AML World Awareness Day 2020 | Outcomes of long-term survivors after hematopoietic stem cell transplantation

On April 21, 2020, the acute myeloid leukemia (AML) World Awareness Day will enable the community to unite, share knowledge, and raise awareness of the advances in the prevention, management, and treatment of AML. To find out how you can participate in AML World Awareness Day, visit www.know-aml.com.

Despite advances in the field of targeted therapies, hematopoietic stem cell transplantation (HSCT) is still an important curative option for a number of hematological and non-hematological disorders.¹ Over the last years, changes such as the use of cord blood (CB) cells or haploidentical donors as stem cell sources, conditioning regimens, and graft-versus-host disease prophylaxis have increased the accessibility to HSCT,¹ augmenting the number of global annual HSCT.²

In a paper, published in Biology of Blood and Marrow Transplantation, David Kliman and colleagues reported the outcome of long-term survivors who underwent HSCT from 2002–2011. Data were obtained from the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) and compared with survivors transplanted between 1992–2001 and with the age-matched general population.³

Study design³

• Of 12,664 recorded transplants between 2002–2011, 2-year disease-free post-HSCT survivors who underwent allogeneic (allo) or autologous (auto) HSCT for specific diseases were included in the study analysis:
  • Allo-HSCT (n = 1562)
    • Acute lymphoblastic leukemia
    • AML
    • Chronic myeloid leukemia (CML)
    • Myelodysplastic syndromes (MDS)
    • Non-Hodgkin lymphoma (NHL)
  • AutoHSCT (n = 3822)
    • Hodgkin lymphoma
    • Multiple myeloma (MM)
    • NHL
  • Median follow up was 5.6 years

Results³

Outcomes after allo-HSCT

Compared with 2-year allo-HSCT survivors from 1992─2001, the 2002─2011 cohort presented different characteristics, reported in Table 1.

Table 1. Patient and transplant characteristics of 2-year allo-HSCT survivors by time periods

Despite the different characteristics, such as transplant age (with an increase from 11% to 21% in patients transplanted at ages 50─59, and from 1% to 7% in patients transplanted over 60 years), cell source, and donors, the 10-year OS was similar between the two cohorts: 78.4% vs 80.3% in the 1992─2001 vs the 2002─2011 cohort, respectively. Favorable factors associated with OS were age < 16 years and transplantation for CML, whereas adverse factors were represented by peripheral blood (PB) stem cell source, transplantation for MDS, male recipient, poor risk disease, and age > 45 years. Hazard ratio (HR), 95% confidence interval (CI), and p values for each variable are reported in Table 2.

Table 2. Risk factors for OS in 2-year allo-HSCT survivors³

• Relative survival was similar to the age-matched population, with survival ratios ranging from 96% to 99%, but still significantly lower than the general population
• By 10-year posttransplant
  • cumulative incidences of chronic GvHD: 30%
  • relapse: 11%
  • death due to relapse: 7%
  • NRM incidence: 14%
  • deaths due to new malignancy: 7%

Outcomes after auto-HSCT

The characteristics of the 2-year auto-HSCT survivors from the 2002─2011 cohort were compared with the 1992─2001 cohort and are reported in Table 3. An increase in median age at transplant (with a greater proportion of patients, 37% vs 16%, transplanted over 60 years in the 2002─2011 cohort vs the 1992─2001 cohort) and a decrease in the use of BM as stem cell source were observed.

Table 3. Patient and transplant characteristics of 2-year auto-HSCT survivors by time period³

Despite these differences, by 10-year post auto-HSCT,

• for lymphoma
  • OS: 61.8% vs 67.7% (p = 0.2) in the 2002─2011 vs the 1992─2001 cohort, respectively
  • cumulative incidences of relapse: 23%
  • death due to relapse: 15%
  • NRM: 23% 
• for MM
  • OS: 42.5% vs 41.2% (p = 0.5) in the 2002─2011 vs the 1992─2001 cohort, respectively
  • cumulative incidences of death: 37%
  • NRM: 21%

Adverse risk factors for OS were

• male recipient, HR 1.15 (95% CI, 1.04─1.26; p = 0.005)
• transplant for myeloma, HR 1.75 (95% CI, 1.59─1.94; p < 0.001)
• age > 45 years, HR 1.97 (95% CI, 1.73─2.25; p < 0.001)

The relative survival ratio was close to the age-matched population but still significantly lower (89–96%), with a better relative survival for patients with lymphoma (91–97%) compared with MM (88–96%).

Conclusion³

• Two-year allo-HSCT and auto-HSCT recent survivors are older and more likely to receive PB stem cells than survivors from the 1992─2001 cohort, but this analysis showed that advancing age (for both allo-HSCT and auto-HSCT) and the use of PB as stem cell source (for allo-HSCT) were an adverse risk factor for OS
• Despite this, OS is similar between the 2002─2011 and the 1992─2001 cohort, and relative survival is similar to the general population but still reduced
• Auto-HSCT for MM has increased but the OS of 42.5% was lower than for patients with lymphoma
• Late mortality, after allo-HSCT, was primarily due to NRM but for auto-HSCT, relapse or disease progression were the major causes of death
• Risk factors, except for the selection of cell source, are not modifiable but might be used to identify high-risk patients requiring additional follow-up after HSCT
• All together, these results, specific to the Australian and New Zealand population, demonstrate that the outcomes of the 2-year HSCT survivors are similar over time, and a tailored risk-specific monitoring for late effects is essential to improve long-term survival