Allogeneic Hematopoietic Cell Transplantation (HCT) after Nonmyeloablative Conditioning for Patients (pts) Aged ≥60 Years.
Authors: Sorror Mohamed L. , Storer Barry , Sandmaier Brenda M. , Maloney David G. , Franke Georg , Shizuru Judith , Chauncey Thomas , Agura Edward , Maziarz Richard T. , Sahebi Firoozeh , Langston Amelia A , Wade James C. , Maris Michael , Bruno Benedetto , Yeager Andrew M. , Pulsipher Michael , Petersen Finn , Bethge Wolfgang A. , McSweeney Peter A. , Niederwieser Dietger , Blume Karl G. , Storb Rainer F. 
Published: April 2020

Median ages of pts with most hematological malignancies are beyond 60 years. The advent of nonmyeloablative conditioning regimens has extended the use of allogeneic HCT to these older pts. Here, we retrospectively investigated outcomes among 280 pts aged ≥60 years, given HCT between 1998 and 2006. Results were broken down in 3 age groups 60–64 (n=166), 65–69 (n=90), and ≥70 (n=24) years old, respectively. Pts aged ≥70 years had less preceding chemotherapy, less often failed autologous HCT, more often had related grafts, and had higher comorbidity scores compared to pts in the other two age groups (table 1). Acute leukemias were more frequent and lymphoma/multiple myeloma were less frequent among pts aged ≥70 years old, resulting in higher risk for relapse (Table 1). After HCT, non-relapse mortality, relapse, and progression free survivals at 5-years for all pts were 26%, 41%, and 32% respectively. Five-year Kaplan Meier rate of overall survival was 35%, of those 12% vs. 23% were with vs. without chronic GVHD requiring immunosuppressive therapy, respectively. There were no statistically significant differences in outcomes among the three age groups except for more infections and days of hospitalization among pts aged 65–69 years compared to the other two age groups (Table 2). In multivariate analyses of risk factors, high HCT-comorbidity index (1–2 and ≥3) independently predicted higher NRM (HR: 2.84 and 3.0, respectively, p=0.01) and, not surprisingly, previously defined high relapse risk predicted relapse (HR: 2.17, p=0.06); both predicted worse OS (p=0.005 and p=0.0009, respectively) and PFS (p=0.01 and p=0.02, respectively). Pts given unrelated grafts did as well as recipients of related grafts. In conclusion, nonmyeloablative allogeneic HCT can be curative among pts older than 60 years with resolution of chronic GVHD among a majority of pts. Comorbidities and relapse risk rather than age should be used for benefit-risk assessment. Continued enrollment of elderly pts in prospective studies including unrelated donors is warranted.

Table 1: Pt characteristics

Age groups, years (60–64) (n=166) (65–69) (n=90) (70–74) (n=24) Median Interval from Dx to HCT, months 19 15 8 Median (range) # of prior regimens 3 (0–14) 3 (0–13) 2 (0–10) Median CD34+ cell number x 106/kg 6.7 6.7 6.5 Median CD3+ cell number x 108/kg 2.9 3.1 3.4 % Prior radiotherapy 18 11 13 Prior HCT Failed 19 12 4 Planned 8 6 4 Positive patient CMV sero-status 58 65 79 HLA-matched related 54 53 83 Donor HLA-matched unrelated 41 44 17 HLA-mismatched unrelated 5 3 0 Conditioning 2 Gy TBI 12 13 21 2 Gy TBI + FLU 88 87 79 HCT-CI scores 0 27 27 15 1–2 30 39 25 3–4 30 17 40 ≥5 13 17 20 Diagnoses Acute leukemia 35 47 62 Chronic leukemia 15 13 13 Lymphoma/myeloma 21 23 8 Myelodysplastic/myeloproliferative 16 16 17 Others 3 1 0 Disease status at HCT CR 46 41 38 PR 15 30 21 Refractory 28 21 33 Relapse 11 8 8 Relapse risk Low 19 17 8 Standard 48 51 38 High 33 32 54

Table 2: Outcomes per age groups

HCT Outcomes Age groups, years P* (60–64) (n=166) (65–69) (n=90) (70–74) (n=24) FUO indicates fever of unknown origin *Test for trend μBased on hazard ratio analysis Bacterial 1.4 2.3 1.7 .0004 Rates of Infection episodes per person Viral 0.7 1.1 0.7 NS within 100 days FUO 0.3 0.4 0.1 NS Fungal 0.3 0.2 0.3 NS Median (range) days of hospitalization 1 (0–60) 4.5 (0–179) 0.5 (0–47) NS % Acute GVHD Grades II–IV 52 49 54 NSμ Grades III–IV 16 12 13 NSμ Chronic extensive GVHD 39 45 54 0.05μ NCI-CTC criteria grades III–IV non-hematological toxicities 42 57 50 NSμ Pts with Full donor chimerism at 1-year CD3/CD33/BM 68/ 84/ 80 66/ 83/ 77 67/ 79/ 71 NSμ CR at 2-years 40 47 63 NSμ 5-years Relapse/progression 38 46 46 NSμ 5-years NRM 28 22 29 NSμ 5-years OS 37 36 23 NSμ 5-years PFS 34 31 25 NSμ Patients alive and off all immunosuppression 24 25 5 NSμ