Highlights:

●      Under the Castleman disease (CD) eponym, three distinct diseases sharing common pathological features have been described over time. See Figure 1 in original paper. 

1.     Unicentric CD (UCD) usually has an indolent course and can be cured by surgical resection. However, a small percentage of UCD patients develop severe autoimmune or malignant complications.

2.     The human herpesvirus 8 (HHV8)–associated multicentric CD (HHV8+ MCD) has been mainly described in human immunodeficiency virus (HIV)-infected patients, but is an emerging condition outside this setting in other populations.

3.     Idiopathic multicentric CD (iMCD) remains a challenging diagnosis as the pathological features observed in these patients are shared with many other conditions, such as lymphoid neoplasia and systemic diseases.

●      Other syndromes such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes), TAFRO (thrombocytopenia, anasarca, fevers, reticulin myelofibrosis, and organomegaly), IgG4-RD (IgG4-related disease) and IPL (idiopathic plasmacytic lymphadenopathy) may also overlap with iMCD and could be considered either associated conditions or differential diagnosis.

●      The clinical phenotype of iMCD exhibits several striking differences among populations, with a much more heterogeneous pattern in Western populations than in patients of Asian ancestry.

In this cohort of 700 patients, most were of European (57.4%) or African (38.1%) ancestry. The high proportion of HHV8+ MCD (49.5%) was due to a recruitment bias (expert center for HIV-related hematological complications). In the UCD group, 5% of the patients presented with autoimmune or neoplastic complications. Complete surgical resection, if not too invasive, remained the best first-line therapy. In HHV8+ MCD, rituximab was highly effective as a first-line therapy and usually remained effective in relapsing patients. Anti-IL-6 therapy was confirmed to be the best first-line therapy for patients with inflammatory iMCD or  IPL. Patients with TAFRO syndrome deserve a more intensive therapy involving high-dose steroids, rituximab and/or mTOR inhibitors. 

Highlights: 

With a follow-up of >5 years, data from the phase III AUGMENT trial continue to support the use of lenalidomide (Revlimid) plus rituximab (R²) as a standard of care for patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL).

Here, the long-term follow-up results and prespecified subgroup analyses of patients with follicular lymphoma (FL), including those aged ≥70 years. Patients with R/R grade 1 to 3a iNHL were randomly assigned 1:1 to receive R² or rituximab with placebo (R-placebo). Of the 358 randomly assigned patients (intent-to-treat [ITT] population), 295 had FL (≥70 years, n=66). At long-term follow-up (median, 65.9 months), in the ITT iNHL population, progression-free survival (hazard ratio [HR], 0.50 [95% confidence interval (CI), 0.38 to 0.66]) and overall survival (HR, 0.59 [95% CI, 0.37 to 0.95]) were improved with R² versus R-placebo. Safety findings were consistent with the primary analysis. 

Highlights:

●      Receipt of thiotepa-allogeneic stem cell transplantation (ASCT) was the prognostic variable most favorably associated with survival in a landmark 6-month multivariable analysis.

●      Central nervous system (CNS)-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

●      These findings are consistent with the phase 2 IELSG42 MARIETTA trial, in which intensive methotrexate, cytarabine, thiotepa, and rituximab (MATRix)-based induction followed by rituximab, ifosfamide, carboplatin, and etoposide (RICE) and thiotepa-ASCT achieved durable remissions in secondary CNS lymphoma.

A total of 1139 patients were included in the analysis (de novo: 537; relapsed secondary CNS lymphoma [SCNSL]: 602). Two-year progression-free survival (PFS) estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month cumulative incidence of relapse, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P=0.005; and overall survival (OS): HR, 0.62; P=0.023) and CNS-isolated relapse (PFS: HR, 0.55; P=0.002; and OS: HR, 0.39; P<0.0001).

Highlights:

●      Survival in systemic light chain (AL) amyloidosis is strongly influenced by the severity of cardiac involvement.   

●      In stage IIIb AL amyloidosis, the prognostic impact of global longitudinal strain (GLS) was diminished by effective treatment with daratumumab.

●      Left ventricular ejection fraction (LVEF) <50%, difference between involved and uninvolved free light chains (dFLC) ≥180 mg/L, and receipt of daratumumab-based therapy outperformed GLS as predictors of survival.

In this study, the authors evaluated the AL International Staging System (AL-ISS) GLS cutoff of 9% in 53 patients with newly diagnosed stage IIIb AL amyloidosis. Patients classified as proposed stage IIIc (GLS 0–9%) had higher baseline difference between idFLC (300 vs. 167 mg/L; p=0.08), similar left ventricular wall thickness (14.5 vs. 15.0 mm; p=0.57), and lower LVEF; 45% vs. 55%; p=0.02) compared with those with GLS >9%. GLS correlated moderately with LVEF (p=0.47; p<0.001). On multivariable analysis, LVEF <50% (hazard ratio [HR] 3.18; p=0.006) and dFLC ≥180 mg/L (HR 3.26; p=0.003) independently predicted overall survival (OS), whereas GLS did not. Median OS was longer in proposed stage IIIc disease (31 vs. 13 months), reflecting greater use of daratumumab-based therapy (82% vs. 25%). Among daratumumab-treated patients, survival did not differ by GLS category. 

Key points:

●      Morbidity and mortality in bone marrow failure syndromes such as acquired aplastic anemia (AA) are driven by severe and prolonged cytopenia.

●      Allogeneic hematopoietic stem cell transplantation (alloHSCT) is potentially curative and offers a rapid route to hematopoietic reconstitution.

●      If alloHSCT is a realistic option, as it is likely to be for more patients than ever before, proceeding earlier rather than later generally minimizes downstream problems.

●      In 2026, reduced-toxicity conditioning, improved supportive care, and novel graft-versus-host disease prevention through post-transplant cyclophosphamide -based platforms have brought alternative donor transplantation into the mainstream.

●      The answers to many pressing questions, such as the best donor choice in older adults and whether upfront alternative donor transplants can be delivered with the same degree of success as matched sibling donor transplants, are being addressed in ambitious prospective trials (NCT06517641; NCT05600426).

●      However, these may not comprehensively address real-world constraints, including resource limitations, vast differences in regional infectious disease patterns, supportive-care infrastructure, and inequitable access to alternative donor sources (particularly unrelated and cord blood donors for underrepresented minorities).