Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma

Abstract

Central nervous system (CNS) involvement in systemic B-cell non-Hodgkin lymphoma (B-NHL) at diagnosis (sysCNS) is rare. We investigated the outcome of 21 patients with sysCNS, most commonly diffuse large B-cell lymphoma, treated with high dose methotrexate (HD-MTX) and R-CHOP. The median number of cycles of HD-MTX and R-CHOP was 4 (range 1-8) and 6 (range 0-8), respectively. Consolidative whole brain radiotherapy (WBRT) was given to 33% (7/21) patients. With a median follow-up of 44 months the 3-year progression free survival (PFS) and overall survival (OS) were 45% (95%CI 34-56%) and 49% (95%CI 38-60%), respectively. Over 90% of patients had an unfavorable international prognostic index score, reflected by treatment-related mortality of 19% (4/21) and relapse-related mortality of 28% (6/21). The outcome of these patients was, however, unexpectedly good when compared to secondary CNS relapses. Prospective studies are needed to define the optimal treatment for patients with sysCNS, but its rarity might be challenging.

Management of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center experience

“…After achieving remission, whole brain radiotherapy was given for consolidation. The complete response rate 57%, with 3 years PFS and OS 45% (95% CI 34-56%) and 49% (95% CI 38-60%); [11]Those were comparable to gures reported here.…”

“…Therefore, several studies explored the effectiveness of non-transplant regimens in SCNSL and indicated that this can be an effective treatment for SCNSL. [11][12][13] Nijland et al retrospectively investigated the outcome of SCNSL patients treated with HD-MTX and R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone regimen) without ASCT, the 3-year OS was 49% which was comparable to patient outcomes with more intensive treatment including ASCT. [11] Moreton et al carried out a pilot study using IDARAM regimen in 16 SCNSL among which 12 achieved CR, seven remained CR at median follow-up of 24 months.…”

“…[11][12][13] Nijland et al retrospectively investigated the outcome of SCNSL patients treated with HD-MTX and R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone regimen) without ASCT, the 3-year OS was 49% which was comparable to patient outcomes with more intensive treatment including ASCT. [11] Moreton et al carried out a pilot study using IDARAM regimen in 16 SCNSL among which 12 achieved CR, seven remained CR at median follow-up of 24 months. [14] We observed an promising response in SCNSL treated with the combination of rituximab, HD-MTX, ifosfamide, cytarabine, liposomal formulation of doxorubicin, thus we retrospectively analyze the effectiveness of this regimen in order to explore novel treatment combination for SCNSL patients.…”

Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma

“…Thus, our data support CNS staging as part of the routine staging work-up in patients at high risk of SCNS based on current risk models,(4, 9, 11) as patients with concurrent CNS and systemic disease at initial diagnosis may have better outcomes with intensive treatment strategies containing both HDMTX and anthracycline-based immunochemotherapy. (26)…”

Proteomic changes in cerebrospinal fluid from primary central nervous system lymphoma patients are associated with protein ectodomain shedding

“…Based on our identification of the ectodomain of HLA-DRB1 in the CSF of PCNSL patients, we suggest an alternative mechanism of cancer-associated immune evasion, which, to our knowledge, has not been described so far. The combined loss of HLA class I and HLA class II antigens is known to occur at a high frequency in PCNSL, thus allowing immune escape [ 44 ]. Until now, the loss or aberrant expression of HLA on the cell surface has mostly been linked to cytosolic retention [ 45 ] or incorrect loading of the antigen-binding groove [ 46 ].…”