Primary Large B-cell Lymphomas of Immune-Privileged Sites [Review]

This article is part of the High-Risk Aggressive Lymphoma Review Series from Blood Journal. In this review, M. Roschewski, J.D. Phelan, and E.S. Jaffe describe the overlapping clinical (see Table 1 of the original paper), pathological, and molecular features of primary large B-cell lymphoma of immune-privileged sites (IP-LBCL). They highlight important considerations for diagnosis (see Table 2 of the original paper), staging, and treatment.

Here are some key points:

●       Most cases of diffuse large B-cell lymphoma (DLBCL) involving the central nervous system (CNS), vitreous, and testis exhibit immunophenotypic features suggesting an activated B-cell origin.

●       Shared molecular features include frequent co-mutations of MYD88 (L265P) and CD79B (termed "MCD") and frequent genetic alterations promoting immune evasion. These lymphomas primarily arise within anatomical sanctuaries, exhibiting a strong predilection for extranodal confinement and CNS tropism.

●       The umbrella term "primary IP-LBCL" was proposed due to shared clinical and molecular features. Conversely, extranodal DLBCL involving the breast, adrenal glands, and skin are more heterogeneous and arise in sites not considered immune-privileged.

Treatment highlights:

1. Primary CNS lymphoma:
   • High-dose methotrexate regimens are the cornerstone of treatment.
   • Complete response rates to induction regimens are ~50%, necessitating postremission consolidation in most cases.
   • Younger patients may undergo high-dose chemotherapy with autologous stem cell transplantation, while older or unsuitable patients face poorer prognoses.
2. Primary testis lymphoma:
   • Orchiectomy is necessary but insufficient as a standalone therapy.
   • Systemic therapy (e.g., rituximab plus CHOP) is recommended even in limited-stage disease.
   • CNS prophylaxis and contralateral testis irradiation reduce relapse risks. Testosterone replacement should be considered to mitigate hypogonadism.
3. Primary vitreoretinal lymphoma:
   • Localized therapy (e.g., intravitreal methotrexate or rituximab) addresses vision loss but not CNS relapse.
   • High-dose methotrexate may be used to prevent CNS progression, though its efficacy remains uncertain.
4. Intravascular B-cell lymphoma:
   • Treated as a disseminated disease with anthracycline-based chemotherapy.
   • CNS prophylaxis is essential due to high progression risks.

How I Treat Sickle Cell Disease with Gene Therapy [Review]

In this How I Treat article, A. Sharma discusses selecting and preparing individuals with sickle cell disease (SCD) for autologous gene therapy, focusing on post-infusion care, immune monitoring, and infection prevention.

Key points:

●       Two gene therapies were approved in 2023 for severe SCD, showing dramatic short-term efficacy in reducing vaso-occlusive crises. However, long-term safety and efficacy remain uncertain.

●       SCD is an ideal candidate for genetic manipulation due to its single-gene pathogenesis. Techniques include ex vivo gene addition, switching, or

precise correction in hematopoietic stem cells.

●       Candidate selection should consider organ function, infection status, and fertility preservation options.

For clinical nuances, including genetic pathways and therapeutic techniques, see Figure 1 and Table 1 in the original paper.

Integration of Clinical Outcomes and Molecular Features in Extramedullary Disease in Multiple Myeloma [Retrospective Study]

Highlight(s):

●       This study reveals that RAS/BRAF mutations likely drive extramedullary disease (EMD) development in multiple myeloma (MM).

●       Poor prognostic markers (e.g., duplication 1q, deletion 17p) are linked to EMD, yet TP53 mutations remain an independent poor prognostic factor.

The cohort analysis of 528 MM patients identifies mutation-specific survival outcomes, emphasizing molecular profiling's role in managing EMD.

Identification of Factors Predicting Low-Risk Febrile Neutropenia Admissions in Adults with Acute Myeloid Leukemia [Retrospective Study]

Highlight(s):

●       A new tool using physiological parameters (e.g., heart rate, blood pressure, fever height) shows promise for identifying low-risk febrile neutropenia (FN) admissions.

●       This approach may reduce hospitalization burdens for acute myeloid leuekmia patients while improving quality of life.

The retrospective analysis of 397 FN admissions outlines physiologic predictors for low-risk outcomes, though standard hospitalization remains essential for most patients.