Outcomes for Patients Aged 60 and Over Are Similar to Younger Patients Following Reduced-Intensity Allogeneic Stem Cell Transplant for CLL
Authors: Toze Cynthia L. , Dalal Chinmay B. , Nevill Thomas J. , Barnett Michael J. , Nantel Stephen H. , Forrest Donna L. , Hogge Donna E. , Sutherland Heather J. , Song Kevin W. , Mourad Yasser Abou , Broady Raewyn , Power Maryse M. , Narayanan Sujaatha , Gillan Tanya L. , Smith Clayton A. , Shepherd John D. 
Published: October 2019

Abstract
Abstract 3100
The advent of reduced intensity (RI) conditioning for allogeneic stem cell transplant (HSCT) has brought the question of safe application of this therapy (tx) to older patients. This is of particular importance in CLL where the median age at diagnosis (dx) is 65 yrs. This study compares outcome post RI HSCT in those aged 60 and older (older group, n=23 pts) to those less than age 60 (younger group, n=35 pts) who received RI HSCT at the Leukemia/BMT Program of BC 2001 - June 2011 (total group n=58). Forty-two of 58 (73%) were male. Racial origin was mostly white with only 2/58 (3%) Asian pts. Max stage (Rai) pre-HSCT was advanced (III + IV) in most (31/58, 53%); 13 pts (22%) had B symptoms. Characteristics of the entire group (n=58) include (med, range): interval from dx to HSCT 7.4 yrs (0.4–29); number of prior tx 4 (1–14) and % lymphocytes in pre-HSCT marrow 71 (3–98). 22% (13/58) had bulky nodes (>5cm). Six (10%) had Richter's transformation. HSCT comorbidity index (Sorror) was 0 in 33 (57%), 1–2 in 18 (31%) and >= 3 in 7 pts (12%). Most received prior nucleoside analog (57/58, 99%) and rituxan (47/58, 81%) tx. Twenty-five (43%) were resistant (RES) to last tx given; 30 of 56 pts (54%) were fludarabine (flu) RES. The younger and older group were similar apart from age at dx and HSCT (med, range) which were 47 (26–57) vs 54 (36–55) yrs and 56 (42–59) vs 63 (60–68) yrs respectively. Med donor age was 46 yrs (19–76); 39 (67%) were male; 83% of female donors were parous; 27 (47%) were unrelated (UD); and 12 (21%) mismatched. Stem cells were peripheral blood. Conditioning was non-myeloablative (flu/cy) in 14 pts (24%), and reduced intensity (fludarabine/busulfan) in the remainder (44 pts, 76%). For UD HSCT campath was added to flu/bu in 19 and thymoglobulin in 8 pts. Gvhd prophylaxis was cyclosporine and methotrexate. Count recovery occurred in 97%; 2 pts did not recover (both <60yrs); 1 died (H1N1) and 1 is > 1 year post 2nd RI UD HSCT. Graft failure (GF) occurred in 8 pts (14%) predominantly related to campath; 1 pt died (H1N1), 1 is well with autologous recovery 3 yrs post GF and 6 of 8 required further HSCT (including 2 older pts who survive > 1 yr post 2nd HSCT). Acute graft vs host disease (gvhd) grades 2–4 occurred in 83% of pts and chronic gvhd in 54% and was neither more severe nor prevalent in older pts. CR post HSCT has occurred in 26 /58 pts (45%), a med (range) of +108 days (0 days -5.4 yrs). DLI was given to 11 pts (4 older pts). At median (range) follow up of 20 months (0.3–120) post HSCT and 10.1 yrs (0.7–37) post dx 44 / 58 pts (75%) survive in the whole group, including 25/35 pts (71%) younger group and 19/23 pts (83%) older group. Death in CR occurred in only 2/14(14%) deaths or 2/58 pts (3%), both of whom were younger pts. Time of death post HSCT was similar in the younger and older groups. Pre-HSCT FISH was performed in 52 /58 pts; results were abn in 47/52 pts (90%); 28/29 (97%) younger and 19/23 (83%) older group and included: del 17p in 15 pts (26%); del 11q in 15 (26%); trisomy 12 in 11 (19%); del 13q in 29 (50%) and bi-allelic del 13q in 11 (19%). Abn FISH normalized pre-HSCT in 8 /52 (15%) and post-HSCT in 18/40 pts (45%), leaving only 22/54 (40%) with currently abnormal FISH tests. Donor chimerism >=90% was achieved to date in 43/50 assessable pts (86%) and occurred with similar frequency in younger and older age groups. Survival analysis for the whole group demonstrated the following had a positive impact on OS (p value): achievement of donor chimerism > 90% (0.006); CR post HSCT (0.010) and normal FISH or clearance of previously abn FISH (0.007). Non-significant factors included FISH (Dohner ranking); 17p del; acute gvhd gr 2–4; cgvhd; and patient age. KM estimate for OS at 1, 2, and 5 years is: whole group 85%, 73%, 73%; younger 82%, 73%, 73; older 90%, 72%; 72%. There is no difference in OS for the younger vs older group (p= 0.7). In conclusion advances have now made it possible to safely and successfully perform RI HSCT for fit older pts with CLL and obtain similar outcome and overall survival to younger pts. This allows application of this potentially curative therapy to this important patient population.

Disclosures:
No relevant conflicts of interest to declare.