at our center utilized HLA mismatched donors. In a majority of our sensitized patients, the availability of multiple eligible donors allowed for either the avoidance of DSA or the minimization of DSA to levels that did not warrant desensitization. But, in 6% of the cases evaluated in 2016, DSA caused roadblocks requiring alternate pathways. The case of a 41 year old female with Acute Lymphocytic Leukemia illustrates the “Moving onto Plan C” mantra. Plan A: A related haploidentical transplant was diverted due to crossmatch positive DSA against the patient’s four eligible donors. Plan B: An unrelated matched transplant was deterred due to DRB3*01 allele specific DSA against several 10/10 HLA loci matched donors with the DRB1*13:01/DRB3*01 association instead of patient’s DRB1*13:01/DRB3*02 association. Plan C: An unrelated mismatched donor search was initiated to identify 9/10 HLA loci matched donors with a DRB1 mismatch likely to avoid the patient’s broad specificity and eliminate the potential of a DRB3*01 typed donor. Conclusion Even though there is a low incidence of patients requiring an alternate route due to DSA, the impact of the DSA is life-threatening to the individuals in this cohort. With the increase of HLA mismatched transplants, there is a greater need for initial HLA antibody assessments, continual HLA antibody monitoring, alternative back-up plans and creative solutions in order to offer all patients the best chance of survival.