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IACH NEWS OF THE WEEK

January 25, 2026
Prepared by Dr Edwin Uriel Suárez

Multinational assessment of absolute neutrophil counts and white blood cell counts among healthy Duffy-null adults [Cross-sectional study].  

Highlights:

●       Current absolute neutrophil count (ANC) reference intervals misclassify up to half of Duffy-null individuals as neutropenic, contributing to global health inequities.

●       The Duffy-null variant lowers ANC, but existing dedicated reference intervals are based on a single African American cohort.

●       In this study, novel ANC and white blood cell count  (WBC) reference intervals for Duffy-null adults were established and are consistent across ethnic groups and 4 continents.

 

A cross-sectional study was conducted assessing healthy Duffy-null individuals from dedicated cohorts (blood donors in Namibia, Saudi Arabia, and the United Kingdom [UK]; primary care patients in the United States [US]) and biobanks (participants from the UK and the US). Among 8018 participants (880 from dedicated cohorts and 7138 from biobanks), novel ANC and WBC reference intervals were established (Namibia [ANC, 820/μL to 6370/μL; WBC, 2.51 × 109/L to 9.85 × 109/L]; Saudi Arabia [ANC, 1140/μL to 5290/μL; WBC, 3.72 × 109/L to 10.71 × 109/L]; UK (ANC, 1185/μL to 5462/μL; WBC, 3.1 × 109/L to 8.8 × 109/L]; US [ANC, 1210/μL to 5390/μL; WBC, 3.00 × 109/L to 9.66 × 109/L]), with no significant differences between cohorts. Institutional reference intervals misclassified 27.9% (Namibia), 50.9% (Saudi Arabia), 26.0% (UK), and 21.7% (US) as neutropenic. Biobank analyses confirmed no significant difference in ANC between Black and non-Black Duffy-null participants. Implementing Duffy-specific reference intervals is essential for equitable and accurate clinical decisions worldwide.
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Time to Revise Myeloma Diagnostic Criteria? A Decade of Accumulated Evidence on Serum Free Light Chain Ratio ≥100 [Discussion section in Blood Journal].  

The authors of this discussion section propose:

●       Immediate revision of the diagnostic criteria to remove serum free light chain (sFLC) ratio ≥100 as a standalone myeloma-defining event and exclusion of patients with sFLC ratio ≥100 from trials of newly diagnosed myeloma.

●       These patients should be included in prospective studies on therapeutic interventions in high-risk smoldering myeloma as well as active surveillance with modern imaging to define their natural history in the contemporary era.

 

In 2014, the International Myeloma Working Group expanded multiple myeloma diagnostic criteria to include sFLC ratio ≥100 as a standalone myeloma-defining biomarker based on studies suggesting ~ 80% risk of progression to overt myeloma at 2 years.  However, subsequent studies demonstrate a substantially lower risk of progression, with  population-based registry data showing 2-year risk as low as 30.4% in this group. (Table 1 in original paper).

 

Among patients with isolated sFLC ratio ≥100, emerging data have identified three complementary risk stratification models that dissect this heterogeneous population into clinically relevant subgroups with divergent progression risks to CRAB criteria (hypercalcemia, renal insufficiency secondary to cast nephropathy, anemia attributable to underlying MM, and bone lesions) (Figure 1 in original paper). 
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How I manage mycosis fungoides and Sézary syndrome: Current  controversies and unmet needs [Review].

Key points:

●       Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of non-Hodgkin lymphomas characterized by the clonal proliferation of T lymphocytes within the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) represent the most common types of CTCL.

●       MF presents with localized lesions and progresses slowly (6% per year), while SS shows leukaemic involvement and carries a poorer prognosis.

●       Recent evidence has cast doubt on the adequacy of the current staging approach (TNMB [tumour size, lymph node, metastasis, blood] system).

●       Current guidelines define SS as “T4N2/3/xM0B2” (TNMB system), yet SS patients without classic erythroderma are not uncommon, and staging does not capture this heterogeneity.

●       Moreover, no independent category exists for ‘pre-Sézary’, such as erythrodermic patients with no MF history who display a circulating clone that does not fulfill B2 criteria (Table 1 in original paper). 

●       Treatment depends on stage and aims at symptom control, quality-of-life improvement and induction of remission, as curative outcomes remain rare.

○       In early stage (I–IIA), skin-directed therapies constitute the mainstay of treatment, while  advanced (IIB–IV) or refractory cases require systemic options, with allogeneic haematopoietic stem cell transplantation reserved for select cases.

○       In practice, the initial management of patients categorized as B2 stage can be influenced by the absolute circulating tumour burden; those at the lower end of B2 may be managed differently from patients with markedly higher counts (e.g. >10 000 malignant cells/μL), despite no solid data on significantly different prognostic trajectories.

○       Bridging strategies vary widely, from chemotherapy (single versus poly-chemotherapy) to total skin electron beam irradiation or newer agents (e.g. brentuximab vedotin), with over a dozen combinations used in the only randomized trial.

○       The role of maintenance therapy remains undefined, with no regimen showing consistent superiority. So far, only resminostat has been tested in a randomized trial for maintenance.

●       Because the availability of approved and off-label therapies for CTCL varies across centres and countries, the approaches discussed may not be universally applicable and should be interpreted in the context of local regulatory approvals and access. 
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How I treat breakthrough thrombosis in cancer patients [Review].  

Key points:

●       Cancer patients face an increased risk of venous thromboembolism, and breakthrough thrombosis despite anticoagulation, with a six-month cumulative incidence of 5-8%. The management of these events is clinically challenging.

●       Confirming suspected breakthrough thrombosis requires imaging review, ideally by comparison with post-index baseline studies, as residual thrombus is common and may mimic recurrence.

●       When true breakthrough thrombosis is confirmed, several potential contributing factors should be assessed (Figure 1 in original paper).

○       Tumor extension can lead to mechanical vein compression and thrombus formation.

○       Non-adherence is common among anticoagulated patients and should be evaluated through a detailed medication history.

○       Measurement of drug-specific plasma levels, when available, may assist in confirming non-adherence.

○       In patients on low-molecular-weight heparin (LMWH), underlying prothrombotic conditions such as heparin-induced thrombocytopenia or acquired antithrombin- deficiency must also be considered.

○       In patients receiving oral anticoagulants, drug-drug interactions and impaired gastrointestinal absorption should be excluded.

●       Therapeutic strategies are guided by limited evidence, primarily from observational studies (Figure 2 in original paper).

○       Current practice generally favors switching to therapeutic LMWH if the patient was on oral anticoagulation, escalating LMWH dosing by 25-33% if already on therapeutic LMWH (reassess after 5-7 days), or

○       Increase LMWH to weight-adjusted therapeutic dose if treatment was subtherapeutic (reassess after 1 month).

●       Despite treatment adjustments, recurrence and bleeding risks remain substantial.
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