Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.
BACKGROUND
We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma.


METHODS
Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT.


RESULTS
Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively.


CONCLUSIONS
MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.
Montemurro
M
M
Department of Internal Medicine C, Hematology and Oncology, Stem Cell Transplantation, Ernst-Moritz-Arndt-University, Sauerbruchstrasse, 17475 Greifswald, Germany. michael.montemurro@chuv.ch
Kiefer
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Schüler
F
F
Al-Ali
H K
HK
Wolf
H-H
HH
Herbst
R
R
Haas
A
A
Helke
K
K
Theilig
A
A
Lotze
C
C
Hirt
C
C
Niederwieser
D
D
Schwenke
M
M
Krüger
W H
WH
Dölken
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D013852:Thiotepa / Q000008:administration & dosage
D013852:Thiotepa; D002066:Busulfan; D008727:Methotrexate