Non-relapse mortality (NRM) after reduced-intensity allogeneic transplants is likely to be influenced by abnormalities in renal function. We hypothesized that moderate to mild renal function impairment increases NRM in this setting.

Methods: We studied 141 patients diagnosed with AML (n=131) or high-risk MDS (n=10) who underwent allogeneic transplantation with Fludarabine (Flu)/Melphalan (Mel)-based regimens between August 1996, and May 2006 in our institution. Flu dose was 30–40mg/m2 for 4 days and Mel doses were100–180mg/m2. ATG was added for recipients of unrelated donor (UD) HSCT. GVHD prophylaxis was tacrolimus and mini-methotrexate for all but 2 patients. Donors were HLA-compatible siblings (n=69) and matched UD (n=72). Disease status at transplant was complete remission (n=56, 40%) or active disease (n=85, 60%). The influence of the estimated glomerular filtration rate (GFR) measured before transplant on outcomes was analyzed. GFR was calculated by both the Cockcroft Gault (CG) and the Modified Diet in Renal Disease (MDRD) equations, using the creatinine value obtained prior to starting chemotherapy. We considered GFR ≥ 90 as normal and GFR < 90 as decreased. Evaluated outcomes were overall survival, NRM, and regimen-related mortality (RRM) at day 100 and 1-year post transplant.

Results: Median age was 55 years (range, 21–74); 59% of the patients were male. Estimated GFR by CG was normal for 45 patients (32%), and decreased for 96 patients (68%). When estimated by MDRD, 65 patients (46%) had normal and 76 (54%) had reduced GFR. The majority of patients by both estimations had a GFR between 60 and 89 (n= 78 by CG and n= 66 by MDRD) with no difference in the evaluated outcomes between this group and the subgroup of patients with a GFR <60 (p>0.05). There was no difference in overall and NRM at day 100 and 1 year post transplant in both groups by any GFR estimation method. There was a small trend towards lower RRM at day-100 for patients with GFR ≥ 90 when using CG, but this was not statistically significant.

Conclusion: A mild to moderate decrease in GFR is not associated with an increase in non-relapse mortality.

Transplant outcomes as a function of GFR at start of conditioning regimen

OutcomeN100-Day MortalityHRp1-year MortalityHRp
Abbreviations: NRM: non-relapse mortality; RRM: regimen-related mortality (excludes deaths due to GVHD); GFR: glomerular filtration rate (estimated by CG) 
Survival- GFR ≥ 90 45 11 (25%) 0.9 0.9 24 (53%) 1.2 0.5 
Survival- GFR < 90 96 24 (25%)   44 (46%)   
NRM* - GFR ≥ 90 45 9 (21%) 0.9 0.9 14 (31%) 0.98 0.9 
NRM* - GFR < 90 96 19 (20%)   31 (32%)   
RRM* - GFR ≥ 90 45 3 (7%) 0.5 0.3 6 (13%) 0.9 0.9 
RRM* - GFR < 90 96 12 (13%)   14 (15%)   
OutcomeN100-Day MortalityHRp1-year MortalityHRp
Abbreviations: NRM: non-relapse mortality; RRM: regimen-related mortality (excludes deaths due to GVHD); GFR: glomerular filtration rate (estimated by CG) 
Survival- GFR ≥ 90 45 11 (25%) 0.9 0.9 24 (53%) 1.2 0.5 
Survival- GFR < 90 96 24 (25%)   44 (46%)   
NRM* - GFR ≥ 90 45 9 (21%) 0.9 0.9 14 (31%) 0.98 0.9 
NRM* - GFR < 90 96 19 (20%)   31 (32%)   
RRM* - GFR ≥ 90 45 3 (7%) 0.5 0.3 6 (13%) 0.9 0.9 
RRM* - GFR < 90 96 12 (13%)   14 (15%)   
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Topics:
allogeneic hematopoietic stem cell transplant, chemotherapy regimen, complete remission, creatinine, fludarabine, glomerular filtration rate, glomerular filtration rate, estimated, graft-versus-host disease, hematopoietic stem cell transplantation, human leukocyte antigens

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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