Co-transplantation of umbilical cord mesenchymal stem cells and peripheral blood stem cells in children and adolescents with refractory severe aplastic anemia

Objectives: The purpose of our study was to analyze the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs), which is considered as a novel approach for refractory severe aplastic anemia (RSAA) in children and adolescents. Methods: Thirty-two children and adolescents with RSAA were retrospectively reviewed. According to the source of PBSCs, all patients were divided into two groups (matched sibling donor group and matched unrelated donor group). Engraftment, graft-versus-host disease (GVHD) and overall survival (OS) were analyzed. Results: No adverse events related to UC-MSCs infusion occurred in all patients. The median time for neutrophil engraftment was 13 (10~23) days and 15 (11~28) days for platelet. Grade Ⅰ ~ Ⅱ acute GVHD and moderate chronic GVHD were observed in 21.88% and 12.50% of the cases. No statistically significance was observed between the MSD and MUD group on engraftment, GVHD and complications including infection and hemorrhagic cystitis. The median follow-up time was 38.60 (1.37~140.83) months. To the date of October 31th 2021, 5 died and 27 (84.38%) survived. The 5-year OS rate was not statistically significant between the MSD and MUD group (84.8% ± 10.0% vs 82.4% ± 9.2%, P = 0.674). Conclusions: The application of UC-MSCs in the treatment of RSAA in PBSC transplantation is reliable and safe, which can significantly reduce the incidence of GVHD and severe transplantation-related complications and effectively improve patients’ life quality. Therefore, the method can be used as an active treatment option for patients with RSAA.

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Reduced-dose of Posttransplant Cyclophosphamide and Cotransplantation of Peripheral Blood Stem Cells and Human Umbilical Cord-derived Mesenchymal Stem Cells in Severe Aplastic Anemia

10.21203/rs.3.rs-31898/v1 ◽

2020 ◽

Author(s):

Yingling Zu ◽

Jian Zhou ◽

Yuewen Fu ◽

Baijun Fang ◽

Xinjian Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Aplastic Anemia ◽

Peripheral Blood ◽

Control Group ◽

Human Umbilical Cord ◽

Peripheral Blood Stem Cells ◽

Reduced Dose ◽

Blood Stem Cells ◽

The Times

Abstract Background Posttransplant cyclophosphamide (PTCY) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). Methods We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in the MSD-HSCT group and 25 mg/kg for 22 patients in the haplo-HSCT group, on days +3 and +4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for patients with severe aplastic anemia (SAA) retrospectively. Results In the MSD-PTCY group, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control group (P<0.05), 11 (range 10 to 14) days and 12 (range 9 to 15) days. The cumulative incidence of acute GVHD (aGVHD) at day +100 (15.4%) was lower in the MSD-PTCY group than in the MSD-control group(P=0.050). No patient developed chronic GVHD (cGVHD). The 1-year overall survival (OS) and event-free survival (EFS) rates in the MSD-PTCY group were 100% and 92.3%. In the haplo-PTCY group, the times to neutrophil and platelet engraftment were significantly shorter than those in the haplo-control group (P<0.05), 12 (range 9 to 15) days and 11.5 (range 9 to 17) days. The cumulative incidences of aGVHD at day +100 and 1-year cGVHD in the haplo-PTCY group were 31.8% and 18.2%. The 1-year OS and EFS rates in the haplo-PTCY group were 81.8% and 66.9%. Conclusions Reduced-dose PTCY and cotransplantation of PBSCs and UC-MSCs is feasible for patients with SAA, especially for overcoming the high incidences of aGVHD and cGVHD due to PBSCs.

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Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia

American Journal of Hematology ◽

10.1002/ajh.10015 ◽

2001 ◽

Vol 69 (1) ◽

pp. 15-22 ◽

Cited By ~ 10

Author(s):

Chang-Ki Min ◽

Dong Wook Kim ◽

Jong Wook Lee ◽

Chi Wha Han ◽

Woo Sung Min ◽

...

Keyword(s):

Stem Cells ◽

Aplastic Anemia ◽

Peripheral Blood ◽

Adult Patients ◽

Severe Aplastic Anemia ◽

Peripheral Blood Stem Cells ◽

Blood Stem Cells

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Infusion of autologous peripheral blood stem cells in an unrelated donor who developed severe aplastic anemia following stem cell donation

Bone Marrow Transplantation ◽

10.1038/bmt.2011.174 ◽

2011 ◽

Vol 47 (6) ◽

pp. 869-869 ◽

Cited By ~ 3

Author(s):

H Frangoul ◽

W H Navarro ◽

D L Confer ◽

M Jagasia

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Aplastic Anemia ◽

Peripheral Blood ◽

Severe Aplastic Anemia ◽

Unrelated Donor ◽

Peripheral Blood Stem Cells ◽

Blood Stem Cells ◽

Stem Cell Donation

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Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2016.01.012 ◽

2016 ◽

Vol 22 (5) ◽

pp. 932-940 ◽

Cited By ~ 19

Author(s):

Rajat Kumar ◽

Fumihiko Kimura ◽

Kwang Woo Ahn ◽

Zhen-Huan Hu ◽

Yachiyo Kuwatsuka ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Aplastic Anemia ◽

Peripheral Blood ◽

Severe Aplastic Anemia ◽

Peripheral Blood Stem Cells ◽

Blood Stem Cells ◽

Matched Sibling ◽

Economic Regions

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Feasibility of reduced-dose posttransplant cyclophosphamide and cotransplantation of peripheral blood stem cells and umbilical cord-derived mesenchymal stem cells for SAA

Scientific Reports ◽

10.1038/s41598-020-80531-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yingling Zu ◽

Jian Zhou ◽

Yuewen Fu ◽

Baijun Fang ◽

Xinjian Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Peripheral Blood ◽

Control Cohort ◽

Peripheral Blood Stem Cells ◽

Hematopoietic Stem ◽

Reduced Dose ◽

Blood Stem Cells ◽

The Times

AbstractPosttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P < 0.05). The cumulative incidence of acute GVHD (aGVHD) at day + 100 (15.4%) was lower than that in the MSD-control cohort (P = 0.050). No patient developed chronic GVHD (cGVHD). The 1-year overall survival (OS) and event-free survival (EFS) rates were 100% and 92.3%. In haplo-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the haplo-control cohort (P < 0.05). The cumulative incidences of aGVHD at day + 100 and 1-year cGVHD were 31.8% and 18.2%, and the 1-year OS and EFS rates were 81.8% and 66.9%. Reduced-dose PTCy and cotransplantation of PBSCs and UC-MSCs is an acceptable alternative to patients with SAA.

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Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia

BMC Pediatrics ◽

10.1186/s12887-021-02562-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yang Lan ◽

Fang Liu ◽

Lixian Chang ◽

Lipeng Liu ◽

Yingchi Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Aplastic Anemia ◽

Umbilical Cord ◽

Pediatric Patients ◽

Statistical Significance ◽

Severe Aplastic Anemia ◽

Control Group ◽

Open Label ◽

Cell Counts

Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).

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