Blood Res 2021; 56(4):
Published online December 31, 2021
https://doi.org/10.5045/br.2021.2021073
© The Korean Society of Hematology
Correspondence to : Jeong-Ok Lee, M.D., Ph.D.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam 13620, Korea
E-mail: jeongok77@gmail.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL).
Methods
In this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Those who showed complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa- based conditioning regimen but did not undergo radiotherapy.
Results
The PCNSL patients had a median age of 57 years (range, 49‒67 yr); of the total patients, 9.1% had a performance status of 2 or higher, and 72.1% had multiple lesions. Approximately 82% of patients received six cycles of induction chemotherapy, which was well tolerated with excellent disease control. The rate of confirmed or unconfirmed complete response increased from 45.5% at the period of interim analysis to 81.8% prior to the initiation of HDC-ASCT. With a median follow-up of 19.6 months (range, 7.5‒56.5 mo), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. No treatment-related deaths occurred. Grade 3 toxicity was recorded in 90.9% of the patients after undergoing the HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis.
Conclusion
The discussed treatment approach is feasible in patients with newly diagnosed PCNSL, yielding encouraging results.
Keywords Primary CNS lymphoma, Autologous stem-cell transplantation, Consolidation, Thiotepa
Blood Res 2021; 56(4): 285-292
Published online December 31, 2021 https://doi.org/10.5045/br.2021.2021073
Copyright © The Korean Society of Hematology.
Ji Yun Lee1, Jin Ho Paik2, Koung Jin Suh1, Ji-Won Kim1, Se Hyun Kim1, Jin Won Kim1, Yu Jung Kim1, Keun-Wook Lee1, Jee Hyun Kim1, Soo-Mee Bang1, Jong-Seok Lee1, Jeong-Ok Lee1
1Department of Internal Medicine, 2Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
Correspondence to:Jeong-Ok Lee, M.D., Ph.D.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam 13620, Korea
E-mail: jeongok77@gmail.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL).
Methods
In this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Those who showed complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa- based conditioning regimen but did not undergo radiotherapy.
Results
The PCNSL patients had a median age of 57 years (range, 49‒67 yr); of the total patients, 9.1% had a performance status of 2 or higher, and 72.1% had multiple lesions. Approximately 82% of patients received six cycles of induction chemotherapy, which was well tolerated with excellent disease control. The rate of confirmed or unconfirmed complete response increased from 45.5% at the period of interim analysis to 81.8% prior to the initiation of HDC-ASCT. With a median follow-up of 19.6 months (range, 7.5‒56.5 mo), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. No treatment-related deaths occurred. Grade 3 toxicity was recorded in 90.9% of the patients after undergoing the HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis.
Conclusion
The discussed treatment approach is feasible in patients with newly diagnosed PCNSL, yielding encouraging results.
Keywords: Primary CNS lymphoma, Autologous stem-cell transplantation, Consolidation, Thiotepa
Table 1 . Patient’s baseline characteristics (N=22)..
Characteristics | N | % |
---|---|---|
Age, median years (range) | 57 (49–67) | |
Age >60 years | 7 | 31.8 |
Male sex | 13 | 59.1 |
ECOG PS ≥2 | 2 | 9.1 |
Elevated LDHa) | 5 | 26.3 |
Elevated CSF proteinb) | 21 | 95.5 |
Deep brain lesions | 16 | 72.7 |
IELSG risk groupa) | ||
Low | 2 | 10.5 |
Intermediate | 14 | 73.7 |
High | 3 | 15.8 |
Positive CSF cytology | 2 | 9.1 |
Ocular involvement | ||
Positive or suspicious | 3 | 13.6 |
Negative | 16 | 72.7 |
Unknown | 3 | 13.6 |
Multiple lesions | 16 | 72.7 |
a)Data regarding serum LDH and IELGS risk groups were available in 19 patients. b)The cutoff values for normal CSF protein con-centration were 45 mg/dL in patients ≤60 years old and 60 mg/dL in patients older than 60 years..
Abbreviations: CSF, cerebrospinal fluid; ECOG PS, Eastern Cooperative Oncology Group performance status; IELSG, international extranodal lymphoma study group; LDH, lactate dehydrogenase..
Table 2 . Treatment response..
Response | Induction_interim | Pre-HDC-ASCT | Post-HDC-ASCT | Follow-up | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
N | % | N | % | N | % | N | % | ||||
CR | 3 | 13.6 | 8 | 36.4 | 18 | 81.8 | 16 | 72.7 | |||
CRu | 7 | 31.8 | 10 | 45.4 | 4 | 18.2 | 2 | 9.1 | |||
PR | 12 | 54.5 | 4 | 18.2 | 0 | 0 | 0 | 0 | |||
PD | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 18.2 |
Abbreviations: CR, complete response; CRu, CR unconfirmed; HDC-ASCT, high-dose chemotherapy, and autologous stem cell transplant; PD, progressive disease; PR, partial response..
Table 3 . HDC-ASCT characteristics..
N | % | |
---|---|---|
Conditioning regimen | ||
TBC | 12 | 54.5 |
Bu/TT | 10 | 45.5 |
Number of infused CD34+ cells (×106 cells/kg), median (range) | 6.7 (4.1–21.1) | |
Neutrophil engraftment, median days (range) | 9 (7–11) | |
Platelet engraftment, median days (range) | 10 (7–12) | |
Transplantation hospitalization, median days (range) | 21 (18–44) |
Abbreviations: Bu/TT, busulfan/thiotepa; TBC, thiotepa, busulfan, and cyclophosphamide..
Table 4 . HDC-ASCT as upfront treatment in previous studies in PCNSL..
Reference | N | Median age (range) | Induction therapy | CR/ORR to induction | Transplanted patients | Conditioning regimen | WBRT | OS | Median FU (mo) | TRM |
---|---|---|---|---|---|---|---|---|---|---|
[10] | 28 | 53 (25–71) | HD-MTX→ARAC | 29%/50% | 50% | BEAM | No | 2 years: 55% | 28 | 4% |
[15] | 30 | 54 (27–64) | HD-MTX→ ARAC+TT | 20%/70%→38%/92% | 77% | BCNU/TT | Yes | 5 years: 69% | 63 | 3% |
[11] | 25 | 52 (21–60) | MBVP→IFO+ARAC | 44%/84% | 68% | BEAM | Yes | 4 years: 64% | 34 | 4% |
[13] | 23 | 55 (18–69) | HD-MTX | 17%/65% | 70% | Bu/TT | Yes | 2 years: 48% | 15 | 13% |
[12] | 11 | 52 (33–65) | HD-MTX→ARAC | 73%/100% | 100% | BUCYE | Yes | 2 years: 89% | 25 | 0% |
[24] | 21 | 56 (34–69) | MPV→ARAC | 24%/86% | 100% | TBC | No | 5 years: 44% | 60 | 14% |
[14] | 13 | 56 (35–65) | MPV→ARAC | 31%/100% | 46% | LEED | Yes | 3 years: 76% | 44 | 0% |
[16] | 33 | 57 (23–67) | R-MPV | 68%/97% | 81% | TBC | No | 3 years: 81% | 45 | 12% |
Abbreviations: ARAC, cytarabine; BEAM, carmustine, etoposide, cytarabine, and melphalan; BCNU, carmustine; Bu, busulfan; BUCYE, busulfan, cyclophosphamide, and etoposide; CR, complete response; FU, follow-up; HD-MTX, high-dose methotrexate; IFO, ifosfamide; LEED, cyclophosphamide, etoposide, melphalan, and dexamethasone; MBVP, methotrexate, carmustine, etoposide, and methylprednisolone; MPV, methotrexate, vincristine, and procarbazine; ORR, overall response rate; OS, overall survival; R-MP, MPV plus rituximab; TBC, thiotepa, busulfan, and cyclophosphamide; TRM, treatment-related mortality; TT, thiotepa; WBRT, whole-brain radiotherapy..
Jeong Eun Kim, Dok Hyun Yoon, Shin Kim, Dae Ho Lee, Jeong Hoon Kim, Young Hee Yoon, Hyun Sook Chi, Sang Wook Lee, Chan-Sik Park, Jooryung Huh, and Cheolwon Suh
Korean J Hematol 2012; 47(1): 60-66Hee Je Kim, Jong Wook Lee, Soo JeongPark, Jung Gon Suh, ChangKi Min, Hyeon Seok Eom, Dong Wook Kim, Woo Sung Min, Chun Choo Kim, Dong Jip Kim
Korean J Hematol 1999; 34(2): 288-296