Journal of hematology最新文献

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by enlarged lymph nodes and systemic inflammation, often involving multiple organ dysfunction. However, cutaneous involvement in iMCD is rare and heterogeneous, and studies on the treatment of iMCD with skin involvement are scarce. Here, we present a rare case of iMCD with prominent facial skin involvement, which showed significant improvement with rituximab-based regimen treatment.

Background: Castleman disease (CD) is a very rare, non-malignant lymphoproliferative disorder that can be classified as unicentric or multicentric (MCD). MCD is associated with systemic symptoms, including organ dysfunction due to cytokine dysregulation, primarily interleukin-6 (IL-6). The anti-IL-6 monoclonal antibody siltuximab is recommended as a frontline treatment for idiopathic MCD (iMCD), but real-world data on its use in routine clinical practice are limited. This study aimed to assess disease response and survival outcomes in patients with iMCD treated with siltuximab therapy in real-world settings in Greece and Romania.

Methods: This retrospective cohort study included adult patients with iMCD treated with siltuximab in clinical practice across Greece and Romania between January 2017 and December 2022. The primary endpoint was overall response rate and secondary endpoints included survival and safety outcomes. Response assessments were performed according to the Castleman Disease Collaborative Network guidelines. Patients were followed until death, loss to follow-up or study conclusion (October 2023).

Results: Forty-eight patients with iMCD were included in the study. Mean age at baseline was 65 years, with significant age differences between patients from Greece (74 years) and Romania (54 years). The majority of patients were male (68.8%) and received one prior line of therapy (75%). Patients included in the study received a median of nine cycles of siltuximab. Response data were available for 38 patients. The overall response to siltuximab was 71.1%, with 55.3% of patients achieving a complete response, and 15.8% a partial response. The estimated overall survival rate at 3 years was 74% and the median survival was 123 months. The most common adverse events (> 5%) included elevated liver enzymes, anxiety, allergic reactions and nausea/diarrhea. Serious adverse events were experienced by 16.7% of the patients.

Conclusions: Our results suggest that siltuximab-based therapy is effective in treating iMCD in real-world settings in Greece and Romania. To our knowledge, this study represents the largest real-world analysis of siltuximab in European patients with iMCD so far.

Background: Exosomes are a group of extracellular vesicles that are influential in intercellular signaling and can affect aging. Hypoxia-inducible factor 1α (HIF-1α) is the principal mediator in response to hypoxia and can regulate aging. Moreover, P21 is a part of the downstream signaling pathway of hypoxia and is elevated during aging. Therefore, this research was conducted to investigate the effect of plasma exosomes of younger and older individuals on the expression of HIF-1α gene and P21 protein in hematopoietic stem cells (HSCs).

Methods: Plasma exosomes were derived from older and younger men and were characterized. Then, HSCs were isolated from cord blood samples and treated with exosomes of older and younger men. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to evaluate cell viability. Next, the expression of HIF-1α gene and P21 protein were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively.

Results: HIF-1α gene expression was considerably increased in HSCs treated with 10 µg/mL of exosomes isolated from younger men (Y10-Exo) compared to the untreated group (P = 0.002). Moreover, HIF-1α gene expression was remarkably decreased in HSCs treated with 10 µg/mL of exosomes obtained from older men (O10-Exo) in comparison with the untreated group (P < 0.001). Additionally, the expression of P21 protein was significantly increased in HSCs treated with 5 µg/mL of exosomes derived from older individuals (O5-Exo) and O10-Exo compared to the untreated group (P = 0.000 and P = 0.002, respectively).

Conclusions: Our findings showed that exosomes isolated from younger participants cause elevation in HIF-1α and may lead to delayed aging in HSCs. In addition, exosomes isolated from older participants can probably lead to aging through the reduction in HIF-1α and elevation in P21.

Patients who receive solid organ transplants often require lifelong immunosuppression, which increases their risk for hematologic disorders. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential curative treatment option for these patients. However, there is still a lack of understanding and guidance on graft-vs-host disease (GVHD) immunosuppression regimens, potential complications, and outcomes in patients with solid organ transplants who undergo HSCT. The rate of solid organ transplantation continues to increase annually, making this a common clinical scenario that hematologists encounter. In this case series, we present three patients who underwent liver, kidney and cardiac transplants and each developed hematological malignancies requiring allogeneic stem cell transplant. This is the first case report of two patients who received post-transplant cyclophosphamide with mycophenolate mofetil and tacrolimus GVHD prophylaxis. We also review recent advances in GVHD prophylaxis in allogeneic HSCT and solid organ transplantation including immune tolerance and immunosuppression-free protocols. Our case series support the use of post-transplant cyclophosphamide with mycophenolate mofetil and tacrolimus as post-transplant GVHD prophylaxis, which does not appear to compromise solid organ graft function. Our case series also provides evidence that allogeneic HSCT is a feasible and potentially life-saving treatment option in patients who develop hematologic malignancies after solid organ transplantation.

Discordant lymphomas are defined as two or more distinct pathological lymphomas occurring in the same patient. Due to the rarity of discordant lymphomas, which is due in large part to the difficulty in establishing the diagnosis, the literature is limited to small case series and case reports. Consequently, guidelines on therapeutic strategies are lacking. This article presented a case of primary refractory discordant large B-cell lymphoma and classic Hodgkin lymphoma in a young man based on cervical node and mediastinal mass biopsy, respectively. This case illustrates the difficulty in establishing the diagnosis, which ultimately warranted a high index of clinical suspicion and pursuit of multiple sequential biopsies, as well as a novel treatment strategy using an immune checkpoint inhibitor.

Background: Inactivating TP53 mutations in mantle cell lymphoma (MCL) are associated with poor prognosis. While next-generation sequencing (NGS) is the gold standard for assessing TP53, p53 immunohistochemistry (IHC) is an orthogonal means of evaluating TP53 status that has not been well characterized in MCL. In this single tertiary care center laboratory study, we aimed to evaluate the concordance of p53 IHC with the TP53 status in cases of MCL in hopes of evaluating if the former could act as an accurate, timely and cost-effective way of risk stratifying these patients.

Methods: A total of 47 cases of MCL that had TP53 NGS performed were included in this study. The main objective was to correlate NGS findings with p53 IHC results. Secondary objectives included assessment of possible associations between TP53 status and other variables (demographics, unique histopathological and IHC features). The turn-around time and cost for NGS and p53 IHC were also compared.

Results: Thirteen out of 47 (28%) cases were TP53-mutated by NGS. p53 IHC showed good concordance with NGS, with moderate to high sensitivity (11/13, 85%) and excellent specificity (34/34, 100%). Secondary objectives revealed increased SOX11-negative status in TP53-mutated cases (3/13, 23% vs. 1/29, 3%, P = 0.045). The cost and turn-around time of NGS were approximately of 30- and sixfold those of p53 IHC, respectively.

Conclusion: p53 IHC shows good concordance with NGS in MCL, with high specificity and moderate sensitivity for identifying inactivating TP53 mutations. Based on our findings, p53 IHC may be an efficient and cost-effective tool in risk stratification of MCL.

Background: Current knowledge on iron's role in lymphoma development is very limited, with studies yielding inconsistent findings. To address this gap, we conducted a rigorous two-sample mendelian randomization study, aiming to elucidate the potential associations between iron storage and the risk of developing lymphoma.

Methods: This study leveraged extensive genetic data derived from a comprehensive genome-wide association study (GWAS) comprising 257,953 individuals. The primary objective was to pinpoint single-nucleotide polymorphisms (SNPs) that are significantly associated with iron storage. Subsequently, this genetic information was analyzed in conjunction with summary-level data pertaining to lymphoma cases and controls, sourced from the IEU open GWAS project, which included a sample size of 3,546 lymphoma cases and 487,257 controls. To evaluate the relationship between iron storage and lymphoma risk, an inverse variance-weighted method with random effects was employed, complemented by rigorous sensitivity analyses.

Results: Genetic predisposition to high ferritin and serum iron status was causally associated with lower odds of lymphoma. Ferritin exhibited an odds ratio (OR) of 0.777 (95% confidence interval (CI): 0.628 - 0.961, P = 0.020), indicating 22.3% reduced odds of lymphoma associated with a one standard deviation increase in ferritin levels. Similarly, serum iron demonstrated an OR of 0.776 (95% CI: 0.609 - 0.989, P = 0.040), corresponding to 22.4% decreased odds of lymphoma for a one standard deviation increase in serum iron.

Conclusions: This study suggests that individuals with genes linked to higher iron storage levels have a lower risk of developing lymphoma, but further research is necessary before making any clinical recommendations.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) transforming into a more aggressive lymphoma (i.e., Richter syndrome) is well documented in the literature. In recent years, transdifferentiation of CLL/SLL to histiocytic/dendritic/Langerhans cell sarcomas has also been reported. We hereby describe a case of a 55-year-old female who was incidentally diagnosed with CLL after presenting to the hospital for symptoms of undiagnosed rheumatoid arthritis. At the time of presentation, CLL was stage 1, and the patient was placed on observation. Eight years after being diagnosed with CLL, and after several treatment modalities for her rheumatoid arthritis, the patient re-presented with progression of adenopathy, intermittent fevers, 5-pound weight loss, and worsening respiratory status requiring airway management. Computed tomography (CT) imaging revealed a soft tissue mass in the nasopharynx, lingual tonsillar hypertrophy with airway compromise, and bulky cervical, supraclavicular, and axillary lymphadenopathy. A biopsy of an enlarged cervical lymph node yielded a diagnosis of histiocytic/dendritic cell sarcoma favoring interdigitating dendritic cell sarcoma, likely representing transdifferentiation from CLL/SLL, of which there are no standard of care treatment guidelines. The patient was treated with ifosfamide, carboplatin, and etoposide (ICE) for three cycles, followed by rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) in combination with zanubrutinib. She then underwent haploidentical hematopoietic stem cell transplantation. At the time of the making of this manuscript, the patient was 45 days post-transplant without any notable complications.