Shahrukh Hashmi1, Mohammad Ahmed2, M Hassan Murad3, Mark R Litzow4, Roberta H Adams5, Lynne M Ball6, Vinod K Prasad7, Partow Kebriaei8, Olle Ringden9. 1. Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address: Hashmi.shahrukh@mayo.edu. 2. Department of Internal Medicine, Providence Hospital, Washington, DC, USA. 3. Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA. 4. Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. 5. Department of Pediatrics, Phoenix Children's Hospital, Phoenix, AZ, USA. 6. Department of Pediatrics, LUMC, Leiden, Netherlands. 7. Department of Pediatrics, Duke University, Durham, NC, USA. 8. Department of Stem Cell Transplant, M D Anderson Cancer Center, Houston, TX, USA. 9. Department of Laboratory Medicine, Karolinska Institute, Solna, Sweden.
Abstract
BACKGROUND: Graft-versus-host disease (GVHD) is the major limitation of allogeneic haemopoietic stem-cell transplantation (HSCT), for which no approved treatments are available. Use of mesenchymal stromal cells (MSCs) has become standard practice in some European countries, but controversy exists for their benefit. The aim of this meta-analysis was to analyse available evidence for the benefit of MSC treatments in steroid-resistant acute GVHD. METHODS: We did a systematic review and meta-analysis to assess response to and survival after MSC treatment in patients with steroid-refractory acute GVHD. We searched MEDLINE, Embase, Ovid, and Cochrane Central databases for published studies, and we used ClinicalTrials.gov and other websites to find unpublished studies and conference abstracts. We included prospective and retrospective studies in which MSCs were administered to patients with steroid-refractory acute GVHD. Data were extracted independently by two investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies because of anticipated heterogeneity. Our primary outcome was survival at 6 months from the first infusion of MSCs. FINDINGS: We identified 628 citations with our search, of which 610 were excluded after review and a further five did not contain pertinent data. Thus, our meta-analysis included 13 non-randomised studies at moderate risk of bias, comprising a total of 336 patients. Six studies provided data for the primary outcome analysis (119 patients). Survival at 6 months after MSC treatment was 63% (95% CI 50-74; I(2)=41%). Survival did not differ with respect to age, MSC culture medium, or dose of MSCs delivered. INTERPRETATION: Available evidence suggests that infusion of MSCs could be an acceptable treatment for patients with steroid-refractory acute GVHD. Randomised clinical trials are needed urgently to assess different treatment modalities for steroid-refractory acute GVHD. FUNDING: None.
BACKGROUND:Graft-versus-host disease (GVHD) is the major limitation of allogeneic haemopoietic stem-cell transplantation (HSCT), for which no approved treatments are available. Use of mesenchymal stromal cells (MSCs) has become standard practice in some European countries, but controversy exists for their benefit. The aim of this meta-analysis was to analyse available evidence for the benefit of MSC treatments in steroid-resistant acute GVHD. METHODS: We did a systematic review and meta-analysis to assess response to and survival after MSC treatment in patients with steroid-refractory acute GVHD. We searched MEDLINE, Embase, Ovid, and Cochrane Central databases for published studies, and we used ClinicalTrials.gov and other websites to find unpublished studies and conference abstracts. We included prospective and retrospective studies in which MSCs were administered to patients with steroid-refractory acute GVHD. Data were extracted independently by two investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies because of anticipated heterogeneity. Our primary outcome was survival at 6 months from the first infusion of MSCs. FINDINGS: We identified 628 citations with our search, of which 610 were excluded after review and a further five did not contain pertinent data. Thus, our meta-analysis included 13 non-randomised studies at moderate risk of bias, comprising a total of 336 patients. Six studies provided data for the primary outcome analysis (119 patients). Survival at 6 months after MSC treatment was 63% (95% CI 50-74; I(2)=41%). Survival did not differ with respect to age, MSC culture medium, or dose of MSCs delivered. INTERPRETATION: Available evidence suggests that infusion of MSCs could be an acceptable treatment for patients with steroid-refractory acute GVHD. Randomised clinical trials are needed urgently to assess different treatment modalities for steroid-refractory acute GVHD. FUNDING: None.
Authors: U Salmenniemi; M Itälä-Remes; J Nystedt; M Putkonen; R Niittyvuopio; K Vettenranta; M Korhonen Journal: Bone Marrow Transplant Date: 2016-12-12 Impact factor: 5.483
Authors: G M Dotoli; G C De Santis; M D Orellana; K de Lima Prata; S R Caruso; T R Fernandes; V A Rensi Colturato; A T Kondo; N Hamerschlak; B P Simões; D T Covas Journal: Bone Marrow Transplant Date: 2017-03-13 Impact factor: 5.483
Authors: Myriam N Bouchlaka; Andrea B Moffitt; Jaehyup Kim; John A Kink; Debra D Bloom; Cassandra Love; Sandeep Dave; Peiman Hematti; Christian M Capitini Journal: Biol Blood Marrow Transplant Date: 2017-02-28 Impact factor: 5.742
Authors: Partow Kebriaei; Jack Hayes; Andrew Daly; Joseph Uberti; David I Marks; Robert Soiffer; Edmund K Waller; Elizabeth Burke; Donna Skerrett; Elizabeth Shpall; Paul J Martin Journal: Biol Blood Marrow Transplant Date: 2019-09-07 Impact factor: 5.742