Specific granule deficiency type II (SGD2) is a rare heterogeneous congenital disease characterized by early-onset life-threatening infections. SGD2 is caused by autosomal recessive mutations in the SMARCD2 gene.
Prenatal screening in our patient revealed a novel homozygous nonsense mutation in SMARCD2 (c.208C>T, p.Gln70*).
Postnatally, she suffered from infections, pneumonia, cholestasis, mucocutaneous bleeding, and dysmorphic features, including clubfoot. Hematological findings included neutropenia, monocytosis, myelodysplasia, and thrombocytopenia. In contrast to previous cases, this patient presented with dysplasia of all myeloid lineages, including hypogranular neutrophils, pseudo Pelger–Huët, macrothrombocytes, bilobular monocytes, and dysplastic erythroblasts. Due to the severity of her condition, she passed away after 1.5 months.
This report illustrates the role of SMARCD2 in hematopoiesis and provides an overview of all previously described SGD2 patients.
The authors have confirmed clinical trial registration is not needed for this submission.
The cumulative incidence and risk of cytomegalovirus (CMV) reactivation in patients with relapsed/refractory multiple myeloma (RRMM) receiving elranatamab remain unclear.
We retrospectively analyzed RRMM patients treated with elranatamab to assess cumulative incidence and risk factors for CMV reactivation.
Among 32 patients, the 6-month cumulative incidence of CMV reactivation was 37.3%. High CMV immunoglobulin G (IgG) titers were significantly associated with CMV reactivation (57.9% vs. 9.1%, p = 0.012), while prophylactic immunoglobulin reduced CMV reactivation risk within high CMV IgG group.
Baseline CMV IgG titers may help guide risk-adapted monitoring and prevention strategies during elranatamab therapy.
Treatment with luspatercept may improve transfusion requirements in transfusion-dependent thalassemia (TDT), but the improved erythroid maturation in the bone marrow influences body iron distribution.
We report on sequential organ iron measurements in a TDT patient under luspatercept treatment. Despite a decline in transfusion requirement and ferritin, we observed a redistribution of body iron stores from spleen and bone marrow to the liver, increasing liver iron concentration (LIC).
Luspatercept treatment affects the informative value of ferritin and LIC in the assessment of total body iron stores, which should be considered in the management of iron chelation therapy.
Chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment for relapsed or refractory large B-cell lymphoma (LBCL), but clinical experience in people living with HIV (PLWH) remains limited due to their exclusion from pivotal trials. We report the case of a 55-year-old man with HIV and high-grade B-cell lymphoma who developed severe anaphylaxis during axicabtagene ciloleucel (axi-cel) infusion, requiring early termination after approximately 50% of the planned dose was delivered. The patient experienced only Grade 1 cytokine release syndrome and no neurotoxicity. Despite incomplete infusion, he achieved a sustained partial metabolic response on PET/CT imaging at Days +30, +60, and +110 post-infusion. HIV remained well-controlled throughout, and no infectious complications were observed. This case highlights both the feasibility of administering CAR T-cell therapy in virologically suppressed PLWH and the potential for clinical benefit even with partial cell delivery. In addition, it draws attention to anaphylaxis as a rare but serious infusion-related adverse event. To our knowledge, this is the first report of anaphylaxis to axi-cel in a PLWH. The case underscores the need for enhanced pharmacovigilance and pre-infusion risk assessment. It also supports growing evidence that PLWH should not be categorically excluded from CAR T-cell access or clinical trials.
Expression of B-cell antigens is rare in T-lymphoblastic leukemia/lymphoma (T-LBLL), and the significance is uncertain.
We present a pediatric case of acute leukemia characterized by the expression of T-cell markers and CD19, as determined by multicolor flow cytometry (MFC). Next-generation sequencing (NGS) revealed a SET::NUP214 gene fusion. The patient was treated with conventional intensive acute lymphoblastic leukemia (ALL) therapy. The end-of-induction evaluations showed significant residual disease.
While the patient failed high-risk T-LBLL induction therapy, blinatumomab followed by decitabine and venetoclax induced a morphologic remission. He then underwent a bone marrow stem cell transplant (BMSCT) and achieved a complete molecular remission.
This case illustrated the importance of integrating MFC analysis with NGS data to provide individualized patient treatment.
The authors have confirmed clinical trial registration is not needed for this submission.
5-Azacitidine (AZA) is a major treatment option for myelodysplastic neoplasms (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Here we evaluate the efficacy and toxicity of an alternative AZA regimen (100 mg/m2/day for 5 days/28 days) in 68 patients (51 MDS, 17 MDS/MPN) treated between 2008 and 2018.
Median patient age was 66 years, with most patients (98%) having intermediate or high-risk disease. Overall response rate (ORR) was 62% with 22% complete responses (CR). Median OS and median PFS were 22.5 and 18.2 months, respectively. Inferior response rates were calculated in therapy-related MDS (t-MDS) and MDS with excess blast II, with t-MDS having also statistically worse OS and PFS. MDS/MPN patients showed 73.6% ORR with 31.5% CR. Transfusion independence (TI) for red blood cells (RBC) was achieved in 45.9% of transfusion-dependent patients and in 30% for platelets. CR patients showed longer mOS and mPFS (70.6 and 64.7 months, respectively). Longer mOS was also correlated with allogeneic transplantation (48.8 vs. 16.9 months, p = 0.01) and RBC TI (25.4 vs. 13.3 months, p = 0.01). Grade 3/4 cytopenias occurred in 41.1% (neutropenia in 33.8%), and treatment-related mortality was 7.4%.
This study demonstrates that this alternative AZA regimen has comparable efficacy and safety to the standard regimen, compared with historical data.
The authors have confirmed clinical trial registration is not needed for this submission.
Epcoritamab, a bispecific CD3×CD20 antibody, offers a promising treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Its efficacy and safety after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear.
In a 64-year-old man with relapsed DLBCL, epcoritamab showed limited efficacy, achieving stable disease prior to allo-HSCT; nevertheless, re-administration after donor T-cell engraftment resulted in a complete response without severe graft-versus-host disease or cytokine release syndrome.
This observation suggests that donor-derived T-cell redirection with epcoritamab may enhance antitumor efficacy while maintaining safety in the post-transplant setting, supporting its potential as a salvage therapy for relapsed DLBCL post-allo-HSCT.
VEXAS syndrome is an adult-onset, X-linked autoinflammatory disorder resulting from somatic variations in the UBA1 gene.
To evaluate the adequacy of the digital PCR (dPCR) to follow up the variant allele frequency (VAF) on response to the treatment in patients with VEXAS.
This study is a 1-year follow-up of a 76-year-old male VEXAS patient treated with azacitidine. The VAF of UBA1 was serially quantified using next-generation sequencing (NGS) and dPCR.
There was a high concordance between the two methods. Azacitidine treatment results in a progressive clinical improvement, normalisation of haematologic parameters and a marked reduction in VAF.
These findings support dPCR as a sensitive and easy-to-manage tool for monitoring therapeutic responses in VEXAS syndrome, providing a method with a quick and cost-effective response.
The authors have confirmed clinical trial registration is not needed for this submission
Malignant plasma cells in multiple myeloma (MM) reprogram the bone marrow microenvironment to support tumor expansion. This myeloma cell–hematopoietic stem cell interaction leads to fewer hematopoietic stem cells in the bone marrow and altered differentiation of megakaryocytes, which can contribute to MM disease-related thrombocytopenia. Given the development of novel therapies for MM and the need for biomarkers reflecting the bone marrow microenvironment, we evaluated peripheral blood platelet count at diagnosis and during treatment of MM.
We retrospectively evaluated 14,313 patients diagnosed with MM between 2000 and 2019 at Veterans Administration hospitals using platelet count obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into four categories: moderate-severe thrombocytopenia, mild thrombocytopenia, normal platelets, and thrombocytosis (< 100, 100–149, 150–349, and ≥ 350 per microliter, respectively).
Thrombocytopenia, present in 25% of patients at diagnosis, corresponded to inferior overall survival (OS). During follow-up, persistent or new thrombocytopenia was also associated with inferior OS. Moreover, the negative prognostication afforded by baseline moderate–severe thrombocytopenia remained despite standard therapies (hazard ratio [HR] 1.83; 95% confidence interval [CI] 1.70–1.97) and stem cell transplant (HR 1.41; 95% CI 1.34–1.48).
Our findings support the use of platelet count in MM as an easily accessible prognostic marker.
The authors have confirmed clinical trial registration is not needed for this submission.
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