Corticosteroids for preventing graft-versus-host disease after allogeneic myeloablative stem cell transplantation

Some types of blood cancer can be treated by transplanting stem cells from the patient's blood relatives or siblings. Unfortunately, transplanted stem cells (also called the 'graft') can sometimes induce an inflammatory reaction in the patient (or the 'host'). This reaction is called 'graft-versus-host disease' (GvHD), and once it occurs it is difficult to treat. GvHD can adversely affect the patient's quality of life and often causes death. Drug therapies have been developed to prevent GvHD. Even so, many patients still suffer this complication. Preventive therapy against GvHD must be optimised. Since corticosteroids are the first-line treatment used after GvHD occurs, it is a hypothesis that if used in prophylaxis regimens, corticosteroids can decrease the occurrence of GvHD and improve patient survival rates.

Five RCTs involving 604 people were included in this review. Analyses of these studies showed that the incidence of moderate forms of GvHD can be reduced by prophylactic corticosteroid regimens. However, there is no evidence that the incidence of life-threatening forms or patient mortality can be reduced. Effects on quality of life could not be estimated because this information was not systematically collected during these studies. Further studies are needed to determine if the timing of steroid administration influences the outcomes of GvHD.

Authors' conclusions: 

The addition of corticosteroids reduces the incidences of acute GvHD grade I to IV and II to IV. This reduction, however, did not show any effect on overall survival and disease-free survival. Further randomised controlled studies are needed to evaluate if the timing of steroid administration has a significant influence on the outcome; data on quality of life should be assessed systematically.

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Background: 

Despite ongoing progress, acute and chronic GvHD still represent major drawbacks in the context of allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) due to their high morbidity and mortality. Corticosteroids are used as first-line treatment of acute and chronic GvHD. However, their role for preventing GvHD is unclear as the published study results are controversial.

Objectives: 

To determine the effectiveness of corticosteroids used for the prophylaxis of GvHD in adults following allogeneic myeloablative HSCT. in improving overall survival, disease-free survival, relapse incidence, non-relapse mortality, acute GvHD grade I to IV, II to IV and III to IV, chronic GvHD, incidence of infectious complications, other adverse effects and cause of deaths.

Search strategy: 

We searched the Cochrane Haematological Malignancies Group trials register, CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (January 1999 to February 2006), EMBASE (January 1999 to 2004), LILACS covering publications until 2004, as well as handsearched conference proceedings, including citations until 2005.

Selection criteria: 

Randomised controlled trials (RCT) comparing the addition of corticosteroids to a GvHD prophylaxis regimen in adult patients having undergone allogeneic myeloablative HSCT were included into the review. All types and stages of the underlying disease as well as all types of possible HLA-matching were considered.

Data collection and analysis: 

Trial eligibility and quality assessment, data extraction and analysis were done in duplicate.

Main results: 

Five RCTs involving 604 people were included. The pooled results revealed that the addition of corticosteroids reduces statistically significant the risk for acute GvHD grade I to IV (HR 0.58; 95% CI 0.45 to 0.76) and II to IV (HR 0.69; 95% CI 0.51 to 0.92). No evidence was found that it has any clinical relevance on overall survival (HR 0.99; 95% CI 0.79 to 1.25) or disease-free survival (HR 0.95; 95% CI 0.74 to 1.23). As well, no statistically significant influence was found for acute GvHD grade III to IV (HR 0.78; 95% CI 0.52 to 1.15), chronic GvHD (HR 1.21;95% CI 0.89 to 1.65]), relapse incidence (HR 0.82; 95% CI 0.57 to 1.18) or non-relapse mortality (HR 0.88;95% CI 0.61 to 1.26). No clear evidence was found that the rate of infectious complications (under the concomitant use of antiviral or antibacterial medication or both) increases with the addition of corticosteroids. With respect to the other outcomes no significant differences could be detected.