Clinical Features and Prognostic Factors for Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: A Systematic Review

Abstract

Primary anaplastic large cell lymphoma (ALCL) of the central nervous system (CNS) is a subtype of primary CNS lymphoma (PCNSL). There are very few comprehensive reports on this extremely rare tumor. Therefore, it is necessary to investigate the clinical features and prognostic factors for primary ALCL of the CNS. We performed a systematic review of the published literature. Past cases were comprehensively searched using PubMed, Cochrane Library, and Web of Science. Clinical information, such as age, sex, anaplastic lymphoma kinase (ALK) status, lesion sites, treatment methods, and survivorship were extracted. Thirty-nine cases with information on ALK status and treatment course were identified. The average observation period was 13 months, and the overall 2-year survival rate was 58%. Univariate analyses showed a statistically significantly better prognosis among patients < 40 years of age (p = 0.039, HR 0.32 (0.11–0.95)) and in relation to ALK positivity (p = 0.010, HR 0.24 (0.08–0.71) and methotrexate treatment (p = 0.003, HR 0.17 (0.05–0.56)). Because of the sparsity of cases, it is necessary to accumulate cases in order to perform more detailed analyses.

Rare central nervous system lymphomas

“…Owing to their rarity, no standard treatment protocol has been established for PCNS‐TCL. Similar to CNS‐DLBCL, most regimens described within the literature include systemic HD‐MTX and/or IT‐MTX 148,151,154,155 . Intravitreal MTX and local RT have been reported as treatment options for ocular involvement 155 .…”

“…149,150 Interestingly, a recent systematic review described a much lower median age at diagnosis for those with primary CNS anaplastic large cell lymphoma (PCNS-ALCL), at 21 years (range 1-82 years). 151 Mature peripheral TCLs comprise a spectrum of biologically and clinically heterogeneous malignancies. In two large retrospective studies of primary and secondary CNS-TCL, the commonest histopathological subtype was peripheral TCL-not otherwise specified (PTCL-NOS) (83% and 54% respectively), with other subtypes also described; ALCL, angioimmunoblastic lymphoma, adult TCL/leukaemia, and extra-nodal natural killer TCL.…”

“…In particular, ALCL has a predilection for the meninges with one review suggesting 80% of reported PCNS-ALCLs exhibit meningeal involvement. 151 Morphologically, PCNS-PTCL-NOS can be difficult to distinguish from reactive Tcell infiltrates and B-cell lymphomas; these neoplasms may be CD4 or CD8 positive. 147 By contrast, ALCL may manifest as large pleomorphic populations of cells with horse-shoe shaped or multi-lobated nuclei with vesicular chromatin and Abbreviations: ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; AraC, cytarabine; ASCT, autologous stem cell transplantation; BEAM, carmustine, etoposide, cytarabine, and melphalan; BNS, Bing-Neel syndrome; BL, Burkitt lymphoma; BR, bendamustine and rituximab; BTKi, Bruton's tyrosine kinase inhibitor; CNS, central nervous system; CT, computed tomography; FL, follicular lymphoma; HD, high dose; HL, Hodgkin lymphoma; ICE, ifosfamide, carboplatin, and etoposide; IT, intrathecal; IVL, intravascular lymphoma; MCL, mantle cell lymphoma; MRI, magnetic resonance imaging; MTX, methotrexate; MZL, marginal zone lymphoma; NHL, non-Hodgkin lymphoma; PCNS-LPL, primary central nervous system lymphoplasmacytic lymphoma; PCNS-TCL, primary central nervous system T-cell lymphoma; PET, positron emission tomography; RBAC, rituximab, bendamustine, and cytarabine; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; R-CODOX-M/ RIVAC, rituximab, cyclophosphamide, vincristine, doxorubicin, methotrexate, ifosfamide, etoposide, and cytarabine; RT, radiotherapy; TCL, T-cell lymphoma.…”

“…147 Similar to their systemic counterparts, PCNS-ALCL may be anaplastic lymphoma kinase (ALK) positive or negative (Figure 7B). 151 Owing to their rarity, no standard treatment protocol has been established for PCNS-TCL. Similar to CNS-DLBCL, most regimens described within the literature include systemic HD-MTX and/or IT-MTX.…”

“…Similar to CNS-DLBCL, most regimens described within the literature include systemic HD-MTX and/or IT-MTX. 148,151,154,155 Intravitreal MTX and local RT have been reported as treatment options for ocular involvement. 155 For PCNS-DLBCL, HDT-ASCT has demonstrable efficacy as the preferred consolidation strategy.…”