It cannot be ruled out that the COVID-19 pandemic since early 2020 has also affected the medical care of patients with life threatening hematological disorders, who required an autologous or allogeneic stem cell transplant. These patients have a notably increased mortality risk as a result of their substantially reduced immunocompetence if they contract COVID-19 (1, 2). The European Society for Blood and Marrow Transplantation (EBMT) published recommendations regarding this risk—also in association with the increasing capacity problems regarding intensive care beds and the temporary closure of borders, which substantially impaired the stem cell transport from voluntary, non-related donors—in order to ensure donor and patient safety. In addition to preventive measures, the EBMT also recommends delaying less urgently needed transplantations and freezing allogeneic stem cell products.
The present study aimed to compare data on stem cell transplantations in Germany from 2020 and 2021 with those of earlier years, in order to determine the effects of the COVID-19 pandemic on this potentially curative treatment modality in mostly malignant hematological disorders. Germany‘s transplantation centers collect the data of patients who received an autologous or allogeneic stem cell transplant in the German Registry for Stem Cell Transplantation (DRST). The DRST‘s annual survey captures the number of stem cell transplantations carried out in Germany as well as that of CAR-T cell therapies separated by type and indication almost in its totality.
Acknowledgments
Translated from the original German by Birte Twisselmann, PhD.
Acknowledgment
Sandra Frank received support from the German Research Foundation, grant application BE4500/4–1.
Footnotes
Conflict of interest statement
Nicolaus Kröger is the first chair of the DRST and was, until March 2022, president of the European Society for Blood and Marrow Transplantation.
Helga Neidlinger is employed by the DRST and Sandra Frank was employed there until September 2021.
Katharina Fleischhauer is the co-chair of the DRST.
Peter Dreger is the spokesperson of the Deutsche Arbeitsgemeinschaft für Stammzelltransplantation und Zelluläre Therapie [the German working group for stem cell transplantation and cellular therapy].
Methods
We analyzed survey data from 2020 and 2021 and compared these with data from the 2018 and 2019 surveys. The data are from 133 German transplantation centers. We obtained specific data for covariables from the associated database ProMISe (Project Manager Internet Server). We used Poisson regression to analyze the effect of the year of the transplant and the center on the number of autologous and allogeneic stem cell transplantations. The factors of influence year of transplantation and center were included in the analysis as categorical variables. We report so called relative risks (RR) with 95% confidence intervals; the estimated RR is the exposed estimated regression coefficient of the Poisson regression. We adjusted for overdispersion.
Results
Compared with 2018 no statistically significant change in allogeneic transplantation numbers was seen for a significance level of 5% in 2019 and 2021. In both years the number of allogeneic transplantations fell by 4.0% (2019: RR 0.960; 95% confidence interval [0.916; 1.007]; P value=0.0912; 2021: RR 0.960 [0.916; 0.007]; P value=0.0941). In 2020, the first year of the pandemic, the number of allogeneic stem cell transplantations fell significantly by 5.8% compared with 2018 (RR 0.942 [0.898; 0.988]; P value=0.0138) (table 1).
Table 1. Allogeneic stem cell transplantation in adults (> 18 years).
| 2018 | 2019 | 2020 | 2021 | |
| Total (data from 133 transplantation centers) | ||||
| 3507 | 3395 | 3326 | 3378 | |
| Median age (> 18 years) | ||||
| 58 | 58.1 | 58.7 | 58.5 | |
| Acute myeloid leukemia | ||||
| 44.7 % | 42.9 % | 44.5 % | 46.0 % | |
| Acute lymphatic leukemia | ||||
| 8.4 % | 8.7 % | 8.8 % | 8.3 % | |
| Myelodysplastic syndrome plus myeloproliferative neoplasm | ||||
| 22.3 % | 24.0 % | 23.0 % | 22.0 % | |
| Peripheral blood stem cells | ||||
| 93.4 % | 94.3 % | 95.2 % | 94.8 % | |
| Myeloablative versus non-myeloablative | ||||
| 48.3 % | 51.8 % | 51.2 % | 52.4 % | |
| Related versus non-related | ||||
| 27.3 % | 26.6 % | 27.8 % | 28.0 % | |
| Non-malignant (aplastic anemia, hemoglobinopathy, or others) | ||||
| 2.5 % | 1.7 % | 2.5 % | 1.6 % | |
| Other diagnoses | ||||
| 1.5 % | 2.1 % | 1.9 % | 1.9 % | |
| Other acute leukemias | ||||
| 4.0 % | 5.4 % | 5.3 % | 6.4 % | |
| Chronic leukemias | ||||
| 3.4 % | 3.1 % | 3.3 % | 3.2 % | |
| Non-Hodgkin’s lymphoma and lymphomas | ||||
| 9.4 % | 8.9 % | 8.2 % | 8.2 % | |
| Multiple myeloma and “plasma cell disorder” | ||||
| 3.9 % | 3.2 % | 2.8 % | 2.3 % | |
Autologous transplantations increased in subsequent years compared with 2018. The increase did, however, not reach significance. In 2019 the rate of autologous transplantations rose by 5.5% (RR 1.055 [0.993; 1.121]; P value=0.0864); in 2020, by 4.1% (RR 1.041 [0.979; 1.106]; value=0.2047); and in 2021, by 5.3% (RR 1.053 [0.990; 1.119]; P value=0.1023) (table 2).
Table 2. Autologous stem cell transplantations in adults (> 18 years).
| 2018 | 2019 | 2020 | 2021 | |
| Total (data from 133 transplantation centers) | ||||
| 4366 | 4531 | 4510 | 4582 | |
| Median age (> 18 years) | ||||
| 59.9 | 59.9 | 60.4 | 60.9 | |
| Myeloma | ||||
| 61.8 % | 61.3 % | 60.4 % | 62.9 % | |
| Non-Hodgkin’s lymphoma | ||||
| 25.0 % | 26.4 % | 27.4 % | 26.7 % | |
| Hodgkin’s disease | ||||
| 3.2 % | 3.3 % | 3.8 % | 3.0 % | |
| Germ cell tumors (autoimmune disorders, acute myeloid leukemia) | ||||
| 2.2 % | 2.1 % | 2.1 % | 2.5 % | |
| Amyloidosis | ||||
| 0.7 % | 0.7 % | 0.8 % | 0.9 % | |
| Solid tumor | ||||
| 7.2 % | 6.2 % | 5.5 % | 4.1 % | |
The transplantation rate per month was analyzed for 2020 and for April and December 2020 (after the outbreak of the pandemic) was found to be lower for autologous transplantation than the average for 2018 and 2019 (April: 7.32% versus 8.47%; December: 5.62% versus 6.08%), whereas the rate of allogeneic transplantations increased (April: 9.12% versus 7.87%; December 8.28% versus 7.44%).
Discussion
Our study shows that for autologous stem cell transplantation during the COVID-19 pandemic in 2020/2021, case numbers did not noticeably fall compared with 2018/2019, whereas case numbers for allogeneic stem cell transplantation fell by 3.9% for the average of 2020/2021 compared with 2018/2019. A similar reduction for allogeneic stem cell transplantations by 2.4% in 2020 was reported by the Italian Bone Marrow Transplant Group (GITMO) (3). The European stem cell registry of the EBMT reported for 2020 a fall of 7.5% for autologous and 5.1% for allogeneic stem cell transplantation (4). What is of note is the slight increase in normally urgent indications—for example, acute myeloid leukemia and acute lymphatic leukemia—whereas the transplantation numbers in less urgent indications—such as myelodysplastic syndromes or myeloproliferative neoplasms and lymphatic disorders—showed a downward trend. In this context it should be borne in mind that the introduction of novel, effective medications for malignant lymphomas and multiple myeloma prompted a fall in allogeneic transplantations even in the preceding years and showed a corresponding trend in the EBMT registry (5).
Even though the described changes in numbers of autologous and allogeneic stem cell transplantations in 2020/2021 compared with 2018/2019 can be explained with the measures and recommendations from the medical specialty societies, variations in the transplantation numbers as a result of changes in indicators and new alternative therapies cannot be ruled out. Overall, our analysis does not show a severe effect of the COVID-19 pandemic on the numbers of stem cell transplantations in Germany in 2020 and 2021.
References
- 1.Ljungman P, de la Camara R, Mikulska M, et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia. 2021;35:2885–2894. doi: 10.1038/s41375-021-01302-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Passamonti F, Cattaneo C, Arcaini L, et al. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020;7:e737–e745. doi: 10.1016/S2352-3026(20)30251-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Russo D, Polverelli N, Malagola M, et al. Changes in stem cell transplant activity and procedures during SARS-CoV2 pandemic in Italy: an Italian Bone Marrow Transplant Group (GITMO) nationwide analysis (TransCOVID-19 Survey) Bone Marrow Transplant. 2021;56:2272–2275. doi: 10.1038/s41409-021-01287-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Passweg JR, Baldomero H, Chabannon C, et al. Impact of SARS-CoV-2 pandemic on hematopoietic cell transplantation and cellular therapies in Europe 2020 A report from the EBMT activity survey. Bone Marrow Transplant. 2022;57:742–752. doi: 10.1038/s41409-022-01604-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Passweg JR, Baldomero H, Chabannon C, et al. Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trend over 30 years. Bone Marrow Transplant. 2021;56:1651–1664. doi: 10.1038/s41409-021-01227-8. [DOI] [PMC free article] [PubMed] [Google Scholar]