scholarly journals Increased Serum Beta-2 Microglobulin during Induction Chemotherapy Associated with Poor Prognosis in Primary Central Nervous System Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2995-2995
Author(s):  
Jaewon Hyung ◽  
Jung Yong Hong ◽  
Dok Hyun Yoon ◽  
Shin Kim ◽  
Jung Sun Park ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Factors ◽  
Induction Chemotherapy ◽  
Poor Prognosis ◽  
Central Nervous System Lymphoma ◽  
Survival Outcomes ◽  
Induction Treatment ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Abstract Introduction Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma that exclusively involves the brain, leptomeninges, eyes, or spinal cord. Due to the rare incidence of PCNSL, therapeutic decisions and predictions of outcomes rely on phase 2 clinical trials and retrospective studies. Indeed, it is important to continuously search potential prognostic factors. Serum beta-2 microglobulin (B2MG) is thought to be associated with prognosis in several lymphomas and multiple myeloma. Previous study in our center showed that increased serum B2MG of ≥ 1.8 μg/mL at diagnosis was associated with poor prognosis in PCNSL. In this study, we investigated association of serum B2MG level changes with survival outcomes in PCNSL patients during induction chemotherapy who had elevated serum B2MG level at diagnosis. Methods We retrospectively reviewed prospectively collected PCNSL registry data for patients treated from March 1993 to May 2017 at Asan Medical Center in Seoul, Korea. Patients with serum B2MG of ≥ 1.8 μg/mL at diagnosis who had at least two or more measurement of serum B2MG including at diagnosis, 6 weeks, and 3 months from the initiation of induction chemotherapy were included in the analysis. Two weeks of window period was allowed for measured B2MG at 6 weeks and 3 months from the beginning of treatment. Overall survival (OS) was defined as the time from the initiation of induction treatment to death from any cause, and progression-free survival (PFS) was defined as the time from the initiation of induction treatment to disease progression or death. Univariate analyses were performed to compare survival outcomes using log-rank tests. Multivariate analyses were performed to identify independent prognostic factors for PFS and OS using a Cox proportional hazards model. Results Among 241 patients with diagnosis of PCNSL, 42 patients were included in the study. Median follow-up period was 4.0 years (range, 0.1-9.7). Median OS and PFS was 2.3 years (95% CI 1.9-2.6), and 1.2 years (95% CI 0.6-1.8), respectively. Median age was 67 years old (range, 28-85) and 26 patients (61.9%) were male. All patients received methotrexate-based combination chemotherapy as induction treatment and 31 patients (88.6%) showed complete response or partial response as best responses. Ten patients (23.8%) received consolidation treatment with high-dose chemotherapy followed-by autologous stem cell transplantation. Patients were classified into two groups according to serum B2MG level difference compared to B2MG level at diagnosis with the B2MG level at 6 weeks and 3 months from the initiation of induction treatment. Median B2MG at diagnosis, 6 weeks, and 3 months was 2.4 μg/mL (range, 1.9-11.7), 2.5 μg/mL (range, 1.3-8.7), and 2.6 μg/mL (range, 1.4-8.7), respectively. There was no statistically significant difference in terms of OS between patients with increased B2MG level at 6 weeks (16 patients) and patients with no increment (10 patients) with median OS of 1.4 years (95% CI 0.1-2.8) and 3.0 years (95% CI 1.1-4.9), respectively (P = 0.065). Patients with increased B2MG level at 3 months (23 patients) significantly poor prognosis in terms of OS compared to patients with same or decreased level (13 patients). Median OS was 1.4 years (95% 0.6-2.3) for the increased patients and not reached in patients with no increment (P < 0.001). Multivariate analysis with other factors showed significantly poor outcomes in patients with increased serum B2MG level at 3 months from the initiation of induction treatment in terms of OS with hazard ratio of 14.3 (95% CI 2.1-100.0, P = 0.007). Conclusion Among PCNSL patients who had serum B2MG level of ≥ 1.8 μg/mL at diagnosis, which was associated with poor prognosis in our previous study, patients with no increment of serum B2MG level at 3 months from the initiation of induction chemotherapy was associated with better survival outcomes in terms of OS compared to those with increased level. Disclosures No relevant conflicts of interest to declare.

scholarly journals Beta-2 microglobulin as a prognostic factor of primary central nervous system lymphoma

2019 ◽  
Vol 54 (4) ◽  
pp. 285-288
Author(s):  
Jaewon Hyung ◽  
Jung Yong Hong ◽  
Shin Kim ◽  
Jin Sook Ryu ◽  
Jooryung Huh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Factor ◽  
Central Nervous System Lymphoma ◽  
Beta 2 ◽  
Beta 2 Microglobulin

scholarly journals Effect of Tumor Microenvironment and Angiogenesis on Clinical Outcomes of Primary Central Nervous System Lymphoma

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hui-Ching Wang ◽  
Hui-Hua Hsiao ◽  
Jeng-Shiun Du ◽  
Shih-Feng Cho ◽  
Tsung-Jang Yeh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Microenvironment ◽  
Induction Chemotherapy ◽  
Central Nervous System Lymphoma ◽  
Survival Outcomes ◽  
Short Term ◽  
Genomic Alterations ◽  
Baseline Characteristics

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma, and the disease course is often aggressive with poor prognosis outcomes. PCNSL undergoes germinal center reactions and impairs B-cell maturation. However, angiogenesis is also involved in the tumorigenesis and progression of PCNSL. This study investigated the effects of the tumor microenvironment and angiogenesis-associated genomic alterations on the outcomes of PCNSL. The analysis also evaluated the influence of treatment modality and timing on PCNSL survival using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and disease outcomes with a small sample of measurements and structural models. A total of 19 immunocompetent PCNSL samples were analyzed by exome sequencing. Our results suggest that the timing of radiotherapy and mutations of ROBO1 and KAT2B are potential indicators of PCNSL outcomes and may be affected by baseline characteristics such as age and sex. Our results also showed that patients with no mutations of ROBO1 and KAT2B, SubRT subgroup showed favorable survival outcomes compared with no SubRT subgroup in short-term follow-up. All SubRT patients have received high-dose methotrexate induction chemotherapy in the initial treatment. Therefore, initial induction chemotherapy combined with subsequent radiotherapy might improve survival outcomes in PCNSL patients who have no ROBO1 and KAT2B somatic mutations in short-term follow-up. The overall findings suggest that the tumor microenvironment and angiogenesis-associated genomic alterations and treatment modalities are potential indicators of overall survival and may be affected by the baseline characteristics of PCNSL patients.

scholarly journals Patients with Primary Central Nervous System Lymphoma Not Eligible for Clinical Trials: Prognostic Factors, Treatment and Outcome

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2934
Author(s):  
Sabine Seidel ◽  
Michelle Margold ◽  
Thomas Kowalski ◽  
Alexander Baraniskin ◽  
Roland Schroers ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Prognostic Factors ◽  
Central Nervous System Lymphoma ◽  
Initial Response ◽  
Early Response ◽  
Multicenter Trial ◽  
High Dose ◽  
Therapeutic Trials

Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1–141) in non-study patients and 51 months (1–105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) < 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0–21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0–45)/21 months (95% CI 18–25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.

scholarly journals Primary Central Nervous System Lymphoma: A Retrospective Study of the Population of Texas and Florida with an Emphasis on Survival Outcomes on Hispanics Vs Non-Hispanics

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1443-1443
Author(s):  
Kana Tai Lucero ◽  
Lakene Raissa Djoufack Djoumessi ◽  
Joel E Michalek ◽  
Qianqian Liu ◽  
Adolfo Enrique Diaz Duque
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retrospective Study ◽  
Research Funding ◽  
Central Nervous System Lymphoma ◽  
Survival Outcomes ◽  
P Value ◽  
Poverty Index ◽  
Significant Difference ◽  
The U.S

Abstract Introduction Primary central nervous system lymphoma (PCNSL) is a devastating subtype of extranodal non-Hodgkin's lymphoma (NHL) that accounts for ~4% of newly diagnosed central nervous system (CNS) tumors. (NeuroOncol PMID: 21915121) The age-adjusted incidence of PCNSL in the U.S. has increased since the 1970s. (ACS PMID: 19273630) despite advances in the treatment of lymphoma, and clinical outcomes remain poor with an estimated 5- year survival for immunocompetent patients at 30%. (NCBIPMID:31424729) Trends in outcomes of PCNSL have been reported, but sub-analyses for minorities like Hispanics (HI), have not been widely studied. Understanding ethnic disparities on outcomes and patterns of care in PCNSL are crucial given the rapid growth of HI in the U.S. This study aims to examine the demographics, treatment patterns, and survival outcomes of PCNSL in HI compared to Non-Hispanics (NH) in Texas (TX) and Florida (FL). Methods This is a retrospective study of a cohort of patients diagnosed with lymphoma (Hodgkin and Non-Hodgkin) from the TX Cancer Registry (TCR) and the FL Cancer Data System (FCDS) from 2006-2017. Patients with PCNSL were identified by the International Classification of Diseases for Oncology Third Edition (ICD-O-3) code list. Standard demographic variables collected include gender, ethnicity, dates at diagnosis and death, primary payer at diagnosis, type of treatment and poverty index (PI). The significance of variation in the distribution of categorical outcomes with ethnicity (HI and NH) was assessed with Fisher's Exact tests or Pearson's Chi-square tests as appropriate; age was assessed with T-tests or Wilcoxon tests as appropriate. Survival distributions were described with Kaplan-Meier curves and significance of variation in median survival with ethnicity was assessed with log rank testing. All statistical testing was two-sided with a significance level of 5%. Results The study included 1969 patients (TX: n=297 HI, n= 708 NH; FL: n=149 HI, n=415 NH). PCNSL was diagnosed at younger median age in HI (TX: 59,FL:59) compared to NH (TX: 62, FL:63),with a significant difference noted within each state (TX: p= 0.005; FL: p=0.007). HI in TX were identified primarily as Mexican, Spanish or NOS/Hispanic. There was a significant predominance of overall males (M) in TX (p=0.009). There was a non-significant predominance of M in FL. Regarding poverty index (PI), there were more HI (TX:51% and FL: 35%) in the 20-100% bracket than NH (TX: 25%; FL: 22%). Conversely there were more NH in all other PI in TX and FL. Government sponsored insurance was the most common insurance in all subgroups. This reached a significant predominance in HI (54%) and NH (54%) in TX (p&lt;0.001). There was no significant difference in insurance types between HI and NH in FL(p=0.772). Regarding chemotherapy there was a trend to either use multiple agents [(TX: 34% in HI vs 32% in NH; p=0.68); (FL: 33% in HI vs 67% in NH; p=0.042)] or to not offer chemotherapy at all [(TX: 26% in HI vs 29% in NH; p= 0.68); (FL: 44% in HI vs 33% in NH; p=0.042)] with significant differences noted in FL only. (Table 1) The median survival (MS) for HI and NH in TX was similar in years (y) at 0.8 while the MS time in FL for HI vs NH was higher (1.3 vs 0.6 respectfully) Thus, the MS for HI in FL was higher compared to NH in FL and HI and NH in both TX and FL. (Table 2) The survival probability for HI was shorter at 2 and 5 years compared to NH in TX with a non-significant overall survival (OS) probability (p-value=0.19) seen in Figure 1. Significantly, the survival probability of HI in FL at 2, 5 and 10 years was higher compared to NH with an OS probability (p-value=0.0063) seen in Figure 2. Conclusion This retrospective study showed a statistically significant difference in OS probabilities at all years between HI and NH in FL with PCNSL. The OS probability also remained higher in HI in FL compared to both HI and NH in TX. In addition, the study demonstrated a longer MS in HI in FL compared to not only HI in TX, but also both NH in TX and FL. Sociodemographic differences like gender and insurance types were noted between HI in TX and FL. HI origin groups are also a subject of interest. The primary HI origin group in TX were Mexican and not otherwise specified (NOS). This data was missing for FL HI. Future studies should be conducted to uncover any further disparities between these two HI populations to explore the impact of access to care and disease biology on PCNSL survival outcomes. Figure 1 Figure 1. Disclosures Diaz Duque: Incyte: Consultancy; Morphosys: Speakers Bureau; Astra Zeneca: Research Funding; Hutchinson Pharmaceuticals: Research Funding; Epizyme: Consultancy; ADCT: Consultancy.

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