Prognostic Value of Charlson Comorbidity Index (CCI) and Hematopoietic Cell Transplantation Specific-Comorbidity Index (HCT-CI) in Reduced Intensity Conditioning (RIC) Umbilical Cord Blood (UCB) Transplant

TRM, poor quality of life, graft versus host disease are significant risks of hematopoietic cell transplantation (HCT). In addition to the risks of HCT, pre-transplant comorbidities significant impact transplant outcomes. A comparison of CCI and HCT-CI revealed that HCT-CI was prognostic and better at predicting TRM and overall OS. However, HCT-CI and CCI have been inconsistent in validation studies. Patient heterogeneity in age, disease, disease-risk, comorbidities, and conditioning regimens may limit their usefulness in UCB recipients. The design of this research was to explore if HCT-CI and/or CCI can accurately predict post-transplant outcomes in the setting of uniform RIC UCB transplantation.

A retrospective chart review was performed on 87 consecutive UCB recipients receiving fludarabine, cyclophosphamide, ATG, and 200 cGy TBI. GVHD prophylaxis was cyclosporine and mycophenolate mofetil. Between 2005 and 2011, 87 patients age 19 – 71 (median 50) years, 51 males (59%) and 36 females (41%), underwent RIC UCB transplantation with the above regimen.

Most patients had advanced stage or high risk hematologic malignancies; 56 had MDS/AML (64%), 9 had ALL (10%), while 22 had other. Half of the patients were in CR > 2, with the same number receiving more than 2 prior therapies.

14 patients had received a prior autologous HCT, 9 prior allo-HCT, and three had failed a previous UCB transplantation. 14 patients failed to engraft. Median time to neutrophil engraftment was 26 days (95% CI: 24 – 32 d), and to platelet engraftment 39 days (95% CI: 31 – 71 d). No patient developed grade 4 acute GVHD. Grade 3 acute GVHD was seen in 15 / 87 patients (17%). Chronic GVHD was seen in 18 patients (21%). To date 27 patients (31%) have relapsed. OS was 42% and PFS was 37% at one year. Median PFS and median OS were 9 months and 8 months, respectively (PFS 95% CI: 4 – 12 months, OS 95% CI: 5 – 13 months). Neither CCI, nor HCT-CI were significant predictors of OS and PFS, however ECOG PS was significantly associated with outcome (Table).

			OS				PFS
		N	1 yr	2 yr	4 yr	p	1 yr	2 yr	4 yr	p
ECOG	0	56	30%	23%	11%	0.029	28%	23%	10%	0.042
	1 - 2	31	16%	8%	3%		14%	8%	3%
CCI	2 or less	68	39%	25%	10%	0.129	34%	25%	9%	0.125
	more than 2	9	7%	6%	5%		7%	6%	5%
HCT CI	0 - 1	58	31%	21%	7%	0.238	28%	21%	6%	0.275
	more than 1	19	15%	10%	8%		14%	10%	8%

TRM occurred in 26 patients (30%). Neither comorbidity indices, nor the performance status were correlated to TRM (p > 0.05). For ECOG PS, OR 0.9, p = 0.86, CI 0.28 - 2.88; CCI OR = 1.1, p = 0.87, CI 0.28 - 4.37, HCT-CI OR = 0.9, p = 0.98, CI 0.31 - 3.19.

In a previous paper our group concluded that CCI performs better than HCT-CI in elderly patients undergoing UCB, but not in a population younger than 55 years. This pooled analysis shows that we were unable to validate the generally accepted prognostic indices. The majority of our patients were in CR ≥ 2 and had very high risk disease. These factors need to be taken into account in creating a new prognostic index for UCB transplantation.