Impact of Myeloablative and Reduced Intensity Conditioning On Outcomes After Unrelated Cord Blood Transplantation for Adults with ACUTE Lymphoblastic Leukemia

Allogeneic hematopoietic stem cell transplantation is the only curative option for high risk adult acute lymphoblastic leukemia (adALL). In the absence of an HLA identical sibling donor, HLA matched unrelated donor or HLA mismatched cord blood are alternative stem cell sources. However, very few data on the outcomes after umbilical cord blood transplantation (UCBT) for adALL using myeloablative (MAC) or reduced intensity (RIC) conditioning regimens have been reported.   We conducted a retrospective survey on the outcomes after UCBT for adALL and a more specific analysis for patients with cytogenetic data transplanted in remission with either MAC or RIC. From 1996 to 2011, 433 adult patients (pts) received a UCBT for ALL. Overall 2-year LFS was 37% for pts in first complete remission (CR1, n=199), 32% for CR2 (n=138) and 9% for advanced disease (n=96). Complete cytogenetic data at diagnosis was available for 316 pts, of whom 251 were transplanted in CR1 (63%, n=157) or CR2 (37%, n=94). Median age at UCBT was 33 years (18 to 66) and 76% of the pts (n=191) had an abnormal karyotype at diagnosis. Pts were analyzed according to the presence of t(9;22) as Ph+ (n=115) and Ph- (n=136). Double CBT was performed in 109 pts (43%) and the median total nucleated cell dose at freezing was 4.02x10⁷/kg. Most pts received CBU with 1 (n=74) or 2 (n=136) HLA disparities. MAC was given to 177 pts (70%) and 73 (30%) received RIC. Overall 2-year leukemia- free survival (LFS) was 36±3%; 37% for Ph- and 35% for Ph+ pts (p=NS). On multivariate analysis, 3 factors were associated with improved LFS: age <44 years (HR: 0.6, p=0.004), CR1 at transplant (HR: 0.6, p=0.005) and use of RIC (HR: 0.6, p=0.015).

In pts transplanted with MAC (n=177), most used regimens were Cy-TBI (27%) and Bu+Flu+Thio (25%). Median follow-up (FU) was 26 and 35 months for CR1 (n=107) and CR2 (n=70). Cumulative incidence (CI) of 60-day neutrophil recovery was 87% (CR1) and 83% (CR2); acute GVHD was 43% and 37%, respectively. Two-year CI of NRM was 41% and 49%; 2-year RI was 24% and 22% for CR1 and CR2, respectively. Two-year LFS was 35% for CR1 and 30% for CR2. No factor was found to be associated with LFS, relapse or NRM.

In pts transplanted with RIC (n=73), Cy+Flu+TBI was used in 74% (n=54). Median FU was 31 and 34 months and median age was 50 and 39 years for CR1 (n=49) and CR2 (n=24), respectively. At 2 years, CI of NRM was 22% (CR1) and 17% (CR2). Two-year RI was 30% and 47%, respectively. Two-year LFS was 49% (CR1) and 36% (CR2). For pts in CR1, univariate analysis showed that younger age (< 50 years) was associated with improved LFS (62% x 36%, p=0.042) and lower NRM.

UCBT is an option to treat high risk adALL. MAC was associated with a LFS comparable with that reported with other stem cell sources, but strategies to reduce toxicity are still needed. Results with RIC are encouraging and may be considered in younger pts. Importantly, in this large series outcomes after UCBT were similar for Ph+ and Ph- ALL.