The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study

Abstract

In this open-label randomized clinical trial, HLA-identical sibling-matched hematopoietic stem cells (HSC) were transplanted (non-MSCs group, n ¼ 15) or cotransplanted with mesenchymal stem cells (MSCs) (MSCs group, n ¼ 10) in hematologic malignancy patients. The median number of MSCs infused was 3.4 Â 10 5 kg À1 (range, 0.3-15.3 Â 10 5 kg À1 ). MSCs infusions were well tolerated. The median time to neutrophil engraftment (absolute neutrophil count 40.5 Â 10 9 l À1 ) was 16 days for MSCs group and 15 days for non-MSCs group. The median time to platelet engraftment (platelet count 450 Â 10 9 l À1 ) was 30 and 27 days, respectively. Grades II-IV acute graft-versus-host disease (GVHD) was observed respectively, in one (11.1%) and eight (53.3%) evaluable patients. Chronic GVHD was found in one (14.3%) and four (28.6%) evaluable patients. The number of patients who relapsed were six (60.0%) and three (20.0%), and the 3-year disease-free survivals were 30.0 and 66.7%, respectively. Thus cotransplantation of MSCs and HSCs may prevent GVHD, but the relapse rate is obviously higher than the control group. We conclude that use of MSCs must be handled with extreme caution before a large-scale clinical trial is performed.

Cotransplantation of mesenchymal cells and a higher relapse rate: a role for HLA-G molecules?

“…We have read with interest the paper by Ning et al 1 reporting a correlation between the cotransplantation of mesenchymal stem cells (MSCs) in allogeneic haemapoietic stem cell transplantation and a higher recurrence rate of malignant haematologic diseases. The authors concluded their paper by suggesting that 'the use of MSCs must be handled with extreme caution before a large-scale trial is performed'.…”

“…1,2 We further proposed that Notch pathway inhibition in MM cells is a promising new therapeutic approach as it controls Notch ligand-induced myeloma cell growth. 1 We and others provided evidence that Notch receptors are expressed on primary MM cells and that Notch ligands on MM and bone marrow stroma cells activate Notch signaling through homotypic as well as heterotypic interactions in MM cells. 1,3 In addition, Houde et al 4 published that the Notch ligand, JAG2, is overexpressed in myeloma cells and activates Notch signaling in bone marrow Letters …”

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

“…Although these encouraging results support an effect of infused MSCs in the prevention of GVHD, an increased occurrence of leukemia relapses has been reported because of the inhibition of leukemic cell-specific T-cell responses. 85 MSCs from human autoimmune disease Autologous BM-derived MSCs have been shown to be potently antiproliferative to stimulated T-cells from normal participants and autoimmune (RA, SSc, Sjoegren's, SLE) patients, 86 and in SSc patients these MSCs were normal with respect to proliferation, clonogenicity and differentiation to bone and fat. 87 However, one group has shown defective differentiation into endothelial precursors in BM-derived MSCs from SSc patients, 88 which should be considered when choosing autologous or allogeneic MSC sources for SSc treatment.…”

Stromal cells–are they really useful for GVHD?

“…Co-transplantation of BM-MSCs was found to be associated with a higher rate of occurrence of leukemic relapse. 24 BM-MSCs have also been suggested to be involved in the progression of oncogenesis in multiple myeloma, 25 which can be mediated by MSC-derived exosomes. 26 The anticipation of using BM-MSCs as GVHD treatment dramatically declined in the scientific community when the negative results of the randomized clinical trial by Osiris Therapeutics were released.…”