Reduced-Intensity Cord Blood Transplantation without Preceding Remission Induction Therapy Induces Durable Remission in Patients with Relapsed Acute Leukemia After the First Allogeneic Stem Cell Transplantation.
Authors: Ueki Toshimitsu , Nasu Kentaro , Shimizu Ikuo , Sumi Masahiko , Ueno Mayumi , Ichikawa Naoaki , Kobayashi Hikaru 
Published: October 2019

Abstract
Abstract 4341
Relapses in acute leukemia (AL) following allogeneic stem cell transplantation (allo-SCT), particularly those relapses within 1 year after transplantation, are often refractory to induction chemotherapy. Patients with this type of relapse rarely achieve long-term remission even after the second SCT. Cord blood transplantation, performed in a timely manner, may improve treatment outcomes in these patients. To assess the effectiveness of second cord blood transplantation (CBT) with a reduced intensity conditioning (RIC) regimen early after the diagnosis of leukemia relapse, we retrospectively analyzed outcomes from RIC-CBT without preceding remission induction therapy in 11 consecutive patients.
Between 2007 and 2009, we performed CBTs with a RIC regimen for 11 patients with AL who relapsed after allo-SCT. Seven patients were diagnosed with acute myeloid leukemia and four with acute lymphoblastic leukemia. Median duration between the first and the second SCT was six months (range: 3-24 months). Median duration between the relapse and the second SCT was 39 days (range: 22-60 days). All but one patient didnot receive induction chemotherapy due to the low probability of achieving complete remission (CR),and another patient didnot receive induction chemotherapy due to low blast percentage in bone marrow. Mean blast counts in bone marrow and peripheral blood were 39.3% and 22.1%, respectively. All but one patient were conditioned with fludarabine (25 mg/m2/day) from Day -8 to Day -4, with L-PAM (40 mg/m2/day) from Day -3 to Day -2, and with TBI (4Gy) on Day -1. Only FK506 was administered to patients as a graft versus host disease (GVHD) prophylaxis. Mean concentrations of FK506 during the first, second, third, and fourth 10-day period after CBT were 8.9, 8.9, 10.2, and 9.8 ng/ml, respectively. Median follow-up period was 12 months after transplantation in patients who survived.
Six patients were alive at the last follow-up with a 1-year and 2-year OS rate of 72.7% and 36.4%, respectively. Five of these 6 patients have been maintaining CR. Four of the 5 patients maintaining CR were considered to be at an extremely high risk for relapse because they relapsed within 8 months (median: 5.5 months, range: 5 to 8 months) after the first SCT. These 4 patients have maintained CR with a median follow-up of 12 months (range: 7 to 32 months). The 2-year probabilities of transplant-related mortality (TRM), relapse-free survival (RFS), and relapse were 27.3%, 40.9%, and 42.9%, respectively. RIC-CBT without preceding remission induction therapy using a relatively low concentration of FK506 as a GVHD prophylaxis may be a promising therapeutic option for patients with AL who relapse shortly after the first transplantation.
Age/Sex Disease Donor type of 1st SCT Preparative regimen of 1st SCT Time (months) from 1st SCT to relapse Time (days) from relapse to 2nd SCT Blast BM Blast PB Status last follow up Overall Survival (months) 53/F AML MUD TBI-CY 12 42 31.8% 3% death no relapse 3 42/M AML CB TBI-CY 5 37 49.4% 6% alive CR 32 40/F AML CB BU-CY-TBI 5 32 29.0% 81% death relapse 15 38/M AML MUD TBI-CY 21 28 64.8% 80% death no relapse 2 28/F AML SIB Flu-Mel-TBI 24 60 6.4% 1% alive CR 23 19/M ALL SIB TBI-CY 8 35 50.0% 49% death relapse 15 21/M ALL MUD TBI-CY 8 22 73.8% 1% alive CR 7 50/M AML MUD TBI-CY 5 39 9.0% 2% alive CR 9 45/F ALL SIB TBI-CY 6 41 57.8% 4% alive CR 15 55/F ALL(Ph1) SIB TBI-CY 4 41 51.2% 16% alive relapse 6 21/F AML Related TBI-CY 6 42 9.2% 0% death no relapse 3

Disclosures:
No relevant conflicts of interest to declare.