Safety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

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dc.authorid0000-0002-2035-9462
dc.contributor.authorKeklik, Muzaffer
dc.contributor.authorDeveci, Burak
dc.contributor.authorÇelik, Serhat
dc.contributor.authorDeniz, Kemal
dc.contributor.authorGönen, Zeynep Burçin
dc.contributor.authorZararsız, Gökmen
dc.contributor.authorSaba, Rabin
dc.contributor.authorÜnal, Ali
dc.date.accessioned2024-02-22T06:21:38Z
dc.date.available2024-02-22T06:21:38Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, İç Hastalıkları Ana Bilim Dalı
dc.description.abstractGraft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) x 10(6)/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) x 10(6)/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had >= 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had >= 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD.
dc.identifier.citationKeklik, M., Deveci, B., Çelik, S., Deniz, K., Gönen, Z. B., Zararsız, G. ... Ünal, A. (2023). Safety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Annals of Hematology, 102(6), 1537-1547. https://dx.doi.org/10.1007/s00277-023-05216-3
dc.identifier.doi10.1007/s00277-023-05216-3
dc.identifier.endpage1547
dc.identifier.issn0939-5555
dc.identifier.issn1432-0584
dc.identifier.issue6
dc.identifier.pmid37067556
dc.identifier.scopus2-s2.0-85153111378
dc.identifier.scopusqualityQ1
dc.identifier.startpage1537
dc.identifier.urihttps://dx.doi.org/10.1007/s00277-023-05216-3
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12299
dc.identifier.volume102
dc.identifier.wos000970703200001en_US
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorKaynar, Leylagül
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofAnnals of Hematologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAllogeneic Hematopoietic Stem Cell Transplantation
dc.subjectGraft-Versus-Host Disease
dc.subjectMesenchymal Stromal Cells
dc.titleSafety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation
dc.typeArticle

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