Clinical Predictors of Transplant Related Mortality after Reduced Intensity Allogeneic Stem Cell Transplantation (RIST).
Authors: Pollyea Daniel A. , Artz Andrew S. , Stock Wendy , Smith Sonali M. , Daugherty Christopher , Godley Lucy , Zimmerman Todd , Odenike Olatoyosi M. , Thirman Michael , Rich Elizabeth , Larson Richard , Van Besien Koen 
Published: April 2020

Reduced intensity conditioning regimens and improvements in supportive care have allowed for the expansion of allogeneic stem cell transplantation to those previously ineligble. However, such patients remain at significant risk for regimen related toxicity. We examined whether clinical predictors that influence toxicity after standard chemotherapy, such as age, comorbidity and functional status similarly predict increased transplant related mortality (TRM) and decreased survival after a RIST with in-vivo T-cell depletion. We analyzed 81 consecutive patients on a single protocol with high-risk and refractory hematologic malignancies transplanted at our institution from 2002 to 2004. The conditioning regimen consisted of fludarabine 30 mg/m2/d (D-7 to D-3), Campath-1H 20 mg/d (D-7 to D-3), and melphalan 140 mg/m2 (D-2) with tacrolimus given for post-transplant immunosuppression. Comorbidity was scored from a retrospective chart review using the Charlson Comorbidity Index (CC) and the Kaplan-Feinstein scale (KF). Eastern Cooperative Oncology Group performance status (PS) and age at transplant were tabulated. TRM was defined as any death occurring without disease progression. Median age was 51 years (range 17–68). Fifty-five percent had HLA-identical sibling donors, 5% had mismatched related donors, 35% had matched unrelated donors and 5% had mismatched unrelated donors. KF served as a more sensitive indicator of comorbidity than CC. Fifty-three percent of patients scored at least one point for a comorbid condition by KF, as opposed to 25% by CC (P&lt;.001 by Chi square), and 28% scored at least 2 points by KF versus 8% by CC (P&lt;.001 by Chi square). PS was 0, 1, and &gt;1 for 61%, 28% and 11% of patients, respectively. The cumulative incidence of 100 and 180 day TRM was 21% and 30%, respectively, with an overall survival (OS) of 15.4 months. Comorbidity, PS, and age greater than 50 predicted increased TRM and decreased OS. In a multivariable model incorporating these predictors (using either CC or KF), age and PS were significant for TRM, while comorbidity and PS were significant for OS. Simple measures of comorbidity, functional status and age predict adverse outcomes after transplantation for hematologic malignancies, even with a reduced intensity regimen. Prospective studies could provide a more accurate estimation of regimen tolerability, particularly in older or sicker patients.

Clinical Predictors for Mortality After Allogeneic Stem Cell Transplantation

Transplant Related Mortality (TRM) Overall Survival (OS) Predictor Incidence at Day 180 Univariate Hazard Ratio Univariate P Value Multivariate P Value* Univariate Hazard Ratio Univariate P Value Multivariate P Value* CC= Charlson Comorbidity Index, KF= Kaplan-Feinstein Scale; *Multivariate analyses include only one comorbidity measure, either KF or CC. Age and PS determined using KF. **Comorbidity scores exclude underlying hematologic malignancies Performance Status PS=0 0.86 4.2 0.002 0.007 2.78 0.003 0.016 PS&gt;0 0.53 Comorbidity** CC, no comorbidity 0.76 2.3 0.042 0.089 2.25 0.014 0.03 CC, ≥1 comorbidity 0.52 KF, no comorbidity 0.85 2.7 0.027 0.183 2.74 0.004 0.03 KF, ≥1 comorbidity 0.56 Age Age&lt;50 0.80 3.5 0.13 0.47 1.73 0.98 0.34 Age&gt;50 0.63