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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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Figure. 1a. Acute GVHD and transplant-related mortality (TRM) in patients with (grades I–IV) and without any acute GVHD by day 100 (Landmark analysis)Figure. 1b. Chronic GVHD and transplant-related mortality (TRM) in patients with and without chronic GVHD within one year (Landmark analysis)
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Figure 1: Figure. 1a. Acute GVHD and transplant-related mortality (TRM) in patients with (grades I–IV) and without any acute GVHD by day 100 (Landmark analysis)Figure. 1b. Chronic GVHD and transplant-related mortality (TRM) in patients with and without chronic GVHD within one year (Landmark analysis)

Mentions: At one year, TRM was 15% (95% CI, 10–20%), and at five years it was 25% (95% CI, 17–34%). In multivariate analysis, acute GVHD was associated with an increased risk of TRM (Table 3, RR 2.42, p=0.016). Chronic GVHD, whether limited or extensive, had no significant impact on TRM. Figures 1a and 1b represent the landmark analyses for TRM in those developing aGVHD by day 100 vs. those who did not, and those developing cGVHD within 1 year vs. those who did not.


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)

Figure. 1a. Acute GVHD and transplant-related mortality (TRM) in patients with (grades I–IV) and without any acute GVHD by day 100 (Landmark analysis)Figure. 1b. Chronic GVHD and transplant-related mortality (TRM) 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 1: Figure. 1a. Acute GVHD and transplant-related mortality (TRM) in patients with (grades I–IV) and without any acute GVHD by day 100 (Landmark analysis)Figure. 1b. Chronic GVHD and transplant-related mortality (TRM) in patients with and without chronic GVHD within one year (Landmark analysis)
Mentions: At one year, TRM was 15% (95% CI, 10–20%), and at five years it was 25% (95% CI, 17–34%). In multivariate analysis, acute GVHD was associated with an increased risk of TRM (Table 3, RR 2.42, p=0.016). Chronic GVHD, whether limited or extensive, had no significant impact on TRM. Figures 1a and 1b represent the landmark analyses for TRM in those developing aGVHD by day 100 vs. those who did not, and those developing cGVHD within 1 year vs. those who did not.

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