Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients

Ding, Li; Han, Dongmei; Yan, Hu; Zhou, Jie-Xin; Zheng, Xianyou; Zhu, Ling; Xue, Mei; Liu, Jing; Mao, Ning; Guo, Zi-Kuan; Ning, Hongmei; Wang, Heng-Xiang; Zhu, Heng

doi:10.1038/s41409-022-01688-5

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…However, there was no significant difference in the overall cases of aGVHD and cGVHD, and there was a trend of an increasing 3-year leukemia relapse rate (37.9% vs 26.7%; P = .19). 22 To further improve the preventive effect of MSCs, we infused UC-MSCs earlier dur- ing the early stage after haplo-HSCT. There were significant reductions in the number of overall and severe cases of cGVHD, with a similar incidence in the leukemia relapse rate, with this protocol compared with the control protocol.…”

Section: Discussionmentioning

confidence: 99%

“…A recent retrospective clinical trial evaluated the prophylactic efficacy of the coinfusion of MSCs with HSCT in grade III to IV aGVHD (9.1% vs 22.8%; P = .03) and severe cGVHD (10.3% vs 22.2%; P = .04). However, there was no significant difference in the overall cases of aGVHD and cGVHD, and there was a trend of an increasing 3-year leukemia relapse rate (37.9% vs 26.7%; P = .19) . To further improve the preventive effect of MSCs, we infused UC-MSCs earlier during the early stage after haplo-HSCT.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant

Huang,

Chen,

Wang

et al. 2024

JAMA Oncol

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ImportanceChronic graft-vs-host disease (GVHD) limits the long-term benefit of haploidentical hematopoietic stem cell transplant (HSCT). This clinical trial evaluated repeated infusions of umbilical cord mesenchymal stem cells (MSCs) during the early stage (45 days and 100 days) after haplo-HSCT to prevent chronic GVHD.ObjectiveTo determine whether repeated infusions of MSCs during the early stage after haplo-HSCT decreases the incidence of severe chronic GVHD.Design, Setting, and ParticipantsThis open-label, multicenter, parallel randomized clinical trial was conducted from April 2016 to January 2022. Eligibility criteria included a diagnosis of acute leukemia and having a haploidentical, suitable related donor for HSCT. The median (range) follow-up time was 39.0 (1.5-67.0) months.InterventionsThe enrolled patients with a haploidentical relative for HSCT received the modified busulfan/cyclophosphamide + antithymocyte globulin modified regimen and standard GVHD prophylaxis. Patients were randomly chosen to receive MSCs (the MSC group) (1 × 106 cells/kg, every 2 weeks, starting from 45 days after transplant, 4 times total) or regular prophylaxis (control group).Main Outcome and MeasureThe cumulative incidence of severe chronic GVHD.ResultsOf 158 patients, 58 (36.7%) were female individuals; the median (range) age for the MSC and control groups was 28 (18-60) years and 28 (18-56) years, respectively. A total of 158 patients were screened, and 148 patients were randomly assigned to the MSC group (n = 74) or control group (n = 74) 1 day before MSCs infusion. The estimated 2-year cumulative incidence of severe chronic GVHD was 5.4% (95% CI, 1.8%-14.0%) in the MSC group and 17.4% (95% CI, 10.1%-28.5%) in the control group (hazard ratio [HR], 0.29; 95% CI, 0.10-0.88; P = .03). There was no difference between the MSC and control groups in the cumulative incidence of leukemia relapse (HR, 1.17; 95% CI, 0.55-2.47; P = .68). The cumulative incidence of stage II to IV acute GVHD in the MSC group was significantly lower than that in the control group (HR, 0.25; 95% CI, 0.09-0.67; P = .01). The MSC group had better GVHD-free and relapse-free survival rates than the control group (HR, 0.62; 95% CI, 0.39-0.98; P = .04).Conclusions and RelevanceThe results of this randomized clinical trial show that early repeated infusions of MSCs decreased the incidence and severity of chronic GVHD, and the incidence and severity of acute GVHD manifested as a better GVHD-free and relapse-free survival rate for patients after haplo-HSCT.Trial RegistrationChinese Clinical Trial Registry: ChiCTR-IIR-16007806

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant

Huang,

Chen,

Wang

et al. 2024

JAMA Oncol

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“…In contrast, research on MSCs for treating PGF is ongoing. MSCs are important components of the bone marrow niche, play an important role in maintaining the proliferation and homeostasis of hematopoietic stem cells, and can improve the poor implantation after allogeneic HSCT [24,25]. Previous studies have mostly focused on BMSCs [26,27].…”

Section: Discussionmentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway

Wang,

Bi,

Zhang

et al. 2023

Stem Cells International

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Background. Poor graft function (PGF) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT). Current therapies, such as CD34+ cell infusion, have shown limited effectiveness. Conversely, mesenchymal stem cells (MSCs) show potential in addressing PGF. Adipose-derived mesenchymal stem cells (ADSCs) effectively support long-term hematopoietic stem cell proliferation. Therefore, this study aimed to investigate the mechanisms underlying the long-term hematopoietic support provided by ADSCs. Methods. ADSCs were isolated from mice and subsequently identified. In vitro experiments involved coculturing ADSCs as feeders with Lin-Sca-1+c-kit+ (LSK) cells from mice for 2 and 5 weeks. The number of LSK cells was quantified after coculture. Scanning electron microscopy was utilized to observe the interaction between ADSCs and LSK cells. Hes-1 expression was assessed using western blot and real-time quantitative PCR. An γ-secretase inhibitor (GSI) was used to confirm the involvement of the Jagged-1/Notch-1/Hes-1 pathway in LSK cell expansion. Additionally, Jagged-1 was knocked down in ADSCs to demonstrate its significance in ADSC-mediated hematopoietic support. In vivo experiments were conducted to study the hematopoietic support provided by ADSCs through the infusion of LSK, LSK + fibroblasts, and LSK + ADSCs, respectively. Mouse survival, platelet count, leukocyte count, and hemoglobin levels were monitored. Results. ADSCs showed high-Jagged-1 expression and promoted LSK cell proliferation. There was a direct interaction between ADSCs and LSK cells. After coculture, Hes-1 expression increased in LSK cells. Moreover, GSI-reduced LSK cell proliferation and Hes-1 expression. Knockdown of Jagged-1 attenuated ADSCs-mediated promotion of LSK cell proliferation. Furthermore, ADSCs facilitated hematopoietic recovery and promoted the survival of NOD/SCID mice. Conclusion. The hematopoietic support provided by ADSCs both in vivo and in vitro may be mediated, at least in part, through the Jagged-1/Notch-1 signaling pathway. These findings provide valuable insights into the mechanisms underlying ADSCs-mediated hematopoietic support and may have implications for improving the treatment of PGF following HSCT.

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The efficacy and safety of third-party umbilical blood/umbilical cord mesenchymal stem cell assisted related haploid hematopoietic stem cell transplantation in pediatric patients with acute leukemia: an observational study

Liu,

Liu

et al. 2024

Therapeutic Advances in Hematology

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Background: There is limited data on third-party umbilical cord blood (UCB) or mesenchymal stem cell (MSC) transplantation-assisted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients. Objective: To evaluate the efficacy and safety of UCB and MSC transplantation-assisted haplo-HSCT in pediatric patients with acute leukemia (AL). Design: Observational study. Methods: Clinical data of 152 children with AL undergoing haplo-HSCT at the Children’s Hospital of Soochow University between January 2020 and June 2022 were collected. The patients were divided into the haplo-HSCT + UCB group ( n = 76), haplo-HSCT + MSC group ( n = 31), and haplo-HSCT group ( n = 45). Hematopoietic reconstruction time, complications within 30 days after transplantation, and survival and recurrence at 3 years after transplantation were compared among the groups. Results: Multivariate analysis revealed that haplo-HSCT with MSC and human leukocyte antigen (HLA) matching ⩾6/10 were independent factors reducing engraftment syndrome (ES) incidence. There were no significant differences among the groups in the hematopoietic reconstruction time or incidence of complications within 30 days after transplantation ( p > 0.05). Overall survival, relapse-free survival, cumulative incidence of relapse, cumulative incidence of hematological relapse, and 3-year transplant-related mortality were not significantly different ( p > 0.05). The incidence of adverse reactions in the haplo-HSCT + UCB group was 97.3% within 4 h after UCB infusion, with a particularly high occurrence rate of 94.7% for hypertension. No transfusion-related adverse reactions occurred after the transfusion of umbilical cord MSC in the haplo-HSCT + MSC group. Conclusion: MSC-assisted haplo-HSCT can reduce ES incidence after transplantation in pediatric patients with AL. UCB infusion is associated with a high incidence of reversible hypertension. However, no adverse reactions were observed in umbilical cord MSC transfusion.

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Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients

Cited by 4 publications

References 49 publications

Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant

Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant

Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway

The efficacy and safety of third-party umbilical blood/umbilical cord mesenchymal stem cell assisted related haploid hematopoietic stem cell transplantation in pediatric patients with acute leukemia: an observational study

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