Outcomes of Patients Older than Age 70 Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies

Allogeneic hematopoietic stem cell transplantation (HSCT) can achieve durable remissions in a number of advanced hematologic malignancies. The advent of reduced intensity conditioning (RIC) regimens has allowed HSCT to be offered to increasingly older adults. However, little is known about the safety of HSCT in patients over the age of 70 years. The purpose of this retrospective study was to describe the overall outcomes of patients older than age 70 who underwent HSCT for hematologic malignancies. We identified 56 consecutive patients age 70 or older who underwent HSCT at Massachusetts General Hospital or the Dana-Farber Cancer Institute between January 2007 and July 2012. Patients were included in this study if age 70 or older on the day of transplantation. All patients met standard institutional criteria for HSCT eligibility. The majority of patients underwent transplant for acute leukemia or myelodysplastic syndrome (AML 26, MDS 15, CLL 5, NHL 4, ALL 3, MPD 2, CML 1). Median follow-up for survivors was 15 months (range 2-86). The median age at transplant was 71 years (range 70-76) and 66% (37/56) were male; the median HCT-CI score was 1 (range 0-5). All patients received RIC regimens with 93% receiving a busulfan / fludarabine regimen. All patients received peripheral blood stem cell grafts; 44 from an 8/8 matched unrelated donor (MUD), 10 from a matched related donor (MRD), and 2 from a 7/8 matched unrelated donor. 95% of patients received calcineurin inhibitor-based GVHD prophylaxis regimens, most in combination with sirolimus or methotrexate (Table 1). Of these 56 patients, 2 died prior to engraftment, one from graft failure and one from disease progression. Of the 46 patients who experienced a nadir, the median time to neutrophil engraftment was 13 days (range 2-31). Maximum cumulative grade II-IV acute GVHD incidence was 13% and grade III-IV acute GVHD 7%. One year cumulative chronic GVHD incidence was 37%. One-year progression-free survival was 42% and one-year overall survival was 55%. The cumulative incidence of relapse was 34% and non-relapse mortality was 3.6% at day 100 and 5.5% at 1-year after HSCT. HSCT is a safe and effective option for patients over the age of 70. Further follow-up and analysis are needed to determine which patients will derive benefit from allogeneic transplantation; however, for carefully selected elderly patients, age over 70 should not preclude consideration of HSCT.

Table 1: Patient Characteristics

Age (median, range)	71 (70-76)
Male (n, %)	37 (66%)
HCT-CI score (median, range)	1 (0-5)
Disease (n, %)
AML	26 (46%)
MDS	15 (27%)
CLL	5 (9%)
NHL	4 (7%)
ALL	3 (5%)
MPD	2 (4%)
CML	1 (2%)
Donor Type (n, %)
MUD	44 (79%)
MRD	10 (18%)
Mismatched UD	2 (4%)
Conditioning Regimen (n, %)
Busulfan/Fludarabine	53 (93%)
Melphalan/Fludarabine	2 (4%)
Clofarabine/ATG/TLI	1 (2%)
GVHD Prophylaxis (n, %)
CNI + Siro ± MTX	34 (61%)
CNI + MTX	9 (16%)
CNI + ATG + MTX	7 (13%)
CNI + MMF	3 (5%)
Other	3 (5%)