Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia.

BACKGROUNDS: The incidence of extramedullary diseases (EMDs) in patients diagnosed with acute myeloid leukemia (AML) is approximately 10-20%. These patients exhibit a significantly distinct etiology, therapeutic response, and prognosis compared to patients without EMDs. CLL1 CAR-T therapy has been demonstrated satisfactory efficacy and safety in the treatment of refractory and relapsed AML patients. However, concerns have been raised regarding the potential impact of extramedullary niduses on the effectiveness of CLL1 CAR-T therapy. METHODS: A total of 47 patients were enrolled in this study, including 27 patients with isolated AML tumor bone marrow infiltration and 20 patients with both extramedullary and bone marrow infiltration of AML. CLL1 CAR-T cells were manufactured and subjected to rigorous quality control in the hematology laboratory of Tianjin First Central Hospital. The efficacy and adverse reactions were assessed following CAR-T cell infusion, while expansion of CAR-T cells, levels of cytokines releasing, and other indicators were closely monitored. RESULTS: Among the 20 patients with EMDs and the 27 individuals without EMDs, complete remission in bone marrow was achieved by 65.00% and 81.48% of patients, respectively. Meanwhile, among the patients with EMDs, 55.00% achieved complete remission while 10.00% achieved partial remission when assessing the efficacy of CLL1 CAR-T cells against extramedullary niduses. Although the overall survival, progression-free survival, and duration of remission period appeared to be shorter for patients with EMDs compared to those without EMDs, this difference did not reach statistical significance. The incidence rates of complications were comparable between both groups. Meanwhile, there were no significant differences observed in the levels of CAR-T cell expansion and accompanying cytokines release between patients with and without EMDs. CONCLUSIONS: Our study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence rates of complications within a tolerable range. The CLL1 CAR-T therapy, serving as an ideal strategy for AML patients irrespective of the presence of EMDs, effectively ameliorates the conditions of AML patients and provides them with an opportunity to undergo curative hematopoietic stem cell transplantation while significantly enhancing their prognosis.

Adding Evidence to Plasmacytoma: A Case Series.

Plasmacytoma is a rare tumor of plasma cells with two primary variants: solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP). It poses diagnostic challenges at times. Radiotherapy (RT) is the curative modality in the majority of cases. We share a case series with the aim of adding evidence to the literature about plasmacytoma and its clinical presentation, diagnostic challenges, and outcome with RT.

Prognostic impact of nodal involvement in Waldenström macroglobulinaemia.

The clinical and prognostic implications of nodal involvement (NI) in Waldenström macroglobulinaemia (WM) are largely unknown. In this study, we explored the impact of NI on clinical presentation and outcome in a population-based cohort of 469 patients with WM, consecutively diagnosed between 2000 and 2022. NI was detected in 34% of patients and was associated with symptomatic disease, adverse prognostic factors, an increased risk of transformation, and lymphoma-related death. Our findings indicate that NI is of prognostic significance in WM, suggesting a need for enhanced surveillance in these patients.

Immunoglobulin D-Lambda Multiple Myeloma Initially Presenting in the Sphenoid Sinus, Orbital Apex, and Skull Base: A Systematic Review with a Case Report.

Objectives Multiple myeloma (MM) with initial manifestations in the sphenoid sinus, orbital apex, and skull base is exceedingly rare. A systematic review was conducted to investigate the epidemiology and advancements . Methods Relevant cases were identified by searching CNKI, WanFang Data, CQVIP databases, PubMed, Embase, and Web of Science. Additionally, we present a case of IgD-λ (immunoglobulin D-lambda) MM with initial symptoms of dizziness, unilateral pain, blindness, and ophthalmoplegia, leading to a 4-month overall survival. Strictly based on PRISMA standards, we included and summarized existing cases and reflected our case. Results Our systematic review includes 34 case reports, revealing 67.6% of patients initially presented with diplopia and 44.1% underwent endoscopic procedures, notably with only two cases of IgD-λ subtype. In our case, we performed an endoscopic wide trans-ethmoidal sphenoidotomy and biopsy of the skull base and orbital apex lesion. Postoperative pathology confirmed a highly active plasmacytoma, clinically diagnosed as IgD-λ MM with a TP53 deletion mutation and multiple extramedullary metastases. A range of diagnostic tools was employed, including hemoglobin, immunoglobulin, urinary protein analysis, positron emission tomography-computed tomography (CT), bone marrow cytology, and gene detection. Conclusion The subtle clinical manifestations of IgD-λ MM in the paranasal sinuses and skull base hinder early diagnosis. There is a paucity of literature describing MM initially presenting in these locations. CT/magnetic resonance scans are necessary to identify characteristic bone destruction. An endoscopic approach is popular for tissue biopsy. Bone marrow biopsy with a smear, serum or urine protein electrophoresis, and immunofixation electrophoresis are crucial upon the appearance of target organ damage.

Case Report: Extramedullary Hematopoiesis in the Prostate.

Extramedullary hematopoiesis is the physiological process of hematopoiesis occurring outside of the bone marrow and is an extremely rare occurrence in the prostate, with only 1 previously documented report in the English literature. We present a specimen from a 56-year-old man who was found to have a palpable nodule on digital rectal examination and visible findings on ultrasound, confirmed to be extramedullary hematopoiesis on the prostate core.

Angelica sinensis polysaccharides ameliorate 5-FU-induced stress anemia via promoting extramedullary erythroblastic island central macrophage-mediated erythroid differentiation.

BACKGROUND: Chronic anemia, especially chemotherapy-induced anemia, is a common and intractable symptom. Puzzlingly, the conventional anemic treatment may lead to various side effects, and the mechanism of stress anemia remains unclear. METHODS: Here, peripheral blood, histopathological and transmission electron microscopical examination, colony forming test, flow cytometry, and qRT-PCR assay were used to investigate the effects of Angelia sinensis polysaccharide (ASP), one main active ingredient of Chinese herb medicine Angelica sinensis, on ameliorating 5-fluorouracil (5-FU)-induced stress anemia. RESULTS: We found that intraperitoneal injection to a C57BL/6J mouse ASP 100 mg/kg per day for consecutive 10 days or 14 days, remarkably accelerated the recovery of RBC, hemoglobin, and hematocrit in blood. ASP alleviated 5-FU-caused impairment of bone marrow cell and BFU-E enumeration. Meanwhile, ASP antagonized 5-FU promoting extramedullary erythropoiesis in the spleen, inducing splenomegaly due to stress erythroblastic islands, and occurrence of megakaryocytes and hematopoietic precursors in splenic colonies. ASP increased splenic stress BFU-E enumeration, driving BFU-E differentiation towards Pro-E and end-stage erythroblasts. Furthermore, ASP increased the number of F4/80+VCAM-1+ splenic erythroblastic island central macrophages, upregulating genetic expression of EPOR, Emp, VCAM-1, Hmox-1, Trf, TfR1, Fpn1, Spi-C, DNase2a, Tim4, MertK, and Klf1 in splenocytes. CONCLUSIONS: Our findings indicate that the possible mechanism of chemotherapy-induced anemia is related to stress erythroid maturation arrest. Whereas, ASP may promote stress erythroid differentiation via elevated EPO sensitivity in extramedullary hematopoietic organs and enhanced macrophage-mediated adhesion, iron homeostasis and transfer, and nuclear engulfment, which may represent a promising therapeutic strategy.

Intradural extramedullary cervical cavernoma.

Background: Spinal cavernomas (SCs) account for about 5% of all spinal vascular malformations. Intradural SCs occur in just 3% of cases and are typically intramedullary. Case Description: A 58-year-old female presented with progressive left occipital neuralgia, left cervicobrachial neuralgia, and paresthesia of all four extremities. The magnetic resonance imaging (MRI) revealed an intradural extramedullary C2-C4 lesion causing significant spinal cord compression. Gross total tumor excision was accomplished through a midline laminectomy pathologically; the lesion proved to be a cavernoma. The postoperative follow-up MRI obtained 4 months postoperatively showed complete tumor resection. Conclusion: A 58-year-old female successfully underwent gross total excision of a C2-C4 intradural extramedullary SC.

A rare case of maxillary sinus and buccal space involvement of extramedullary plasmocytoma: Cross-sectional imaging findings and review of the literature.

Extramedullary plasmacytoma (EMP) belongs to the group of plasma cell neoplasms, which include following entities: multiple myeloma (MM), lymphoplasmacytic lymphoma, solitary plasmacytoma of the bone (SBP) and EMP. Localization in the maxillary sinus with simultaneous involvement of the buccal cavity is rare. Misdiagnosis may lead to inappropriate or delayed management. X-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) scan provide useful information for diagnosis. Many CT and MRI features are not specific and it is important to find specific imaging characteristics for making differential diagnosis. Our case has shown how, in the context of advanced MRI techniques, DWI is decisive in achieving the correct diagnosis of EMP The peculiarity of this case, in addition to showing the possibility, although rare, of a simultaneous involvement of EMP of the buccal cavity and of the ipsilateral maxillary sinus, presents the behavior of the EMP in various imaging methods, highlighting how diffusion-weighted imaging (DWI) played an important role to suggest the correct diagnosis and differentiating it from squamous cell carcinoma (SCC) and non-Hodgkin lymphoma (NHL).

Splenectomy unveils thrombocytosis in underlying myeloproliferative neoplasms with extrahepatic portal vein obstruction.

Extrahepatic portal vein obstruction (EHPVO) is a rare disease with myeloproliferative neoplasm (MPN) as the most common cause. We report that hypersplenic hematologic changes in EHPVO might be eliminated by MPN. Through experience with splenectomy for variceal control with EHPVO, we suspected that spleen might mask MPN-induced thrombocytosis, and that MPN might have a significant influence on excessive thrombocytosis after splenectomy. To clarify the influence of MPN and spleen on platelet trends, we conducted a retrospective hospital database analysis, evaluating 8 EHPVO patients with splenectomy (2 males, 6 females; from 17 years to 64 years, mean 38.3 years). Three (37.5%) of 8 were diagnosed as MPN by JAK2V617F mutation. The perioperative serum platelet counts in EHPVO without MPN were 10.5, 35.4, and 36.6 (x104/µL) preoperatively, after 1 week and 3 weeks, respectively. The platelet counts in EHPVO with MPN were 34.2, 86.4, and 137.0 (x104/µL), respectively. Splenectomy and MPN showed positive interaction on platelet increasing with statistical significance. We also examined the spleen volume index (SpVI: splenic volume (cm3) / body surface area (m2) and postoperative platelet elevations ratio (PER: 3-week postoperative platelet counts / preoperative platelet counts). However, both SpVI and PER showed no significant difference with or without MPN. Histological examination revealed splenic congestion in all 8 EHPVO cases, and splenic extramedullary hematopoiesis in 2 of 3 MPN. In EHPVO with MPN, hypersplenism causes feigned normalization of platelet count by masking MPN-induced thrombocytosis; however, splenectomy unveils postoperative thrombocytosis. Spleen in EHPVO with MPN also participates in extramedullary hematopoiesis.

A rare encounter in the nasopharynx: Extramedullary plasmacytoma.

Extra-medullary plasmacytoma (EMP) is a rare tumor that most frequently occur in the head and neck region, with the paranasal sinuses, nasopharynx and tonsils being the most common sites. Diagnostic criteria for EMP include histological confirmation of a solitary plasma cell lesion, the presence of fewer than 5% plasma cells in the bone marrow, and the absence of end-organ damage commonly associated with multiple myeloma. CT scans and MRI features are nonspecific and can mimic those of other conditions. EMP of the nasopharynx presents as a slow-growing, radiosensitive mass with a favorable prognosis. We present the case of a 55-year-old male patient who sought medical attention for recurrent epistaxis. An endoscopic examination revealed a tumor located in the nasopharynx, which was confirmed by MRI as a confined nasopharyngeal mass. Subsequent pathology studies, laboratory results, and bone marrow biopsy were consistent with a solitary EMP of the nasopharynx.

IgG-k/IgG-λ Para-Osseous Plasmacytoma Relapsed as Soft-Tissue Plasmacytoma with IgA-k Immunophenotype: A Case Report and Review of the Literature on Related Biochemical Aspects.

Neoplastic plasma cells (PCs) proliferation at anatomic sites dislocated from the bone marrow (BM) or their contiguous growth from osseous lesions that disrupt the cortical bone is termed extramedullary multiple myeloma (EMD). EMD still remains challenging from a therapeutic and biological perspective. Pathogenesis has not been completely clarified, and it is generally associated with high-risk cytogenetics (HRCAs). In order to emphasize the clinical and biochemical complexity of this disease, we have decided to describe the case of a patient affected by relapsed-refractory (RR) EMD, which presented as para-osseous plasmacytoma with a bi-phenotypical immunoglobulin (Ig) component and lately relapsed as soft-tissue plasmacytoma with a total immunophenotype switch. We have also hypothesized a correlation between Ig patterns and prognosis and suggested the possible inclusion of these biochemical features in the general risk assessment.

Transcranial Corticospinal Motor-Evoked Potentials in Cases of Ventral and Ventrolateral Intradural Extramedullary Cervical Spinal Cord Tumors.

Background and Objectives: We studied the clinical significance of an amplitude decrement and disappearance alarm criteria in transcranial motor-evoked potential (MEP) monitoring during surgeries on extramedullary tumors at the cervical spine with reference to postoperative morbidity. Material and Methods: We diagnosed and surgically treated fourteen patients with intradural extramedullary ventral or ventrolateral lesions to the cervical spinal cord in the Clinic of Neurosurgery at the University Hospital St Ivan Rilski from January 2018 to July 2022. Eight cases were diagnosed with schwannoma, and the remaining six had meningiomas. The follow-up period for neurological assessment was six months. Results: A decrease in the intraoperative transcranial MEPs of 50% or more compared to baseline in two cases (14.3%) resulted in an immediate postoperative motor deficit. One patient demonstrated full neurological recovery within six months, while the other exhibited only partial improvement. In six cases (42.9%) with preoperative motor deficits, tumor resection and decompression of the cervical spinal cord led directly to an increment of the transcranial MEPs by more than 20%. Postoperatively and at the 6-month follow-up, these patients showed recovery from the preoperative deficits. In the remaining cases, MEPs were stable during surgery with no clinical deterioration of the motor function. Conclusions: The decremented MEP criteria corresponded to postoperative motor deficit, whereas the improvement of the same parameters after decompression implied future recovery of preoperative motor deficits. The combination of different MEP criteria is likely to be helpful when tailored to a specific case of ventral or ventrolateral extramedullary lesions in the cervical spine.

Septal plasmacytoma: Dilemma of diagnosis.

Plasmacytomas are malignant tumours characterised by abnormal monoclonal proliferation of plasma cells. They may be osseous or may arise from soft tissues. Extramedullary plasmacytoma (EMP) accounts for only 1% of all head and neck malignancies. Septal plasmacytomas are extremely rare. Here, we report a case of an 80-year-old male patient with alocalised plasmacytoma arising from the nasal septum, which was resected endoscopically, with post-op radiotherapy and no recurrence in 1 year of follow-up. A multidisciplinary approach is required for the optimal diagnosis and management. It is essential to exclude any systemic involvement before arriving at a diagnosis of solitary plasmacytoma. Depending on lesion resectability, a combined therapy is the treatment of choice.

Clinical value of 18F-FDG PET/CT in patients with newly diagnosed acute leukemia.

PURPOSE: To explore the correlation between semi-quantitative parameters of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans findings and the clinical features of patients with acute leukemia (AL), as well as to evaluate the clinical utility of 18F-FDG PET/CT in the management of AL. METHODS: A retrospective study was conducted with 44 patients newly diagnosed with acute leukemia (AL) at Zhongnan Hospital of Wuhan University between January 2019 and August 2024. RESULTS: Multivariate analysis revealed that age at diagnosis of AL (odds ratio [OR]: 0.888, P < 0.01) and percentage of blasts in the peripheral blood (PB) (OR: 1.061, P < 0.05) were independent predictors of the appearance of active extramedullary disease (EMD). Kaplan-Meier survival analysis for patients with EMD(+) indicated that those with organ infiltration beyond the lymph nodes experienced markedly reduced overall survival (OS) compared to those without such infiltration (157 days and 806 days, respectively). Furthermore, in the AL subgroup with EMD, the ratio of the maximum standardized uptake value (SUVmax) in the bone marrow (BM) to SUVmax of the liver emerged as an independent prognostic factor for OS (Hazard ratio [HR]: 2.372; 95% confidence interval [CI]: 1.079-5.214, P < 0.05). CONCLUSION: 18F-FDG PET/CT offers the benefits of being non-invasive and highly sensitive for the thorough evaluation of disease status in patients newly diagnosed with AL. Furthermore, the SUVmax BM/liver ratio is of significant clinical importance for prognosticating outcomes in patients with AL presenting EMD.

Sequential therapy for extramedullary plasmacytoma of the palate: a rare case report with seven years of follow-up and literature review.

BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare solitary malignancy that accounts for 3% of plasma cell neoplasms, and EMP with a primary occurrence in the palate is extremely uncommon. Owing to the long course of EMP and the limited available data on treatment outcomes, there are no definitive guidelines for its management, especially for high-risk patients who are more susceptible to early progression to multiple myeloma. CASE PRESENTATION: In this study, we review nine relevant studies and describe a 54-year-old woman who presented with an asymptomatic nonulcerative mass localized in the palate. After initial radical surgical resection of the lesion, the patient was definitively diagnosed with EMP with minimal plasmacytosis in the bone marrow, and adjuvant intensity-modulated radiation therapy with a minimum dose of 39.6 Gy was administrated in the surgical area. There was no evidence of local recurrence, nodal metastasis or progression to multiple myeloma (MM) during the seven-year follow-up period. CONCLUSION: Given the atypical clinical features of palate EMP reported in the literature and the encouraging results of our patient, sequential therapy involving surgery and adjuvant radiotherapy for primary palatal lesions in high-risk EMP patients without nodal involvement could be an effective treatment modality.

Minimally Invasive Far-Lateral Hybrid Exoscopic-Endoscopic Lateral Rolling Technique for T1-2 Anterior Intradural Extramedullary Meningioma.

Anterior intradural extramedullary meningiomas are intimidating, especially in the thoracic spine due to the spinal cord impeding conventional surgical corridor, restricted space, and precarious cord vascularity.1,2 This is possibly the first report in the literature of a minimally invasive surgery: far-lateral hybrid exoscopic and angled endoscopic approach for an anterior thoracic spine meningioma. A 60-year-old woman presented with an anterior T1-2 meningioma with a flattened cord draping over the tumor more toward the right, leaving a potential corridor on the left lateral aspect (Video 1). Under a three-dimensional exoscope, a minimally invasive retractor was placed through the left paramedian incision centered on the lamina-transverse process junction; lateral fenestration and T1-2 facetectomy were carried out with a high-speed drill and rongeurs, meticulously preserving C7-T1 articulations.3,4 Following coagulation of the anterolateral dura over the tumor, a lateral longitudinal durotomy with a T-shaped anterolateral extension was performed around the tumor. Following devascularization, disconnection, and extra-arachnoidal dissection, a unique lateral rolling technique was employed, wherein the tumor was bimanually rolled onto the bony gutter created earlier without disturbing the spinal cord. This was followed by coagulation and excision of the dural tail. A 45° endoscope was then inserted to look for any residual tumor or dural tail.5 As the durotomy was lateral with excision of the dural tail, a multilayered soft tissue closure without dead space was sufficient to prevent cerebrospinal fluid leak.3 Fixation was not needed as only a single thoracic spine facet was disrupted.4 The patient recovered fully with radiology confirming total excision. This minimally invasive lateral rolling technique is safe and effective for anterior meningioma with the ergonomics of exoscope & the angled optics of endoscope complementing each other.

Solitary Testicular Plasmacytoma: A Case Report.

INTRODUCTION: Plasmacytoma of the testis is an extremely rare malignancy that may occur as a solitary tumor, also known as solitary testicular plasmacytoma (STP), or in conjunction with multiple myeloma (MM). Previous studies have shown that STP has a good prognosis and can be cured with localized treatments like radiotherapy or surgery. We report a case of STP with dissemination to the ribs. The patient required systemic chemotherapy. CASE PRESENTATION: A 69-year-old man was referred to our hospital due to swelling of the left scrotum. The patient underwent left inguinal high orchiectomy. Based on pathological examination, the specimen was diagnosed as testicular plasmacytoma. As the tests for MM were negative, the patient was followed up. Sixteen months later, multiple bone lesions were detected in the left rims, although serum protein electrophoresis did not show the presence of M protein. Therefore, the patient received 4 courses of chemotherapy, and no signs of recurrence have been detected so far. CONCLUSION: STP is an extremely rare disease, which obscures its true prognosis. Systemic chemotherapy should be considered for patients with STP in case of recurrence, and long-term follow-up is necessary to understand the nature of the disease.

A case of posttransplant isolated extramedullary relapse of acute lymphoblastic leukemia achieving durable treatment-free remission with blinatumomab and donor lymphocyte infusion.

Acute lymphoblastic leukemia (ALL) relapsed after allogeneic hematopoietic cell transplantation (allo-HCT) has a catastrophic prognosis. Blinatumomab, a CD3/CD19-directed bispecific T cell engager, is reportedly effective for advanced B-cell ALL (B-ALL), even after allo-HCT. However, the efficacy of blinatumomab in extramedullary relapse (EMR) is controversial. Donor lymphocyte infusion (DLI) is another immunological treatment worth considering for ALL relapsed after allo-HCT. We report the case of a 56-year-old woman with B-ALL. Allo-HCT was performed during the second complete remission (CR). Thirteen months after allo-HCT, isolated EMR (iEMR) of B-ALL developed without bone marrow lesions. A third CR was achieved with 2 cycles of blinatumomab. An additional four cycles each of blinatumomab and DLI were then administered. The patient did not develop graft-versus-host disease and has confirmed 2-year treatment-free remission without a second allo-HCT. Therefore, blinatumomab was considered an effective salvage therapy for iEMR of B-ALL after allo-HCT, because iEMR could have a lower tumor burden than that seen in systemic relapse, and low tumor burden was a prognostic factor for response to blinatumomab. Furthermore, immunological consolidation therapies could only provoke graft-versus-leukemia effects if the imbalanced effector/target ratio was restored and the tumor burden was lowered through immunosurveillance.

The Role of Epithelial-to-Mesenchymal Transition Transcription Factors (EMT-TFs) in Acute Myeloid Leukemia Progression.

Acute myeloid leukemia (AML) is a diverse malignancy originating from myeloid progenitor cells, with significant genetic and clinical variability. Modern classification systems like those from the World Health Organization (WHO) and European LeukemiaNet use immunophenotyping, molecular genetics, and clinical features to categorize AML subtypes. This classification highlights crucial genetic markers such as FLT3, NPM1 mutations, and MLL-AF9 fusion, which are essential for prognosis and directing targeted therapies. The MLL-AF9 fusion protein is often linked with therapy-resistant AML, highlighting the risk of relapse due to standard chemotherapeutic regimes. In this sense, factors like the ZEB, SNAI, and TWIST gene families, known for their roles in epithelial-mesenchymal transition (EMT) and cancer metastasis, also regulate hematopoiesis and may serve as effective therapeutic targets in AML. These genes contribute to cell proliferation, differentiation, and extramedullary hematopoiesis, suggesting new possibilities for treatment. Advancing our understanding of the molecular mechanisms that promote AML, especially how the bone marrow microenvironment affects invasion and drug resistance, is crucial. This comprehensive insight into the molecular and environmental interactions in AML emphasizes the need for ongoing research and more effective treatments.