scholarly journals Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation

2017 ◽  
Vol 52 (12) ◽  
pp. 1637-1642 ◽  
Author(s):  
C Almici ◽  
C Skert ◽  
B Bruno ◽  
A Bianchetti ◽  
R Verardi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Endothelial Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Count ◽  
Cell Transplantation ◽  
Endothelial Damage ◽  
Hematopoietic Stem ◽  
Endothelial Cell Count ◽  
Reliable Marker

Prophylaxis Against Endothelial Damage Using Recombinant Human Soluble Thrombomodulin (rTM) In Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4523-4523
Author(s):  
Kazuyoshi Ishii ◽  
Michiomi Shimizu ◽  
Shosaku Nomura
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Inflammatory Cytokines ◽  
Marrow Transplant ◽  
Endothelial Damage ◽  
Hematopoietic Stem ◽  
Soluble Thrombomodulin ◽  
Recombinant Human Soluble Thrombomodulin

Abstract Abstract 4523 Thrombomodulin (TM) is a vascular endothelial cell protein which controls coagulation. Recombinant human soluble thrombomodulin (rTM) is a new agent for treatment of disseminated intravascular coagulation. rTM also exhibited anti-inflammatory effects and ameliorated endothelial injuries in our pilot study where rTM was administered to a patient during cord blood transplantation (CBT) as a prophylaxis against veno-occulsive disease (VOD). Major complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT) triggered by endothelial damage not only include VOD, but also thrombotic microangiopathy (TMA). Two case reports showed that rTM dramatically ameliorated VOD and TMA (Bone Marrow Transplant. 2010;45:783 and 803, respectively) following allo-peripheral blood stem cell transplantation (PBSCT). In the present study, we examined the effectiveness of rTM as a prophylaxis against endothelial damage in patients receiving allo-HSCT. We evaluated seven patients (age range 50–72 y; median 61 y) with hematological malignancies receiving allo-HSCT at our institute from July 2009 to February 2010. Each patient provided written informed consent prior to inclusion in the study. One patient received conventional SCT, and the others received reduced-intensity SCT using a fludarabine-based conditioning regimen. Two patients were transplanted from related PBSC and the others were transplanted from unrelated CB using rabbit anti-thymoglobulin (rATG) before transplantation as a prophylaxis against graft-versus-host disease (GVHD). Four patients received rTM as a prophylaxis against endothelial damage from day −6 to day 30 (long period) based on the day they received transplantation, and three patients received rTM from day 6 to day 19 (short period) and heparin on the other days. IL-1β, IL-6, IL-8, TNFα, HMGB1, RANTES, SDF-1, E-selectin, and VCAM-1 levels were measured using ELISA before and after rTM administration, and changes were evaluated using a two-tailed Wilcoxon test. IL-1β (p=0.018), IL-6 (p=0.018), IL-8 (p=0.018), TNFα (p=0.017), RANTES (p=0.017), HMGB1 (p=0.018) decreased significantly following rTM administration. No significant change in CRP level, considered to affect cytokine measurements, was observed (p=0.063), and neither E-selectin nor VCAM-1 level increased. No significant differences were observed between changes in these parameters among patients treated with rTM during the long and short periods. All patients achieved engraftment by the mean post-transplantation day as previously reported (range 16–29 days; median 22 days). Of the seven patients, only one developed VOD, and no patients developed TMA or acute GVHD. Pre-engraftment immune reaction was not observed in any patients who underwent CBT. Four patients were alive and three patients were deceased as of July 30, 2010, with main causes of death being cerebral hemorrhage, VOD and relapse of primary disease, respectively. Median event-free survival and overall survival after transplantation were 54 days (26–283 days) and 168 days (55–283 days), respectively. rTM showed potent inhibitory effects on inflammatory cytokines, including TNFα, IL-1β, IL-6, IL-8, and prevented the release of HMGB1 through absorption of alarmin. It has been reported that rATG contributes to an increase in inflammatory cytokines; however, rTM treatment prohibited these increases among patients receiving CBT. We previously observed increased levels of E-selectin and VCAM-1 after allo-HSCT (Biol Blood Marrow Transplant. 2008;14:766); however, rTM prohibited these increases in the present study, indicating that it prevents allo-HSCT-induced endothelial injuries. One patient died of cerebral hemorrhage 26 days after the end of prophylactic administration of rTM. An association between this major bleeding event and rTM administration is unlikely because the t1/2 of rTM is approximately 20 h. One patient developed fatal VOD, despite controlled cytokine levels. This patient underwent CBT on primary disease progression. We speculated that disease progression in this case contributed to the development of VOD in spite of prophylactic administration of rTM. Although this study involved a small number patients and median follow-up was relatively short, given the present findings, rTM may prevent VOD and TMA following allo-HSCT. Disclosures: No relevant conflicts of interest to declare.

Circulating endothelial cells as a marker of endothelial damage in allogeneic hematopoietic stem cell transplantation

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3603-3605 ◽  
Author(s):  
Alexander Woywodt ◽  
Johanna Scheer ◽  
Lothar Hambach ◽  
Stefanie Buchholz ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Endothelial Damage ◽  
Circulating Endothelial Cells ◽  
Hematopoietic Stem ◽  
Cell Numbers ◽  
Conditioning Regimens

Abstract Damage to endothelial cells is the common feature of vascular disorders associated with hematopoietic stem cell transplantation (HSCT). Elevated numbers of circulating endothelial cells reflect the extent of endothelial damage in a variety of disorders but their use in HSCT has not been investigated so far. We studied 39 patients undergoing allogeneic HSCT with different conditioning regimens and 22 healthy controls. Circulating endothelial cells were enumerated with immunomagnetic isolation during the course of HSCT. After conditioning, cell numbers were significantly elevated (median 44 cells/mL) compared with baseline (median 16 cells/mL) and controls (median 8 cells/mL). Patients who received radiation had an earlier peak when compared with patients who received chemotherapy. Patients who received reduced-intensity conditioning had significantly lower cell numbers (median 24 cells/mL) than those who received standard conditioning. These observations provide a novel marker to investigate microvascular endothelial damage and the effects of different conditioning regimens in patients undergoing HSCT. (Blood. 2004;103:3603-3605)

Longitudinal Corneal Endothelial Cell Changes in Patients Undergoing Hematopoietic Stem Cell Transplantation

Cornea ◽  
2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Marco Pellegrini ◽  
Giuseppe Giannaccare ◽  
Federico Bernabei ◽  
Fabiana Moscardelli ◽  
Mariarosaria Sessa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Endothelial Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Corneal Endothelial Cell ◽  
Hematopoietic Stem ◽  
Cell Changes

scholarly journals Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 325
Author(s):  
Maciej Majcherek ◽  
Agnieszka Matkowska-Kocjan ◽  
Donata Szymczak ◽  
Magdalena Karasek ◽  
Agnieszka Szeremet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Count ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Univariate Analysis ◽  
Humoral Response ◽  
Hematopoietic Stem

Vaccination against SARS-CoV-2 is currently the best tool in the fight against the COVID-19 pandemic. However, there are limited data on its efficacy and safety after hematopoietic stem cell transplantation (HCT). We present the results of a prospective analysis of the humoral response to two doses of BNT162b2 mRNA vaccine in 93 adult patients, including 29 after autologous HCT (autoHCT) and 64 after allogeneic HCT (alloHCT). Positive anti-SARS-CoV-2 antibodies were detected before vaccination in 25% of patients despite a negative medical history of COVID-19. Seroconversion after vaccination was achieved in 89% of patients after alloHCT and in 96% after autoHCT, without grade 3/4 adverse events. Post-vaccination anti-SARS-CoV-2 antibody level correlated with the time from transplant and absolute B-cell count at the vaccination. In univariate analysis restricted to the alloHCT group, short time since transplantation, low B-cell count, low intensity conditioning, GvHD, and immunosuppressive treatment at the vaccination were associated with lack of seroconversion. In the multivariate model, the only negative predictor of seroconversion remained treatment with calcineurin inhibitor (CNI). In conclusion, the BNT162b2 mRNA vaccine is highly immunogenic in patients after HCT, but treatment with CNI at the time of vaccination has a strong negative impact on the humoral response

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