The Clinical Outcome of Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for Elderly Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) in the Era of Tyrosine Kinase Inhibitor (TKI) : A Single Institute Experience

<Background>

Treatment with TKIs has greatly improved the outcome of patients with Ph+ALL. However most older patients are excluded from clinical studies, the curative potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been fully analyzed. We examine the clinical features and transplant outcome of elderly Ph+ALL patients in the era of TKI.

<Methods>

 We analyzed the data from 30 Ph+ALL patients aged 50 years or older who had used TKI before allo-HSCT.

<Results>

The median age was 59 years (range<r>: 50-71);15 patients (50%) were older than 60 years. Subjects comprised 13 males and 17 females. The disease status at allo-HSCT was complete remission (CR) in 23 patients and non-CR in 7 patients. Before HSCT, 23 patients received imatinib-based chemotherapy, and 7 patients received dasatinib-based chemotherapy. The majority of the donors were HLA-matched unrelated (n=16) and related (n=6), followed by mismatched unrelated cord blood (n=7). Median follow-up for survivors was 247 days (r :16- 4,156). The median HCT comorbidity index score was 1 (r : 0-3). Median white blood cell counts at diagnosiswas 26.3X10⁹/L(r: 4.2-301.9 X10⁹/L). Type of BCR breakpoint was minor in 23 patients (67%). Graft-versus-host-disease (GVHD) prophylaxis was calcineurin inhibitor-based in all patients (CsA:13 patients, FK506:17). Eleven patients received reduced-intensity conditioning regimens, nineteen patients received myeloablative conditioning regimens. The median duration from the diagnosis to HSCT was 197 days (95-763). No patient received TKIs after HSCT.

The probability of overall survival (OS) and disease free survival (DFS) at 1 year after HSCT were 46.0% and 42.0%, respectively. These results were not statistically different compared to the 35 patients aged under 50 years who had used TKIs before allogeneic HSCT. Multivariate analysis showed that the factor to influence OS was disease status (CR or nonCR) (p=0.01). Cumulative incidence of nonrelapse mortality (NRM) was 23.1% at 100 days after HSCT, and 52.0% at 1 year. The cumulative incidence of acute graft-versus-host disease <GVHD> (gradeII-‡W) and chronic GVHD at 1 year were 51.8% and 23.1%. Four patients relapsed after HSCT with a median of 329 days (r : 112-475 days). The estimated cumulative incidence of relapse at 1 year was 8%. These outcomes (OS, DFS, NRM, relapse rate) were not significantly different when stratified by age groups (under vs. older than 60 years old). Increasing age was not associated with increases in acute or chronic GVHD. All of patients aged more than 60 years had HCT comorbidity index scores of 2 or less.Eighteen patients died at 139 days (r:16-1,219). The main cause of death was infection (10 patients).

<Conclusion>

Allo-HSCT for elderly Ph+ALL patients may be one of the promising strategy. Allo-HSCT would be effective option for carefully selected patients aged 60 or older with Ph+ALL.