Professor Liu Jiajun talks about the treatment progress of primary central nervous system lymphoma (part 2)

Author: LIU Jia Jun, Third Affiliated Hospital of Sun Yat-sen Hematology article is the author's permission NMT Medical publish, please do not reprint without authorization
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Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin’s lymphoma that originates in the central nervous system.
And spinal cord) [1]
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The disease has a low incidence, accounting for only 4% of intracranial tumors and 4%-6% of all extranodal lymphomas.
The prognosis is poor and the recurrence rate is high.
Nearly half of patients relapse within 2 years [2,3]
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One of the main risk factors for the onset of PCNSL is immunodeficiency.
Since 2000, the incidence of PCNSL has been increasing at an annual rate of 1.
6%, especially in patients with normal immune function and the elderly (>60 years old) [ 4]
.

Because of the blood-brain barrier, standard lymphoma chemotherapy has limited effects on PCNSL.
High-dose methotrexate (HD-MTX) with or without whole brain radiation therapy (WBRT) is the most effective treatment
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Although PCNSL has a high response rate to initial treatment, the overall prognosis is still poor
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With the continuous in-depth study of the pathophysiology of PCNSL, it has been found that the B cell receptor pathway (BCR), Toll-like receptor pathway (TLR), immune evasion mechanism, and suppression of tumor immune microenvironment are the key mechanisms in the pathogenesis of PCNSL
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The treatment of PCNSL gradually has a new direction, and targeted therapy, immunotherapy and related combination drugs have become research hotspots
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This article systematically reviews the treatment of PCNSL from six aspects: surgical treatment, radiotherapy, chemotherapy, hematopoietic stem cell transplantation, targeted therapy and immunotherapy, and summarizes the existing clinical evidence of new drugs for the reference of readers
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 In the last two articles, we summarized the surgical treatment, radiotherapy, chemotherapy, hematopoietic stem cell transplantation and targeted therapy of PCNSL (for details, please click "Professor Liu Jiajun on the treatment progress of primary central nervous system lymphoma (part 1)" , "Professor Liu Jiajun talks about the progress of the treatment of primary central nervous system lymphoma (middle)", today, let’s take a look at the progress of the immunotherapy of PCNSL! Immunotherapy 01 Immunomodulator Immunomodulator (IMiD) can have a variety of effects Mechanisms interfere with the growth and survival of aggressive lymphomas [55], including changing the lymphoma cell microenvironment and stimulating effector cells, such as cytotoxic T cells and natural killer cells [56,57]
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IMiD includes lenalidomide and pomadin They not only inhibit the activity of NF-κB, but also inhibit the PI3K/AKT pathway.
Lenalidomide maintenance therapy has been shown to improve PFS in elderly patients with newly diagnosed DLBCL
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In addition, lenalidomide and pomalidomide can penetrate BBB has become a considerable drug for the treatment of PCNSL
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A multi-center, single-arm study in France [65] reported 49 patients with relapsed and refractory PCNSL who received lenalidomide combined with rituximab treatment, and patients who achieved at least PR continued Receiving lenalidomide maintenance treatment, 49% of patients showed progressively poor clinical performance, and the best remission rate was 67%.
After induction therapy, the remission rate dropped to 36%, and the median PFS was 8.
1 months.
median OS was 19.
2 months
.

based on these results, version 2018 NCCN guidelines recommend, for the treatment of relapsed or refractory PCNSL may include the use of single-agent lenalidomide or in combination with rituximab and lenalidomide treatment
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Park horse Pomalidomide is the third-generation IMiD.
It was found in a preclinical study that pomalidomide showed significant therapeutic activity in 2 mouse PCNSL models
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Tun et al.
[58] studied the dose of pomalidomide treatment in 25 patients with relapsed and refractory PCNSL and ocular lymphoma.
The maximum tolerated dose was 5 mg for 21 days and a cycle every 28 days (the first 2 Cycle of 20 mg dexamethasone per week), 9 of the 21 evaluable patients (43%) responded to treatment
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 02 Immune checkpoint inhibitors can often find 9p24.
1/PD-L1/PD-L2 copy number changes and translocations in PCNSL, which indicates that there is a genetic basis for immune evasion in PCNSL [59]
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In systemic Hodgkin's lymphoma, increased 9p24.
1 copies and increased PD-L1 expression on Reed-Sternberg cells are associated with the efficacy of nivolumab treatment [60]
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Whether this principle also applies to PCNSL is unclear
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In preclinical studies, immune checkpoint suppression by anti-PD1 monoclonal antibody has significant therapeutic activity on CNS lymphoma [61]
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There is no clinical evidence from prospective studies
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A retrospective case series study [62] reported 5 patients with relapsed and refractory PCNSL who received single-agent nivolumab treatment, of which 4 patients got CR and 1 patient got PR
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But before starting nivolumab, one patient received WBRT and the other received focal radiotherapy
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Currently, clinical trials of PD-1 monoclonal antibody in the treatment of PCNSL are underway, including a multi-center clinical trial investigating the single-agent treatment of nivolumab in the treatment of PCNSL and testicular lymphoma (NCT02857426)
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Another single-center trial using pembrolizumab (NCT02779101) is further studying the correlation between immune evasion and PD-1 blockade in PCNSL
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Other clinical trials plan to combine checkpoint inhibitors with targeted drugs such as Ibrutinib or IMiD
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 03CAR-T cell therapy Chimeric antigen receptor (CAR) T cell therapy has been approved for the treatment of relapsed and refractory DLBCL
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Studies have found that CAR-T cells can penetrate the central nervous system, and treatment responses have been observed in patients with secondary central nervous system lymphoma [63]
.

Currently, a phase I clinical trial of CAR-T cells for the treatment of relapsed/refractory CD19+ PCNSL is ongoing (NCT04443829)
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 In summary, the limited understanding of the pathophysiology of PCNSL for decades is mainly due to the rare occurrence of the disease, the difficulty and limited access to pathological tissues, and the difficulty in carrying out related clinical trials
.

With the gradual in-depth understanding of PCNSL, radiotherapy, surgery, and HD-MTX-based combined chemotherapy have become feasible treatments for PCNSL.
The first-line treatment plan for PCNSL has been continuously optimized, but the treatment effect is still not optimistic, and it is difficult to treat relapse Sexual PCNSL is even more tricky
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In addition, based on the high invasiveness and morbidity of PCNSL, it is necessary to explore more feasible and effective treatment methods, improve survival rate, and prolong survival
.

Recently, new progress has been made in large-scale genomics research through the use of databases, new drivers of PCNSL have been discovered, and research objects targeted at small molecule inhibitors and immune checkpoint inhibitors have been provided
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According to current research on new drugs for PCNSL, Ibrutinib and lenalidomide are the only new drugs that have shown clinical significance, and clinical research on other new drugs is also being actively carried out
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In short, the exploration of the treatment of PCNSL still requires more clinical trials and prospective studies.
The multi-drug combination therapy of chemotherapy, targeted therapy, and immunotherapy provides considerable therapeutic prospects for PCNSL
.

References[1].
Louis, DN, et al.
, The 2021 WHO Classification of Tumors of the Central Nervous System: a summary.
Neuro Oncol, 2021.
23(8): p.
1231-1251.
[2].
Ostrom , QT, et al.
, CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014.
Neuro Oncol, 2017.
19(suppl_5): p.
v1-v88.
[3].
Yuan , XG, et al.
, Primary central nervous system lymphoma in China: a single-center retrospective analysis of 167 cases.
Ann Hematol, 2020.
99(1): p.
93-104.
[4].
Langner-Lemercier, S .
, et al.
, Primary CNS lymphoma at first relapse/progression: characteristics, management, and outcome of 256 patients from the French LOC network.
Neuro Oncol, 2016.
18(9): p.
1297-303.
[5].
Bataille, B.
, et al.
, Primary intracerebral malignant lymphoma: report of 248 cases.
J Neurosurg, 2000.
92(2): p.
261-6.
[6].
Weller, M.
, et al.
, Surgery for primary CNS lymphoma? Challenging a paradigm.
Neuro Oncol, 2012.
14(12): p.
1481-4.
[7].
Haque, S.
, et al.
, Imaging of lymphoma of the central nervous system, spine, and orbit.
Radiol Clin North Am, 2008.
46(2): p.
339-61, ix.
[8].
Weller, M.
, et al.
, Surgery for primary CNS lymphoma? Challenging a paradigm .
Neuro Oncol, 2012.
14(12): p.
1481-4.
[9].
Labak, CM, et al.
, Surgical Resection for Primary Central Nervous System Lymphoma: A Systematic Review.
World Neurosurg, 2019.
126: p .
e1436-e1448.
[10].
Correa, DD, et al.
, Cognitive functions in primary CNS lymphoma after single or combined modality regimens.
Neuro Oncol, 2012.
14(1): p.
101-8.
[11].
Hottinger, AF, et al.
, Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma.
Neurology, 2007.
69(11): p.
1178-82.
[12].
Rubenstein, JL, et al.
,How I treat CNS lymphomas.
Blood, 2013.
122(14): p.
2318-30.
[13].
Sun, A.
, et al.
, Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non -small-cell lung cancer: neurocognitive and quality-of-life analysis.
J Clin Oncol, 2011.
29(3): p.
279-86.
[14].
Batchelor, T.
, et al.
, Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07.
J Clin Oncol, 2003.
21(6): p.
1044-9.
[15].
Gerstner, ER, et al.
, Long-term outcome in PCNSL patients treated with high-dose methotrexate and deferred radiation.
Neurology, 2008.
70(5): p.
401-2.
[16].
Herrlinger, U.
, et al.
, NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report.
Ann Neurol, 2005.
57(6): p.
843-7.
[17].
Bokstein, F.
, et al.
,Central nervous system relapse of systemic non-Hodgkin's lymphoma: results of treatment based on high-dose methotrexate combination chemotherapy.
Leuk Lymphoma, 2002.
43(3): p.
587-93.
[18].
Skarin, AT, et al.
, High-dose methotrexate with folinic acid in the treatment of advanced non-Hodgkin lymphoma including CNS involvement.
Blood, 1977.
50(6): p.
1039-47.
[19].
Nabors, LB, et al.
, Central Nervous System Cancers, Version 3.
2020, NCCN Clinical Practice Guidelines in Oncology.
J Natl Compr Canc Netw, 2020.
18(11): p.
1537-1570.
[20].
Reni, M.
, et al.
, Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate.
Int J Radiat Oncol Biol Phys, 2001.
51(2): p.
419-25.
[21].
Li, Q.
, et al .
,Improvement of outcomes of an escalated high-dose methotrexate-based regimen for patients with newly diagnosed primary central nervous system lymphoma: a real-world cohort study.
Cancer Manag Res, 2021.
13: p.
6115-6122.
[22].
Sieg , N.
, et al.
, Treatment patterns and disease course of previously untreated Primary Central Nervous System Lymphoma: Feasibility of MTX-based regimens in clinical routine.
Eur J Haematol, 2021.
107(2): p.
202-210.
[ 23].
Khan, RB, et al.
, Is intrathecal methotrexate necessary in the treatment of primary CNS lymphoma? J Neurooncol, 2002.
58(2): p.
175-8.
[24].
Ferreri, AJ, et al.
, Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002.
J Clin Oncol, 2003.
21(12): p.
2407-14.
[25].
Ferreri, AJ, et al.
,High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial.
Lancet, 2009.
374(9700): p.
1512-20.
[26].
Ferreri, AJ , et al.
, Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial.
Lancet Haematol, 2016.
3(5): p.
e217-27.
[27].
Yu, J.
, et al.
, High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials.
Sci Rep, 2021.
11(1): p.
2125.
[28].
Bergner, N.
, et al.
, Role of chemotherapy additional to high-dose methotrexate for primary central nervous system lymphoma (PCNSL).
Cochrane Database Syst Rev, 2012.
11: p.
CD009355.
[29].
Soussain, C.
, et al.
, Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma .
J Clin Oncol, 2001.
19(3): p.
742-9.
[30].
Illerhaus, G.
, et al.
, High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma.
J Clin Oncol, 2006.
24(24): p.
3865-70.
[31].
Illerhaus, G.
, [Primary CNS lymphoma].
Dtsch Med Wochenschr, 2013.
138(49): p.
2515 -8.
[32].
Soussain, C.
, et al.
, Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases.
Haematologica, 2012.
97(11): p.
1751-6.
[33].
Schorb, E.
, et al.
, High-dose thiotepa-based chemotherapy with autologous stem cell support in elderly patients with primary central nervous system lymphoma: a European retrospective study.
Bone Marrow Transplant, 2017.
52(8): p.
1113-1119.
[34].
Schorb, E.
, et al.
, Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation.
Haematologica, 2013.
98(5): p.
765-70.
[35].
Pennese, E.
, et al.
, Complete response induced by fotemustine given as single agent in a patient with primary central nervous system non-Hodgkin aggressive lymphoma relapsed after high-dose chemotherapy and autologous stem cell support.
Leuk Lymphoma, 2011.
52(11): p.
2188-9.
[36].
Gritsch, D.
, et al.
,Is Autologous Stem Cell Transplantation a Safe and Effective Alternative to Whole Brain Radiation as Consolidation Therapy in Patients With Primary Central Nervous System Lymphoma?: A Critically Appraised Topic.
Neurologist, 2021.
26(4): p.
137-142.
[37] .
Illerhaus, G.
, E.
Schorb and B.
Kasenda, Novel agents for primary central nervous system lymphoma: evidence and perspectives.
Blood, 2018.
132(7): p.
681-688.
[38].
Pang, DW, et al.
, [Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma].
Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2021.
29(4): p.
1175-1180.
[39].
Fu, J.
and X.
Ma, High-dose methotrexate combined with rituximab improves the survival rate of patients with primary central nervous system lymphoma.
J BUON, 2021.
26(2): p.
366-372.
[ 40].
Miyakita, Y.
,et al.
, Immunochemotherapy using rituximab (RTX) and high-dose methotrexate (HD-MTX): an evaluation of the addition of RTX to HD-MTX in recurrent primary central nervous system lymphoma (PCNSL).
Jpn J Clin Oncol, 2017.
47(10): p.
919-924.
[41].
Bromberg, J.
, et al.
, Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study.
Lancet Oncol, 2019.
20(2): p.
216-228.
[42].
Grommes, C.
, et al.
, Introduction of novel agents in the treatment of primary CNS lymphoma.
Neuro Oncol, 2019.
21( 3): p.
306-313.
[43].
Grommes, C.
, et al.
, Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.
Cancer Discov, 2017.
7(9): p.
1018-1029 .
[44].
Grommes, C.
, et al.
, Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma.
Blood, 2019.
133(5):p.
436-445.
[45].
Lv, L.
, et al.
, Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis.
Front Oncol, 2021.
11: p.
707285.
[46].
Narita, Y.
, et al.
, Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma.
Neuro Oncol, 2021.
23(1 ): p.
122-133.
[47].
Fingar, DC and J.
Blenis, Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression.
Oncogene, 2004.
23 (18): p.
3151-71.
[48].
Korfel, A.
, et al.
, Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma.
J Clin Oncol, 2016.
34(15): p.
1757 -63.
[49].
Montesinos-Rongen, M.
, R.
Siebert and M.
Deckert, Primary lymphoma of the central nervous system:just DLBCL or not? Blood, 2009.
113(1): p.
7-10.
[50].
Chapuy, B.
, et al.
, Targetable genetic features of primary testicular and primary central nervous system lymphomas.
Blood, 2016.
127(7): p.
869-81.
[51].
Courts, C.
, et al.
, Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression.
J Neuropathol Exp Neurol, 2007.
66(3): p.
230-7.
[52].
Braaten, KM, et al.
, BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma.
Clin Cancer Res, 2003 .
9(3): p.
1063-9.
[53].
Makino, K.
, et al.
, BCL2 expression is associated with a poor prognosis independent of cellular origin in primary central nervous system diffuse large B-cell lymphoma.
J Neurooncol, 2018.
140(1): p.
115-121.
[54].
Ackler, S.
, et al.
,Clearance of systemic hematologic tumors by venetoclax (Abt-199) and navitoclax.
Pharmacol Res Perspect, 2015.
3(5): p.
e00178.
[55].
Gribben, JG, N.
Fowler and F.
Morschhauser, Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma.
J Clin Oncol, 2015.
33(25): p.
2803-11.
[56].
Zhu, D.
, et al.
, Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation.
Cancer Immunol Immunother, 2008.
57(12): p.
1849-59.
[57].
Wu, L.
, et al.
, lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells.
Clin Cancer Res, 2008.
14(14): p.
4650-7.
[58].
Tun, HW, et al.
, Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma.
Blood, 2018.
132(21): p.
2240-2248.
[59].
Chapuy, B.
, et al.
, Targetable genetic features of primary testicular and primary central nervous system lymphomas.
Blood, 2016.
127(7): p.
869-81.
[60].
Roemer, M.
, et al.
, Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma.
J Clin Oncol, 2018.
36( 10): p.
942-950.
[61].
Qiu, Y.
, et al.
, Immune checkpoint inhibition by anti-PDCD1 (anti-PD1) monoclonal antibody has significant therapeutic activity against central nervous system lymphoma in an immunocompetent preclinical model .
Br J Haematol, 2018.
183(4): p.
674-678.
[62].
Nayak, L.
, et al.
, PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma.
Blood , 2017.
129(23): p.
3071-3073.
[63].
Abramson, JS,et al.
, Anti-CD19 CAR T Cells in CNS Diffuse Large-B-Cell Lymphoma.
N Engl J Med, 2017.
377(8): p.
783-784.
[64]Grommes C, Pentsova E, Nolan C, et al.
Phase II study of single agent buparlisib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).
Ann.
Oncol.
2016;27(suppl_6):103-113.
[65]Ghesquieres H, Houillier C, Chinot O, et al.
Rituximab-lenalidomide (REVRI) in relapse or refractory primary central nervous system (PCNSL) or vitreo retinal lymphoma (PVRL): results of a “proof of concept” phase II study of the French LOC Network [abstract] Blood.
2016;128(22):785.
Professor Liu Jiajun, Chief Physician, Doctoral Supervisor, Director of Department of Hematology, The Third Affiliated Hospital of Sun Yat-Sen University, Member of Anticancer Branch of European Cancer Society Member of Chinese Society of Immunization Member of Guangdong Medical Industry Association Standing Committee of Guangdong Province The main research directions of the members of the Society of Hematology: the mechanism of leukemia cell apoptosis signal transduction, hematopoietic stem cell transplantation, molecular targeted therapy of hematological tumors, gene therapy and the mechanism research of new anti-tumor drugs, etc.
Pentsova E, Nolan C, et al.
Phase II study of single agent buparlisib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).
Ann.
Oncol.
2016;27(suppl_6):103-113.
[65] Ghesquieres H, Houillier C, Chinot O, et al.
Rituximab-lenalidomide (REVRI) in relapse or refractory primary central nervous system (PCNSL) or vitreo retinal lymphoma (PVRL): results of a “proof of concept” phase II study of the French LOC Network [abstract].
Blood.
2016;128(22):785.
Professor Liu Jiajun, Chief Physician, Doctoral Supervisor, Director of the Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Member of the Anti-Cancer Branch of the European Cancer Society Member of the Chinese Society of Immunology, Guangdong Province Member of the Standing Committee of the Medical Industry Association, Member of the Guangdong Society of Hematology, and other major research directions: the mechanism of leukemia cell apoptosis signal transduction, hematopoietic stem cell transplantation, molecular targeted therapy of hematological tumors, gene therapy and the mechanism research of new anti-tumor drugs, etc.
Pentsova E, Nolan C, et al.
Phase II study of single agent buparlisib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).
Ann.
Oncol.
2016;27(suppl_6):103-113.
[65] Ghesquieres H, Houillier C, Chinot O, et al.
Rituximab-lenalidomide (REVRI) in relapse or refractory primary central nervous system (PCNSL) or vitreo retinal lymphoma (PVRL): results of a “proof of concept” phase II study of the French LOC Network [abstract].
Blood.
2016;128(22):785.
Professor Liu Jiajun, Chief Physician, Doctoral Supervisor, Director of the Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Member of the Anti-Cancer Branch of the European Cancer Society Member of the Chinese Society of Immunology, Guangdong Province Member of the Standing Committee of the Medical Industry Association, Member of the Guangdong Society of Hematology, and other major research directions: the mechanism of leukemia cell apoptosis signal transduction, hematopoietic stem cell transplantation, molecular targeted therapy of hematological tumors, gene therapy and the mechanism research of new anti-tumor drugs, etc.
Rituximab-lenalidomide (REVRI) in relapse or refractory primary central nervous system (PCNSL) or vitreo retinal lymphoma (PVRL): results of a “proof of concept” phase II study of the French LOC Network [abstract].
Blood.
2016;128 (22):785.
Professor Liu Jiajun, Chief Physician, and Doctoral Supervisor, Director of the Department of Hematology, The Third Affiliated Hospital of Sun Yat-Sen University, Member of the Anti-Cancer Branch of the European Oncology Association Member of the Chinese Immunization Association Member of the Guangdong Medical Industry Association Member of the Guangdong Hematology Society, etc.
Directions: Leukemia cell apoptosis signal transduction mechanism, hematopoietic stem cell transplantation, molecular targeted therapy of hematological tumors, gene therapy and mechanism research of new anti-tumor drugs, etc.
Rituximab-lenalidomide (REVRI) in relapse or refractory primary central nervous system (PCNSL) or vitreo retinal lymphoma (PVRL): results of a “proof of concept” phase II study of the French LOC Network [abstract].
Blood.
2016;128 (22):785.
Professor Liu Jiajun, Chief Physician, and Doctoral Supervisor, Director of the Department of Hematology, The Third Affiliated Hospital of Sun Yat-Sen University, Member of the Anti-Cancer Branch of the European Oncology Association Member of the Chinese Immunization Association Member of the Guangdong Medical Industry Association Member of the Guangdong Hematology Society, etc.
Directions: Leukemia cell apoptosis signal transduction mechanism, hematopoietic stem cell transplantation, molecular targeted therapy of hematological tumors, gene therapy and mechanism research of new anti-tumor drugs, etc.

.

Medical expertise: More than 20 years of clinical medical work in internal medicine and hematology
.

For many years, he has been engaged in the research of leukemia cell apoptosis signal transduction mechanism and molecular targeted therapy of hematological tumors
.

Proficient in diagnosis and treatment of various anemias, bleeding diseases and hematological tumors
.

Diagnosis and treatment of diseases including hematopoietic stem cell transplantation for hematological diseases, chemotherapy for leukemia, malignant lymphoma and multiple myeloma and other individualized treatment options for malignant hematological diseases, various unexplained anemia, unexplained long-term fever, and differential diagnosis of lymphadenopathy and treatment
.

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