New strategies in the treatment of graft-versus-host disease

Basara, N; Blau, IW; Willenbacher, Wolfgang; Kiehl, M. G.; Fauser, A.A.

doi:10.1038/sj.bmt.1702345

Cited by 15 publications

(11 citation statements)

References 19 publications

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“…Severe aGvHD continues to be a source of significant morbidity and mortality in patients undergoing HSCT. [1][2][3][4] The development of mild aGvHD may paradoxically increase overall survival in patients with leukemia because of a graft versus leukemia (GvL) effect. [5][6][7] The balance between allowing the occurrence of mild aGvHD and preventing progression to severe aGvHD is difficult to achieve and maintain in practice.…”

Section: Introductionmentioning

confidence: 99%

Achievement of Target Cyclosporine Concentrations as a Predictor of Severe Acute Graft Versus Host Disease in Children Undergoing Hematopoietic Stem Cell Transplantation and Receiving Cyclosporine and Methotrexate Prophylaxis

Punnett

Sung²,

Price³

et al. 2007

Therapeutic Drug Monitoring

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This study evaluates our institution's target trough cyclosporine (CSA) concentrations as predictors of severe acute graft versus host disease (aGvHD) in children receiving either matched related or unrelated hematopoietic stem cell transplantation (HSCT). The outcomes of 87 consecutive children who underwent allogeneic HSCT and received CSA and methotrexate as prophylaxis against aGvHD between October 1, 1999 and September 30, 2002 were retrospectively evaluated. The proportion of time that each patient maintained a whole blood CSA concentration within or above the initial target range (105-155 ng/mL or 155-210 ng/mL) was calculated for each of the following time periods: in each week after HSCT from day 0 to +28; in the week preceding engraftment; and in the week preceding the onset of aGvHD. Patients were prospectively evaluated twice weekly for the presence and severity of aGvHD by senior attending physicians. The relationship between potential predictors and the development of severe aGvHD was examined using univariate logistic regression. The main variables of interest were the proportion of time that therapeutic or supratherapeutic CSA concentrations were maintained; median CSA concentrations; the number of methotrexate doses received; and the use of folinic acid rescue. Mean follow-up time was 3.0+/-1.9 years among children who survived beyond day +100. Three variables were significantly associated with the development of severe aGvHD on univariate analysis: initial CSA target concentration [odds ratio (OR), 0.24; P=0.03], proportion of time the target CSA concentration was achieved during the second week after transplant (OR, 0.16; P=0.02), and proportion of time the target CSA concentration was achieved during the week before engraftment (OR, 0.22; P=0.0489). Multivariable analysis demonstrated an inverse relationship between the median CSA concentration during the week before engraftment and the development of severe aGvHD (OR, 0.99; P=0.045). These results suggest that achievement of our CSA target concentrations is important to aGvHD outcomes.

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Section: Introductionmentioning

confidence: 99%

Achievement of Target Cyclosporine Concentrations as a Predictor of Severe Acute Graft Versus Host Disease in Children Undergoing Hematopoietic Stem Cell Transplantation and Receiving Cyclosporine and Methotrexate Prophylaxis

Punnett

Sung²,

Price³

et al. 2007

Therapeutic Drug Monitoring

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“…Steroid administration while continuing prophylaxis is still the first-choice treatment for aGVHD and relieves symptoms in approximately 40% of patients (Basara et al, 2000;Couriel et al, 2004). Patients with at least overall grade II aGVHD after steroid administration have a significantly worse overall survival than steroid responders (Martin et al, 1990;Weisdorf et al, 1990;Martin et al, 1991).…”

mentioning

confidence: 99%

Efficacy of the interleukin‐2 receptor antagonist basiliximab in steroid‐refractory acute graft‐versus‐host disease

et al. 2005

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Acute graft-versus-host disease (aGVHD) occurs in up to 80% of patients who undergo allogeneic stem cell transplantation (SCT) and contributes significantly to transplant-related mortality (TRM). We conducted a prospective phase II trial to assess the efficacy and feasibility of treating steroid-refractory aGVHD with basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor. Basiliximab was administered intravenously at a dose of 20 mg on days 1 and 4. Twenty-three patients were enrolled between October 1999 and July 2004. We found a primary overall response rate of 82AE5% with four patients (17AE5%) showing a complete response and 15 patients (65%) a partial response. Six patients were again treated successfully with an IL-2 receptor antagonist because of recurrence of aGVHD. The rates of infections, chronic GVHD, malignancy recurrence and 1-year TRM following immunosuppression with basiliximab were comparable with those found with other treatment modalities for aGVHD. We conclude that basiliximab is efficient and feasible for steroid-refractory aGVHD and merits further evaluation.

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“…In this regard, the use of mycophenolate mofetil (MMF) for prophylaxis of aGVHD is rapidly increasing. [12][13][14][15][16][17][18] This report investigated the use of MMF/cyclosporin A (CsA) combination for GVHD prophylaxis in patients aged over 50 years receiving an HLA-identical sibling RIC allo-SCT.…”

mentioning

confidence: 99%

Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation

Mohty

Lavallade

Faucher

et al. 2004

Bone Marrow Transplant

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Summary:The use of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) can result in a significant decrease in early procedure-related toxicity in patients not eligible for standard myeloablative regimens. However, acute graft-versus-host disease (aGVHD) remains a matter of concern after RIC allo-SCT, and its incidence might be expected to be higher in elderly and high-risk patients. This report investigated mycophenolate mofetil (MMF) and cyclosporin A (CsA) combination (n ¼ 14) in comparison to CsA alone (n ¼ 20) for GVHD prophylaxis in cancer patients aged over 50 years (27 haematological malignancies and seven solid tumours) receiving an HLA-identical sibling antithymocyte-globulin (ATG)-based RIC allo-SCT. Baseline demographic characteristics and risk factors for aGVHD were comparable between both groups. Although MMF administration was not associated with any significant toxicity, the cumulative incidence of any form of GVHD was comparable between both groups (cumulative incidence of grade II-IV aGVHD, 50% (95% CI, 28-72%) for CsA alone, as compared to 64% (95% CI, 39-89%) to CsA and MMF, P ¼ NS), suggesting that adjunction of MMF to CsA is feasible, but does not translate towards a significant reduction of aGVHD, at least in the context ATG-based RIC allo-SCT.

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New strategies in the treatment of graft-versus-host disease

Cited by 15 publications

References 19 publications

Achievement of Target Cyclosporine Concentrations as a Predictor of Severe Acute Graft Versus Host Disease in Children Undergoing Hematopoietic Stem Cell Transplantation and Receiving Cyclosporine and Methotrexate Prophylaxis

Achievement of Target Cyclosporine Concentrations as a Predictor of Severe Acute Graft Versus Host Disease in Children Undergoing Hematopoietic Stem Cell Transplantation and Receiving Cyclosporine and Methotrexate Prophylaxis

Efficacy of the interleukin‐2 receptor antagonist basiliximab in steroid‐refractory acute graft‐versus‐host disease

Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation

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