Intravascular Lymphoma Research Articles

Intravascular Large B-Cell Lymphoma: A Review with a Focus on the Prognostic Value of Skin Involvement.

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive Non-Hodgkin lymphoma (NHL) characterised by the presence of neoplastic lymphoid cells within small- and medium-sized blood vessels. According to the clinical presentation, the current WHO classification distinguishes the ‘classic’ (formerly ‘Western’) from a hemophagocytic syndrome-associated (formerly ‘Asian’) variant. A third ‘cutaneous’ variant has been proposed, characterised by a good prognosis and unique clinical features. While laboratory findings can hint at diagnosis, symptoms are rather nonspecific, and deep skin biopsy supported by further measures such as bone marrow aspiration and positron emission tomography-computed tomography scanning is needed to make a definite diagnosis. Treatment is comprised of anthracycline-based chemotherapy supplemented with rituximab and central nervous system prophylaxis. While there are various prognostic models for NHL, only one is specific to IVLBCL, which does not sufficiently represent some patient groups, especially regarding the lack of differentiation within the patient collective with skin involvement. This underlines the necessity for the establishment of further prognostic models in particular for IVLBCL patients with cutaneous manifestations.

The Relevance of Skin Biopsies in General Internal Medicine: Facts and Myths.

IntroductionNon-dermatology medical specialties may refer patients for skin biopsies, searching for a particular diagnosis. However, the diagnostic impact of the skin biopsy is not clearly established. This article aims to assess the indications for, and evaluate the clinical relevance of, skin biopsies in non-dermatology medical specialties.MethodsA questionnaire was sent to 23 non-dermatology specialty departments in a university medical center, requesting a list of indications for skin biopsies, as well as to 10 staff dermatologists to collect the indications of skin biopsies requested by non-dermatology specialties. Once the indications were collected, a literature search was performed to evaluate their clinical value and relevance.ResultsEleven non-dermatology specialties provided a list of skin biopsy indications, to which staff dermatologists added seven more indications. A literature search revealed evidence-based medicine data for six diseases, that is, amyloidosis, peripheral autonomic neuropathy, Sneddon’s syndrome, intravascular lymphoma, sarcoidosis, and chronic graft-versus-host disease. Results were questionable concerning infectious endocarditis, acute graft-versus-host-disease, and the lupus band test. Skin biopsy were not evidenced as useful for the diagnosis of calciphylaxis, systemic scleroderma, Behçet’s disease, or hypermobile Ehlers–Danlos syndrome. For the diagnosis of Alport’s syndrome, pseudoxanthoma elasticum, and vascular Ehlers–Danlos syndrome, skin biopsy is currently outperformed by genetic analyses. For diagnoses such as Henoch–Schönlein purpura and Sjögren’s syndrome, skin biopsy represents an additional item among other diagnostic criteria.ConclusionThe usefulness of skin biopsy as requested by non-dermatology specialties is only evidenced for amyloidosis, peripheral autonomic neuropathy, Sneddon’s syndrome, intravascular lymphoma, sarcoidosis, chronic graft-versus-host-disease, Henoch–Schönlein purpura, and Sjögren’s syndrome.

Intramural Great Vessel Lymphoma in a Patient with Left Ventricular Assist Device

<h3>Introduction</h3> Intramural Great Vessel lymphoma (IMGVL) is an extremely rare lymphoma proliferating within the lumina of large vessels like Superior vena cava and Aorta. We present a case of an IMGVL presenting in a patient with a Left Ventricular Assist Device (LVAD). <h3>Case Report</h3> A 63-year-old male with ischemic cardiomyopathy and advanced systolic failure supported by an LVAD as a bridge to transplant, presented to the clinic complaining of claudication symptoms. He has known peripheral vascular disease and underwent Aortobifemoral stenting in the past. Coronary Tomography with Angiography (CTA) showed a large intraluminal thrombus above the iliac limbs with severe narrowing of the lumen thought to be flow-limiting (Figure 1). He underwent a mechanical thrombectomy. Intra-operatively, a large mural thrombus with near occlusion of the descending aorta was noted (Figure 2). Pathology revealed diffuse large B-cell lymphoma (DLBCL) with immunohistochemistry positive for BCL2, MYC, Ki-67 and CD20. EBV status was negative. A whole-body Positron Emission Tomography (PET) scan was negative for malignancy elsewhere. He was initiated on chemotherapy. <h3>Summary</h3> Primary IMGVL is a rare subtype of extranodal lymphoma with only 4 cases reported in literature. It is distinct from Intravascular Large B-cell Lymphoma (IVLBCL) which is limited to small vessels. Furthermore, only a single case of aortic IMGVL found on autopsy of an EBV positive patient, has been reported. DLBCL is known to be an aggressive subtype of lymphoma often requiring a combination of chemotherapy and immune therapy. Long term prognosis in our patient awaiting heart transplant is rather uncertain.

Intravascular large B-cell lymphoma associated with sudden stridor arising from thyroid mucormycosis and concomitant bacterial infection

Dear Editor, Mucormycosis is a life-threatening fungal infection that mainly affects immunocompromised patients. It typically has low prevalence, but fatality rate is as high as 50%. We present a patient with intravascular lymphoma with secondary bacterial infection and invasive mucormycosis involving the thyroid gland, who experienced good outcomes following surgical decompression and prolonged intravenous antibiotics.

Clinical impact of central nervous system-directed therapies on intravascular large B-cell lymphoma: A single institution's experience.

Intravascular large B‐cell lymphoma (IVLBCL) is a rare subtype of B‐cell lymphoma characterized by aggressive disease progression with a high incidence of central nervous system (CNS) involvement. We retrospectively analyzed 16 patients with de novo IVLBCL treated at our hospital between 2004 and 2018 with either standard therapy plus CNS‐directed therapy or standard therapy alone. CNS‐directed therapy was associated with a significantly better 2‐year CNS‐free survival (100% vs. 63%, p = 0.0191), despite no significant effects on progression‐free or overall survival. Further studies should assess CNS‐focused treatment in patients with IVLBCL with or without primary CNS involvement.

Immunohistochemistry of the oncofetal protein IMP3 is helpful in the diagnosis of intravascular large B-cell lymphoma using skin biopsy.

The oncofetal protein insulin-like growth factor 2 mRNA binding protein-3 (IMP3) is expressed in various cancers. In this study, we examined the diagnostic utility of IMP3 immunohistochemistry in the context of intravascular large B-cell lymphoma (IVL). We obtained 25 skin biopsy (SB) specimens diagnosed as IVL and nine IVL-negative SB specimens from 27 IVL patients. Additionally, 27 negative SB specimens from 26 non-IVL patients were obtained from our pathology archives. We performed IMP3 immunohistochemistry on these 61 SB specimens, considering IMP3 expression in any mononuclear cell as positive. In selected cases, triple immunostaining for IMP3, PAX5, and CD34 was performed to analyze the origin and location of IMP3-positive cells. IMP3 was expressed in most intravascular lymphoma cells in all the 25 SB specimens diagnosed as IVL. Furthermore, our evaluation revealed the presence of intravascular IMP3-positive B-cells in five of the nine negative SB specimens from IVL patients; however, this was not observed in the 27 SB specimens from non-IVL patients. IMP3 was expressed in most IVL cells, and IMP3 immunohistochemistry could serve as a sensitive diagnostic aid for detecting IVL cells in SB.

Intravascular Large B-Cell Lymphoma

Intravascular large B-cell lymphoma (IVLBCL) is a rare hematopathologic entity, posing both a clinical and histologic challenge for diagnosis. Numerous pitfalls can hinder making the diagnosis. To summarize recent developments in literature pertaining to IVLBCL and point out key pitfalls pathologists should be prepared to encounter. Literature review via PubMed search and hospital (Darnall Medical Library) resources. The 3 primary pitfalls of IVLBCL include masking of IVLBCL, mimicry by IVLBCL, and mimicry of IVLBCL. These scenarios illustrate the importance of histologic pattern recognition and subsequent usage of immunohistochemistry, especially in context of a clinical history that may be noncharacteristic.

Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVL) is a rare type of lymphoma characterized by tumor growth selectively within the vessels. The 5th edition of the World Health Organization classification defines IVL as a large B-cell lymphoma, the same as diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Since the clinical manifestations of IVL are nonspecific, the diagnosis is time-consuming, and the course is often fatal. Serum soluble interleukin-2 receptor (sIL-2R) and serum lactate dehydrogenase (LDH) levels are known to be elevated in a variety of lymphomas. However, the mechanism of sIL-2R elevation in B-cell lymphomas is not fully understood. In this study, we analyzed the serum level of laboratory findings, including sIL-2R and LDH, as well as the presence of B symptoms in 39 patients with IVL, and compared them with 56 patients with stage IV DLBCL. Both sIL-2R and LDH levels were significantly higher in IVL than in DLBCL (p = 0.035 and p = 0.002, respectively). In IVL, there were no significant differences in both sIL-2R and LDH levels between patients with and without B symptoms (p = 0.206 and p = 0.441, respectively). However, in DLBCL, both sIL-2R and LDH levels were significantly higher in the presence of B symptoms (p = 0.001 and p < 0.001, respectively). The high sIL-2R and LDH levels in IVL may be related to the peripheral blood microenvironment, but further studies are needed to verify this.

The sellar region as presenting theater for hematologic malignancies-A 17-year single-center experience.

Hematological neoplastic mass lesions of the sellar region are rare. We identified five cases of hematological malignancy with first presentation in the sellar region from our departmental database of 1,405 patients (0.36%) with sellar lesions diagnosed over the 17-year period (2005-2021). All patients were females (mean age 55.2 ± 3.4 years). One patient had multiple myeloma (MM), one patient had acute myeloid leukemia (AML), while three other patients had lymphoma (intravascular lymphoma (IVL, n = 1) or non-Hodgkin's lymphoma (NHL, n = 2). Most patients presented with ophthalmoplegia, and one patient with diabetes insipidus (DI), with short duration of symptoms (median 30 days). All patients had an elevated erythrocyte sedimentation rate and altered blood count, while patients with lymphoma had elevated lactate dehydrogenase (LDH). Sellar mass was demonstrated in three patients while the patient with IVL had an empty sella and in the AML patient posterior lobe T1W hyperintensity was lost. Two patients (IVL and NHL) presented with multiple anterior pituitary deficiencies and one patient (AML) had DI. All patients were treated with chemotherapy. Two patients responded well to treatment (one had reversed hypopituitarism), while three patients died. Differential diagnosis of sellar-parasellar pathology should include suspicion of hematological malignancy, particularly in patients with short duration of nonspecific symptoms, neurological signs (ophthalmoplegia), blood count alterations and LDH elevation, pituitary dysfunction and imaging features atypical for pituitary adenoma. Early diagnosis is crucial for timely initiation of hematological treatment aimed at inducing disease remission and partial or full recovery of pituitary function.

Clinical relevance of serum-derived exosomal messenger RNA sequencing in patients with non-Hodgkin lymphoma.

Background: The clinical utility of mRNA cargo in exosomes is unclear, although exosomes have potential as non-invasive biomarkers. This study aimed to investigate the feasibility of exosomal mRNA sequencing for monitoring disease status and predicting outcomes in non-Hodgkin lymphoma (NHL) patients.Methods: Exosomes were isolated from archived serum samples of 33 patients with NHL who were registered into our prospective cohort: diffuse large B-cell lymphoma (DLBCL, n = 17), intravascular B-cell lymphoma (IVL, n = 1), primary mediastinal large B-cell lymphoma (PMBL, n = 4), follicular lymphoma (FL, n = 3), mantle cell lymphoma (MCL, n = 3), and extranodal NK/T-cell lymphoma (ENKTL, n = 5). Exosomal mRNA sequencing was performed, and its concordance with clinical course was analyzed and compared with those of circulating tumor DNA (ctDNA) mutations.Results: Exosomal mRNA sequencing was performed successfully in 26 cases (79%, 26/33), whereas the remaining seven cases were not completed due to their small amount of RNA. The exosomal mRNA sequencing of DLBCL showed gene expression profiles consistent with activated B-cell-like and germinal center type. The longitudinal assessment of exosomal mRNA sequencing results in accordance with the clinical course showed that the post-treatment changes of exosomal mRNA expression were more consistent with treatment outcome than were those of ctDNA mutations. In particular, the exosomal mRNA expression of genes such as BCL2 and BCL6 was increased at the time of disease progression in DLBCL and FL patients.Conclusions: This study demonstrated the feasibility of exosomal mRNA expression profiles as a biomarker for NHL patients. Our results might provide the rationale for studies to explore the potential of exosomal mRNA as a biomarker in NHL patients.

Finding smudge cell aggregations in a bone marrow smear preparation may be helpful in the diagnosis of intravascular large B-cell lymphoma

Finding smudge cell aggregations in a bone marrow smear preparation may be helpful in the diagnosis of intravascular large B-cell lymphoma

Intravascular large B-cell lymphoma diagnosed by skin biopsy of a cellulitis-like skin lesion: Case report and review of literature

Intravascular large B-cell lymphoma diagnosed by skin biopsy of a cellulitis-like skin lesion: Case report and review of literature

Orbital Intravascular Natural Killer/T-cell Lymphoma: An Unusual Cause of Ocular Symptoms

Orbital intravascular lymphoma is rare and typically of B-cell lineage. In this study, we report a patient who developed orbital lesions of intravascular natural killer/T-cell lymphoma (IVNKL), an extremely rare lymphoma. An 88-year-old man presented with rapidly progressive right vision loss and double vision. A neurological examination revealed that he had decreased visual acuity and severe oculomotor impairment in the right eye. Magnetic resonance imaging showed right-dominant, nonmass lesions in both orbits. No lesions were found in the lymph nodes, skin, or brain. The patient received immunosuppressive and antifungal therapy, but his clinical condition rapidly deteriorated, and he died of multiple organ failure. Autopsy revealed natural killer/T-cell lymphoma proliferation within the lumina of small blood vessels in multiple organs, including the ocular adnexa of the right orbit. These findings show that he was ultimately diagnosed with IVNKL. IVNKL could initially cause ocular symptoms due to the involvement of the ocular adnexa. Ocular involvements have not been described previously. Even if patients initially present with only ocular symptoms, IVNKL should be considered.

STMO-14 Clinical experience of brain tumor surgery using middleware “OPeLiNK”

PURPOSEThe removal of brain tumors requires not only imaging information such as MRI and navigation systems, but also a variety of other information such as neurological function and biological information. To integrate this information, a novel operating room, “Smart Cyber Operating Theater (SCOT)”, which connects the medical devices in the operating room via a network has developed. In this SCOT, the intraoperative information is time-synchronized, recorded, and stored by the middleware “OPeLiNK”. Clinical experience of brain tumor surgery using OPeLiNK in our institute is reported.MethodsBrain tumor surgeries performed at SCOT, which had been started since July 2018, was enrolled. In all surgeries intraoperative information was integrated by OPeLiNK. Surgical procedure was discussed between main surgeon and supervising surgeon in the Strategy Desk through OPeLiNK intraoperatively, if necessary. Clinical and radiological data from patients who underwent resection at SCOT were analyzed retrospectively.ResultsSixty patients were involved. Histopathological diagnosis was glioma in 29 patients, pituitary adenoma in 29 patients, acoustic tumor in 1 patient and intravascular lymphoma in 1 patient. Intraoperative discussion with Strategy Desk through OPeLiNK was useful for not only surgeons but also for medical staff in operation room. Advice for extent of resection and craniotomy from Strategy Desk was conducted by OPeLiNK using conversation and drawing. Intraoperative comment was useful for postoperative review. OPeLiNK, which display multiple intraoperative information, was also used at postoperative conference.ConclusionWe have reported clinical experience with OPeLiNK for brain tumor surgery in our institute. OPeLiNK was useful for not only sharing intraoperative information with doctors outside the operation room but also postoperative review and education for young doctors.

A challenging case of intravascular large B-cell lymphoma presenting as pyrexia of unknown origin

Abstract Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of large cell lymphoma, characterized by the growth of neoplastic cells within the lumina of small blood vessels, without an obvious extravascular tumor mass or presence of circulating lymphoma cells in the peripheral blood. Patient concern: A 68-year-old woman presented with fever of unknown origin and abdominal pain. Diagnosis: Bone marrow aspiration showed abnormally large cells with increased hemophagocytic activity. Trephine biopsy showed moderate to large neoplastic cells with single and multiple prominent nucleoli sequestered in the blood vessel lumen. Immunohistochemistry was positive for CD20, PAX5, CD79a, MUM1, and BCL2 and showed a high proliferative fraction of 80% confirming the diagnosis of IVLBCL. Interventions: The patient received six cycles of R-CHOP chemotherapy. Outcomes: The patient has been in remission for nearly two years after completing the treatment. Conclusion: Clinical recognition of IVLBCL remains a challenge. Standard staging and therapeutic approaches need to be addressed to further elucidate the characterization and management of this rare disease.

Susceptibility-Weighted Imaging of Intravascular Lymphoma of the Central Nervous System

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Characteristics, Management and Outcomes of Patients with Intravascular Lymphoma: A Mayo Clinic Experience

Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL.Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method.Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was <2 in 66%.The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse.Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (>30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29].Conclusion:1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected.2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations.3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions.4.Overall prognosis in the literature was poor with most patients surviving <1 year. Our cohort has mOS of 57 months. The reason(s) for better survival in our cohort could not be definitively determined.5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size.6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL.7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. [Display omitted] DisclosuresNowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

The Interim Analysis from a Prospective Single-Center Phase 2 Study of Zanubrutinib Plus R-CHOP in Treat-Naïve Intravascular Large B Cell Lymphoma

Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. Zanubrutinib is a selective Bruton Tyrosine kinase(BTK) inhibitor and has shown activity in several B cell lymphomas. We aimed to ascertain the safety and activity of zanubrutinib plus R-CHOP (rituximab, cyclophosphamide, epirubicin, vindesine, and prednisolone) for patients with previously untreated IVLBCLMethods: This is a prospective, single-arm, phase 2 trial at Peking Union Medical College Hospital in China. Eligible patients had untreated histologically confirmed IVLBCL, were aged>18 years, had adequate bone marrow and organ function, had no active infections or bleeding. Patients received 8 cycles of zanubrutinib (160mg bid orally) plus R-CHOP (rituximab 375 mg/m² intravenously on day 1; cyclophosphamide 750 mg/m², epirubicin 70 mg/m², and vindesine 4mg intravenously on day 1 and prednisolone 100 mg orally on days 1-5) every 3 weeks. The primary endpoint was 2-year progression-free survival. Secondary end points included safety profile. The trial is registered at ClinicalTrials.gov (NCT 04899570) and is still recruiting.Results: By 15 th July,2021, 9 patients were enrolled into the study, 5 patients had finished 8 cycles treatment and 4 were still under treatment. All 9 patients were Ann Arbor IVB stage (median age 58, 5 males), and in intermediate-high/high risk group (IPI 3-5). 8 patients had the interim and/or end of treatment evaluation and in the efficacy population. All of them achieved response (overall response rate 100%), and the 5 patients who finished treatment achieved complete remission. 5 patients who had central nerves system involvement all got significant improvement in symptoms and MRI scans. Median follow-up was 10.0 months (range 1-18), no relapsing occurred and 1 patient died of septic shock 3 months after the completion of treatment. Every patient was enrolled into the safety population. The most common adverse effect (AE) were hematological toxicities, including Grade 3-4 neutropenia (6/9), Grade 3 anemia (2/9) and Grade 3-4 thrombocytopenia (2/9); all the hematological AE were mainly occurred in the first cycle. Any grade non-hematological toxicities included: fatigue(6/9)，infection(6/9)，infusion action(5/9)，anorexia(5/9), vomiting(5/9)，hypertention(1/9). There was no dose modification due to AE.Conclusion: Zanubrutinib plus R-CHOP demonstrated promising efficacy as front-line regimen in IVLBCL, even in the CNS involvement patients. This regimen is well tolerated and it warrants future investigation in larger scale population and long-term follow-up. DisclosuresLi: Astellas Pharma, Inc.: Research Funding. OffLabel Disclosure:Zanubrutinib is a selective Bruton Tyrosine kinase(BTK) inhibitor and is approved for WM, MCL and CLL/SLL in the Unite States and China. BTK inhibitors are highly effective in B cell NHL which carried MYD88 and/or CD79b mutations. Intravascular Large B-cell Lymphoma has high frequency of MYD88/CD79b mutations. Here, we use this medication for patients with untreated IVLBCL.

Favorable Outcomes with Thiotepa/Busulfan-Based Conditioning and Autotransplant for Patients with Aggressive B-Cell Lymphoma and Secondary CNS Involvement

Introduction: Central nervous system (CNS) relapse is a devastating complication affecting ~5% of patients with diffuse large B-cell lymphoma (DLBCL). The optimal management is unknown and survival rates are ~20% in contemporary series. Thiotepa/busulfan-based high-dose chemotherapy (HDT) and autotransplant (ASCT) has demonstrated efficacy in primary CNS lymphoma, but there have been fewer studies of this conditioning regimen in secondary CNS lymphoma (SCNSL).Methods: This multicenter retrospective study included all consecutive patients ≥18 years old with aggressive B-cell lymphoma and secondary CNS involvement treated with thiotepa/busulfan-based HDT/ASCT at the University of Calgary and University of Alberta since 2005. Kaplan-Meier curves were used to estimate progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) from the time of ASCT. Data collection is underway for all consecutively diagnosed SCNSL patients at our institutions to evaluate frequency and predictors of HDT/ASCT use.Results: This study included 57 patients with DLBCL (n=45), double-hit lymphoma (n=6), high-grade B-cell lymphoma NOS (n=2), intravascular large B-cell lymphoma (n=2), or T-cell/histiocyte-rich large B-cell lymphoma (n=2). Two (4%) had previously treated indolent B-cell lymphoma and 1 (2%) had multiply relapsed DLBCL. Median International Prognostic Index was 4 (range 0-5) at DLBCL diagnosis and median time to CNS relapse was 4 months (range 0-139). Median age was 58 years (range 20-73) and median ECOG was 3 (range 0-4) at diagnosis of SCNSL. CNS involvement was present at initial diagnosis in 20 (35%) patients or developed during frontline treatment in 10 (18%) or after completion of treatment in 27 (47%). For those without SCNSL at diagnosis, isolated CNS relapse occurred in 31 (84%) patients while 6 (16%) had concurrent CNS and systemic relapse.Most patients (n=54, 94%) received high-dose methotrexate (HD-MTX)-based multiagent induction chemotherapy (median HD-MTX doses 4, range 1-5) followed by peripheral blood stem cell mobilization with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in 41 (72%). HDT conditioning regimens were thiotepa, busulfan, melphalan, rituximab (TBMR, n=52, 91%) or thiotepa, busulfan, cyclophosphamide (TBC, n=5, 9%). Median time from SCNSL diagnosis to ASCT was 116 days (range 7-201). Median time to neutrophil engraftment was 10 days (range 7-15) and to platelet engraftment 16 days (range 9-93).Overall response rates (ORR) for systemic/CNS disease were 93%/89% pre-ASCT and 95%/100% post-ASCT. Combined ORR pre-ASCT was 88%, with complete response in 21% and partial response in 67%. Two (4%) patients who developed CNS relapse immediately prior to ASCT achieved long-term remission after TBMR conditioning without any other systemic chemotherapy. With a median follow-up time of 4.0 years (range 0.1-15.9), PFS was 75% (95% CI 61-85%), OS was 76% (95% CI 62-86%), and DSS was 79% (95% CI 64-88%) at 4 years after ASCT. Lymphoma recurred in 9 (16%) patients at median 88 days (range 54-346) after ASCT with CNS relapse (n=4), systemic relapse (n=3), or both (n=2). There were 2 (4%) deaths due to peri-transplant toxicity and 1 (2%) death at 1.5 years due to therapy-related acute myeloid leukemia; no other unexpected toxicities of HDT/ASCT were observed. Among the 45 (79%) patients achieving long-term disease-specific survival, none were treated with CNS radiation therapy and only 1 (2%) had persistent neurocognitive impairment. There were no significant differences in DSS with respect to timing of CNS relapse, concurrent presence of systemic disease, or TBMR versus TBC conditioning (78% vs 80%, p=0.87).Conclusion: In one of the largest studies of this conditioning regimen in SCNSL to date, we found that high-dose thiotepa/busulfan-based conditioning with ASCT is associated with favorable outcomes for patients with aggressive B-cell lymphoma and secondary CNS involvement, with 4-year OS ~75% in this study. Although SCNSL has been historically associated with a poor prognosis, an increasing proportion of patients may achieve long-term survival after intensive therapy with HD-MTX-based induction and thiotepa/busulfan-based HDT and ASCT. [Display omitted] DisclosuresChua: Eisai: Honoraria; Pfizer: Honoraria; Merck: Honoraria; Gilead: Honoraria. Stewart: Novartis: Honoraria; AstraZeneca: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Roche: Honoraria; Sandoz: Honoraria; Teva: Honoraria.

Intravascular lymphoma involving the bladder: A case report

Intravascular lymphoma involving the bladder: A case report