HLA-Matched Related (MRD) or Unrelated Donor (URD) Non-Myeloablative Hematopoietic Cell Transplantation (HCT) for Patients (pts) with Refractory and Relapsed Aggressive Non Hodgkin Lymphoma (NHL).
Authors: Norasetthada L. , Maris M. B. , Sandmaier B. M. , Gooley T. , Forman S. , Agura E. , Maziarz R. T. , Shizuru J. , Niederwieser D. , Storb R. , Maloney D. G. 
Published: April 2020

Abstract
There are few treatment options for pts with relapsed aggressive T and B cell NHL after failure of auto HCT and subsequent high dose allo HCT has resulted in high rates of non-relapse mortality (NRM). We evaluated utility of allo HCT after non-myeloablative conditioning for these pts to reduce NRM risks while exploiting graft versus tumor (GVT) effects. Between 12/1999 and 2/2004, 42 pts, median age 50 (range, 17–66) years, with refractory or relapsed aggressive NHL [diffuse large B cell (DLBCL) (n=32), T-cell anaplastic large cell (ALCL) (n=4), T-cell lymphoblastic (n=3), T- cell immunoblastic (n=2) and Burkitt’s (n=1)] were studied. Median time from dx to allo HCT and number of prior regimens were 40 (range, 7–222) months and 4 (range, 1–6), respectively. Twenty-seven pts (62%) had previous auto HCT: 24 had relapsed while 3 had planned auto HCT for cytoreduction before allo HCT. Median time from auto to allo HCT was 15 (range, 2–29) months. Allo conditioning consisted of 2 Gy TBI alone (n = 3 MRD) or with added fludarabine (90 mg/m2) (n = 39; 26 MRD, 13 URD) followed by mycophenolate mofetil and cyclosporin. PBSC (n = 41) or marrow (n = 1) were infused from MRD (n = 29) or URD (n = 13). At HCT, 18 pts were in complete remission (CR) and 24 had measurable disease [10 partial remission (PR) 14 untreated relapse and refractory]. All pts engrafted (see table). The overall incidences of grades II, III and IV acute GVHD were 33%, 15% and 4%, respectively. 2-year probability of chronic GVHD was 57%. Early death from aspergillosis occurred in 2 pts. Of the 18 pts given HCT in CR, 13 (72%) remained in CR after HCT, while 64% of pts (7/11) who were in PR and 23% of pts (3/13) who had relapsed/refractory disease at HCT, achieved CR. The overall response rate was 46%. Of the 24 pts who had relapsed after auto HCT, 2 died early, 11 (46%) achieved CR and 11 progressed after allo HCT. With a median follow up of 19 (range, 6–50) months, 20 of 42 pts (48%) (12 MRD, 8 URD) were alive: 18 in CR (43%) (10 MRD, 8 URD) and 2 with progressive disease. Twenty two pts died a median of 5 (range, 3–26) months after HCT: 14 from relapse and 8 from non-relapse causes (7/8 from infections + GVHD). Day 100, and 1-year NRM* were 10% and 15%, respectively. One year overall* (OS) and progression free survivals* (PFS), and relapse rates* were 63% (MRD: 62%; URD: 85%), 49% (MRD: 45%; URD: 62%) and 36% (MRD: 34%; URD: 38%), respectively. Allo HCT after non-myeloablative conditioning offers a therapeutic option for pts with relapsed aggressive NHL including those in relapse after auto HCT, especially when the disease can be cytoreduced before HCT.
All pts (n=42) MRD (n=29) URD (n=13) Rel : Relapse; Ref : Refractory;*Cumulative probability Disease status at HCT 18 CR, 10 PR, 10 Rel, 4 Ref 12 CR, 8 PR, 6 Rel, 3 Ref 6 CR, 2 PR, 4 Rel, 1 Ref Overall response rate 11/24 (46%);(10 CR, 1 PR) 8/17 (47%);(7 CR, 1 PR) 3/7 (43%); (3 CR) CR at HCT, sustained CR 13/18 (72%) 8/12 (67%) 5/6 (83%) PR at HCT, sustained CR 7/11 (64%) 5/9 (56%) 2/2 (100%) Rel or Ref at HCT, sustained CR 3/13 (23%) 2/8 (25%) 1/5 (20%) Living pts status 18 CR, 2 PD 10 CR, 2 PD 8 CR Day 100 NRM* 10% 14% 0% 1 year NRM* 15% 21% 0% 1 year OS* 63% 62% 63% 1 year PFS* 49% 45% 62% 1 year Rel rate* 36% 34% 38%