Intravascular large B-cell lymphoma: an elusive diagnosis with challenging management
Accepted for publication November 2, 2018
Correspondence Akash Mukherjee, MD; AMukherjee21@mdanderson.org
Disclosures The authors report no disclosures/conflicts of interest.
©2018 Frontline Medical Communications
doi https://doi.org/10.12788/jcso.0425
Genetics
No pathognomic cytogenetic abnormalities have been reported in IVBCL to date, and the genetic features of this disease are not yet completely understood.2,7
Management
IVBCL is considered a stage IV disseminated disease with an International Prognostic Index score of high-intermediate to high in most cases. Half of the patients with IVBCL who were treated with anthracycline-based chemotherapy relapsed and died within 18 months of diagnosis. One third of the relapses involved the CNS, thereby highlighting the importance of prophylactic CNS-directed Intrathecal therapy in an induction treatment regimen.2-4 Ferreri and colleagues reported in their case series response rates of about 60%, with an overall survival (OS) of 3 years of 30% in patients who were treated with anthracycline-based chemotherapy. A multivariate analysis of the entire series showed cutaneous variant of the disease to be an independent favorable prognostic factor for OS.3
In the Murase and colleagues case series, the authors reported 67% response rates and a median OS of 13 months with CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) or CHOP-like regimens. Multivariate analysis showed older age, thrombocytopenia, and absence of anthracycline-based chemotherapy to be an independent negative prognostic factor for OS.4 Another retrospective analysis by Shimada and colleagues of 106 patients with IVBCL showed improved outcome with the addition of rituximab to CHOP-based chemotherapy (R-CHOP). Complete response rate (CR), 2-year progression-free survival, and OS were significantly higher for patients in rituximab-chemotherapy group than for those in the chemotherapy-alone group (CR, 82% vs 51%, respectively, P = .001; PFS, 56% vs 27%; OS, 66% vs 46%, P = .001), thereby establishing rituximab with CHOP-based therapy as induction therapy for IVBCL patients.8
,The role of high-dose chemotherapy followed by ASCT could also be used as consolidation therapy to improve clinical outcomes as reported in 7 patients, showing durable remission after transplant in these 2 case series.3,4 Another retrospective analysis of 6 patients with IVBCL who were treated with 6 cycles of R-CHOP as induction therapy and consolidated with ASCT reported all patients to be alive and in complete remission after a median follow-up of 56 months.9 Based on the retrospective case series data by Kato and colleagues and considering that more than 80% of the patients with IVBCL were in the high-risk International Prognostic Index group, ASCT in first remission might be a useful treatment option for durable remission; however, because the median age for the diagnosis of IVBCL is about 70 years, ASCT may not be a realistic option for all patients.
Conclusions
IVBCL is a rare, aggressive, and distinct type of DLBCL with complex constellations of symptoms requiring strong clinical suspicion to establish this challenging diagnosis. Rituximab with anthracycline-based therapy along with prophylactic CNS-directed therapy followed by consolidative ASCT may lead to long-term remission. More research is needed into the genetic features of this disease to better understand its pathogenesis and potential targets for treatment.
