Comparison of Allogeneic Hematopoietic Cell Transplantation (HCT) after Nonmyeloablative Conditioning with HLA-Matched Related (MRD), Unrelated (URD), and Related Haploidentical (Haplo) Donors for Relapsed or Refractory Hodgkin Lymphoma (HL).
Authors: Burroughs Lauri , O’Donnell Paul , Sandmaier Brenda M. , Storer Barry , Luznik Leo , Symons Heather , Maris Michael , Blume Karl G. , Niederwieser Dietger W. , Bruno Benedetto , Maziarz Richard T. , Pulsipher Michael , Petersen Finn , McSweeney Peter A. , Chauncey Thomas , Agura Edward , Wade James C. , Storb Rainer F. , Fuchs Ephraim J. , Maloney David G. 
Published: April 2020

We evaluated the utility of allogeneic HCT using nonmyeloablative conditioning as a potential treatment option for 79 patients (pts) with HL who were ineligible for high dose conventional allogeneic HCT and compared outcome based on donor cell source (MRD n=34, URD n=24, Haplo n=21). Conditioning consisted of 2 Gy TBI alone (n=15, MRD) or combined with either 90 mg/m2 (MRD n=19, all URD) or 150 mg/m2 (all Haplo) fludarabine. All haplo recipients also received cyclophosphamide pre (29 mg/kg) and post (50 or 100 mg/kg) HCT. GVHD prophylaxis consisted of mycophenolate mofetil and a calcineurin inhibitor. Pts were heavily pretreated with a median number of 5 (range, 2–10) prior regimens. Most pts failed prior autologous HCT (91%) and radiation therapy (86%). There were no graft rejections. The incidences of acute grades III–IV and extensive chronic GVHD were 15%/47% (MRD), 8%/60% (URD), and 10%/31% (Haplo). There were no statistically significant differences in the ability to discontinue immunosuppression based on donor cell sources. With a median follow up of 20 (range, 4–91) months for living pts; the 18 month overall survivals (OS), progression free survivals (PFS), and incidences of relapse/progressive disease (PD) were 47%, 20%, and 55% (MRD), 74%, 27%, and 65% (URD), and 71%, 60%, and 35% (Haplo), respectively. Nonrelapse mortalities (NRM) were significantly lower for URD (HR 0.16; p=0.03) and Haplo (HR 0.13; p=0.02) recipients compared to MRD recipients. There were also significantly decreased risks of relapse for Haplo recipients compared to MRD (HR 0.35; p=0.03) and URD (HR 0.36; p=0.02) recipients. These data suggest that salvage allogeneic HCT using nonmyeloablative conditioning provides anti-tumor activity in pts with very advanced disease; however, Rel/PD continue to be major problems regardless of stem cell source. Importantly, alternative donor sources are a viable option particularly for those pts who may have a limited window of opportunity to proceed to HCT.

Pt Characteristics MRD (n=34) URD (n=24) Haplo (n=21) Median Age (yrs) 33 28 31 Disease Status at HCT CR 11 (32%) 5 (21%) 5 (24%) PR 16 (47%) 8 (33%) 5 (24%) Rel/Ref 7 (21%) 11 (46%) 11 (52%) Disease Bulk &gt; 5cm 3 (9%) 3 (13%) 3 (14%) HCT-Comorbidity Index &gt;2 21 (62%) 17 (74%) 13 (62%) Regimens &gt; 5 16 (47%) 16 (67%) 12 (57%) Failed Prior Auto HCT 30 (88%) 23 (96%) 19 (90%) Median Time Diagnosis - Allo HCT (months) 33 31 32 Median Time Auto-Allo HCT (months) 16 19 17 Outcomes by donor type MRD (n=34) URD (n=24) Haplo (n=21) Median f/u living pts months (range) 15 (4–91) 26 (8–58) 15 (4–49) Acute GVHD grade II–IV, III–IV 53%, 15% 50%, 8% 43%, 10% 18 month extensive chronic GVHD 47% 60% 31% Day 200 NRM 18% 0% 0% 18 month OS 47% 74% 71% NRM 25% 8% 5% Rel/PD 55% 65% 35% PFS 20% 27% 60%