Allogeneic hematopoietic stem cell transplantation in patients aged 60-79 years in Germany (1998-2018): a registry study

Abstract

Incidences of diseases treated with transplantation frequently peak at higher age. The contribution of age to total risk of transplantation has not been estimated amidst an aging society. We compare outcomes of 1,547 patients aged 70-79 years and 9,422 patients aged 60-69 years transplanted 1998-2018 for myeloid, lymphoid and further neoplasia in Germany. To quantify the contribution of population mortality to survival, we derive excess mortality based on a sex-, year- and agematched German population in a multistate model that incorporates relapse and graft-versus-host-disease (GvHD). Overall survival, relapse-free survival (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients aged 70-79 years, compared to patients aged 60-69 years, with 36% (95% Confidence Interval [CI]: 34-39%) versus 43% (41-44%), 32% (30- 35%) versus 36% (35-37%) and 23% (21-26%) versus 27% (26-28%) three years post-transplant (P<0.001). Cumulative incidences of relapse at three years are 27% (25-30%) for patients aged 70-79 versus 29% (29-30%) (60-69 years) (P=0.71), yet the difference in non-relapse mortality (NRM) (40% [38-43%] vs. 35% [34-36%] in patients aged 70-79 vs. 60-69 years) (P<0.001) translates into survival differences. Median OS of patients surviving >1 year relapse-free is 6.7 (median, 95% CI: 4.5-9.4, 70-79 years) versus 9 (8.4-10.1, 60-69 years) years since landmark. Three years after RFS of one year, excess NRM is 14% (95% CI: 12-18%) in patients aged 70-79 versus 12% [11-13%] in patients aged 60-69, while population NRM is 7% (6-7%) versus 3% (3-3%). Mortality for reasons other than relapse, GvHD, or age is as high as 27% (24-29%) and 22% (22-23%) four years after transplantation. In conclusion, survival amongst older patients is adequate after allogeneic stem cell transplantation.

Figure 1.

Epidemiology of reported population. (A) Frequency of age groups among all patients. (B) Frequency of disease among all patients. (C) Frequency of age groups in patients with acute leukemia. (D) Frequency of age groups in patients with myelodys-plasia. (E) Frequency of age groups in patients with chronic leukemia. (F) Frequency of age groups in patients with lymphoma. (G) Frequency of age groups in patients with other diseases than those described above (bone marrow failure, solid tumors, hemoglobinopathies, etc.). HSCT: hematopoietic stem cell transplantation.

Figure 2.

Survival analysis. (A) Kaplan-Meier estimations of overall survival (OS) and relapse-free survival (RFS) by age group. (B) Kaplan-Meier estimations of OS after having reached 1-year failure-free survival of different definitions: death (OS), death + relapse (RFS), death + relapse + severe graft-versus-host disease (GvHD) (graft-versus-host-relapse-free-survival; GRFS). All patients with respective events before 1-year landmark (LM) were excluded. (C) Kaplan-Meier estimations of age-group-specific OS during 1998-2008 and 2009-2018. (D) Competing risk analysis of relapse and non-relapse mortality (NRM). (E) Competing risk analysis of severe GvHD and non-GvHD-mortality (NGM). (F) Competing risk analysis of relapse and NRM with regards to low versus intermediate versus high TCI. alloSCT: allogeneic stem cell transplantation; TCI: total conditioning intensity.

Figure 3.

Multistate modeling of relapse-free survival and graft-versus-host-relapse-free-survival. (A) Multistate progress of follow-up after one year without failure (death / relapse) in patients aged 70-79 years. (B) Multistate progress of follow-up after one year without failure (death / relapse) in patients aged 60-69 years. (C) Multistate progress of follow-up after one year without failure (death / relapse / severe graft-versus-host disease [GvHD]) in patients aged 70-79 years. (D) Multistate progress of follow-up after one year without failure (death / relapse / severe GvHD) in patients aged 60-69 years. NRM: non-relapse-mortality; DAR: death after relapse; NRNGM: non-relapse-non-GvHD-mortality; DaGvHD+R: death after GvHD and relapse; DaGvHD: death after GvHD; R: Relapse; p: due to population mortality (NRM and NRNGM in bold); e: due to excess mortality.