Conditioning intensity matters for allogeneic stem cell transplantation in blastic plasmacytoid dendritic cell neoplasm

Using the European Society for Blood and Marrow Transplantation ProMISe databank, we found myeloablative induction therapy and total body irradiation to be the main determinants of long-term response to allogeneic stem cell transplantation in blastic plasmacytoid dendritic cell neoplasm.
Published in Cancer
Like

Share this post

Choose a social network to share with, or copy the shortened URL to share elsewhere

This is a representation of how your post may appear on social media. The actual post will vary between social networks

Background

Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare and clinically aggressive myeloid malignancy preferentially involving skin, bone marrow, and, occasionally, lymphatic organs and the central nervous system.  Although response rates to induction chemotherapy regimens are generally high and targeted therapy with tagraxofusp, the first CD123-targeted treatment for BPDCN, has been approved (Pemmaraju et al. 2019), remission duration after those therapies is generally short (Laribi et al. 2020; Taylor et al. 2019).

In contrast, case series and registry analyses suggest that hematopoietic cell transplantation (HCT) could provide durable disease control in patients with BPDCN, in particular if administered in first complete remission . Due to the low incidence of BPDCN and the lack of prospective trials, allogeneic HCT (alloHCT) is considered as a standard treatment option for consolidating BPDCN treatment responses based on case series and retrospective analyses (Dietrich et al. 2011; Roos-Weil et al. 2013; Aoki et al. 2015). Due to the small sample size in previously published studies, the impact of different induction therapies before alloHCT is unclear. The role of autologous HCT (autoHCT) is still a matter of discussion due to inconsistent results from different case series analyses (Aoki et al. 2015; Kharfan-Dabaja et al. 2018)

Methodology

Initially, a prospective non-interventional study was launched in 2019 to register all HCT performed for BPDCN in EBMT centers. Since only 25 of 50 planned patients had been accrued as of March 28, 2017, the prospective study was terminated and the enrolled patients were pooled with all patients receiving HCT for BPDCN registered with the EBMT ProMISe databank during the same time period. In total, we analyzed 146 alloHCT patients and 16 patients who received autoHCT. 

Findings

Patients that received myeloablative conditioning (MAC) therapy before alloHCT were significantly younger than those that received reduced intensity chemotherapy (RIC); likely reflecting a selection bias inherent in the retrospective nature of our study. Additionally, MAC alloHCT patients received total body irradiation (TBI) significantly more often than RIC alloHCT patients. 

In a multivariate analysis adjusting for potentially influencing factors, we found MAC with TBI lead to longer overall survival and progression free survival compared to all other conditioning therapy groups. Competing risk regression analysis showed a reduced incidence of relapse in MAC TBI alloHCT patients compared to all other alloHCT patients, while non-relapse mortality did not significantly differ. 

While only comprising 16 patients, the presented cohort of autoHCT for BPDCN is the largest reported study of this kind to date. Overall survival and progression free survival did not significantly differ between alloHCT and autoHCT. 

Discussion

Our study highlights the efficacy of HCT to induce lasting responses in BPDCN. The strong impact of MAC and TBI on lasting response after alloHCT has potential strong impact on clinical procedures, highlighted by the overall high number of RIC alloHCT performed and registered in the EBMT database. Although we have adjusted our analyses for age and performance index imbalances, the observed difference between MAC and RIC alloHCT is potentially biased by the selection of younger patients with less comorbidities and better overall performance to receive more intensive conditioning therapy (i.e. MAC). Nevertheless, the strong advantage of MAC TBI compared to other conditioning therapies suggests this treatment option as a preferred alternative for patients eligible for alloHCT and intensive conditioning therapy. 

The observed high efficacy of autoHCT is reassuring for patients which are ineligible for alloHCT, either due to insufficient overall performance or due to a missing stem cell donor. Due to the low number of autoHCT patients and the retrospective nature of our study, the presented evidence is likely not sufficient to replace alloHCT with autoHCT as standard consolidation therapy in BPDCN. However, for patients ineligible for MAC alloHCT, autoHCT should be considered as an alternative. 

While our observations have strong clinical implications, the retrospective nature and still small cohort size limit the direct transfer into clinical guidelines. Randomized controlled trials should ideally be performed to validate our findings. For patients which are eligible for alloHCT and intensive conditioning therapy MAC with and without TBI should be compared, while autoHCT and RIC alloHCT should be compared for patients which are ineligible for MAC HCT. However, carrying out prospective clinical trials is very challenging in this entity, inter alia, due to the relatively low incidence of BPDCN.

Conclusion

Myeloablative conditioning, especially when based on TBI, should be preferred for patients receiving alloHCT for BPDCN. For patients that are ineligible for MAC alloHCT, autoHCT should be considered. Further studies should be performed to validate these observations and transfer them into clinical practice.

References

Aoki, Tomohiro, Ritsuro Suzuki, Yachiyo Kuwatsuka, Shinichi Kako, Katsuya Fujimoto, Jun Taguchi, Tadakazu Kondo, et al. 2015. “Long-Term Survival Following Autologous and Allogeneic Stem Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm.” Blood 125 (23): 3559–62.


Dietrich, Sascha, Mindaugas Andrulis, Ute Hegenbart, Thomas Schmitt, Frauke Bellos, Uwe M. Martens, Julia Meissner, Alwin Krämer, Anthony D. Ho, and Peter Dreger. 2011. “Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC) in Elderly Patients: Results of a Treatment Algorithm Employing Allogeneic Stem Cell Transplantation with Moderately Reduced Conditioning Intensity.” Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation 17 (8): 1250–54.

Kharfan-Dabaja, Mohamed A., Tea Reljic, Hemant S. Murthy, Ernesto Ayala, and Ambuj Kumar. 2018. “Allogeneic Hematopoietic Cell Transplantation Is an Effective Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm in First Complete Remission: Systematic Review and Meta-Analysis.” Clinical Lymphoma Myeloma and Leukemia. https://doi.org/10.1016/j.clml.2018.07.295.

Laribi, Kamel, Alix Baugier de Materre, Mohamad Sobh, Lorenzo Cerroni, Caterina Giovanna Valentini, Tomohiro Aoki, Ritsuro Suzuki, et al. 2020. “Blastic Plasmacytoid Dendritic Cell Neoplasms: Results of an International Survey on 398 Adult Patients.” Blood Advances 4 (19): 4838–48.

Pemmaraju, Naveen, Andrew A. Lane, Kendra L. Sweet, Anthony S. Stein, Sumithira Vasu, William Blum, David A. Rizzieri, et al. 2019. “Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm.” The New England Journal of Medicine 380 (17): 1628–37.

Roos-Weil, Damien, Sascha Dietrich, Ariane Boumendil, Emmanuelle Polge, Dominique Bron, Enric Carreras, Arturo Iriondo Atienza, et al. 2013. “Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasm: A Retrospective Study from the European Group for Blood and Marrow Transplantation.” Blood. https://doi.org/10.1182/blood-2012-08-448613.

Taylor, Justin, Michael Haddadin, Vivek A. Upadhyay, Erwin Grussie, Neha Mehta-Shah, Andrew M. Brunner, Abner Louissaint, et al. 2019. “Multicenter Analysis of Outcomes in Blastic Plasmacytoid Dendritic Cell Neoplasm Offers a Pretargeted Therapy Benchmark.” Blood. https://doi.org/10.1182/blood.2019001144.

Please sign in or register for FREE

If you are a registered user on Research Communities by Springer Nature, please sign in

Follow the Topic

Cancer Biology
Life Sciences > Biological Sciences > Cancer Biology
  • Leukemia Leukemia

    This journal publishes high quality, peer reviewed research that covers all aspects of the research and treatment of leukemia and allied diseases. Topics of interest include oncogenes, growth factors, stem cells, leukemia genomics, cell cycle, signal transduction and molecular targets for therapy.