Am J Blood Res 2013;3(3):225-238
Original Article
Treatment of severe steroid resistant acute GVHD with mesenchymal stromal
cells (MSC)
Igor B Resnick, Claudine Barkats, Michael Y Shapira, Polina Stepensky, Allan I Bloom, Avichai Shimoni, David Mankuta, Nira
Var-da-Bloom, Lyudmila Rheingold, Moshe Yeshurun, Bella Bielorai, Amos Toren, Tsila Zuckerman, Arnon Nagler, Reuven Or
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center,
Jerusalem; Depart-ment of Pediatric Hemato-oncology, Hadassah-Hebrew University Medical Center, Jerusalem; Department
of Vascular and Interventional Radiology, Hadassah-Hebrew University Medical Center, Jerusalem; Hematology Division,
Chaim Sheba Medical Center, Tel Hashomer; Department of Obstetrics and Gynecology, Hadassah-Hebrew University
Medical Center, Jerusalem; Bone Marrow Transplantation Unit, Davidoff Center - Rabin Medical Center, Petah Tikva; Pediatric
Hemato-oncology, Chaim Sheba Medical Center, Tel Hashomer; Bone Marrow Transplantation, Rambam Medical Center,
Haifa
Received May 19, 2013; Accepted August 6, 2013; Epub August 19, 2013; Published August 30, 2013
Abstract: Background: Several studies revealed that MSC from human bone marrow can downregulate graft-versus-host
disease (GVHD) after allogeneic HSCT. Methods: Herein we present 50 patients with acute GVHD who got 74 (1-4) MSC
infusions for 54 separate episodes of aGVHD. Results: aGVHD was defined as steroid resistant grade IV aGVHD in 42 cases.
The major presentation was gastrointestinal GVHD; two (n=18) or more (n=21) systems were involved in the majority of
cases. The 1st infusion with MSC was given on day +27 (range, 1 to 136); d+45 (range, +11 to +150) post diagnosis of aGVHD
and HSCT, respectively. In 2/3 of the cases treatment was performed with frozen stocked MSCs; in 62 cases early passages
(1-3) were used. The median number of infused cells was 1.14±0.47 million per kg in the first injection and up to 4.27
(1.70±1.10) millions in total. The two patients with aggressive liver GVHD received MSCs injections intra hepatic arteries
without changes of blood flow or evidence cytolysis, but also without a visible effect. Disease free survival at 3.6 years was
56%. We observed better overall survival in patients with GVHD grade <4, in responders to the 1st treatment with MSC, and in
pediatric group. The multivariate analysis demonstrated independent influence on survival of initial response and younger
age. There were no immediate or late toxicity or side effects. Conclusion: Injection of MSCs seems to be a promising and safe
treatment of GVHD. The encouraging results obviously should be confirmed in a randomized prospective study.
(AJBR1305002).
Keywords: Mesenchymal stromal cells (MSC), mesenchymal stem cells, hematopoietic stem cell transplantation, graft versus
host disease, steroid resistance
Address correspondence to: Dr. Igor B Resnick, Department of Bone Marrow Transplantation and Cancer Immunotherapy,
Hadassah Hebrew University Medical Center, Sharett Bld., 3rd floor PO Box 12000, Jerusalem ISRAEL 91120. Tel:
972-2-6778353; Fax: 972-2-6422731; E-mail: gashka@hadassah.org.il
Original Article
Treatment of severe steroid resistant acute GVHD with mesenchymal stromal
cells (MSC)
Igor B Resnick, Claudine Barkats, Michael Y Shapira, Polina Stepensky, Allan I Bloom, Avichai Shimoni, David Mankuta, Nira
Var-da-Bloom, Lyudmila Rheingold, Moshe Yeshurun, Bella Bielorai, Amos Toren, Tsila Zuckerman, Arnon Nagler, Reuven Or
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center,
Jerusalem; Depart-ment of Pediatric Hemato-oncology, Hadassah-Hebrew University Medical Center, Jerusalem; Department
of Vascular and Interventional Radiology, Hadassah-Hebrew University Medical Center, Jerusalem; Hematology Division,
Chaim Sheba Medical Center, Tel Hashomer; Department of Obstetrics and Gynecology, Hadassah-Hebrew University
Medical Center, Jerusalem; Bone Marrow Transplantation Unit, Davidoff Center - Rabin Medical Center, Petah Tikva; Pediatric
Hemato-oncology, Chaim Sheba Medical Center, Tel Hashomer; Bone Marrow Transplantation, Rambam Medical Center,
Haifa
Received May 19, 2013; Accepted August 6, 2013; Epub August 19, 2013; Published August 30, 2013
Abstract: Background: Several studies revealed that MSC from human bone marrow can downregulate graft-versus-host
disease (GVHD) after allogeneic HSCT. Methods: Herein we present 50 patients with acute GVHD who got 74 (1-4) MSC
infusions for 54 separate episodes of aGVHD. Results: aGVHD was defined as steroid resistant grade IV aGVHD in 42 cases.
The major presentation was gastrointestinal GVHD; two (n=18) or more (n=21) systems were involved in the majority of
cases. The 1st infusion with MSC was given on day +27 (range, 1 to 136); d+45 (range, +11 to +150) post diagnosis of aGVHD
and HSCT, respectively. In 2/3 of the cases treatment was performed with frozen stocked MSCs; in 62 cases early passages
(1-3) were used. The median number of infused cells was 1.14±0.47 million per kg in the first injection and up to 4.27
(1.70±1.10) millions in total. The two patients with aggressive liver GVHD received MSCs injections intra hepatic arteries
without changes of blood flow or evidence cytolysis, but also without a visible effect. Disease free survival at 3.6 years was
56%. We observed better overall survival in patients with GVHD grade <4, in responders to the 1st treatment with MSC, and in
pediatric group. The multivariate analysis demonstrated independent influence on survival of initial response and younger
age. There were no immediate or late toxicity or side effects. Conclusion: Injection of MSCs seems to be a promising and safe
treatment of GVHD. The encouraging results obviously should be confirmed in a randomized prospective study.
(AJBR1305002).
Keywords: Mesenchymal stromal cells (MSC), mesenchymal stem cells, hematopoietic stem cell transplantation, graft versus
host disease, steroid resistance
Address correspondence to: Dr. Igor B Resnick, Department of Bone Marrow Transplantation and Cancer Immunotherapy,
Hadassah Hebrew University Medical Center, Sharett Bld., 3rd floor PO Box 12000, Jerusalem ISRAEL 91120. Tel:
972-2-6778353; Fax: 972-2-6422731; E-mail: gashka@hadassah.org.il
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