The role of collateral related donors in haploidentical hematopoietic stem cell transplantation

Mo, Xiao‐Dong; Zhang, Yuanyuan; Zhang, Xiao-Hui; Xu, Lei; Wang, Yu; Yan, Chen‐Hua; Chen, Huan; Chen, Yuhong; Chang, Ying‐Jun; Liu, Kai-Yan; Huang, Xiao‐Jun

doi:10.1016/j.scib.2018.08.008

Cited by 28 publications

(22 citation statements)

References 35 publications

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“…The current results suggest that the administration of low-dose PTCy along with ATG/GCSF significantly decreased the rate of both acute and chronic GVHD as compared to contemporary controls who were also transplanted from MDs or CRDs proved to be at particular high GVHD risk under "Beijing protocol" in both single-center and multi-center studies [3,5,6,19,20]. Furthermore, grade III-IV aGvHD or severe cGVHD GVHD was the main cause of death in 7 out of 27 patients in the control cohort, in contrast to none in the combined treatment cohort (Table 3).…”

Section: Discussionmentioning

confidence: 72%

“…We compared our novel GVHD prevention strategy (lowdose PTCy in ATG/GCSF-based regimen) with contemporary control patients all transplanted from maternal donors or collateral relatives at particular high GVHD risk [3,19,20]. Cumulative incidence of acute GVHD, grade III-IV aGVHD, and chronic GVHD was significantly lower without GVHD-related death in the ATG-PTCy cohort as compared with the control cohort.…”

Section: Discussionmentioning

confidence: 99%

“…With the aim to assess the efficacy of this regimen in haplo-HCT, we extended our prospective study in consecutive patients treated with ATG/GCSF-PTCy (lowdose) regimen and initiated a multicenter analysis on comparing the results to the contemporary cohort of patients who received ATG/GCSF without low-dose PTCy. In the current study, patients in both study group and contemporary control group are all transplanted from maternal donor (mother donors, MDs) [3] or collateral relative donors (CRDs, e.g., uncle, aunt, nephew, niece, and cousins) [19,20] who had especially high risk of GVHD occurrence under "Beijing protocol." Herein, we tested the efficacy of ATG/PTCy (low-dose) as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives.…”

Section: Introductionmentioning

confidence: 99%

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Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients

et al. 2019

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Background: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. Methods:We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. Results: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). Conclusions: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients

et al. 2019

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“…Human leukocyte antigen (HLA)-haploidentical related donor (haplo-RD) and HLA-unrelated donor (URD) groups received rabbit anti-thymocyte globulin. All patients received granulocyte colony-stimulating factor (G-CSF)-mobilized, fresh, and unmanipulated bone marrow cells plus peripheral blood stem cells in the present study (Supplementary methods) [52][53][54][55][56][57] .…”

Section: Methodsmentioning

confidence: 99%

Preemptive interferon-α treatment could protect against relapse and improve long-term survival of ALL patients after allo-HSCT

Liu¹,

Luo²,

Zhang³

et al. 2020

Sci Rep

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Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).

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“…The immunosuppressants included cyclosporine A (CsA), mycophenolate mofetil (MMF), and shortterm methotrexate (MTX). G-CSF was administered subcutaneously to patients at 5 ug/kg per day from day +6 until myeloid recovery (23)(24)(25).…”

Section: Transplant Protocolsmentioning

confidence: 99%

G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study

Zhang

et al. 2021

Front. Oncol.

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G-CSF-mobilized peripheral blood (G-PB) harvest is the predominant graft for identical sibling donor and unrelated donor allogeneic hematopoietic stem cell transplantation (HSCT) recipients, but it was controversial in haploidentical related donor (HID) HSCT. In this registry study, we aimed to identify the efficacy of HID G-PB HSCT (HID-PBSCT) for acute leukemia (AL) patients in first complete remission (CR1). Also, we reported the outcomes for the use of G-PB grafts in comparison with the combination of G-BM and G-PB grafts in HID HSCT recipients. Sixty-seven AL patients in CR1 who received HID-PBSCT were recruited at Institute of Hematology, Peking University. Patients who received haploidentical HSCT using the combination of G-BM and G-PB harvests in the same period were enrolled as controls (n=392). The median time from HSCT to neutrophil and platelet engraftment was 12 days (range, 9–19 days) and 12 days (range, 8–171 days), respectively. The 28-day cumulative incidence of neutrophil and platelet engraftment after HSCT was 98.5% and 95.5%, respectively. The cumulative incidences of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) were 29.9% (95%CI 18.8–40.9%) and 7.5% (95%CI 1.1–13.8%), respectively. The cumulative incidences of total and moderate-severe chronic GVHD were 54.9% (95%CI 40.9–68.8%) and 17.4% (95%CI 6.7–28.0%), respectively. The cumulative incidences of relapse and non-relapse mortality were 13.9% (95%CI 5.4–22.5%) and 3.4% (95%CI 0–8.1%), respectively. The probabilities of overall survival (OS) and leukemia-free survival (LFS) were 84.7% (95%CI 74.7–94.7%) and 82.7% (95%CI 73.3–92.1%) respectively. Compared with the HID HSCT recipients using the combination of G-BM and G-PB grafts, the engraftments of neutrophil and platelet were both significantly faster for the G-PB group, and the other clinical outcomes were all comparable between the groups. In multivariate analysis, graft types did not influence the clinical outcomes. Overall, for the patients with AL CR1, G-PB graft could be considered an acceptable graft for HID HSCT recipients. This study was registered at https://clinicaltrials.gov as NCT03756675.

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The role of collateral related donors in haploidentical hematopoietic stem cell transplantation

Cited by 28 publications

References 35 publications

Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients

Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients

Preemptive interferon-α treatment could protect against relapse and improve long-term survival of ALL patients after allo-HSCT

G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study

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