Journal of hematology最新文献

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by uncontrolled activation of cytotoxic T cells and macrophages, leading to cytokine storm and organ failure. Secondary HLH is the acquired form that is commonly triggered by underlying malignancies, autoimmune diseases, or infections. While Epstein-Barr virus (EBV) is a common infectious trigger for HLH, hepatitis C virus (HCV) is rarely reported in the literature. Herein, we present the case of a patient with HLH with multiple possible infectious triggers that was ultimately attributed to HCV. A 61-year-old male with a history of untreated HCV was admitted with concerns for septic shock. Infectious workup was largely negative throughout his hospitalization. Lumbar puncture was concerning for a fungal meningitis, but fungal workup was negative except for a positive Blastomyces dermatitidis antibody. In addition, acid-fast bacilli culture eventually grew Mycobacterium porcinum (M. porcinum). He was treated with broad-spectrum antibiotics and anti-fungals but continued to fever. He met five of eight criteria per HLH-2004 protocol and was initiated on HLH-directed therapy with immediate resolution of his fevers. A Karius test did not identify pathogenic levels of Blastomyces dermatitidis or M. porcinum in the serum, and the causative trigger was determined to be his untreated HCV. This case highlights the importance of early recognition and treatment of HLH in a patient with fever of unknown origin. It brings attention to HCV as a highly unusual trigger of HLH. It also illustrates the difficulty in addressing the underlying source of secondary HLH when a broad infectious workup yields several rare but possible pathogens.

The gastrointestinal tract is the most frequent extranodal site for lymphomas. Primary gastrointestinal B-cell lymphomas represent a distinct group of lymphoproliferative disorders and are the most common type of gastrointestinal lymphomas. Their pathogenesis, clinicopathological characteristics, and prognosis may differ from their nodal or systemic counterparts, emphasizing the importance of accurately identifying them. This review incorporates some of the latest literature on common primary gastrointestinal B-cell lymphomas focusing on their unique pathogenic mechanisms, clinical features, and pathological findings. It also addresses the prognostic outcomes associated with these lymphomas and provides a brief overview of the available treatment options.

Background: This study aimed to investigate the efficacy and safety of orelabrutinib monotherapy in Chinese patients with marginal zone B-cell lymphoma (MZL).

Methods: We conducted a retrospective analysis of MZL patients treated with orelabrutinib monotherapy (n = 30) or rituximab/rituximab plus bendamustine (R/BR) (n = 81) at the Affiliated Hospital of Qingdao University from January 1, 2019, to December 31, 2023. Orelabrutinib monotherapy was assigned to the experimental group. Propensity score matching (PSM) was applied to match 30 MZL patients treated with the R/BR regimen as a control group, comparing the efficacy and safety between the two groups.

Results: In both the orelabrutinib group and the control group, patients who developed relapsed or refractory (R/R) disease after non-rituximab/rituximab-based chemotherapy (non-R/R-CT) therapies (including anti-infective treatment and localized radiotherapy) achieved clinical responses. For 17 patients with R/R disease following R/R-CT treatment, no statistically significant differences were observed between the orelabrutinib group and the BR group in disease control rate (DCR) (82.35% vs. 88.23%, P = 1.00), overall response rate (ORR) (64.70% vs. 76.47%, P = 0.70), and complete response (CR) (17.64% vs. 29.41%, P = 0.68). There was no statistically significant difference in 1-year event-free survival (EFS) (86.66% (95% confidence interval (CI): 68.27 - 94.77) vs. 83.33% (95% CI: 64.49 - 92.70), P = 0.66). Hematologic adverse events (66.66% vs. 86.66%, P = 0.10), lymphopenia (6.66% vs. 40.00%, P < 0.01), and grade 3/4 adverse events (10.00% vs. 33.33%, P = 0.03) were all lower in the orelabrutinib group compared to the control group. Neither group had patients who discontinued treatment due to adverse reactions.

Conclusion: Orelabrutinib monotherapy in MZL possesses favorable efficacy and safety in our study. Given the limited sample size, further clinical research with larger cohorts and extended follow-up is necessary.

Background: Relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) remains associated with poor outcomes in children. Achieving measurable residual disease (MRD) negativity prior to allogeneic hematopoietic stem cell transplantation (HSCT) is critical for durable remission. Blinatumomab, a bispecific CD19-CD3 T-cell engager, induces deep remissions with minimal myelosuppression and is increasingly utilized as a bridge to HSCT. We describe our institutional experience with HSCT following blinatumomab-induced remission in pediatric R/R B-ALL.

Methods: This retrospective single-center study included five pediatric patients with R/R B-ALL who received blinatumomab bridging therapy prior to allogeneic HSCT between January 2020 and June 2025. Clinical data included demographics, prior therapies, blinatumomab dosing and duration, MRD status, conditioning regimen, donor source, stem cell dose, engraftment kinetics, donor chimerism, and complications. The endpoints included MRD clearance before HSCT, engraftment kinetics, donor chimerism, viral reactivation, bacterial infections post-transplant, and overall and failure-free survival at last follow-up.

Results: All five patients completed one to two 28-day cycles of blinatumomab and achieved MRD negativity (< 0.01%) prior to HSCT. Donor sources comprised one matched sibling and four haploidentical family donors. The median interval between blinatumomab completion and HSCT was 32 days. Median neutrophil and platelet engraftment occurred on days +12 and +9, respectively. Full donor chimerism was achieved within 1 - 3 months and sustained throughout follow-up. Post-transplant complications included engraftment syndrome (n = 4), cytomegalovirus (CMV) reactivation (n = 4), Epstein-Barr virus (EBV) reactivation (n = 1), Clostridioides difficile enterocolitis (n = 1), and steroid-refractory acute graft-versus-host disease (GVHD) (n = 2). No transplant-related mortality was observed. At a median follow-up of 173 days (range, 52 - 1,015 days), all patients remained alive and in continuous complete remission with no active GVHD.

Conclusions: In this single-center experience from a low-/middle-income country (LMIC), blinatumomab served as an effective bridge to HSCT, enabling MRD-negative remissions with favorable post-transplant outcomes. Viral reactivations and steroid-refractory GVHD were reported, underlining the need for robust surveillance. Broader access to blinatumomab and prospective studies are needed to validate these findings and to evaluate cost-effectiveness in LMICs.

Background: Daratumumab is a monoclonal antibody targeting CD38, which has demonstrated efficacy in both newly diagnosed and relapsed or refractory multiple myeloma (MM). The objective of our study was to evaluate the effectiveness and safety of the daratumumab, lenalidomide, and dexamethasone (D-Rd) regimen as a second-line therapy in a real-world clinical setting.

Methods: A total of 55 Hungarian patients with MM were enrolled, all of whom received D-Rd at first relapse through a special reimbursement program between February 2022 and August 2023. Treatment responses, progression-free survival (PFS), and overall survival (OS) were assessed in the intent-to-treat population as well as in selected subgroups. Safety outcomes were also systematically collected.

Results: Treatment response was observed in 49 patients (89%), with 12 complete responses, 22 very good partial responses, and 15 partial responses. After a median follow-up of 36.6 months, the median PFS for the entire cohort was 22.0 months, while median OS had not been reached yet. Patients with advanced-stage disease (Revised International Staging System stage 3) showed significantly poorer survival outcomes compared with those in stage 1 or 2 (PFS: P < 0.001; OS: P = 0.015). High-risk cytogenetic abnormalities and frailty were also associated with markedly inferior prognosis. In contrast, neither prior autologous stem cell transplantation nor lenalidomide maintenance therapy had a significant impact on survival. During the study period, three deaths due to severe infections occurred, while the most common adverse events were mild hematologic toxicities and injection-related reactions.

Conclusions: Our findings support the use of D-Rd as an effective option for first relapse in MM patients. However, our survival data are inferior to the results of the pivotal studies targeting the same population.

Acute undifferentiated leukemia (AUL) is a rare, aggressive type of acute leukemia associated with poor prognosis, in which the blasts lack lineage commitment to either the myeloid or lymphoid lineages. It is classified according to the World Health Organization (WHO) classification under the category of acute leukemias of ambiguous lineage (ALAL). Here we present a case of a 20-year-old man, who was referred to Military Cancer Center in February 2025, as a case of mediastinal myeloid sarcoma, which was diagnosed by biopsy of the mass. Bone marrow examination was performed in our center and showed infiltration by blasts, flow cytometry of bone marrow aspirate specimen revealed that blasts do not express lineage-specific markers with expression of primitive markers, so the diagnosis of AUL was established. For precise diagnosis of AUL, a comprehensive and broad panel of immunomarkers should be run to rule out any lineage commitment for the clone. Review of literature revealed only one previously published similar case.

Background: Emicizumab (Hemlibra) became more accessible for Canadians in 2021, when Canadian Blood Services approved it under formulary for prophylaxis in patients with severe hemophilia A (PWHA) without inhibitors. This offered an alternative to factor VIII (FVIII) prophylaxis. Starting in November 2021, a coordinated effort to offer and support the transition to emicizumab was initiated for all eligible adult PWHA living in British Columbia (BC) and Yukon Territory. Of the 69 PWHA who transitioned to emicizumab, it was observed that some were early adopters whereas others demonstrated more caution and transitioned later. Our aim was to better understand patient and clinical practice factors associated with the early and late transition to emicizumab.

Methods: Retrospective data were assessed from clinical records, transition documents and available pre-transition patient-reported surveys for both patient and clinical factors.

Results: Of the 83 patients with PWHA eligible for transition, 69 transitioned to emicizumab between November 2021 and December 2023. Median time to emicizumab transition was 10 months. Younger PWHA and those with fewer cumulative comorbidities tended to delay transition to emicizumab. Geographic distance from Vancouver was not significantly associated with transition timing. In multivariable analysis, younger age remained independently associated with longer time to transition (P = 0.0008), while having five or more joints affected by hemophilic arthropathy was associated with later transition (P = 0.007).

Conclusions: Using a standardized transition program offered an opportunity to gain a deeper understanding of patient and clinical factors associated with transition to a novel agent. This analysis highlights that certain clinical factors may influence uptake of new therapies within hemophilia care and the importance of early identification of barriers to facilitate treatment uptake.

Sickle cell trait (SCT) is generally considered a benign carrier state, unlike sickle cell disease (SCD), which is frequently associated with complications such as avascular necrosis (AVN). While AVN affects approximately 30% of patients with SCD, it is rarely reported in individuals with SCT and is not well understood. A 29-year-old African American male with SCT presented with progressively worsening hip pain. He reported chronic heavy alcohol use but denied steroid use, trauma or previous sickle cell crises. Physical exam demonstrated severely limited hip range of motion and antalgic gait. Laboratory studies were unremarkable aside from elevated C-reactive protein. Radiographs revealed bilateral femoral head AVN greater than stage II, with partial collapse on the left. He was managed conservatively with nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and counseling on alcohol reduction, and was referred to orthopedics for long-term management. Although rare, AVN can occur in individuals with SCT, particularly when compounded by modifiable risk factors such as chronic alcohol use, which can impair bone remodeling, promote fat embolism, and exacerbate microvascular compromise from intermittent sickling. It highlights the importance of early recognition and intervention in patients with unexplained joint pain, and that clinicians should maintain a high index of suspicion for AVN in SCT patients, especially in the presence of other comorbidities and risk factors.

Intravenous (IV) iron therapy is a cornerstone in the management of iron deficiency anemia, yet its administration is associated with significant side effects, most notably hypophosphatemia. This adverse event is not a class effect but is disproportionately linked to specific formulations, particularly ferric carboxymaltose (FCM). This review synthesizes the current clinical evidence, elucidates the central pathophysiological role of fibroblast growth factor 23 (FGF23), and explores a potential pharmacogenomic basis for individual susceptibility. Clinical data from numerous randomized controlled trials and meta-analyses confirm that FCM induces hypophosphatemia in over 50% of patients, a rate far exceeding that of other IV iron preparations. The proposed underlying mechanism involves a "two-hit" process: pre-existing iron deficiency upregulates FGF23 gene transcription, while FCM administration is thought to inhibit the proteolytic cleavage of the FGF23 protein. This uncoupling of production and degradation leads to a surge in active, intact FGF23 (iFGF23), causing renal phosphate wasting. We explore the potential for genetic polymorphisms in FGF23 and its key processing enzymes, such as FURIN, GALNT3, and FAM20C, to modulate individual risk. Understanding this complex interplay is crucial for risk stratification, appropriate formulation selection, and patient monitoring to mitigate the acute and chronic consequences of iatrogenic hypophosphatemia, including debilitating fatigue and osteomalacia.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal hyperinflammatory syndrome characterized by uncontrolled activation of the immune system, often secondary to infections, autoimmune diseases, or malignancies. While malignancy-associated HLH is increasingly recognized, its diagnosis remains challenging due to nonspecific clinical features that mimic other systemic illnesses. Mast cell sarcoma (MCS), an exceedingly rare and aggressive neoplasm of aberrant mast cells, is an exceptionally uncommon cause of HLH and is rarely reported in the literature. We described the case of a 70-year-old male who presented with persistent fever, weight loss, night sweats, and pancytopenia. Initial investigations for infectious, autoimmune, and neoplastic etiologies were inconclusive. The patient rapidly deteriorated despite empirical antimicrobial therapy and supportive care. Serial imaging revealed hepatosplenomegaly, and laboratory studies showed markedly elevated ferritin, lactate dehydrogenase (LDH), and soluble interleukin (IL)-2 receptor levels. Bone marrow biopsy demonstrated hemophagocytosis, and he fulfilled both HLH-2004 criteria and had a high HScore, confirming the diagnosis of HLH. Despite initiating HLH-directed therapy with high-dose corticosteroids and etoposide, the patient's condition progressed rapidly, leading to multiorgan failure and death. Post-mortem examination revealed extensive infiltration of atypical mast cells in the bone marrow, spleen, liver, and lymph nodes. Immunohistochemistry confirmed the diagnosis of systemic MCS. This report highlights the diagnostic complexity of HLH, particularly when triggered by rare malignancies like MCS. The case emphasizes the need for high index of suspicion and early, aggressive diagnostic workup - including bone marrow evaluation and molecular studies - in patients presenting with fever of unknown origin, cytopenias, and systemic inflammation. Early identification of malignancy-associated HLH is critical, as targeted treatment of the underlying disease is often necessary for a favorable outcome. Awareness of atypical presentations and rare triggers is essential for timely diagnosis and management of this life-threatening syndrome.