The impact of donor‐specific anti‐human leukocyte antigen antibodies in salvage haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide in patients with nonmalignant disorders

• Published in: HLA : immune response genetics 2021-06, Vol.97 (6), p.493-504
• Main Authors: Lima, Alberto Cardoso Martins, Bonfim, Carmem, Getz, Joselito, Dornelles, Luciana Nasser, Amaral, Geovana Borsato, Petterle, Ricardo Rasmussen, Loth, Gisele, Nabhan, Samir Kanaan, Pereira, Noemi Farah, Pasquini, Ricardo
• Format: Article
• Language: English
• Subjects: donor‐specific anti‐HLA antibodies; graft failure; nonmalignant disorders; posttransplant cyclophosphamide; salvage haploidentical transplant
• ISSN: 2059-2302; 2059-2310
• DOI: 10.1111/tan.14277

The presence of donor‐specific anti‐human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a major risk factor for graft failure (GF) after haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (haplo‐PTCy). However, the role of DSAs in salvage haplo‐PTCy for rescuing patients with nonmalignant disorders (NMDs) has not yet been reported. The present study retrospectively analyzed 22 patients with NMDs who underwent salvage haplo‐PTCy from January 2008 to December 2017. The median age at the time of the rescue haplo‐PTCy was 9 years (range, 1–26 years). Median time from the first transplant to second haplo‐PTCy was 56 days (range, 37–591 days). Among all patients, six (27.3%) had DSAs, with a median DSA strength (mean fluorescence intensity [MFI]) of 5201 (range, 1412–11,543) in the first DSA testing. In addition, the median DSA MFI was 2672 (range, 832–10,498) before the bone marrow infusion. Overall, GF occurred in 5 (25%) of the 20 assessable patients. Three of four (75%) patients with DSAs experienced GF versus 2 of 16 (12.5%) DSA‐negative patients (P = 0.032). The median DSA MFI for patients with GF was 6437 (range, 1412–10,498) versus 1845 (range, 832–2672) for those who engrafted or had early death (P = 0.030). One‐year event‐free survival was significantly lower in DSA‐positive patients than in those without DSAs (16.7% vs. 62.5%, P = 0.002). DSA‐negative patients had an acceptable 1‐year survival of 62.5%. In conclusion, this study suggests that DSAs may be associated with deleterious outcomes after salvage haplo‐PTCy in patients with NMDs.