Liposomal Cytarabine (DepoCyte) Is Effective and Well Tolerated In Prophylaxis of Central Nervous System (CNS) Relapse of High Risk Lymphoma Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4890-4890
Author(s):  
Wojciech Jurczak ◽  
Justyna Dzietczenia ◽  
Beata Piatkowska-Jakubas ◽  
Marcin Sobocinski ◽  
Tomasz Ogorka ◽  
...  
Keyword(s):  
Side Effects ◽  
High Risk ◽  
Adverse Events ◽  
Systemic Disease ◽  
B Cell Lymphoma ◽  
Neurological Symptoms ◽  
Liposomal Cytarabine ◽  
Mediastinal Tumors ◽  
Cns Relapse ◽  
Vena Cava Superior

Abstract Abstract 4890 Background: CNS relapse is a devastating complication in patients with aggressive NHL and occurs in approximately 5 to 20% of cases. Preventing CNS relapse is an important goal of therapy in high-risk patients with aggressive NHL. The aim of this retrospective study was to evaluate safety and efficacy of Liposomal Cytarabine in a prophylaxis of CNS in high risk lymphoma patients. Materials and Methods: Data of patients treated with Liposomal Cytarabine within the last 2 years were retrieved from 2 centres in Poland which routinely administer prophylaxis of CNS in high risk NHL patients. 32 patients were included in this analysis: 26 – DLBCL including Primary Mediastinal B-cell Lymphoma (PMBCL), 2 – PTCL, 2 – LBL and 2 – BL. Demographics: average age: 42 (range 18–75), 12 females and 20 males. High risk was defined as the presence of elevated LDH (average 852 IU/L, range 482–1890 IU/L) and involvement of 2 or more extranodal sites, IPI 3–5 or specific lymphoma localizations (testis, vertebral column, orbits, sinuses, large mediastinal tumors over 10 cm in diameter). None of the patients had neurological symptoms at diagnosis, nor any abnormalities in cerebrospinal fluid analysis (average cellularity 4,7/mm3, range 0–18). Results: Liposomal Cytarabine was incorporated into 1st line systemic chemotherapy. On average, 3,4 doses (range 2–6) were applied every 2 (n=22) or 4 (n=10) weeks. Side effects: 18 out of 32 patients had no side effects. 12 patients experienced transitory, mostly mild, grade 1–2 adverse events; headache (n=10), nausea and vomiting (n=7), dizziness (n=4) or fever (n=3). Only 2 patients developed grade 3 headaches or fever. One patient developed transient neurological symptoms, most likely unrelated to Liposomal Cytarabine (vena cava superior syndrome at diagnosis and cerebralal thromboembolism after systemic immunochemotherapy). After medium observation time of 306 days from the end of therapy (range 36 – 740) 28/32 (87,5%) patients were disease free. Three patients were lost due to systemic disease progression without any signs of CNS relapse on days 36, 101 and 182. One CNS relapse was reported on the day 252 (the patient subsequently died 5 months later). Conclusions: 1) Liposomal Cytarabine is well tolerated, with mild or no adverse events. Its prolonged action allows it to be incorporated into a standard systemic anti-lymphoma therapy, without the necessity of additional hospital admissions. 2) In a described cohort of high risk lymphoma patients, Liposomal Cytarabine reduced the risk of early CNS relapse to 3% at 1 year (1/32 cases) and OS at 1 year 87% (28/32). Disclosures: No relevant conflicts of interest to declare.

Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients

Blood ◽  
2022 ◽  
Author(s):  
Matthew R. Wilson ◽  
Toby Andrew Eyre ◽  
Amy A Kirkwood ◽  
Nicole Wong Doo ◽  
Carole Soussain ◽  
...  
Keyword(s):  
High Risk ◽  
International Prognostic Index ◽  
Multivariable Analysis ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Prophylaxis ◽  
Dose Methotrexate ◽  
Cns Relapse ◽  
Increased Risk

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.

scholarly journals Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL

Blood ◽  
2019 ◽  
Vol 133 (9) ◽  
pp. 919-926 ◽  
Author(s):  
Magdalena Klanova ◽  
Laurie H. Sehn ◽  
Isabelle Bence-Bruckler ◽  
Federica Cavallo ◽  
Jie Jin ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Cns Relapse ◽  
Relapse Prediction ◽  
Expression Status ◽  
Dual Expression

Abstract Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS–International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell‒like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #NCT01287741.

Prolonged Survival with Low Incidence of CNS Relapse and Late Toxicities in a Retrospective Series of 278 Young Patients with High-Risk (aa-IPI 2–3) Diffuse Large B-Cell Lymphoma Treated with Intensified Chemotherapy with or without Rituximab At Diagnosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1606-1606
Author(s):  
Annalisa Chiappella ◽  
Alessia Castellino ◽  
Maria Giuseppina Cabras ◽  
Anna Marina Liberati ◽  
Andrea Evangelista ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Secondary Malignancies ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Dose Dense

Abstract Abstract 1606 Introduction. Diffuse Large B-cell Lymphoma (DLBCL) patients at high-risk (age-adjusted International Prognostic Index (aa-IPI) 2–3), had a dismal prognosis if treated with conventional chemotherapy. The introduction of intensive regimens and the addition of monoclonal antibody anti-CD20, improved prognosis, but some issues remain unresolved such as: the risk of central nervous system (CNS) relapses and the incidence of late toxicities. We analyzed a series of young DLBCL patients at high-risk consecutively treated in four prospective trials by the Italian Lymphoma Foundation (FIL) with the aim to assess the risk of CNS relapses and late toxicities in this series of patients with a prolonged follow-up Methods. From 1986 to 2006, 278 patients with DLBCL with aa-IPI 2–3 at diagnosis, were enrolled in four consecutive trials previously reported. Thirty-two into a phase II study, treated with 12 weekly infusion of MACOP-B; 39 into a phase II trial with eight weekly MACOP-B infusions followed by high-dose cytarabine, mitoxantrone and dexamethasone (MAD) plus standard BEAM and autologous stem cell transplantation (ASCT); 95 in a phase III trial that randomized high-dose sequential (HDS) chemotherapy plus ASCT (45 patients) vs six courses of dose-dense intensified CHOP (iCHOP) (50 patients); 112 into a phase II trial with four courses of iCHOP in combination with Rituximab followed by Rituximab-MAD + BEAM and ASCT. CNS prophylaxis was not mandatory in the four protocols. Updated data regarding of survival, CNS relapses and late toxicities were recorded on June 2011. Results. Clinical characteristics were: aa-IPI 2 in 55%, aa-IPI 3 in 45%, PS > 2 in 66%, LDH upper normal value in 89%, number of extranodal sites > 2 in 35%, bone marrow involvement in 27% of patients, with no statistical differences between the four trials. With a median follow-up of five years, 5-year Overall Survival (OS) was 63% (95% CI: 57–69%) in the whole series; 5-year OS by treatment was 41% (95%CI: 24–74%) in MACOPB, 54% (95%CI: 37–68%) in MACOPB+MAD+BEAM and ASCT; 53% (95%CI: 38–67%) in HDS+ASCT; 58% (95%CI: 43–70%) in iCHOP; 79% (95%CI: 70–86%) in R-iCHOP+R-MAD+BEAM and ASCT. In a multivariate analysis, the risk of death was significantly reduced in R-iCHOP+R-MAD+BEAM and ASCT (p<.001) and was adversely influenced by age with a progressive increase of five years at diagnosis (p.008) or aa-IPI3 (p.001). Four patients experienced CNS relapses, three of them in R-iCHOP+R-MAD+BEAM and ASCT and one in MACOPB. Only one of the four patients received CNS prophylaxis with intrathecal Methotrexate, even if all of them were at risk for CNS relapse according to Italian Society of Hematology guidelines (Barosi, Hematol 2006). Cumulative incidence of CNS recurrence at 10 years for R-iCHOP+R-MAD+BEAM and ASCT regimen was 3.6% (0 to 7.8). Most frequent late toxicities were dyslipidemia and secondary amenorrhea. Regarding to secondary malignancies, myelodisplasia or acute myeloid leukemia were recorded in three patients, two of them treated with R-iCHOP+R-MAD+BEAM and ASCT, at a median time of seven years off therapy. The actuarial risk of secondary malignancies at 10 years for R-iCHOP+R-MAD+BEAM and ASCT was 4.2% (0 to 10). Conclusions. The addition of Rituximab to dose-dense iCHOP plus high-dose chemotherapy plus BEAM and ASCT improved the outcome in young untreated DLBCL patients at poor prognosis, with an acceptable risk of secondary malignancies and late toxicities. A careful identification of patients at risk could avoid the risk of CNS relapse. Disclosures: Vitolo: Roche Italy: Speakers Bureau; Celgene: Speakers Bureau; Jannsen-Cilag: Speakers Bureau.

Diffuse Large B-Cell Lymphoma with Testicular Involvement: Outcome and Risk of CNS Relapse in the Rituximab Era

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 780-780 ◽  
Author(s):  
David Telio ◽  
Diego Villa ◽  
Tamara Shenkier ◽  
Laurie H. Sehn ◽  
Richard Klasa ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Systemic Disease ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Stage Disease ◽  
Large B Cell

Abstract Abstract 780FN2 Background: Testicular involvement of diffuse large B-cell lymphoma (Te-DLBCL) is associated with a poor outcome and a high risk of central nervous system (CNS) relapse. Rituximab is now routinely used into the treatment of both limited (LIM) and advanced (ADV) stage disease but it is unclear if this can reduce the rate of CNS relapse given it's limited penetration of the blood brain barrier and frequent parenchymal relapses in Te-DLBCL. A recent phase II study by the IELSG using R-CHOP, contralateral testicular radiation (RT) and IT prophylaxis in LIM stage patients demonstrated improved survival rates and a lower rate of CNS relapse compared with historical series. Herein, we evaluated the impact of R-CHOP on the natural history in all patients with Te-DLBCL Methods: The Centre for Lymphoid Cancer Database was used to identify patients with Te-DLBCL who were treated with curative intent. LIM stage was defined as stage I/II without bulk (< 10 cm) or B symptoms and also included patients with discordant involvement of the bone marrow with a low grade lymphoma whose stage was otherwise limited stage, and ADV stage included all others. Results: 109 patients with Te-DLBCL treated between 1985–2011 were identified including 10 patients (11%) with discordant non-follicular low grade lymphoma in the bone marrow (9) or lymph node (1). Twenty-one patients were excluded: chemotherapy refusal (7), palliative (n=9), HIV + (2), peritesticular and not testicular involvement (2), clinical information N/A (1). Of the remaining 88 patients, 40 received CHOP-like chemotherapy and 48 received R-CHOP. The median age at diagnosis was 68 y (range 26–83 y) and half the patients had LIM stage disease. Most patients received either prophylactic contralateral testicular RT (59) or had bilateral orchiectomy (11) with few exceptions: refusal (3), PD or death on therapy (12), unknown (3). Five patients with CNS disease at presentation (R-CHOP n=4; CHOP n=1) also received HD methotrexate (HDMtx) and IT CHT. Only nine patients (7 ADV) received CNS prophylaxis (R-CHOP n=4; CHOP n=5) either IT (8) or IT + HDMtx (1) R-CHOP treated patients were more likely to have > 1 extranodal (EN) sites involved (p=0.030), and there was a trend to a greater proportion of patients with ADV disease (p=.087). With a median follow up of 60 mos, the 5 year TTP and OS for the CHOP and R-CHOP treated patients was similar (TTP 52% vs 67.5%, p=.181; OS 52.5% and 57%, p=0.262). However, an improved TTP (p=.025) and a trend to improved OS (p=.085) was observed in ADV stage patients but not LIM stage patients (TTP p=.617, OS p=.407) treated with R-CHOP. In univariate analysis, stage, EN sites > 1, IPI (0-2 v 3–5) and urinary tract (UT) involvement (kidney, adrenal or ureter) were prognostic for both TTP and OS. In multivariate analysis treatment with rituximab, > 1 EN sites and UT disease were prognostic for both TTP (rituximab p=.006, > 1 EN sites, p=.014, and a trend for UT disease p=.067) and OS (rituximab, p=.009, > 1 EN sites p=.025, UT disease p=.016) Excluding patients with CNS disease at diagnosis, there was no difference in the time to CNS relapse (TTCNS) in R-CHOP (5 y 27%) compared to CHOP treated patients (5 y 23%) (p=.789) in both LIM (5 y 16.5% vs 23.5%, p=.901) and ADV disease (5 y 27% vs 23%, p=0.386). In univariate analysis, the IPI, EN sites, PS and UT disease were associated with an increased risk of CNS relapse. In multivariate analysis, only UT disease (HR 9.18, p<.0001) was predictive of CNS relapse. CNS relapse in LIM patients (12) was typically late (≤ 2 years n=9), commonly parenchymal, (n=9 vs leptomeningeal (LM) n=2, both n=1) and usually in the absence of systemic disease (9). In contrast, CNS relapse in ADV patients (12) was usually early (< ∼ 1 year 10/12), preferentially involved the LM either alone (8) or in concert (3) with parenchymal lesions but also in the absence of systemic disease (10/12). Conclusion: Although survival has improved in Te-DLBCL patients since the introduction of rituximab, the benefit is likely primarily through systemic disease control as there remains an inherently high risk of CNS relapse. Patients with ADV stage disease and particularly with UT tract involvement, have frequent early leptomeningeal relapse and should be considered for up-front CNS treatment. Given the propensity for late parenchymal relapses in LIM stage patients, strategies to test agents with CNS penetration need further investigation. Disclosures: Villa: Roche: Research Funding. Shenkier:Roche: Research Funding. Sehn:Roche: Honoraria, Research Funding. Klasa:Roche: Research Funding. Gascoyne:Roche: Research Funding. Connors:Roche: Research Funding. Savage:Roche: Honoraria, Research Funding.

Lack of Influence of Rituximab and CNS Directed Prophylactic Therapy on CNS Relapse in High-Risk Diffuse Large B Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1711-1711
Author(s):  
Mahender Yellu ◽  
Ehsan Malek ◽  
Berry Thavalathil ◽  
Tahir Latif
Keyword(s):  
High Risk ◽  
Cell Lymphoma ◽  
Risk Group ◽  
B Cell Lymphoma ◽  
High Risk Group ◽  
Intrathecal Methotrexate ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Standard Risk

Abstract Background/method: Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) although uncommon, can be devastating. Conflicting reports have been published regarding the reduction in incidence of CNS relapse in post-rituximabera.We retrospectively identified all the patients with DLBCL who has received rituximab-based chemotherapy at initial presentation in our institute between 2004 and 2014. Patients were divided into two groups, ‘high risk’ group and ‘standard risk’ group, based on following definition. High risk group will have at least one of the following risk factors 1) LDH ≥ 650 U/L 2) Age adjusted International Prognostic Index (IPI) of ≥ 4 3) Involvement of > 1 extra nodal site 4) Involvement of testis 5) Breast 6) Bones 7) Kidneys 8) Adrenal glands 9) Retroperitoneal lymph nodes 10) Para-meninges or 11) Bone marrow. Patients without any of these risk factors were deemed standard risk. Descriptive statistics were used to analyze the incidence of CNS relapse, patient and disease characteristics. Historically reported incidence rates were used for comparison. Results:One hundred and forty two consecutive patients with DLBCL were included in our study. One hundred and twenty two patients received rituximab-based therapy at the initial diagnosis. Forty-nine patients (40%) met the criteria for ‘high risk’ based on the above definition. Seventy-three patients (60%) qualified for standard risk group. Standard risk group received no CNS directed prophylaxis and none of these patients had CNS relapses. Thirty-one of 49 ‘high risk’ patients received CNS prophylaxis, mainly intrathecal methotrexate. Total 5 patients (4.09%) developed CNS relapse. CNS relapse in high-risk group was 10.2% (5/49). Median age at diagnosis in patients with CNS relapse was 53 years. Median time to relapse was 8.76 months. Median survival after the CNS relapse was 9.16 months. Four out of 5 patients received CNS prophylaxis with intrathecal methotrexate or systemic methotrexate or systemic cytarabine or a combination of them. Average number of doses of prophylaxis received by each patient was 3.2 (range 1-7). Only one patient who developed CNS relapse did not receive any CNS directed therapy as prophylaxis. Conclusion:No significant reduction in the incidence of CNS relapse was noted with upfront use of rituximab. Our study confirms that majority of the DLBCL patients do not need CNS directed therapy. For high risk DLBCL patients, we not only need to develop better predictive markers for CNS relapse but also need better CNS directed therapies to prevent this fatal complication of highly curable disease. Disclosures No relevant conflicts of interest to declare.

Long-term use of sustained-release cytarabine for symptomatic management and treatment of meningeosis neoplastica.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19579-e19579
Author(s):  
Franziska Jahn ◽  
Timo Behlendorf ◽  
Cordula Globig ◽  
Berit Jordan ◽  
Hans-Heinrich Wolf ◽  
...  
Keyword(s):  
Side Effects ◽  
Cauda Equina ◽  
Neurological Symptoms ◽  
Intrathecal Therapy ◽  
Time Interval ◽  
Tumor Type ◽  
Liposomal Cytarabine ◽  
Treatment Burden ◽  
Meningeosis Neoplastica

e19579 Background: Treatment of meningeosis neoplastica remains challenging due to advanced systematic disease and limited treatment options including a high treatment burden. Liposomal Cytarabine (DepoCyte) is a slow-release formulation of cytarabine that maintains cytotoxic concentrations in the Cerebrospinal fluid (CSF) for >14 days following a single injection. This two week interval has potential benefit due to reduced interventions especially in palliative settings. Methods: We reviewed all patients at our institution treated with liposomal cytarabine (LC) between 3/2004 and 9/2011.The data included tumor type, ICF-cell-count, neurologic disorders due to meningeal affection and time interval from intrathecal therapy to progression and to death of the patient.Assessment for meningeosis neoplastica included neurological examination, CSF assessment and brain MR imaging. LC was administered intralumbar at 50 mg every 2-weeks until progression or appearance of severe side effects. Results: To date 51 adult patients eligible for safety evaluation (48 pts. for efficacy evaluation) (median age 61 y [range 23 - 81 y]) were treated with LC. 72.5% of the included patients had lymphoma, 5.9% breast cancer and 21.6% other solid malignancies. Concurrent systemic chemotherapy was given in 82% of the patients. A total of 160 doses were administered (mean 2.9, range 1- 13). The most frequent side effects were mucositis (21.6%), elevated body temperature (15.7%), backpain (9.8%) and nausea/vomiting (7.8/5.9%). In two lymphoma patients with long term use of LC (13/ 4 applications) cauda equina syndroms appeared. In 61.9% of patients a reduction of neurological symptoms could be achieved; 53% of the patients attained a cytological response in CSF. Median overall survival was 20 months. Conclusions: The obtained results are comparable to those previously reported for methotrexate given 3 times a week. Thus our trial indicates that the 14-day dosing interval is on one hand effective to decrease neurological symptoms caused by meningeosis neoplastica with a favourable safety profile and on the other hand is less burdensome for the patients due to reduced manipulation and treatment burden respectively.

scholarly journals Clinical report of a patient with primary mediastinal B-large cell lymphoma

2021 ◽  
Vol 67 (5) ◽  
pp. 718-723
Author(s):  
Inna Kamaeva ◽  
Irina Lysenko ◽  
Nadezhda Nikolaeva ◽  
Elena Kapuza ◽  
Iurii Lazutin ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cell Lymphoma ◽  
Vena Cava ◽  
Clinical Manifestations ◽  
B Cell Lymphoma ◽  
Diagnostic Error ◽  
Clinical Report ◽  
Morphological Examination ◽  
Mediastinal Tumors ◽  
Vena Cava Superior

Primary mediastinal B-cell lymphoma is a variant of non-Hodgkin's lymphoma with the predominant involvement of mediastinal lymph nodes, which affects young women. Diagnosis of this nosology is difficult due to the rare involvement of peripheral lymph nodes, as well as the rapid increase of clinical manifestations, such as the syndrome of compression of the vena cava superior and the development of the respiratory failure. The article presents a clinical case of a patient who was operated and complications that occurred due to inadequate diagnostic and therapeutic tactics. There aren`t any descriptions of the clinical manifestations of the disease which could led to a diagnostic error in literature. We present our own observation of a patient with PMBCL and discuss a practical diagnostic algorithms for mediastinal tumors. The diagnosis of PMBCL can be established only as a result of morphological examination, it is important that surgeons and pathologists remember about it. This case is important not only because it provides information about such a lymphoproliferative disease as PMBCL, but also reminds about such a diagnostic error in oncology-treatment without verification. We tried to emphasize the nesessary of strict implementation of the algorithm for differential diagnosis of the anterior mediastinal neoplasms, especially for young people. I hope that this case will contribute to the expansion of knowledge and the prevention of errors in order to achieve better results.

scholarly journals Prophylaxis with Intrathecal Chemotherapy and High Dose Methotrexate in Patients with Diffuse Large B Cell Lymphoma at High Risk for Central Nervous System Relapse: A Single Centre Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5420-5420
Author(s):  
Dario Marino ◽  
Silvia Finotto ◽  
Caterina Boso ◽  
Federica Vianello ◽  
Benedetta Chiusole ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Risk ◽  
Complete Remission ◽  
B Cell Lymphoma ◽  
High Dose ◽  
First Line ◽  
Cns Disease ◽  
Cns Prophylaxis ◽  
Cns Relapse

Abstract Central nervous system involvement (CNS) is a serious and mostly fatal complication of aggressive lymphoma. The incidence of CNS disease in diffuse large B-cell lymphoma (DLBCL) is low (about 5%) and there are not randomised prospective trial which specifically address a decision-making process for CNS prophylaxis. Potentially two methods exist for identifying patients requiring CNS directed treatment. Surveillance lumbar puncture and brain magnetic resonance (MRI) at the time of diagnosis could identify the presence of lymphoma; another method is the identification of patients whose characteristics are indicative of a high risk of CNS disease. Several site-specific risks are described in literature such as testicular, breast, paranasal sinuses, epidural spaces, and intravascular involvement with an incidence of CNS relapse ranging from 15% to 50%. Recently a modified IPI score (CNS IPI) was described to predict risk of CNS relapse. The efficacy of different forms of CNS prophylaxis has never formally been demonstrated. In the RICOVER 60 trial, patients treated with R-CHOP-14 instead of CHOP-14 presented a lower incidence of CNS relapse while intrathecal methotrexate (MTX) has not showed a role in preventing CNS disease for patients treated with combined immunochemotherapy. Recently, combination of intrathecal MTX and high dose MTX infusion after R-CHOP treatment was considered an effective strategy of prevention of CNS relapse. In order to evaluate the efficacy and feasibility of intrathecal MTX administration and high dose MTX after first line chemotherapy, we retrospectively reviewed 27 patients (11 males and 16 females, mean age 61 yrs, range 27-79) with newly diagnosed DLBCL at high risk for CNS relapse, treated from January 2009 to April 2018 at Veneto Institute of Oncology IOV-IRCCS. In our cohort 21 (78%) patients were at advanced stage (III-IV Ann Arbor stage) and 15 (56%) belonged to intermediate-high or high risk IPI categories, two patients presented with orbital localization. Almost all patients received R-CHOP as first line treatments, two patients with paravertebral localization received HyperCVAD as front line approach. For 20 patients CNS-IPI was intermediate or high. In the other cases with low CNS-IPI, disease localization was considered at high risk of CNS relapse (breast, paravertebral, orbit, paranasal sinus). In all patients we performed brain MRI and diagnostic lumbar puncture at diagnosis (all negative at flow cytometry analysis). All 14 patients >65 yrs were evaluated with comprehensive geriatric assessment (CGA) and 8 (57%) were considered fit. Nineteen (19) patients (70%) received at least 3 lumbar punctures with MTX and 24 (89%) two courses of high dose intravenous MTX during first line therapy. At the end of planned first line treatment, 24 (89%) patients obtained a complete remission at PET scan evaluation and 3 patients (11%) presented progressive disease, 2 with CNS involvement and another with peritoneal disease; this last patient had a Double Hit lymphoma with BCL6 and c-MYC rearrangements. Another patient in complete remission after R-CHOP chemotherapy, experienced CNS relapse three year after obtaining complete remission. Among the two patients treated with Hyper CVAD regimen, one is still in complete remission 5 years after the end of treatment; another developed early CNS relapse. All the 3 patient who experienced CNS involvement after R-CHOP, didn't receive prophylaxis because were evaluated frail at CGA. So, at a median follow up of 26.2 months (3.5-100 months) all patients who received the planned treatment at full dose including CNS prophylaxis did not experience central nervous system relapse. In conclusion, CNS prophylaxis including intrathecal MTX administration and high dose MTX infusion after first line chemotherapy is feasible and effective. Larger prospective trials are needed to evaluate the most effective prophylactic therapy and the correct timing of intravenous MTX infusion. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and safety of prophylactic high-dose MTX in high-risk DLBCL: a treatment intent–based analysis

2021 ◽  
Vol 5 (8) ◽  
pp. 2142-2152
Author(s):  
Hyehyun Jeong ◽  
Hyungwoo Cho ◽  
Hyeyeong Kim ◽  
Heejung Chae ◽  
Jung-Bok Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Relapse Rate ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Survival Outcomes ◽  
High Dose ◽  
Free Survival ◽  
Cns Relapse ◽  
Treatment Intent

Abstract Despite central nervous system (CNS) relapse occurring in &gt;10% of high-risk diffuse large B-cell lymphoma (DLBCL) patients, the role of CNS-directed prophylaxis is controversial in the absence of randomized controlled trials. In this retrospective study, we aimed to evaluate the safety and efficacy of prophylactic high-dose methotrexate (HD-MTX) on CNS relapse and survival outcomes in 258 newly diagnosed R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)–treated high-risk DLBCL patients, based on the initial treatment intent (ITT) of the physician on the use of prophylactic HD-MTX. Patients were classified into an ITT HD-MTX group (n = 128) and a non-ITT HD-MTX group (n = 130). The CNS relapse rate was not significantly different between these groups, with 2-year CNS relapse rates of 12.4% and 13.9%, respectively (P = 0.96). Three-year progression-free survival and overall survival rates in the ITT HD-MTX and non-ITT HD-MTX groups were 62.4% vs 64.5% (P = 0.94) and 71.7% vs 71.4% (P = 0.7), respectively. Also, propensity score–matched analyses showed no significant differences in the time-to-CNS-relapse, progression-free survival, or overall survival. The ITT HD-MTX group showed a higher incidence of grade ≥ 3 oral mucositis and elevated alanine aminotransferase. Prophylactic HD-MTX does not improve CNS relapse rate or survival outcomes in high-risk DLBCL patients, and it is accompanied by increased toxicities.

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