Hematóloga- Dra María Fernanda Luján

26/09/2025

POEMS Syndrome Without a Detectable Monoclonal Peak: The Critical Role of VEGF and Bone Marrow Biopsy in Diagnosis

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome is a rare paraneoplastic syndrome linked to an underlying plasma cell dyscrasia. Its diagnosis requires both peripheral polyneuropathy as well as a monoclonal plasma cell disorder, along with a minimum of one additional major and one minor criterion. Major criteria include sclerotic bone lesions, Castleman disease, and elevated VEGF levels. Minor criteria consist of organomegaly, endocrinopathy, skin changes, papilledema, extravascular volume overload, and thrombocytosis or polycythemia.
Given its wide range of clinical presentations, POEMS syndrome is often difficult to diagnose and frequently misclassified as CIDP. However, hallmark features of thrombocytosis, elevated VEGF levels, and prominent axonal degeneration on EMG lend credence to a diagnosis of POEMS. Although identification of a monoclonal protein, typically via SPEP or IFE, remains a critical diagnostic step, in one cohort, it was absent in 11% of patients.
Read more: https://onlinelibrary.wiley.com/doi/10.1155/crh/5530850

22/08/2025

Transfusion-related Alpha-Gal Syndrome

Alpha-gal syndrome (AGS), first described in 2009, is associated with a tick bite in which exposed individuals develop IgE antibodies against the alpha-gal oligosaccharide expressed on most mammalian cells and may develop allergies to meat. The alpha-gal antigen is very similar to the RBC Group B antigen, and antibodies may cross react. Two recent case reports describe five Group O transfusion recipients who experienced severe allergic transfusion reactions after receiving Group B plasma (n=4) or platelets (n=1), one of whom died. Transfusion experts from the Biomedical Excellence for Safer Transfusion (BEST) Collaborative suggest that these transfusion reactions may be a new type of clinical transfusion reaction named transfusion-related alpha-gal syndrome (TRAGS). To assess the frequency of Group B and AB plasma and platelet transfusions to Group O recipients and potential TRAGS cases, BEST researchers retrospectively quantified the number of platelet and plasma units transfused during a recent two-year period at 14 sites across 10 countries. Of the 465 to 46,863 plasma units transfused at each site, Group O recipients received Group AB plasma on average 9.9% of transfusions (range, 2.8%- 29.2%) and Group B plasma 3.2% of transfusions (range, 0-12.8%), and plasma wastage would have increased 19.7% if all of the Group B and AB plasma was not transfused. Of the 558 to 74,339 units of platelet units transfused per site, Group O recipients received Group B platelets on average 4.1% (range, 0-14%) and Group AB platelets on average 1.5% of transfusions (range, 0-6%), and platelet wastage would have increased by 9.4% if these units were not transfused. Transfusion services should be aware of the possibility of TRAGS whenever a Group O patient experiences a severe transfusion reaction after exposure to either Group B or AB plasma and platelets.
https://transfusionnews.com/2025/08/13/transfusion-related-alpha-gal-syndrome/

20/08/2025

Atypical cytoplasmic inclusions and erythrophagocytosis in acute myeloid leukemia with KMT2A::MLLT3 and U2AF1 mutation

A 76-year-old man presented with fatigue and thrombocytopenia. Blood tests revealed pancytopenia. Bone marrow aspiration showed an excess of large-sized blasts, 82% of which had atypical cytoplasmic inclusions (panels A-D: red arrows, Wright-Giemsa stain, original magnification ×1000), and 22% exhibited erythrophagocytosis (panels A-D: black arrows). Immunophenotyping revealed expression of CD33, HLA-DR, CD64, CD13, CD11b, CD15, CD56, cCD79a, CD36, CD117, CD34, and CD4, while lacking CD16, CD7, CD14, CD19, myeloperoxidase, and cCD3. Cytochemistry showed the blasts were strongly positive for nonspecific esterase, considering the monocytic subtype based on morphological classification. Cytogenetic assessment demonstrated a complex karyotype: 50,XY,+3,+6,der(9)ins(9;11)(p22;q23q23),+der(9)ins(9;11)del(9)(q13q34),del(20)(q11.2q13.3),+del(20)(q11.2q13.3)[10]/46,XY[10] (panel E). Molecular studies identified a KMT2A::MLLT3 fusion, along with U2AF1 and ETV6 mutations. Fluorescence in situ hybridization also demonstrated a KMT2A rearrangement (panel F: original magnification ×1000). The patient was diagnosed with acute myeloid leukemia (AML) with a KMT2A::MLLT3 rearrangement. Induction therapy with azacitidine, venetoclax, and chidamide achieved partial remission after 1 cycle.
AML with KMT2A::MLLT3 rearrangement is inherently high risk in adults, and the concomitant U2AF1 mutation is rare and may further worsen the poor prognosis. Erythrophagocytosis by blasts is rare in AML and typically linked to specific cytogenetic abnormalities like t(8;16) or inv(8). To our knowledge, this is the first report describing blasts with atypical cytoplasmic inclusions and erythrophagocytosis in AML with ins(9;11).
https://ashpublications.org/view-large/figure/12805308/BLOOD_BLD-2025-029617-gr1.jpg

17/07/2025

02/06/2025

Absolute iron deficiency affects approximately 2 billion people worldwide.

This narrative review examines the screening, diagnosis, and treatment of adults with absolute iron deficiency without anemia and iron-deficiency anemia.

https://ja.ma/4ksYLGQ

30/05/2025

Primary myelofibrosis involving lymph nodes with the same mutational profile in bone marrow

A 56-year-old woman with primary myelofibrosis (PMF) with TET2 (variant allele frequency [VAF] 61%), MPL (VAF 37%), and SRSF2 (VAF 38%) mutations in bone marrow (BM) underwent axillary lymph node (LN) excision for lymphadenopathy to exclude metastasis. The LNs showed distorted architecture with the medulla and paracortical areas replaced by atypical trilineage hematopoietic cells in a fibrovascular background, compressing the lymph node cortex (panel A, 1× lens objective; panel B, 5× lens objective; hematoxylin and eosin [H&E] stain for both panels). The scattered and clustered atypical megakaryocytes with hyperchromatic and bizarre nuclei (panel C, 20× lens objective; panel D, 40× lens objective; H&E stain for both panels) were highlighted by CD61 (panel E, 40× lens objective), in the background of fibrosis shown by reticulin (panel H, 10× lens objective), resembling the findings in BM (panel I, 2× lens objective; panel J, 10× lens objective; panel K, 40× lens objective; panel L, reticulin, 10× lens objective; panel M, trichrome, 10× lens objective; H&E stain for panels I-K). LNs also showed clusters of CD71+ erythroid precursors (panel F, 40× lens objective) and scattered myeloperoxidase-positive myeloid cells (panel G, 40× lens objective). There were no increased CD34+ blasts. CD31 highlighted increased vascularity. Next-generation sequencing on the LN revealed a similar mutational profile as in BM including TET2 (VAF 21%), MPL (VAF 18%), and SRSF2 (VAF 16%).
This case is an example demonstrating that the so-called extramedullary hematopoiesis in PMF represents the same neoplastic process as in the BM that extends to involve extramedullary organs and tissue, most likely via metastasis and implant of the clonal neoplastic hematopoietic stem or progenitor cells.
https://ashpublications.org/blood/article/145/22/2672/537334/Primary-myelofibrosis-involving-lymph-nodes-with

08/05/2025

After a median follow-up of 99 months, salvage high-dose chemotherapy and autologous stem cell transplantation (sHDCT/ASCT) showed no survival benefit compared with continuous lenalidomide/dexamethasone in relapsed multiple myeloma. The absence of benefit was consistent across all subgroups, including patients with time to progression after frontline transplant beyond 48 months. http://ms.spr.ly/6186SVl2Y

04/05/2025

Statin use in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) was associated with significant survival benefits, with a 45% lower risk for overall mortality and 27% reduced risk for disease progression. Benefits remained consistent across treatment types, with no increase in severe adverse effects. http://ms.spr.ly/6183SrlV3

08/04/2025

A new review series on myeloproliferative neoplasms (MPN): prevention, diagnosis and management. A selection of a few key topics of particular interest to the field which have been informed by recent advances in basic or clinical research:
- strategies to prevent or treat the devastating clinical consequence of acute myeloid leukemia arising from antecedent MPN, also known as blast-phase MPN;
- the evolution of MPN from normal blood stem cells;
- clinical and laboratory approaches to target and eradicate early disease-initiating stem cells;
- the pathogenesis and management of patients with molecularly defined high-risk MPN.
https://haematologica.org/article/view/haematol.2024.285414

06/04/2025

Chromoplexy and FNDC3B::RARB fusion: deciphering a rare case of PML::RARA-negative APL

A 30-year-old man was admitted to the hospital with a 1-week history of asthenia and febrile angina. Blood tests revealed pancytopenia and 25% immature myeloid cells, but no blast cells. Coagulation tests were normal. Bone marrow aspiration with 93% blasts and numerous clustered Auer rods was highly suggestive of acute promyelocytic leukemia (APL) (panel A: May-Grünwald Giemsa staining, original magnification ×100). Flow cytometry revealed high side scatter with cMPO+, CD33+, CD117+, CD34− (consistent with promyelocytes), but atypical HLA-DR+. PML::RARA fast fluorescence in situ hybridization (FISH) was negative. Cytogenetics revealed loss of chromosome Y and a complex rearrangement involving chromosomes 3 and 7, with a pericentric inversion on chromosome 3 affecting 3p24, which carries the RARB gene (panel B). Due to the lack of RARB-specific FISH probes, further investigation was conducted using optical genome mapping, which identified a chromoplexy involving a 9-partner translocation, resulting in an FNDC3B::RARB fusion (panel C), confirmed by reverse transcription polymerase chain reaction (panel D).
As the patient did not develop a differentiation syndrome with all-trans retinoic acid alone, an induction chemotherapy was added. He achieved complete remission with minimal residual disease below 0.1% by flow cytometry after 2 cycles. However, all-trans retinoic acid’s specific contribution to this outcome remains uncertain. The patient is awaiting allogeneic transplantation. RAR rearrangements beyond RARA occur in ∼2% of APL cases. RARA-negative APLs are typically retinoid-resistant, and their optimal treatment remains undefined. Advanced genetic techniques, such as optical genome mapping or transcriptomics, are crucial to avoid overlooking these variants.
https://ashpublications.org/blood/article/145/14/1588/536396/Chromoplexy-and-FNDC3B-RARB-fusion-deciphering-a

03/04/2025