Increased Number of Prior Therapies and/or Use of Mismatched Unrelated Donors Adversely Affect Allogeneic Hematopoietic Cell Transplantation (alloHCT) Outcomes in Relapsed/Refractory Hodgkin Lymphoma (HL)

Prognosis is poor for patients (pts) with refractory HL or for those who relapse following autologous HCT (autoHCT). Current salvage options aside from alloHCT remain palliative but the role, timing and utility of alloHCT is not clear.  We report outcomes of 19 consecutive pts (Table) with relapsed/refractory HL receiving alloHCT between 2005 and 2011 at Moffitt Cancer Center.  Data were obtained from the BMT database and supplemented with chart review.  Disease responses are based on Cheson criteria (JCO 2007) and chemotherapy sensitivity is defined as PR or better at time of alloHCT.  Median follow-up for survivors is 44 months (14–56).  Treatment-related mortality (TRM) at day 100 and 1 yr are 27% (95% CI: 10-50) and 44% (95% CI: 23-67).  The 1 yr relapse rate was 32% (95% CI: 13–54). Grade 2 – 4 acute GVHD by day 100 occurred in 82% (95% CI: 54–98); chronic GVHD of any severity at 1 yr was 57% (95% CI: 25–86). Overall survival (OS) and progression-free survival (PFS) at 1 yr are 47% (95% CI: 26-68) and 26% (95% CI: 10-48), respectively.  There were no differences in OS or PFS comparing myeloablative (MAC) to reduced intensity (RIC) conditioning [OS: MAC 55% (95% CI: 26–82) vs RIC 38% (95% CI: 10–71), p=0.39; PFS: MAC 27% (95% CI: 6–56) vs RIC 25% (95% CI: 3–58) p=0.78].   Relapse and TRM did not differ by conditioning intensity. Disease status (CR vs PR/Stable disease) did not impact OS, PFS, relapse or TRM. Pts receiving a mismatched unrelated donor (mMUD), including cord, had higher day 100 TRM compared to pts receiving a fully matched donor [mMUD: 57% (95% CI: 22–88) vs matched: 9% (95% CI:0–32)]. Three pts, including 1 receiving a mMUD, received ≤3 lines of chemotherapy including autoHCT preceding allografting.  In these pts, no TRM occurred compared to pts with >3 lines of prior therapy having TRM of 53% (95% CI: 29–77).  However, the improvement in 1 yr OS and PFS was not significant [≤3 lines=OS 67% (95% CI: 14–100); PFS 68% (95% CI: 14–100); >3 lines=OS 44% (95% CI: 21–68), p=0.08; PFS 19% (95% CI: 4–41), p=0.06] likely due to limited pts.  We conclude that alloHCT for relapsed/refractory HL can induce durable remissions; however, outcomes are impaired due to early TRM in heavily pretreated pts and those receiving mMUD/cord.  While our data are limited by small numbers, they suggest that pts should be referred for discussion of alloHCT earlier to mitigate likely adverse toxicity from repeated therapies.

Variables	N (%)
Age, yrs (median, range)	33 (18 – 52)
Gender, Male	11 (58%)
Median # of prior therapies (range)	6 (2 – 8)
Prior autoHCT, yes	15 (79%)
Conditioning Intensity, Myeloablative	11 (58%)
Conditioning Regimen     Flu/Bu (AUC 5300, MAC)     Flu/Bu (AUC 3500, RIC)     Flu/Cy/TBI 200     Flu/TBI 200     Pento/Bu	9 (47%) 3 (16%) 1 (  5%) 4 (21%) 2 (11%)
Disease status at HCT     Complete Remission     Partial Remission     Stable Disease	5 (26%) 10 (53%) 4 (21%)
Donor Type     Matched related     Matched unrelated     Mismatched unrelated     Cord	6 (32%) 6 (32%) 6 (32%) 1  ( 5%)