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).

Abstract

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 CharacteristicsMRD (n=34)URD (n=24)Haplo (n=21)Median Age (yrs)332831Disease Status at HCTCR11 (32%)5 (21%)5 (24%)PR16 (47%)8 (33%)5 (24%)Rel/Ref7 (21%)11 (46%)11 (52%)Disease Bulk > 5cm3 (9%)3 (13%)3 (14%)HCT-Comorbidity Index >221 (62%)17 (74%)13 (62%)Regimens > 516 (47%)16 (67%)12 (57%)Failed Prior Auto HCT30 (88%)23 (96%)19 (90%)Median Time Diagnosis - Allo HCT (months)333132Median Time Auto-Allo HCT (months)161917Outcomes by donor typeMRD (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–IV53%, 15%50%, 8%43%, 10%18 month extensive chronic GVHD47%60%31%Day 200 NRM18%0%0%18 monthOS47%74%71%NRM25%8%5%Rel/PD55%65%35%PFS20%27%60%