First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas-a single-centre experience in 61 patients

T Brezina; H von Dewitz; T Schroeder; S Ullrich; K Nachtkamp; G Reifenberger; B Malzkorn; M Sabel; R Haas; G Kobbe

doi:10.1007/s00277-021-04745-z

First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas-a single-centre experience in 61 patients

Ann Hematol. 2022 Mar;101(3):607-616. doi: 10.1007/s00277-021-04745-z. Epub 2022 Jan 4.

Authors

T Brezina¹, H von Dewitz², T Schroeder³, S Ullrich⁴, K Nachtkamp³, G Reifenberger⁵, B Malzkorn⁵, M Sabel⁶, R Haas³, G Kobbe³

Affiliations

¹ Department of Oncology, University Hospital Zuerich, Zuerich, Switzerland. tomas.brezina@usz.ch.
² Department of Internal Medicine A, Hospital Merheim, Cologne, Germany.
³ Department of Haematology, Medical Faculty, University Hospital Duesseldorf, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
⁴ Life Science Center for Statistics, Duesseldorf, Germany.
⁵ Department of Neuropathology, University Hospital Duesseldorf, Duesseldorf, Germany.
⁶ Department of Neurosurgery, University Hospital Duesseldorf, Duesseldorf, Germany.

Abstract

Primary central nervous system non-Hodgkin lymphomas (PCNS-NHLs) are extranodal B-cell lymphomas with poor prognosis. The role of high-dose therapy (HDT) followed by autologous blood stem cell transplantation (ASCT) as first-line therapy is still not clear. We retrospectively collected long-term follow up data of 61 consecutive patients with PCNS-NHL at the University Hospital Düsseldorf from January 2004 to December 2016. Thirty-six patients were treated with conventional chemoimmunotherapy (cCIT) only (CT-group). Seventeen patients received an induction cCIT followed by HDT and ASCT. In the CT-group, the overall response rate (ORR) was 61% (CR 47%, PR 14%), and there were 8% treatment-related deaths (TRD). Progression-free survival (PFS) was 31.8 months, and overall survival (OS) was 57.3 months. In the HDT-group, the ORR was 88% (59% CR, 29% PR), and there were 6% TRD. Median PFS and OS were not reached at 5 years. The 5-year PFS and OS were 64.7%. After a median follow up of 71 months, 10 patients (59%) were still alive in CR/PR following HDT and ASCT, one patient was treated for progressive disease (PD), and 7 had died (41%, 6 PD, 1 TRD). All patients achieving CR prior to HDT achieved durable CR. In the CT-group, 8 patients (22%) were alive in CR/PR after a median follow-up of 100 months. Twenty-eight patients died (78%, 24 PD, 2 TRD, 2 deaths in remission). In the univariate analysis, the HDT-group patients had significantly better PFS (not reached vs 31.8 months, p = 0.004) and OS (not reached vs 57.3 months, p = 0.021). The multivariate analysis showed HDT was not predictive for survival. Treatment with HDT + ASCT is feasible and offers the chance for long-term survival with low treatment-related mortality in younger patients. In this analysis, ORR, PFS and OS were better with HDT than with conventional cCIT alone. This result was not confirmed in the multivariate analysis, and further studies need to be done to examine the role of HDT in PCNSL.

Keywords: Hematopoietic stem cell transplantation; High-dose chemotherapy; Methotrexate; Primary CNS lymphoma.

MeSH terms

Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Central Nervous System Neoplasms / therapy*
Female
Hematopoietic Stem Cell Transplantation*
Humans
Lymphoma, Non-Hodgkin / therapy*
Male
Middle Aged
Progression-Free Survival
Retrospective Studies
Transplantation, Autologous