Treatment of allosensitized patients receiving allogeneic transplantation

Abstract

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate day plasma exchange, rituximab, intravenous gamma globulin (IvIg) and an irradiated donor buffy coat for patients with DSA at two institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSA (N=345). Majority of patients in the DSA group were females (83.8% vs. 37.1% in controls, p<0.001) and received stem cells from a child as donor (67.6% vs. 44.1%, p=0.002). Mean DSA level before and after desensitization was 10,198 and 5,937 MFI, respectively with mean differences of 4,030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA >20,000 MFI and with persistent C1q+ after desensitization had a significantly lower engraftment rate, resulted in a significantly higher non-relapse mortality (NRM) and worse overall survival (OS) than controls whereas graft outcome and survivals of patients with initial DSA <20,000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with plasma exchange, rituximab, IvIg and donor buffy coat is effective in promoting engraftment in patients with DSA up to 20,000 MFI.

Donor selection for KIR alloreactivity is associated with superior survival in haploidentical transplant with PTCy

“…All patients received PTCy-based GVHD prophylaxis with tacrolimus and mycophenolate, as previously described by our group ( 34 ). Patients with a high level (mean fluorescence intensity >2,000) of donor-specific anti-HLA antibodies received desensitization therapy before HSCT per institutional protocol ( 35 ). Comorbidities before HSCT were evaluated using the Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI) ( 36 ) and hematologic malignancies were risk-stratified using the refined Disease Risk Index (DRI) ( 37 ).…”

Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant

“…DSA desensitization with daratumumab has been described in solid-organ transplant recipients and in an HLA-mismatched HCT recipient. 5,6,9,11 Interestingly, after receiving daratumumab, patient 5 became negative for C1q-fixing antibodies, which likely improved her prognosis. 4 Although frequent blood product transfusion may be unavoidable, an effort should be made to limit exposure by minimizing both the number and volume of blood products or by choosing platelet units that do not expand sensitization to prevent DSA development.…”

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

“…Chang et al [ 51 ] suggested that high DSA levels were associated with primary engraftment failure and poor primary engraftment in HLA haploidentical transplantation. Ciurea et al [ 52 ] used plasma exchange, rituximab, intravenous immunoglobulins, and irradiated donor buffy coat to intervene in patients with high DSA levels and found that the engraftment success rate was higher in patients with decreased DSAs and negative complement component 1q. Pretreatment protocols can also affect the engraftment success rate.…”