Successful desensitization of high level donor-specific anti-HLA antibody in patients with hematological diseases receiving haploidentical allografts

Zheng, Xianyou; Yan, Hu; Han, Dongmei; Ding, Li; Zhu, Ling; Liu, Jing; Xue, Mei; Li, Sheng; Wang, Hengxiang

doi:10.1007/s00277-022-04844-5

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…27,28 Several previous studies also reported that rituximab could be used for DSA desensitization in patients receiving Haplo-HSCT. 21,[29][30][31][32] Recently, Chang et al 33 demonstrated that treating DSA-positive patients with a single dose of rituximab significantly decreased levels of DSA MFI and reduced primary PGF in patients with DSA 2000 ≤ MFI < 5000. In our protocol, a single dose of rituximab (375 mg/m 2 ) was administrated after completion of DFPP.…”

Section: Discussionmentioning

confidence: 99%

“…Rituximab has been demonstrated to be effective in dealing with DSA‐mediated organ transplant rejection 27,28 . Several previous studies also reported that rituximab could be used for DSA desensitization in patients receiving Haplo‐HSCT 21,29–32 . Recently, Chang et al 33 demonstrated that treating DSA‐positive patients with a single dose of rituximab significantly decreased levels of DSA MFI and reduced primary PGF in patients with DSA 2000 ≤ MFI < 5000.…”

Section: Discussionmentioning

confidence: 99%

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Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Liu,

Ji,

Zhu

et al. 2023

Br J Haematol

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SummaryDonor‐specific anti‐HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo‐HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case–control study. Thirty‐three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10–21) and 13 (10–29) days respectively. Although the cumulative incidence of II–IV aGVHD (41.4% vs. 28.1%) and 3‐year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3‐year non‐relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo‐HSCT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Liu,

Ji,

Zhu

et al. 2023

Br J Haematol

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“…9,[11][12][13][14] To mitigate this risk, pre-transplant desensitization therapy for DSA has shown promise. [12][13][14][15][16][17][18][19][20] However, current approaches, such as plasma exchange (PE), inhibition of DSA production, neutralization of DSA, and inhibition of the complement activation pathway, are still experimental and based on small retrospective studies. [12][13][14][15][16][17][18][19][20] Thus, large-scale clinical trials are still needed.…”

Section: Introductionmentioning

confidence: 99%

“…The occurrence of primary PGF is closely associated with the presence of donor‐specific anti‐HLA antibodies (DSA) in approximately 10%–21% of patients with hematological diseases who undergo HLA‐mismatched allo‐HSCT 9,11–14 . To mitigate this risk, pre‐transplant desensitization therapy for DSA has shown promise 12–20 . However, current approaches, such as plasma exchange (PE), inhibition of DSA production, neutralization of DSA, and inhibition of the complement activation pathway, are still experimental and based on small retrospective studies 12–20 .…”

Section: Introductionmentioning

confidence: 99%

The impact of donor‐specific anti‐HLA antibody levels on primary poor graft function and graft rejection in rituximab desensitized haploidentical stem cell transplantation

Liu,

Zhao,

et al. 2023

HLA

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This study investigates the influence of donor‐specific anti‐HLA antibodies (DSA) levels on primary poor graft function (PGF) and graft rejection (GR) after haploidentical stem cell transplantation (haplo‐SCT) with rituximab desensitization. A total of 155 DSA‐positive haplo‐SCT candidates with mean fluorescence intensity (MFI) between 2000 and 10,000 were enrolled in this prospective clinical trial. Receiver operating characteristic (ROC) curves determined the optimal DSA MFI cutoff for identifying high‐risk patients. Patients were categorized into two groups: DSA low‐level group (2000 ≤ DSA MFI < 5000, Group A) and high‐level group (5000 ≤ DSA MFI ≤ 10,000, Group B). The incidence of primary PGF was 6.5% (2.6%–10.3%), while GR incidence was 0.6% (0.0%–1.9%). Group A had significantly lower primary PGF rates than Group B (2.3% [0.0%–5.7%] vs. 12.9% [4.8%–21.0%], p = 0.017). Only one patient in Group B experienced GR. High DSA levels (5000 ≤ MFI ≤ 10,000) were identified as the sole independent risk factor for primary PGF and GR after haplo‐SCT with rituximab desensitization (HR = 7.282, 95% CI 1.517–34.953, p = 0.013). The 4‐year cumulative incidence of relapse, non‐relapse mortality, disease‐free survival, and overall survival were 14.7% (11.6%–17.8%), 16.3% (13.1%–19.4%), 69.0% (65.9%–76.2%), and 70.6% (66.4%–74.8%), respectively. DSA levels have an impact on efficiency of rituximab desensitization, and a DSA MFI threshold is provided for predicting primary PGF and GR.

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Multiple drugs

2023

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Successful desensitization of high level donor-specific anti-HLA antibody in patients with hematological diseases receiving haploidentical allografts

Cited by 5 publications

References 26 publications

Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

The impact of donor‐specific anti‐HLA antibody levels on primary poor graft function and graft rejection in rituximab desensitized haploidentical stem cell transplantation

Multiple drugs

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