Higher Age (≥60 Years) Increases the Risk for Adverse Events during Autologous Hematopoietic Stem Cell Transplantation

Abstract

Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard of care for patients with hemato-oncologic diseases. This procedure is highly regulated, and a quality assurance system needs to be in place. Deviations from defined processes and outcomes are reported as adverse events (AEs: any untoward medical occurrence temporally associated with an intervention that may or may not have a causal relationship), including adverse reactions (ARs: a response to a medicinal product which is noxious and unintended). Only a few reports on AEs cover the procedure of autoHSCT from collection until infusion. Our aim was to investigate the occurrence and severity of AEs in a large data set of patients who were treated by autoHSCT. In this retrospective, observational, single-center study on 449 adult patients during the years 2016-2019, AEs occurred in 19.6% of the patients. However, only 6.0% of patients had ARs, which is a low rate compared to the percentages (13.5-56.9%) found in other studies; 25.8% of the AEs were serious and 57.5% were potentially serious. Larger leukapheresis volumes, lower numbers of collected CD34+ cells and larger transplant volumes significantly correlated with the occurrence and number of AEs. Importantly, we found more AEs in patients >60 years (see graphical abstract). By preventing potentially serious AEs of quality and procedural issues, AEs could be reduced by 36.7%. Our results provide a broad view on AEs and point out steps and parameters for the potential optimization of the autoHSCT procedure, especially in elderly patients.

Keywords: adverse events; adverse reactions; age; autologous hematopoietic stem cell transplantation; collection; hematopoietic stem and progenitor cells; processing; transplant product; transplantation.

Figure 1

Flow chart of the patient cohorts and transplantations with or without AEs.

Figure 2

AEs per category (collection, processing, transplantation, non-patient assigned) and subcategory (quality, AR, procedure, administration, infrastructure, material). (a) All AEs, (b) graded according to seriousness, (c) according to age (transplantations in patients <60 years, n = 256 and ≥60 years, n = 254), and (d) according to age and seriousness.

Figure 3

Parameters according to AEs and age. (a) Collected volumes and CD34+ cells during leukapheresis, (b) numbers of Lc, MNC, and PNC in the transplant product, (c) total transplanted volumes and times to reach an absolute neutrophil count of >0.5 × 10⁹/L and a platelet count of >20 × 10⁹/L. Data without the CD34+-selected transplants; significance: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001.

Figure 3

Parameters according to AEs and age. (a) Collected volumes and CD34+ cells during leukapheresis, (b) numbers of Lc, MNC, and PNC in the transplant product, (c) total transplanted volumes and times to reach an absolute neutrophil count of >0.5 × 10⁹/L and a platelet count of >20 × 10⁹/L. Data without the CD34+-selected transplants; significance: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001.

Figure 4

Parameters according to number of AEs. (a) Age, sex, and disease (all data included), (b) collected volumes and CD34+ cells during leukapheresis, (c) numbers of Lc, MNC, and PNC in the transplant product, (d) total transplanted volumes and times to reach an absolute neutrophil count of 0.5 × 10⁹/L and a platelet count of >20 × 10⁹/L. Data without the CD34+-selected transplants; significance: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001.