Successful Salvage of High-Risk B-Cell Non-Hodgkin & Hodgkin Lymphoma (NHL/HL) with Double-Unit Cord Blood Transplantation (DCBT) Provides a Platform for Further Optimization

Introduction: While DCBT is an alternative therapy for patients (pts) with high-risk lymphomas its efficacy is not established. Methods: We analyzed overall survival (OS) & progression-free survival (PFS) after 4-6/6 HLA-matched DCBT in adults with B-cell NHL or HL transplanted 2/2006-5/2013. Results: Pt characteristics & outcomes by diagnosis are shown (Table). 47 pts (median 46 years, range 20-70) had a median of 4 prior regimens (range 1-13), 47% had a prior autologous transplant. The median HCT-CI score was 2 (range 0-6). 60% were in CR. Conditioning was reduced intensity (RI) in 16 (8 Cy/Flu/Thio/TBI400, 8 Mel/Flu) or non-myeloablative (NMA, Cy/Flu/TBI200) in 31. CB grafts had a median TNC dose x 10⁷/kg of 2.7 & 1.9, & a median 5/8 (range 1-7) donor-recipient HLA-allele match. 98% engrafted (95%CI:77-99, median 22 & 10 days after RI & NMA conditioning, respectively). Day 100 grade II-IV acute GVHD (20 grade II, 7 grade III, 1 grade IV) & 1-year chronic GVHD were 61% (95%CI:45-74) & 17% (95%CI:8-29), respectively. Day 180 transplant-related mortality (TRM) was 17% (95%CI:8-29) & 3-year disease progression was 22% (95%CI:11-34, median 3.4 months, range 2.8-58.0). With a median 60 month (range 15-101) follow-up, 3-year OS & PFS are 56% (95%CI:44-73) & 44% (95%CI:31-61), respectively (Figure). 7 pts died of progressive disease whereas 16 had TRM. Best PFS was seen in follicular NHL (3-year PFS 62%) & HL (3-year PFS 47%) whereas pts with diffuse large B-cell lymphoma did poorly. There were no differences in 3-year PFS according to age, HCT-CI, number of prior regimens or prior autologous transplant, & 28 CR pts had a 42% 3-year PFS compared to 46% in 19 non-CR pts, p = 0.57. Four of 11 pts who relapsed survive (range 29-81 months) after chemotherapy (n = 3) or CB-derived mobilized peripheral blood stem cell (PBSC) transplant (n = 1). Conclusions: PFS after DCBT in pts with follicular NHL or HL is similar to that of adult donor allografts & warrants further investigation. However, DCBT in other histologies is not as favorable. TRM may be influenced by the extent & intensities of prior therapy. Strategies to risk adapt therapy, reduce TRM & prevent disease progression are all required. Finally, chemotherapy to treat post-CBT relapse & CB-derived PBSC transplant are potential therapeutic options in selected patients.

Table

Disease Type (N)	Median (range) age	Median (range) HCT-CI	Remission status	Median (range) prior regimens / N prior auto	Regimen intensity	PFS
Follicular (n = 13)	52 yrs (29-63)	1 (0-4)	5 CR, 5 PR, 3 SD	4 (2-8) / 3/13 (23%)	3 MA 10 NMA	3-yr: 62%
Diffuse large cell (n = 13)	53 yrs (35-64)	2 (0-6)	8 CR, 4 PR, 1 SD	4 (1-7) / 3/13 (23%)	4 MA 9 NMA	3-yr: 23%
Mantle cell (n = 5)	57 yrs (37-71)	2 (1-6)	5 CR	3 (2-4) / 4/5 (80%)	5 NMA	2 disease-free (29-70 months)
Hodgkins (n = 15)	35 yrs (20-50)	3 (0-5)	10 CR, 3 PR, 1 SD, 1 PD	4 (2-13) / 12/15 (80%)	8 MA 7 NMA	3-yr: 47%
T-cell rich B-cell NHL (n = 1)	38 yrs	2	PR	7 / No auto	1 MA	Died at 1.5 months