Donor HLA-specific Abs: to BMT or not to BMT?

Abstract

The engraftment failure associated with Abs to donor-specific HLA (DSA) limits options for sensitized BMT candidates. Fourteen of fifteen patients with no other viable donor options were desensitized and transplanted using a regimen of plasmapheresis and low-dose i.v. Ig modified to accommodate pre-BMT conditioning. DSA levels were assessed by solid-phase immunoassays and cell-based crossmatch tests. DSA levels were monitored throughout desensitization and on day − 1 to determine if there was any DSA rebound that would require additional treatment. A mean reduction in DSA level of 64.4% was achieved at the end of desensitization, with a subsequent reduction of 85.5% after transplantation. DSA in 11 patients was reduced to levels considered negative post-BMT, whereas DSA in three patients remained at low levels. All 14 patients achieved donor engraftment by day +60; however, seven patients suffered disease relapses. Four patients experienced mild, grade 1 GVHD. Factors influencing the response to desensitization include initial DSA strength, number, specificity, DSA rebound and a mismatch repeated from a prior transplant. While desensitization should be reserved for patients with limited donor options, careful DSA assessment and monitoring can facilitate successful engraftment after BMT.

Guía colombiana de práctica clínica para el uso de inmonuglobulinas en el tratamiento de reemplazo e inmunomodulación

“…Este procedimiento terapéutico inicia una a 2 semanas antes del condicionamiento, dependiendo del título previo de anticuerpos y de la respuesta al tratamiento. (GRADE B1) 283 R Si bien se ha utilizado suplencia de IgIV en niños con hipogammaglobulinemia secundaria a quimioterapia altamente inmunosupresora, así como en protocolos de investigación que incluyen rituximab para enfermedades neoplásicas, no hay evidencia disponible que respalde estas indicaciones. (GRADE D)…”

Selecting the best haploidentical donor

“…In patients without alternative available donors, Gladstone et al found that plasmapheresis combined with anti-cytomegalovirus (CMV) intravenous immunoglobulin, tacrolimus, and mycophenolate mofetil (MMF) starting 1-2 weeks prior to conditioning, depending on the level of DSA, was associated a 64.4% mean reduction in DSA levels [17,20]. Fifteen patients received this treatment and the 14 patients who achieved DSA reduction to negative or weak levels underwent transplantation and engrafted.…”

Erratum: Modern approaches to HLA-haploidentical blood or marrow transplantation.

“…138,139 In patients with detectable DSAs to all potential HLA-haploidentical donors, desensitization procedures can reduce DSA titres such that haploBMT can be successfully performed. 138,140 Notably, Epstein-Barr virus-related post-transplantation lymphoproliferative disease within the first year post-transplantation was not seen among 785 patients treated with PTCy, 141 and no increase in donor-derived malignancies was detected. 142 …”