A Prospective Phase II Comparison of Stem Cell Source Using RICE Re-Induction, Then FluBu and Autologous (ASCT) or Allogeneic (AlloSCT) Hematopoietic Blood Stem Cell Transplantation for MCL & NHL
The American Society of Haematology (ASH) had its annual meeting earlier this month. Haematologists from around the world gathered at the San Diego Convention Centre to provide a forum for discussing critical issues in haematology. Nearly 20,000 clinicians, scientists, and others attended the four-day meeting, which consisted of an educational program and cutting-edge scientific sessions. The following was one of the presentations given at the meeting.
A “genetically-randomized” prospective phase II study was designed to compare stem cell source following novel, uniform and expected low toxicity re-induction and high dose chemotherapy for indolent B-cell NHL.Patients with MCL in 1st remission or 1st relapse, or other indolent B-cell lymphoma in 1st or 2nd relapse were eligible providing adequate organ function and age <65 years. Patients received RICE (Rituximab 375mg/m2 d1,8,15,22, Ifosfamide 1.67g/m2 d16-18, Carboplatin AUC=5 d17, Etoposide 100mg/m2 d16-18), with G-CSF d22-30, and apheresis d29-31 if ASCT, then FluBu (Fludarabine 50mg/m2 d-6to-2, Busulfan 3.2 mg/kg IV daily d-5to-2) and SCT d0. GVHD prophylaxis for AlloSCT involved ATG 4.5mg/kg, MTX and CSA.The initial 43 patients accrued from 06/2001-03/2004 included Follicular=30, MCL=7, SLL=4, other histology=2. Disease status was 1st remission=2, 1st relapse=18, 2nd relapse=12, 10 refractory=11. The median EFS following most recent prior chemotherapy was 7 mos. RICE resulted in an overall RR of 72%. Blood stem cell source was ASCT=27, donor SCT=16 (related=14, unrelated=1, syngeneic=1). For ASCT, a median of 5.9 (1-14.5) x106 CD34+ cells/kg were collected from 1 (n=17) or 2 (n=10) 15-25L aphereses. Three patients required a second mobilization procedure. 16/24 patients converted from positive to negative marrow biopsies post-RICE. Two patients had NHL detected in the autograft. FluBu resulted in no acute Bearman grade 3-4 RRT(overall 100d non-relapse mortality (NRM)=0% for both ASCT and donor SCT). Median engraftment times were slightly longer post AlloSCT than ASCT (ANC>0.5 = 15 vs 11d, and platelets>20 = 12 vs 9d, respectively). Of 15 AlloSCT patients, grade 3-4 aGVHD occurred in 5 (33%), cGVHD occurred in 64%, and death from extensive cGVHD + infection occurred in 5 patients from 7-13mo post-AlloSCT (overall NRM=33% for AlloSCT). With a median follow-up of 22mo, the 2 year projected outcome of ASCT vs Allo/Syngeneic-SCT for relapse-free survival (RFS) was 64% vs 87% (logrank p=0.48), event-free survival (EFS) 63% vs 52% (logrank p=0.38), and overall survival (OS) 86% vs 46% (logrank p=0.0018), respectively. For relapsed follicular lymphoma only, the 2yr EFS was 61% vs 59% (logrank p=0.49) and OS 100% vs 51% (logrank p=0.0009) for ASCT (n=19) vs Allo/Syngeneic SCT (n=11), respectively.These preliminary results suggest that RICE can ‘in-vivo’ purge autografts but mobilizes blood stem cells only moderately well. RICE-FluBu/ASCT may result in prolonged EFS with significantly less NRM than AlloSCT.(Source: American Society of Haematology (ASH): Blood, Volume 104, issue 11, November 16, 2004.)