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Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma.

Ringdén O, Shrestha S, da Silva GT, Zhang MJ, Dispenzieri A, Remberger M, Kamble R, Freytes CO, Gale RP, Gibson J, Gupta V, Holmberg L, Lazarus H, McCarthy P, Meehan K, Schouten H, Milone GA, Lonial S, Hari PN - Bone Marrow Transplant. (2011)

Bottom Line: We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC).In multivariate analysis, aGVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52, P=0.001).The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden.

ABSTRACT
We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52, P=0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage.

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Event-free survival (EFS) in patients with and without chronic GVHD within one year (Landmark analysis)
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Figure 3: Event-free survival (EFS) in patients with and without chronic GVHD within one year (Landmark analysis)

Mentions: At one year, EFS was 64% (95% CI, 57–71%), and at five years, it was 22% (95% CI, 13–34%). In the multivariate analysis, aGVHD and cGVHD overall did not impact EFS (Table 3). However, limited cGVHD was associated with superior EFS (RR for relapse/death =0.40, p=0.027), while extensive cGVHD had no statistically significant impact on EFS. Figure 3 depicts a landmark analysis of EFS in those developing any cGVHD within one year of HSCT vs. those who did not. At one year, EFS was 48% (95% CI 36–60%) in the allo only group, compared to 74% (95% CI 66–83%) in the auto-allo group. At five years, EFS was 17% (95% CI 7–29%) and 24% (95% CI 7–48%) in the two groups, respectively. In the multivariate analysis, the auto-allo group had superior EFS (Table 3, RR=0.57, p=0.008).


Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma.

Ringdén O, Shrestha S, da Silva GT, Zhang MJ, Dispenzieri A, Remberger M, Kamble R, Freytes CO, Gale RP, Gibson J, Gupta V, Holmberg L, Lazarus H, McCarthy P, Meehan K, Schouten H, Milone GA, Lonial S, Hari PN - Bone Marrow Transplant. (2011)

Event-free survival (EFS) in patients with and without chronic GVHD within one year (Landmark analysis)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369112&req=5

Figure 3: Event-free survival (EFS) in patients with and without chronic GVHD within one year (Landmark analysis)
Mentions: At one year, EFS was 64% (95% CI, 57–71%), and at five years, it was 22% (95% CI, 13–34%). In the multivariate analysis, aGVHD and cGVHD overall did not impact EFS (Table 3). However, limited cGVHD was associated with superior EFS (RR for relapse/death =0.40, p=0.027), while extensive cGVHD had no statistically significant impact on EFS. Figure 3 depicts a landmark analysis of EFS in those developing any cGVHD within one year of HSCT vs. those who did not. At one year, EFS was 48% (95% CI 36–60%) in the allo only group, compared to 74% (95% CI 66–83%) in the auto-allo group. At five years, EFS was 17% (95% CI 7–29%) and 24% (95% CI 7–48%) in the two groups, respectively. In the multivariate analysis, the auto-allo group had superior EFS (Table 3, RR=0.57, p=0.008).

Bottom Line: We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC).In multivariate analysis, aGVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52, P=0.001).The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden.

ABSTRACT
We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52, P=0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage.

Show MeSH
Related in: MedlinePlus