See the published version of this article at Stem Cell Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Zhao Wang
Capital Medical University Affiliated Beijing Friendship Hospital
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Stem Cell Research & Therapy.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory state. Epstein–Barr virus (EBV) infection associated HLH (EBV-HLH) is one of the most common secondary HLH and suffers a very poor prognosis. Allo-HSCT is often required for refractory EBV-HLH, but some patients still cannot proceed to the next allo-HSCT due to various factors. This study aimed to observe the efficacy of HLA-mismatched granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (GPBSCs) infusion for refractory EBV-HLH.
Methods: A retrospective case-control study of refractory EBV-HLH patients with GPBSCs infusion from HLA-mismatched donors after chemotherapy (as GPBSCs group) and sole chemotherapy (as control group) was performed. Efficacy was evaluated 2 and 4 weeks and all patients were followed up until 1 March 2018.
Results: There were 18 cases who accepted infusion between March 2016 and Sep 2017 and 19 were randomly selected from refractory EBV-HLH patients who underwent salvage therapy during the same period for the control group. In GPBSCs group, WBC (p=0.017), Fbg (p=0.040), ferritin (p=0.039) improved significantly after treatment. The overall response rate was 66.7% (CR 22.2%, PR 44.4%). However, there is no significant differences in changes of WBC, HGB, PLT, TG, Fbg, Ferritin, AST, ALT, T-bil between two groups. Only the Fbg level was recovered better in the GPBSCs infusion group (p=0.003). In the GPBSCs group, EBV-DNA decreased significantly after 2 weeks (p=0.001) and 4 weeks (p=0.012) after treatment, and the effect of the decrease was significantly better than that of the chemotherapy alone group in 2 weeks but not 4 weeks (p2w=0.011, p4w=0.145). The median survival time in the infusion group was 20.4 weeks [95%CI 10.9, 29.9], and the median survival time in the control group was 10.8 weeks [95%CI 0-24.34]. In the short-term, the infusion group’s survival rate was better (2-month 88.89% vs. 52.63%, p=0.008; 3-month 83.33% vs. 47.09%, p=0.012), but there was no difference in OS (p=0.287).
Conclusions: Infusing GPBSCs combined with chemotherapy is effective, especially in decreasing EBV-DNA, performs better than chemotherapy alone, and improve short term survival rate. GPBSCs infusion is suggested as a bridging treatment method to allo-HSCT.
Keywords
hemophagocytic lymphohistiocytosis, Epstein-Barr virus, GPBSCs infusion, salvage therapy
Figure 1
Figure 2
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Published
On 01 Jul, 2020
No community comments so far
Editorial decision: Accept
On 12 Jun, 2020
Review #1 received
Received 30 May, 2020
Reviewer #1 agreed
On 29 May, 2020
Reviewers invited
Invitations sent on 28 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
Editor invited
On 23 May, 2020
Version 2
Posted 13 May, 2020
No comments provided
Editorial decision: Minor Revision
On 09 May, 2020
Reviewers invited
Invitations sent on 01 May, 2020
Reviewer #1 agreed
On 01 May, 2020
Review #1 received
Received 01 May, 2020
Editor assigned
On 30 Apr, 2020
Submission checks complete
On 29 Apr, 2020
Editor invited
On 29 Apr, 2020
No comments provided
Editorial decision: Minor Revision
On 29 Mar, 2020
Review #3 received
Received 18 Mar, 2020
Reviewer #3 agreed
On 10 Mar, 2020
Review #1 received
Received 18 Feb, 2020
Review #2 received
Received 18 Feb, 2020
Reviewer #2 agreed
On 11 Feb, 2020
Reviewers invited
Invitations sent on 09 Feb, 2020
Reviewer #1 agreed
On 09 Feb, 2020
Editor assigned
On 05 Feb, 2020
Submission checks complete
On 04 Feb, 2020
Editor invited
On 04 Feb, 2020
First submitted
On 02 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
Learn more about our company.
This preprint is under consideration at Stem Cell Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Zhao Wang
Capital Medical University Affiliated Beijing Friendship Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Published
On 01 Jul, 2020
No community comments so far
Editorial decision: Accept
On 12 Jun, 2020
Review #1 received
Received 30 May, 2020
Reviewer #1 agreed
On 29 May, 2020
Reviewers invited
Invitations sent on 28 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
Editor invited
On 23 May, 2020
Version 2
Posted 13 May, 2020
No comments provided
Editorial decision: Minor Revision
On 09 May, 2020
Reviewers invited
Invitations sent on 01 May, 2020
Reviewer #1 agreed
On 01 May, 2020
Review #1 received
Received 01 May, 2020
Editor assigned
On 30 Apr, 2020
Submission checks complete
On 29 Apr, 2020
Editor invited
On 29 Apr, 2020
No comments provided
Editorial decision: Minor Revision
On 29 Mar, 2020
Review #3 received
Received 18 Mar, 2020
Reviewer #3 agreed
On 10 Mar, 2020
Review #1 received
Received 18 Feb, 2020
Review #2 received
Received 18 Feb, 2020
Reviewer #2 agreed
On 11 Feb, 2020
Reviewers invited
Invitations sent on 09 Feb, 2020
Reviewer #1 agreed
On 09 Feb, 2020
Editor assigned
On 05 Feb, 2020
Submission checks complete
On 04 Feb, 2020
Editor invited
On 04 Feb, 2020
First submitted
On 02 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Stem Cell Research & Therapy.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory state. Epstein–Barr virus (EBV) infection associated HLH (EBV-HLH) is one of the most common secondary HLH and suffers a very poor prognosis. Allo-HSCT is often required for refractory EBV-HLH, but some patients still cannot proceed to the next allo-HSCT due to various factors. This study aimed to observe the efficacy of HLA-mismatched granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (GPBSCs) infusion for refractory EBV-HLH.
Methods: A retrospective case-control study of refractory EBV-HLH patients with GPBSCs infusion from HLA-mismatched donors after chemotherapy (as GPBSCs group) and sole chemotherapy (as control group) was performed. Efficacy was evaluated 2 and 4 weeks and all patients were followed up until 1 March 2018.
Results: There were 18 cases who accepted infusion between March 2016 and Sep 2017 and 19 were randomly selected from refractory EBV-HLH patients who underwent salvage therapy during the same period for the control group. In GPBSCs group, WBC (p=0.017), Fbg (p=0.040), ferritin (p=0.039) improved significantly after treatment. The overall response rate was 66.7% (CR 22.2%, PR 44.4%). However, there is no significant differences in changes of WBC, HGB, PLT, TG, Fbg, Ferritin, AST, ALT, T-bil between two groups. Only the Fbg level was recovered better in the GPBSCs infusion group (p=0.003). In the GPBSCs group, EBV-DNA decreased significantly after 2 weeks (p=0.001) and 4 weeks (p=0.012) after treatment, and the effect of the decrease was significantly better than that of the chemotherapy alone group in 2 weeks but not 4 weeks (p2w=0.011, p4w=0.145). The median survival time in the infusion group was 20.4 weeks [95%CI 10.9, 29.9], and the median survival time in the control group was 10.8 weeks [95%CI 0-24.34]. In the short-term, the infusion group’s survival rate was better (2-month 88.89% vs. 52.63%, p=0.008; 3-month 83.33% vs. 47.09%, p=0.012), but there was no difference in OS (p=0.287).
Conclusions: Infusing GPBSCs combined with chemotherapy is effective, especially in decreasing EBV-DNA, performs better than chemotherapy alone, and improve short term survival rate. GPBSCs infusion is suggested as a bridging treatment method to allo-HSCT.
Figure 1
Figure 2
Loading...