Charlson Comorbidity Index (CCI) Not Hematopoietic Cell Transplantation Specific-Comorbidity Index (HCT-CI) Successfully Predicts Transplant Related Mortality and Post-Transplant Outcomes in Elderly Patients Undergoing Reduced Intensity Conditioning (RIC) Umbilical Cord Blood (UCB) Transplantation

Abstract 3006^FN2

Transplant related mortality (TRM), drug toxicities, life-threatening infections, poor quality of life, and graft versus host disease (GVHD) are significant risks of hematopoietic cell transplantation (HCT). In addition, pre-transplant comorbidities can have significant impact on the transplant outcomes of elderly patients (pts). Two comorbidity measurement tools, the CCI and the HCT-CI have been inconsistent in predicting TRM and overall survival (OS) after conventional HCT. The HCT-CI and CCI scores have correlated less well with TRM and OS in UCB transplantation. These results may have been limited by the heterogeneity of the UCB transplantation study population in age, disease, disease-risk, comorbidities, and conditioning regimens used. This study was performed to explore the accuracy of the HCT-CI and CCI in predicting post-transplant outcomes in elderly pts with high risk hematologic malignancies undergoing uniform RIC UCB transplantation.

A retrospective chart review was performed on 35 consecutive elderly (age ≥ 55 years (yrs)) UCB transplant recipients receiving the RIC regimen fludarabine, cyclophosphamide, ATG, and 200 cGy TBI. All pts received cyclosporine and mycophenolate mofetil for GVHD prophylaxis. Information on pre-transplant comorbidities was obtained from each pt's CIBMTR pre-TED form and retrospective chart reviews. Demographic information, ECOG performance status (PS), identification of comorbidities, and post-transplant outcomes were obtained. HCT-CI and CCI scores were distributed in the following comorbidity risk groups 0, 1, > 1.

Between 2002 and 2011, 35 pts underwent UCB transplantation with the above regimen. Median age was 65 yrs (range 55–71), 21 were male (60%) and 14 female (40%). Most pts had advanced stage or high risk hematologic malignancies; 28 had MDS/AML (80%) and 7 had other hematologic malignancies. All pts had a PS ≤ 2. Twenty-seven pts were in CR ≤ 2, with 31 pts having received ≤ 2 prior therapies. Eight pts had received prior transplants, including 2 pts with prior UCB transplantations and 6 pts with prior autografts. UCB cell dose was calculated on actual body weight (median 84 kg, range 56.1–135.1 kg). A total of 66 UCB grafts matched at a minimum 3/6 (3/6 = 4, 4/6 = 34, 5/6 = 22, 6/6 = 6) were infused. Pts received a range of 1 to 5 UCB units (1 unit = 12 pts, 2 units = 19 pts, 3 units = 2 pts, 5 units = 2 pts). VNTR/FISH analyses confirmed engraftment with median time of 21 days (d) (95% CI: 14–40 d) to achieve > 60% chimerism. Nine pts failed to achieve chimerism > 60%, and 3 had secondary engraftment failure. Median time to ANC > 500/μL for 3 consecutive values was 27 d (95% CI: 21–32 d) and median time to platelets > 20, 000/μL on the first day of 7 consecutive days without a platelet infusion was 40 d (95% CI: 35–71 d). No patient developed grade 4 acute GVHD. Grade 3 acute GVHD was seen in 3/35 pts (9%) and chronic GVHD was seen in 6/27 pts (22%). To date 31% (n = 11) of pts have relapsed. Pre-transplant cardiac comorbidities, A-fib/flutter and coronary artery disease, were the most common. Six pts had prior solid tumor malignancies, not active at the time of HCT, including breast (n=2), prostate (n=2), bladder (n=1), and kidney (n=1). After a median follow up of 13 months (range 1–70), 1 yr OS and progression free survival (PFS) were 61% and 55%, respectively. Median PFS and OS were both 16 months (mos) (PFS 95% CI: 8–70 mos, OS 95% CI: 9–70 mos). CCI but not PS or HCT-CI was a significant predictor of OS and PFS (Table and Figure).

.	.	OS (%) .				PFS (%) .
Factor .	N .	1 yr .	2 yr .	4 yr .	p-value .	1 yr .	2 yr .	4 yr .	p-value .
PS
0	17	57	50	33	0.88	52	52	35	0.81
1-2	18	65	45	34		58	45	38
CCI
0	16	80	58	22		67	59	32
1	4	100	50		0.04	100	50		0.04
>1	15	33	33	33		33	33	33
HCT-CI
0	12	54	43	14		56	44	15
1	10	80	69	69	0.29	69	69	69	0.25
>1	13	53	35	35		45	36	36

.	.	OS (%) .				PFS (%) .
Factor .	N .	1 yr .	2 yr .	4 yr .	p-value .	1 yr .	2 yr .	4 yr .	p-value .
PS
0	17	57	50	33	0.88	52	52	35	0.81
1-2	18	65	45	34		58	45	38
CCI
0	16	80	58	22		67	59	32
1	4	100	50		0.04	100	50		0.04
>1	15	33	33	33		33	33	33
HCT-CI
0	12	54	43	14		56	44	15
1	10	80	69	69	0.29	69	69	69	0.25
>1	13	53	35	35		45	36	36

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TRM occurred in 8 pts (23%). CCI was associated with TRM (p=0.05): pts with CCI ≥ 2 had a 40% (6/15) TRM vs 10% (2/20) with CCI 0–1. PS (p=0.69) and HCT-CI (p=0.47) did not correlate to TRM.

In conclusion, elderly pts undergoing RIC UCB transplantation for high risk hematologic malignancies, the CCI was a statistically significant predictor of TRM, PFS, and OS. This index and not HCT-CI or PS identified elderly pts undergoing RIC UCB transplantation at higher risk of TRM and poor post-transplant outcomes. Larger validation studies of the predictive capacity of these comorbidity indexes need to be performed in the multi-institutional setting.