Rituximab for desensitization during HLA-mismatched stem cell transplantation in patients with a positive donor-specific anti-HLA antibody

Chang, Ying‐Jun; Xu, Lei; Wang, Yu; Zhang, Xiao-Hui; Chen, Huan; Chen, Yuhong; Wang, Feng-Rong; Han, Wei; Sun, Yu‐Qian; Yan, Chen‐Hua; Tang, Fei‐Fei; Huo, Ming-Rui; Zhao, Xiang‐Yu; Mo, Xiao‐Dong; Liu, Kai-Yan; Huang, Xiao‐Jun

doi:10.1038/s41409-020-0928-z

Cited by 41 publications

(42 citation statements)

References 42 publications

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“…Detailed information on demographic information, disease information, and first transplantation are summarized in Table 1. At the time of the first transplantation, six patients were DSA positive, among which there were four patients with mean fluorescence intensity >5,000, who were administered rituximab and received third-party cord blood (CB) transplants according to our protocol (12).…”

Section: Patient Characteristicsmentioning

confidence: 99%

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Sun

Wang

et al. 2021

Front. Med.

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Graft failure (GF) is a fatal complication of allogeneic stem cell transplantation, especially after haploidentical transplantation. The mortality of GF is nearly 100% without an effective salvage method. A second transplantation is usually necessary to save the patient's life. However, there is no standardized regimen, and the outcome is usually disappointing. We report on a prospective single-center study using a reduced-intensity conditioning regimen with different haploidentical donors (HIDs). Patients with GF after the first transplantation were enrolled in a prospective single-arm clinical trial (ClinicalTrials.Gov ID: NCT03717545) at the Peking University Institute of Hematology. The conditioning regimen consisted of fludarabine (30 mg/m2) (days−6 to−2) and cyclophosphamide (1,000 mg/m2/day) (days−5 to−4). Patients underwent a second transplant from a different HID using a granulocyte colony-stimulating factor primed bone marrow and peripheral blood stem cells. The primary outcome was neutrophil engraftment at day 28. The secondary outcomes included platelet engraftment at day 100, transplant-related mortality (TRM) at day 30, TRM at day 100, and overall survival (OS) at 1 year. From March 2018 to June 2020, 13 patients were enrolled in this clinical trial. Of the 13 patients, five had acute myeloid leukemia, five had acute lymphoblastic leukemia, two had myelodysplastic syndromes, and one had a non-Hodgkin lymphoma. The median age at first transplantation was 38 years (range, 8–55 years). As for the first transplantation, 11 patients underwent haploidentical transplantations and two underwent unrelated donor transplantations. At the time of GF, three patients had complete donor chimerism, five had mixed chimerism, and five had complete recipient chimerism. The median time from the first transplantation to the second transplantation was 49 (range 35–120) days. The medians of infused cell doses were as follows: mononuclear cells 7.93 (5.95–12.51) × 108/kg and CD34 + cells 2.28 (0.75–5.57) × 106/kg. All 13 patients achieved neutrophil engraftment after the second transplantation, with a median engraftment time of 11 (range 10–20) days after transplantation. The platelet engraftment rate on day 100 after transplantation was 76.9%. The TRMs at day 30, day 100, and 1-year were 0, 0, and 23.1%, respectively. The OS and disease-free survival at 1-year were 56.6 and 48.4%, respectively. For patients with GF after first transplantation, a second transplantation using a fludarabine/cyclophosphamide regimen from a different HID was a promising salvage option. Further investigation is needed to confirm the suitability of this method.

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Section: Patient Characteristicsmentioning

confidence: 99%

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Sun

Wang

et al. 2021

Front. Med.

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“…The desensitization regimen is consisted of plasma exchange with 1 volume of albumin exchange and immunoglobulin 500 mg/kg (days −14, −12, −10, −8, and −1), FK at 1 mg/kg or CsA at 3 mg/kg daily as continuous infusion, and MMF at 1 g twice a day (from day −14 to day −8) ( 26 ). Chang et al reported that the usage of rituximab 375 mg/m 2 in patients with DSA positive (2,000 ≤ MFI <10,000) could effectively prevent the onset of PGF ( 27 ). In our study, DSA in one patient showed positive MFI (8,806.43), and we used immunoglobulin and CsA at the above-mentioned dosage.…”

Section: Discussionmentioning

confidence: 99%

Comparable Outcomes in Acquired Severe Aplastic Anemia Patients With Haploidentical Donor or Matched Related Donor Transplantation: A Retrospective Single-Center Experience

et al. 2022

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Clinical data of patients with severe aplastic anemia (SAA) were retrospectively analyzed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (HID-HSCT) with matched related sibling hematopoietic stem cell transplantation (MSD-HSCT) in complications and survivals. Thirty consecutive patients were enrolled in the study with a median follow-up of 50 months (range 4, 141), and the median age of the patients was 21 years (range 3, 49). All the patients achieved myeloid engraftment in the two cohorts. The cumulative incidences of platelet engraftment were 95.5 and 100% in HID cohort and MSD cohort, respectively. The median time for neutrophil and platelet recovery was 11 (range 9, 19) and 15 (range 10, 25) days in HID cohort, and 12 (range 10, 19) and 14 (range 8, 25) days in MSD cohort. The cumulative incidences of grade II–IV and grade III–IV acute graft vs. host disease (aGvHD) in HID cohort and in MSD cohort were 18.9 vs. 14.3% (p = 0.77) and 10.5 vs. 0% (p = 0.42), respectively. The cumulative incidences of chronic graft vs. host disease (cGvHD) was 22.7% in HID cohort and 25.5% in MSD cohort (p = 0.868). The 5-year overall survival (OS) rates and 5-year failure-free survival (FFS) rates in HID cohort and MSD cohort were 85.1 vs. 87.5% (p = 0.858), 80.3 vs. 87.5% (p = 0.635), respectively. The median time to achieve engraftment, cumulative incidence of aGvHD and cGvHD, and the 5-year OS and FFS rates were not significantly different between the two cohorts. We suggest that HID-HSCT might be a safety and effective option for SAA patients without a matched donor.

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“…DSA-positive patients (2000 ≤ mean fluorescence intensity [MFI] < 10000) were given rituximab 3 days before graft infusion. If available, DSA-negative umbilical cord blood was also infused prior to infusion of allogeneic grafts ( 14 , 15 ). No patients in this study had a DSA MFI of ≥ 10000.…”

Section: Methodsmentioning

confidence: 99%

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

et al. 2022

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Secondary poor graft function (sPGF) increases the risk of life-threatening complications after hematopoietic stem cell transplantation (HSCT). The incidence, clinical outcomes, and risk factors of sPGF have not been elucidated in haploidentical (haplo-) HSCT for acquired aplastic anemia (AA) patients. We retrospectively reviewed 423 consecutive AA patients who underwent haplo-HSCT between January 2006 and December 2020 and report a 3-year cumulative incidence of 4.62% (95% confidence interval [CI]: 3.92%-10.23%) of sPGF. While no primary PGF occurred. The median time to sPGF was 121 days (range 30-626 days) after transplantation. To clarify the risk factors for sPGF, 17 sPGF cases and 382 without PGF were further analyzed. Compared to patients without PGF, the 2-year overall survival was significantly poorer for sPGF patients (67.7% vs 90.8%, p =.002). Twelve sPGF patients were alive until the last follow-up, and 7 achieved transfusion independency. The multivariable analyses revealed that later neutrophil engraftment (OR 2.819, p=.049) and a history of refractory cytomegalovirus viremia (OR=7.038, p=.002) post-transplantation were associated with sPGF. There was weak evidence that a history of grade 3-4 acute graft-versus-host disease increased the risk of sPGF (p=.063). We advocated better post-transplantation strategies to balance the risk of immunosuppression and viral reactivation for haplo-HSCT in AA patients.

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Rituximab for desensitization during HLA-mismatched stem cell transplantation in patients with a positive donor-specific anti-HLA antibody

Cited by 41 publications

References 42 publications

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

Comparable Outcomes in Acquired Severe Aplastic Anemia Patients With Haploidentical Donor or Matched Related Donor Transplantation: A Retrospective Single-Center Experience

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

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