Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in Allo-SCT for leukemia patients with high relapse risk: an observational cohort study

Schleuning, Michael; Judith, Dirk; Jedlickova, Z.; Stübig, Thomas; Heshmat, M.; Baurmann, Herrad; Schwerdtfeger, Rainer

doi:10.1038/bmt.2008.377

Cited by 48 publications

(38 citation statements)

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“…[13][14][15][16] To overcome these limitations, several novel strategies are currently under investigation. The synergistic effects of mTor (mammalian target of rapamycin) and calcineurin inhibitors 17 or mTor inhibitors and mycophenolate mofetil 18 have been explored in prophylaxis regimens. Similarly, specific anti-T-and B-cell antibodies (such as alemtuzumab, 19 antithymocyte globulin, 20 rituximab 21,22 ) or antibodies against soluble GvHD effectors (such as infliximab and etanercept; see below) have been tested to prevent GvHD with some success, counterbalanced by a high incidence of severe opportunistic infections and disease relapse.…”

Section: Prospectsmentioning

confidence: 99%

Progress and prospects: graft-versus-host disease

et al. 2010

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Section: Prospectsmentioning

confidence: 99%

Progress and prospects: graft-versus-host disease

et al. 2010

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“…Seventy-five percent of the patients were alive after a median follow-up of 10 months. 93 In contrast, when combined with CNIs, various groups recently reported that sirolimus-based GVHD prophylaxis in patients receiving myeloablative or RIC-SCT induces severe toxicities, such as transplantation associated microangiopathy or sinusoidal obstructive syndrome. 94,95 When used for treatment but not prophylaxis of GVHD, sirolimus appears to be a promising agent even in steroid-refractory aGVHD.…”

Section: In Vivo Treg Expansion-gvhd Treatment and Prevention By Mtormentioning

confidence: 99%

“…As an example, when combined with mycophenolate mofetil and anti-thymocyte globulin (ATG), CNIs can be replaced by sirolimus within the FLAMSA-RIC protocol. 93 Using this approach, 21% of patients developed grade II-IV aGVHD, 30% cGVHD and nonrelapse mortality rate was 14%. Of note, in this setting sirolimus did not induce transplant-associated thrombotic microangiopathy (TA-TMA).…”

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confidence: 99%

Novel treatment concepts for graft-versus-host disease

Wolf

Lilienfeld‐Toal

Wolf

et al. 2012

Blood

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Acute and chronic graft-versus-host disease (GVHD) are potentially lethal complications after stem cell transplantation (SCT). Steroids are the appropriate firstline treatment for both. However, if patients do not adequately benefit from steroid therapy, mortality is high and standardized treatment algorithms are lacking. This is mainly because of limited data from prospective, randomized clinical trials. In addition, most of the available treatment options only induce clinical benefits in a limited proportion of patients. Thus, there is an urgent clinical need to develop more potent immunosuppressive treatment strategies for patients suffering from acute or chronic steroidrefractory GVHD while maintaining the graft versus tumor effect to avoid a potential rise in relapse-related mortality. The increasing knowledge about host-as well as donor-derived variables favoring GVHD development and the increasing armamentarium of immune-modulatory agents entering preclinical and clinical research will probably allow more effective treatment of GVHD in the future. This review describes novel developments in the treatment of steroid-refractory GVHD, with a special focus on the rationale behind promising pharmacologic compounds or up-coming cellular therapies. (Blood. 2012;119(1):16-25) IntroductionIn 1957, E. D. Thomas and colleagues first described the infusion of bone marrow cells into patients after prior radio-or chemotherapy in their seminal New England Journal of Medicine paper. 1 This work initiated 5 decades of basic and clinical research in the field of stem cell transplantation (SCT) and nowadays SCT is the treatment of choice for many malignant and benign hematopoietic diseases. It was known before 1957 from preclinical animals studies that tranplantation of splenocytes from noncongenic donor strains, while facilitating hematopoietic recovery, induced a severe illness, characterized by progressive weight loss, hunched posture, and diarrhea. 2 In the following years it has become clear that this was not primarily because of the conditioning therapy, but that it was an immune-mediated syndrome, which is now referred to as graft versus host disease (GVHD). GVHD nowadays remains not only a major cause of non-relapse mortality, but also induces substantial morbidity, which can severely affect quality of life. GVHD is a very complex immunologic disorder characterized by a plethora of clinical presentations. 3 Importantly, the predominant use of peripheral blood stem cells (PBSC) rather than bone marrow (BM) and the increasing proportion of reduced intensity conditioning (RIC) regimens has made multifacetted chronic GVHD (cGVHD) more and more clinically relevant. 4,5 The incidence of GVHD thus depends on several variables, including the donor type (related versus unrelated, matched versus mismatched or haploidentical), the type of conditioning (total boby irradiation [TBI] versus nonTBI), the donor's sex (female or male, versus all other sex combinations) and the stem cell source (PBSC versus BM). 6 Despite the inc...

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“…Among the various immunosuppressive drugs (ISDs), cyclosporin A (CsA), rapamycin (Rapa) and mycophenolate mofetil (MMF) have successfully been applied for the prevention of GVHD (Cutler et al, 2007;Haentzschel et al, 2008;Neumann et al, 2005;Schleuning et al, 2008;Vogelsang & Arai, 2001). Therefore, we studied the influence of CsA, Rapa and mycophenolic acid (MPA; the active metabolite of MMF) on NK cell phenotype and function in an in vitro cytokine-based culture system (Eissens et al, 2010b).…”

Section: Interference By Immunosuppressive Drugsmentioning

confidence: 99%

Licensed to Kill: Towards Natural Killer Cell Immunotherapy

Eissens¹

2012

New Advances in Stem Cell Transplantation

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Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in Allo-SCT for leukemia patients with high relapse risk: an observational cohort study

Cited by 48 publications

References 44 publications

Progress and prospects: graft-versus-host disease

Progress and prospects: graft-versus-host disease

Novel treatment concepts for graft-versus-host disease

Licensed to Kill: Towards Natural Killer Cell Immunotherapy

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