Case Scenario: Who, How, What and when not to : of desensitization.
Case Study: 40 year old female (Shanti) with 2 pregnancies and with renal failure post severe PPH in the second pregnancy. She has remained on dialysis for 3 months, no recovery and CT shows cortical necrosis. She is here to see you for discussion of transplant options as has already been refused by 3 centers. Has had multiple potential donors worked up and her crossmatches have been positive. Single antigen bead testing done and report below (PRA 95-98%).
| Sensitization History | 2 Pregnancies and 5 Blood Transfusions | |||||
| HLA Typing | A | B | C | DR | DQ | DP |
| Donor (Mother) | 02:08, 24:02 | 18:01, 35:02 | 04:01, 12:03 | 10:01, 16:02 | 05:01, 05:02 | 04:01, 13:01 |
| Recipient | 02:08, 03:01 | 14:02, 18:01 | 08:02, 12:03 | 15:03, 16:02 | 05:02, 06:03 | 04:01, 13:01 |
| XM | T cells | B Cells | ||||
| CDC XM | Negative | Negative | ||||
| Flow XM | Positive | Positive | ||||
| Single Antigen Bead SAB Report – Click to View |
Class I : Multiple anti HLA Abs | Class II: Multiple Anti HLA Abs. | ||||
Questions & Answers
Q1. What would your discussion be for this recipient and what options would you discuss?
Ans: 2 haploidentical sibling, even if ABO incompatible. Else can consider desensitization with a relative with lowest antibodies, and CDC and Flow negative but will need to be prepared for rejection, treatment of AMR and shorter graft survival. Though still likely lower mortality than continuing on dialysis.
Q2. Would you consider her for desensitization for any of her CDC XM or Flow XM positive relatives? What threshold would you like to use to consider someone for desensitization?
Ans: Preferably CDC and flow negative and single or combined DSA < 10000. Each Transplant program should have their comfort level and focus on that.
Q3. What are the risks for CDC positive or flow XM positive transplant?
Ans: AMR rate of 30-50% within first 3 months, and graft loss 50% in 5 years despite extensive treatment including eculizimab, splenectomy, IL6 inhibitors, etc.
What AMR rate should we expect and what graft survival should we expect ? -Gloor. AJT 2010: 10:582-9 and Segev DL; AJT 2014: 14: 1573-80.
Q3. How can we know if the single antigen bead report is valid and not due to some random cross reactivity with the beads?
Ans: Look for self antigens, they should be negative. If they are positive, usually will be due to some background cross-reactivity, and can either repeat or if only for one antigen like C then can use those as negative threshold. If for DQ or DP then likely a combo antibody or a DQA1 antibody which is not self antigen as the cause for those antibody.
