The MRZ reaction in rheumatological disorders with CNS involvement and primary CNS lymphoma

Primary CNS lymphoma is a rare condition, with annual incidence of about 1400 cases in the US. Patients with aggressive systemic lymphomas also have high incidence of CNS involvement, with poor overall prognosis. Use of high dose methotrexate based therapies has substantially altered the outlook for these patients. We present the outcomes data of patients with primary CNS lymphoma and those with secondary CNS involvement treated with high dose methotrexate from a single , FACT accredited academic transplant center. We reviewed patients treated at our center over a 42 month period between Jan 2017- June 2020. There were 19 patients with primary CNS lymphoma and 24 with secondary CNS involvement who received high dose methotrexate. There were equal number of men and women, and were mostly Caucasian. Median age at diagnosis was 60 years. Majority were HIV negative (95%). 3 of the 19 patients had EBV infection at the time of diagnosis. Majority had performance status of ECOG 1 (range: 0-4). 1 patient had CNS lymphoma in the post transplant setting (had bilateral lung transplant). 2 out of 19 patients had concurrent solid organ malignancies. 17 patients (90 %) had newly diagnosed primary CNS lymphoma. 2 patients (10 %) had relapsed disease. Patients received a median of 6 induction treatments (range 1-12) . Majority of patients (17/19) received high dose methotrexate with rituximab. 1 patient received only high dose methotrexate. 1 patient received methotrexate, procarbazine, rituximab and vincristine (R MPV). 5 patients (26%) progressed during induction. There were 7 deaths (37 %) during induction phase. Majority of the deaths occured early during induction. Majority had partial response. 1 patient had complete response . No patient has received stem cell transplant. There were no chemotherapy delays due to COVID 19 . No patient with primary CNS lymphoma was hospitalized or died due to COVID 19. 1 patient elected to defer chemotherapy due to fear of contracting COVID 19 in the hospital. No patient received the full,planned doses of high dose methotrexate during induction. Dose reductions were due to poor performance status or impaired renal function. Consolidation was mainly with high dose methotrexate. Those progressing received whole brain radiation, Ara C , or best supportive care. The PFS and OS are being evaluated at the time of this submission. There were 24 patients with secondary CNS involvement . 12 had concurrent systemic and CNS involvement. 12 patients had history of systemic lymphoma but with CNS only relapse. There were equal males and females. Median age at diagnosis was 64 years. (range 33-81). They had good performance status, with majority having PS of ECOG 1 (range 1-3). Majority were caucasian. There were 4 patients (17%) with EBV infection. 2 patients (8 %) had HIV. They received a median of 2 high dose methotrexate inductions (range: 1-10). 4 patients (17%) eventually received stem cell transplants. PFS, survival data are being evaluated at the time of this submission. In general, high dose methotrexate was well tolerated in both primary CNS lymphoma and systemic lymphoma with CNS involvement. Stem cell transplants are still being done infrequently for these patients. Disclosures Finn: Jazz Pharmaceuticals:Speakers Bureau;Celgene:Speakers Bureau;Seattle Genetics:Speakers Bureau.

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Combined treatment of primary vitreoretinal lymphomas significantly prolongs the time to first relapse

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-311574 ◽

2018 ◽

Vol 102 (11) ◽

pp. 1579-1585 ◽

Cited By ~ 10

Author(s):

Aneta Klimova ◽

Jarmila Heissigerova ◽

Eva Rihova ◽

Michaela Brichova ◽

Robert Pytlik ◽

...

Keyword(s):

Overall Survival ◽

Combined Treatment ◽

Primary Cns Lymphoma ◽

Progression Free Survival ◽

Cns Lymphoma ◽

Cns Involvement ◽

Free Survival ◽

Primary Vitreoretinal Lymphoma ◽

Vitreoretinal Lymphoma ◽

First Relapse

BackgroundVitreoretinal lymphomas belong to the family of central nervous system (CNS) lymphomas. The optimal approach for the treatment of isolated primary vitreoretinal lymphoma is unclear because of the lack of large comparative clinical series. Combination of intravitreal and systemic chemotherapy is recommended in many reports. The aim of our retrospective study was to compare the survival rate and prognosis of patients with vitreoretinal lymphoma with and without CNS involvement.MethodsTwenty patients with vitreoretinal lymphomas were observed between the years 2004and2016, 10 patients with primary vitreoretinal lymphoma and 10 with primary CNS lymphoma. To compare survival rates, we included 53 patients diagnosed with primary CNS lymphoma without vitreoretinal involvement between the years 2002and2011 from our haemato-oncology department.ResultsThe 5-year survival rate was estimated 71% in patients with vitreoretinal lymphoma in our observation. Significantly longer 5-year overall survival (P˂0.01) was observed in patients with vitreoretinal lymphoma compared with patients with primary CNS lymphoma without vitreoretinal involvement. Progression-free survival was almost equal in both groups of patients with primary vitreoretinal lymphoma and primary CNS lymphoma (P=0.363). The relapse of lymphoma was frequent (50%–60%) with the median time to first relapse of 31 months. Combined treatment (local and systemic) in patients without CNS involvement significantly prolonged progression-free survival in our study (P˂0.05).ConclusionCombined treatment of primary vitreoretinal lymphoma significantly delays the relapse of lymphoma compared with local therapy alone. Intraocular involvement brings significant positive prognostic value when overall survival is compared.

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High-dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) for recurrent/progressive CNS lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2089 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2089-2089 ◽

Cited By ~ 1

Author(s):

Mary Roberta Welch ◽

Craig Steven Sauter ◽

Matthew J. Matasar ◽

Craig Moskowitz ◽

Antonio Marcilio Padula Omuro

Keyword(s):

Primary Cns Lymphoma ◽

High Dose Chemotherapy ◽

Autologous Stem Cell Transplant ◽

Cns Lymphoma ◽

High Dose ◽

Cell Transplant ◽

Cns Involvement ◽

Non Hodgkin Lymphoma ◽

Significant Toxicity

2089 Background: In two reports by Soussain et al, promising efficacy was observed in recurrent primary CNS lymphoma with induction cytarabine/VP-16 (CYVE) followed by HDC-ASCT (busulfan, thiotepa and cyclophosphamide [BTC]), but significant toxicity, mainly from CYVE, has limited widespread use. We report our experience with HDC-ASCT with alternative induction regimens. Methods: Retrospective review of pts with recurrent/refractory non-Hodgkin lymphoma (NHL) with CNS involvement treated with HDC-ASCT (2000-present). Results: Seventeen pts met inclusion criteria: med age= 58 (41-65); 9 were women; med KPS prior to transplant= 90 (range 70-100). At initial presentation, 10 had primary CNS lymphoma (ocular: 1); 7 had systemic NHL without CNS involvement; 1 had both systemic and CNS disease. Pts had been heavily pre-treated. Among those with PCNSL, high dose MTX was used in all pts and WBRT in 4. Two pts had received a previous HDC-ASCT. Among systemic NHL pts, various regimens were used, mostly R-CHOP(4), but also R-EPOCH (1), CVP (1), ICE (1) and CODOX-M (1). At CNS recurrence, pts received various induction regimens prior to HD-ASCT: high-dose methotrexate (MTX)-based chemotherapy (N= 13), cytarabine-based regimens (N=2), and other (N= 2). All pts achieved a CR or near CR prior to HDC-ASCT. Harvesting was obtained with G-CSF alone in 9 pts; 8 required plerixafor. Two pts failed mobilization N=15 received HDC-ASCT. The HDC consisted of BTC (N=13); 1 received BEAM and 1 received reduced intensity fludarabine, melphalan and alemtuzumab. Eight pts experienced a grade III or IV toxicity – most commonly fatigue, febrile neutropenia, and infection. One previously transplanted pt died from sepsis. With a med follow-up of 11 months, post-transplant med-PFS has not been reached. The 12m PFS was 92% (95% CI 56-98). Because no patient has progressed, the OS was identical to PFS. Conclusions: HDC-ASCT was a highly effective salvage approach in this population of recurrent/refractory CNS lymphoma. To reduce the risk of harvesting failure at the time of recurrence, harvesting stem cells at the time of initial treatment could be considered in pts with high risk for relapse.

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A Small Case Series of Intravascular Large B-Cell Lymphoma with Unexpected Findings: Subset of Cases with Concomitant Extravascular Central Nervous System (CNS) Involvement Mimicking Primary CNS Lymphoma

Journal of Pathology and Translational Medicine ◽

10.4132/jptm.2017.02.16 ◽

2017 ◽

Vol 51 (3) ◽

pp. 284-291 ◽

Cited By ~ 3

Author(s):

Kate Poropatich ◽

Dave Dittmann ◽

Yi-Hua Chen ◽

Kirtee Raparia ◽

Kristy Wolniak ◽

...

Keyword(s):

Central Nervous System ◽

Cell Lymphoma ◽

Primary Cns Lymphoma ◽

Case Series ◽

B Cell Lymphoma ◽

Cns Lymphoma ◽

Cns Involvement ◽

Large B Cell Lymphoma ◽

Unexpected Findings ◽

Large B Cell

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Nivolumab in Primary CNS Lymphoma and Primary Testicular Lymphoma with CNS Involvement: Single Center Experience

Blood ◽

10.1182/blood-2020-138924 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 4-4

Author(s):

Andrey N. Gavrilenko ◽

Nikita P. Volkov ◽

Daniil I. Shmidt ◽

Alexey Y. Polushin ◽

Elena Kondakova ◽

...

Keyword(s):

Overall Survival ◽

Poor Prognosis ◽

Primary Cns Lymphoma ◽

Median Number ◽

Remission Induction ◽

Cns Lymphoma ◽

Cns Involvement ◽

First Line ◽

Testicular Lymphoma ◽

Primary Testicular Lymphoma

Background.Most patients with primary CNS lymphoma (PCNSL), an aggressive extranodal lymphoma confined to the CNS, have a poor prognosis in spite of development of chemotherapy regimens. First-line treatment consists of high-dose methotrexate-based (HD-MTX) regimen followed by consolidation with autologous stem cell transplantation or whole brain radiotherapy. Given that this tumor manifests predominantly in older patients with median age of 65 years, many patients are unable to tolerate intensive chemotherapy. Moreover, most patients eventually present with relapsed or refractory (r/r) disease. Relapse or refractory (r/r) PCNSL has a poor prognosis with median overall survival not exceeding 3.5 months (Langner-Lemercier et al, 2016) and these patients should be offered a clinical trial whenever possible. These groups are in need of safe, tolerable and effective therapeutic approaches. Primary testicular lymphoma (PTL) shares biological and clinical similarities with PCNSL and often present with CNS involvement. Such patients are also in need of new approaches, especially if they are refractory or not suitable to HD-MTX. Given high PD-1/PD-L1 expression in tumor microenvironment (Berghoff, 2014), immune checkpoint inhibitors were successfully tested in r/r PCNSL and PTL setting. However, data are still scarce and limited to case series (Nayak et al., 2017; Graber et al. 2020). Here we present Pavlov University experience of the treatment of PCNSL and PTL with CNS involvement with PD-1 inhibitor nivolumab. Methods.Eight patients, 2 men and 6 women, with PCNSL and one patient with PTL with CNS involvement treated at the Pavlov University between 2017 and 2020 were included into analysis. Median age at a diagnosis was 62 (28-66) years. Two patients (22%) had ECOG score 3-4 and therefore could not be considered for intensive MTX containing frontline treatment. In all of the cases the tumor histological type was diffuse large B-cell lymphoma. All patients had parenchymal involvement: 7 patients had multifocal disease; deep structures were involved in 2 patients. One patient had leptomeningeal involvement. Nivolumab was used in a first-line setting in 2 patients (22%). In 7 (78%) patients with relapsed/refractory disease, the median number of treatment lines prior to nivolumab was 1 (1-7). Nivolumab was given every 2 weeks in the 100 mg dose. Adverse events were defined according to NCI CTC-AE 5.0. Results.At the time of analysis, the median follow-up was 18 (3-44) months. Median number of nivolumab cycles was 10 (2-23). Seven (78%) patients had an objective response: complete response in 3 patients (33.3%) and partial response in 4 patients (44.4%). Two patients (22.2%) were refractory to treatment. Two-year overall survival (OS) was 44% with median OS of 12 months. Two-year progression-free survival (PFS) was 26% with median of PFS 12 months. Оne responder had a moderate increase of tumor volume on MRI after two months of therapy followed by complete disappearance of brain lesions on sequential imaging at 4 months after treatment initiation. Nivolumab therapy appeared safe with only one patient (11%) having severe adverse event, namely grade 3 alanine aminotransferase and aspartate aminotransferase increase. Conclusion.Nivolumab appears to be safe and effective therapy in PCNSL and PTL with CNS involvement both in first-line and r/r setting. However, in our cohort majority of patients relapsed that suggest that consolidation therapy after remission induction with nivolumab may be crucial for long-term remissions. We also demonstrate that pseudoprogression might be also observed in PCNSL during immunotherapy. Large-scale trials are needed to generate strong evidence for the use of PD-1 inhibitors in PCNSL. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Nivolumab is an anti-PD-1 inhibitor approved for classical Hodgkin lymphoma. There is early clinical data suggesting the efficiency of nivolumab in PCNS lymphoma (Nayak, 2017)

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Treatment of Hematological Malignancies in Central Nervous System with Idarubicin and Teniposide Containing Regimens.

Blood ◽

10.1182/blood.v106.11.4731.4731 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4731-4731

Author(s):

Chun Wang ◽

Xiaojun He ◽

Qi Cai ◽

Jun Zhu ◽

Haitao Bai

Keyword(s):

Central Nervous System ◽

Bone Marrow ◽

Nervous System ◽

Hematological Malignancies ◽

Primary Cns Lymphoma ◽

Acute Monocytic Leukemia ◽

Cns Lymphoma ◽

Comprehensive Treatment ◽

Combination Regimen ◽

Cns Involvement

Abstract Background: The prognosis of central nervous system(CNS) involvement in hematological malignancies remains poor. Clinical investigation for better protocols is mandatory. Some reports from small samples of clinical trials suggested that the systemic chemotherapy with the agents that better cross the blood-brain barrier may result in disease remission in some patients with CNS lymphoma. Based on the pharmacokinetic properties of each drug, we have developed and evaluated the chemotherapy regimens for patients with hematological malignancies involving central nervous system. Objective: To evaluate a idarubicin (IDA) and teniposide based regimen in the treatment of hematological malignancies with CNS involvement. Patients and Methods: From April 2003 to July 2005, fourteen patients were enrolled onto the study. There were 8 male and 6 female, with a median age of 53(22–75) years. Three patients with primary CNS lymphoma (PCNSL) and 5 patients with secondary CNS lymphoma (SCNSL) were treated with the combination regimen of IT, including idarubicin(8mg/m2/d×3) and teniposide (75mg/m2/d×3). Six cases of acute myeloid leukemia with both bone marrow and CNS relapse, including 2 patients with acute promyelocytic leukemia and 4 patients with acute monocytic leukemia, were treated with the combination regimen of ITA, including IT and conventional cytosine arabinoside. The cycles were repeated at 3-weekly intervals. Patients were followed carefully for evaluation of toxicity and response to treatment. Results: Of the 8 patients with CNS lymphoma, three cases achieved complete remission(CR), four cases achieved partial remission(PR) after 2 cycles of IT regimen. Only one case died of cerebral hemorrhage two days after the delivery of chemotherapy. Among the 6 patients with CNS leukemia, four cases achieved CR and 2 cases achieved PR after 1 cycle of ITA regimen. Three cases achieved CRs of both CNS and bone marrow, which indicates that the regimen may be effective for concurrent relapse of both CNS and bone marrow. Of the 5 patients in coma, all of them regained consciousness during the course of chemotherapy. Rapid effect and well tolerance were observed, which made the following comprehensive treatment possible and were especially valuable for the patients in coma. Although the study was not primarily designed to investigate long term outcomes, the first patient treated with IT regimen remained CR for 26 months at the last follow-up. Conclusion: The promising efficacy of idarubicin and teniposide containing regimens was observed in the treatment of hematological malignancies in central nervous system, indicating that the regimens may be the first line option as primary or salvage therapy in hematological malignancies in central nervous system.

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