Journal of hematology最新文献

Background: CD20-targeted therapies are widely used in the management of B-cell lymphomas. Re-treatment with CD20-directed agents is common; however, previous research has demonstrated loss of CD20 expression at relapse in a subset of patients.

Methods: In this single-center retrospective cohort of 243 patients, CD20 analysis was performed by immunohistochemistry (IHC) and/or flow cytometry at diagnosis and at relapse if a biopsy was performed.

Results: Of 109 patients with relapsed or refractory B-cell lymphoma, 59 patients with CD20-positive lymphoma at diagnosis underwent a biopsy at relapse for a total of 76 biopsies across all relapses. The rate of partial or complete CD20 expression loss was 11.9% (four patients with partial loss, three patients with complete loss). There were four cases of CD20 loss at first relapse (three IHC, one flow cytometry), two at second relapse (one IHC, one IHC and flow cytometry), and one at fifth relapse (IHC and flow cytometry). CD20 antigen escape was observed in marginal zone lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL). All patients with CD20 expression loss previously received rituximab. Among patients with CD20 antigen escape, 85.7% had stage IV disease, and median overall survival after CD20 loss was 4 months. In the group of five patients with indolent lymphoma and CD20 expression loss, three patients (60%) had concurrent transformation to high-grade lymphoma.

Conclusions: This study, which reinforces the importance of repeating a biopsy at relapse before implementing CD20-directed therapy, is particularly relevant given the widespread use of rituximab along with the emerging significance of CD20-targeted bispecific antibodies in the management of B-cell lymphomas.

Immune checkpoint inhibitors (CPIs) can cause immune-related organ dysfunctions, including nephritis, pneumonitis, thyroiditis, hepatitis, colitis and more rarely hematological toxicities like immune-related autoimmune hemolytic anemia (irAIHA). Very few cases of irAIHA associated with immunotherapy have been reported, and treatment protocols remain unclear. This is partly because not all irAIHA cases are Coomb's test positive. Causes of anemia in cancer patients undergoing treatment with chemotherapy with or without immunotherapeutic agents can also be multiple. This makes it difficult to initially diagnose irAIHA, especially when CPIs are used concurrently with chemotherapy. Once alternate causes have been ruled out, a treatment plan for irAIHA is initiated based on grade of the anemia. Grade 1-2 irAIHA cases are managed with supportive interventions. However, cessation of therapy is recommended for life-threatening (grade 4) toxicity, severe (grade 3) toxicity that is recurring, or moderate (grade 2) toxicity that does not resolve with appropriate treatment for 3 months. Management of irAIHA usually involves methylprednisolone for 2 - 4 weeks with a slow taper after hemoglobin has normalized. But some cases do not respond to steroids alone and require cessation of immunotherapy or selecting alternate immunosuppressive agents. We report a protocol for treatment of grade 4 irAIHA secondary to programmed death protein 1 (PD-1) blocker pembrolizumab.

Background: Anemia is a global health issue that affects over 1 billion people and contributes to maternal mortality and birth defects. Low-resource, tropical areas face a dual challenge: high prevalence of anemia and inability to access affordable testing methods. The falling drop hemoglobin method has been developed by our lab to quantify hemoglobin concentration and assess anemia by timing the descent of venous blood in a column of copper sulfate solution, without using electricity or batteries. This research aimed to optimize the falling drop hemoglobin method by evaluating the use of capillary blood to reduce within sample variance and assessing copper sulfate stability to determine shelf life in expected working conditions.

Methods: The falling drop hemoglobin method was performed on both venous and capillary blood samples collected directly from the fingertip by dispensing 44 µL of blood in a copper sulfate column. A microhematocrit was performed on the venous blood sample and converted mathematically to a hemoglobin level to serve as the standard. Copper sulfate stability was assessed for 32 weeks among three solutions: solution prepared fresh on day of testing, solution incubated at room temperature, and solution incubated at 37.7 °C.

Results: Capillary blood yielded higher average descent times and higher standard deviations than venous blood. Collecting precisely 44 µL of capillary blood proved challenging and impractical. In copper sulfate stability testing, freshly prepared solution yielded the highest average descent time. A one-way analysis of variance (ANOVA) test and Tukey's honestly significant difference (HSD) post hoc testing revealed no significant difference between mean descent times of freshly prepared and 37.7 °C solutions (P = 0.26) and between room temperature and 37.7 °C solutions (P = 0.64), but a significant difference between freshly prepared and room temperature solutions (P = 0.04).

Conclusions: This study found that capillary blood did not present a more accurate alternative to venous blood in the falling drop hemoglobin test, and copper sulfate did not degrade over 32 weeks at 37.7 °C. This lends support for the current use of venous blood in the test, and for use of copper sulfate solution in tropical climates, where the test is most necessary, with a shelf life of at least 32 weeks.

Plasmablastic lymphoma (PBL) is a malignant lymphoma with poor prognosis that occurs in immunocompromised and elderly patients. We describe the case of a 75-year-old woman with PBL as a methotrexate-associated lymphoproliferative disorder (MTX-LPD). She presented with multiple oral ulcers and mass-like shadows in the lung fields. Biopsy of the oral ulcer revealed medium to large irregular round monotypic B cells positive for cluster of differentiation (CD)138, CD79a, immunoglobulin λ, and Epstein-Barr virus-encoded small ribonucleic acid in situ hybridization, and PBL was diagnosed. The patient showed negative results for human immunodeficiency virus and had a history of taking MTX for rheumatoid arthritis, suggesting MTX-LPD. Following discontinuation of MTX, the oral ulcers resolved 1 month later without recurrence, and lung lesions decreased in size over time. Because MTX-LPD can take the form of PBL and may resolve with MTX withdrawal alone, therapeutic interventions should be carefully considered. While PBL is typically highly aggressive and requires prompt treatment, MTX-LPD cases can sometimes resolve without further treatment, depending on the clinical course. However, in cases where the disease shows progression or when spontaneous regression does not occur, additional therapeutic interventions may be necessary to manage the disease effectively.

Background: Methionine synthase reductase, which is encoded by the methionine synthase reductase (MTRR) gene, plays a crucial role in the methylation reactions and the production of DNA and its epigenetic processes. There was a correlation between the MTRR (A66G) polymorphism and the likelihood of developing acute lymphoblastic leukemia (ALL). This study was carried out to investigate the correlation among pediatric ALL cases.

Methods: Within the participant population of this case-control study, there were 86 individuals who had been diagnosed with ALL, and there were also 150 healthy persons who acted as the control group. To determine the MTRR (A66G) polymorphism, DNA was first extracted and then observed through the use of real-time polymerase chain reaction.

Results: The results of the flow cytometry analysis showed that the prevalence of B-cell ALL (B-ALL) was much higher than that of T-cell ALL (T-ALL), which accounted for only 20 cases (23.3%). Upon comparing the hematological parameters of ALL subtypes in patients with T-ALL, it was discovered that there was a statistically significant higher mean total white blood count (P < 0.0005) and mean blast percentage (P = 0.050). Upon examination, it was discovered that both of these figures were much higher than the average. In accordance with the results of the molecular analysis, the occurrence of the MTRR homozygous GG genotype was found to be considerably lower in the patients' group (4.65%) than in the control group (20.67%). However, the MTRR homozygous AA and heterozygous AG were nearly similar in the two groups. The risk of acute lymphoblastic leukemia and MTRR genotypes, on the other hand, exhibited a correlation that was not statistically significant (P = 0.082).

Conclusions: The study's findings showed that among pediatric ALL patients, the MTRR A66G polymorphism was not linked to an increased risk of ALL.

Chimeric antigen receptor (CAR) T-cell therapy has transformed treatment of refractory B-cell malignancies; however, treatment puts patients at risk for side effects secondary to the amplified immune response it induces. Fulminant cerebral edema (FCE) is one of the rarest, yet most devastating side effects following CAR T-cell therapy. Due to this rarity, FCE has not been well characterized and the risk factors associated with its development are not fully understood. Here, we present a case of a 42-year-old male who passed away from FCE following CAR T-cell infusion with the primary goal to better understand which patients are at higher risk of developing FCE before and after infusion.

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.