High-Dose Methylprednisolone Treatment for Acute Graft-Versus-Host Disease After Bone Marrow Transplantation in Adults

Kanojia, Mahesh; Anagnostou, Athanasius; Zander, Axel R.; Vellekoop, Lijda; Spitzer, Gary; Verma, Dharmvir S.; Jagannath, Sundar; Dicke, Karel A.

doi:10.1097/00007890-198403000-00005

Cited by 47 publications

(18 citation statements)

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“…Intuitively, this association is not surprising given the well-known deleterious immunosuppressive effects associated with high-dose steroids. [54][55][56][57] Nevertheless, this unveils the major unresolved issue of GVHD management after RIC allo-SCT. Optimal management of GVHD after RIC allo-SCT is still poorly defined.…”

Section: Discussionmentioning

confidence: 99%

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

et al. 2003

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In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P ¼ 0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (42 mg/kg) represented the major risk factor for bacteremia (P ¼ 0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.

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Section: Discussionmentioning

confidence: 99%

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

et al. 2003

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“…The corollary of this approach is that glucocorticoid doses in excess of those needed to control GVHD manifestations cause major morbidity and increase mortality. [13][14][15][16] In support of this view, studies aimed at reducing treatment-related toxicities by limiting the exposure to systemic glucocorticoids have yielded promising results. 17,18 In these studies, patients with mild to moderately severe acute GVHD (rash involving Յ 50% body surface area and stool volumes Յ 1.0 L/day with or without anorexia, nausea, and vomiting) who were initially treated with low-dose systemic glucocorticoids (prednisone-equivalent doses of 1 mg/kg per day) in combination with oral beclomethasone dipropionate (BDP), a topically active glucocorticoid with limited exposure in the systemic circulation, had lower rates of treatment failure and superior survival than those given low-dose systemic glucocorticoids alone.…”

Section: Introductionmentioning

confidence: 99%

Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes

Mielcarek

Storer

Boeckh

et al. 2009

Blood

118

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We hypothesized that initial treatment of acute graft-versus-host disease (GVHD) with low-dose glucocorticoids (prednisoneequivalent dose of 1 mg/kg per day) instead of standard-dose glucocorticoids (prednisone-equivalent dose of 2 mg/kg per day) does not compromise major transplantation outcomes. We retrospectively analyzed outcomes among 733 patients who received transplants between 2000 and 2005 according to initial treatment with low-dose (n ‫؍‬ 347) versus standarddose (n ‫؍‬ 386) systemic glucocorticoids.The mean cumulative prednisoneequivalent doses at day 100 after starting treatment were 44 and 87 mg/kg for patients given low-dose and standarddose glucocorticoids, respectively. Adjusted outcomes between the groups given low-dose versus standard-dose glucocorticoids were not statistically significantly different: overall mortality (hazard ratio [

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“…Immunosuppressants also often have significant acute and chronic adverse effects on organ function. 9,10 Ex vivo T-cell depletion of donor HSCs appears to be more effective at ameliorating or even eliminating GVHD, but this approach is complicated by an unacceptable incidence of graft failure, profound and protracted immunodeficiency, and loss of antitumor immunity. [5][6][7][8] New methods of reducing toxicity while retaining the antitumor potential of BMT, including donor lymphocyte infusion and nonmyeloablative conditioning, have led to a significant decrease in the occurrence of acute GVHD.…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation

Imado

Iwasaki

Kataoka

et al. 2004

Blood

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Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). When GVHD is controlled by T-cell-depleted grafts or immunosuppressants, BM transplant recipients often suffer from an increased rate of leukemic relapse and impaired reconstitution of immunity. Using a mouse BMT model, we investigated the effects of hepatocyte growth factor (HGF) gene transfection on the severity of GVHD, the graft-versus-leukemia effect, and the reconstitution of T cells after BMT. After HGF gene transfer, acute GVHD was reduced, while mature donor T-cell responses to host antigens were preserved, resulting in a significant improvement of leukemia-free survival. HGF gene transfer promoted regeneration of bone marrowderived T cells and the responsiveness of these cells to alloantigens. Furthermore, HGF preserved the thymocyte phenotype and thymic stromal architecture in mice with GVHD. This suggested that HGF exerts a potent protective effect on the thymus, which in turn promotes reconstitution of bone marrow-derived T cells after allogeneic BMT. These results indicate that HGF gene transfection can reduce acute GVHD preserving the graftversus-leukemia effect, while promoting thymic-dependent T-cell reconstitution after allogeneic BMT. IntroductionDonor T cells contaminating hematopoietic stem cells (HSCs) contribute both positively and negatively to the outcome of allogeneic bone marrow transplantation (BMT). Donor T cells play a positive role by facilitating engraftment of the allograft and contributing to antitumor immunity, but are also primarily responsible for graft-versus-host disease (GVHD). [1][2][3][4][5][6][7][8] To date, approaches to control acute GVHD have employed methods that attempt to remove or suppress the function of all T cells regardless of their immunologic specificity. Although the administration of immunosuppressants achieves an acceptable rate of engraftment with reasonable control of GVHD, these drugs induce a generalized decrease of immunocompetence with its attendant morbidity and mortality. Immunosuppressants also often have significant acute and chronic adverse effects on organ function. 9,10 Ex vivo T-cell depletion of donor HSCs appears to be more effective at ameliorating or even eliminating GVHD, but this approach is complicated by an unacceptable incidence of graft failure, profound and protracted immunodeficiency, and loss of antitumor immunity. [5][6][7][8] New methods of reducing toxicity while retaining the antitumor potential of BMT, including donor lymphocyte infusion and nonmyeloablative conditioning, have led to a significant decrease in the occurrence of acute GVHD. Unfortunately, along with the decline of acute GVHD, chronic GVHD has begun to emerge as a major complication of BMT. 11 An important cause of impaired reconstitution of immunity after allogeneic BMT is the thymic damage initiated by hostreactive donor T cells, because reconstitution of T-cell immunity depends on the differentiation of donor HSCs in the thymus. 12,13 It is likely tha...

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High-Dose Methylprednisolone Treatment for Acute Graft-Versus-Host Disease After Bone Marrow Transplantation in Adults

Cited by 47 publications

References 0 publications

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes

Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation

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