OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

BACKGROUND AND OBJECTIVES

Non-Hodgkin Lymphoma (NHL) ranks 11th in cancer incidence and mortality in the Philippines with the combination chemotherapy composed of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) being commonly used as treatment. However, the addition of Rituximab to CHOP (R-CHOP) has been shown to exhibit higher response rates and longer remissions, potentially improving quality of life. Currently, there is conflicting evidence on the cost-utility of CHOP versus R-CHOP. The study aimed to describe the patient- and country-specific factors, and treatment modalities used for NHL and systematically review cost-utility evidence of R-CHOP versus CHOP in adult NHL patients.

A systematic literature search of cost-utility studies on R-CHOP versus CHOP for NHL treatment was performed on eight databases: PubMed/MEDLINE, Scopus, Web of Science, EBSCOHost, Cochrane, York Research Database, Centre for Reviews and Dissemination Database, and HERDIN, where 607 studies were identified. Upon screening using an eligibility criteria, 10 studies were included and critically assessed using four appraisal tools: CHEERS, Drummond, Cooper, and ECOBIAS. These were performed independently by two authors with a third author assisting to help reach a consensus.

All studies from high-income countries (HICs) (n=8) and low-middle-income country (LMIC) (n=1) suggested that R-CHOP was more cost-effective for NHL treatment than CHOP in terms of utility outcomes. The study conducted in a low-income country (LIC) (n=1) suggested the opposite, favoring CHOP over R-CHOP. Methodological differences such as perspective, discount rate, willingness-to-pay (WTP), time horizon, and economic model were observed. Methodological limitations include completeness of data reported and credibility of sources used.

The results of this review shall be interpreted with caution as those favoring R-CHOP over CHOP for NHL treatment in terms of cost-utility were concentrated in HICs. More economic evaluations from LICs, LMICs, and upper-middle income countries (UMICs) are needed for a robust conclusion. Additionally, establishing a universally recognized guideline for economic evaluations is essential to guide researchers effectively.

Introduction: Primary adrenal lymphoma (PAL) is a rare extranodal lymphoma, accounting for less than 1% of cases. It often presents with non-specific constitutional symptoms and features of adrenal insufficiency. The absence of pathognomonic findings frequently leads to delayed diagnosis, by which time the disease is often advanced, contributing to poor prognosis. Case: A 59-year-old male with type 2 diabetes mellitus and previously treated pulmonary tuberculosis presented with 1 month of lethargy, anorexia, weight loss, and abdominal pain. He was cachectic but hemodynamically stable (BP 120/81 mmHg; glucose 5.1 mmol/L), with otherwise unremarkable systemic examination. Laboratory evaluation revealed hyponatremia (120 mmol/L), hyperkalemia (6.0 mmol/L), and severe hypercalcemia (4.4 mmol/L). A short Synacthen test confirmed adrenal insufficiency. Computed tomography demonstrated marked bilateral adrenal enlargement with bulky masses (8.9 × 8.7 × 8.7 cm right; 9.9 × 7.6 × 10.2 cm left), suggestive of malignant infiltration. Adrenal protocol imaging revealed indeterminate lesions with attenuation >40 Hounsfield Unit and relative washout <40%. Ultrasound-guided biopsy of the right adrenal gland was performed. The patient was discharged on hydrocortisone replacement with plans for early follow-up. One week later, he presented again in adrenal crisis with severe hypoglycemia (1.1 mmol/L) and cardiovascular collapse. Despite resuscitative efforts, he succumbed. Histopathology subsequently confirmed diffuse large B-cell lymphoma, activated B-cell subtype, consistent with PAL. Conclusion This case highlights the diagnostic pitfalls of PAL, particularly when constitutional symptoms mimic chronic infections such as tuberculosis. It underscores the need for high clinical suspicion in patients with bilateral adrenal masses and adrenal insufficiency. Early recognition, adequate steroid replacement including mineralocorticoid therapy, and prompt tissue diagnosis are critical to prevent rapid deterioration and improve outcomes.
Lymphoma

Introduction: Sinonasal collision tumors are exceptionally rare, and glomangiopericytoma (GPC) is an uncommon perivascular myoid neoplasm accounting for less than 0.5% of sinonasal tumors. GPC can mimic other spindle-cell tumors, and recognition of perivascular morphology with immunohistochemistry with SMA, nuclear and cytoplasmic β-catenin are essential. Sinonasal B-cell lymphomas are also uncommon and may be difficult to classify in fibrotic biopsies; the coexistence of these two entities appears exceedingly unusual. Case Description: A 69-year-old man presented with progressive left-sided nasal symptoms. Endoscopy showed an obstructing left nasal cavity mass. Biopsy showed two components: a spindle-cell proliferation with thin-walled branching (“staghorn”) vessels and perivascular hyalinization, and scattered monomorphic small round blue cells in dense sclerosis. Spindle cells were SMA-, nuclear and cytoplasmic β-catenin-positive, STAT6- and TLE1-negative, and SS18 FISH-negative, supporting GPC. The round-cell component was CD20-positive but too scant for subclassification. Left partial maxillectomy showed a diffuse monomorphic round-cell infiltrate in sclerotic stroma. Cells were CD79a-, PAX5-, and BCL6-positive, with focal weak CD10 and Ki-67 ~25–45%, confirming B-cell lymphoma. Discussion: The key decision was to evaluate the spindle-cell and round-cell components separately rather than force a single diagnosis. A targeted panel supported GPC and excluded major mimics. The round cell component was identified morphologically and confirmed by immunophenotypic findings as B-cell lymphoma; however, precise subclassification could not be established because of the dense sclerosis, and molecular testing was not performed. Conclusion The sinonasal mass contains two distinct neoplasms. The main lesson is to assess each component independently, use targeted immunohistochemistry, and correlate biopsy with resection.
Nasal Cavity ; Neoplasms ; Lymphoma, B-Cell

Introduction: Ovarian lymphoma is rare and often misdiagnosed, as its clinical presentation can be similar to other more frequent tumors. It accounts for <1% of all non-Hodgkin lymphomas, with high-grade B-cell lymphoma being the most frequently implicated subtype. Case Description: A 48-year-old woman presented with bilateral ovarian masses, elevated CA-125, and extensive abdominal and thoracic lymphadenopathy. She was managed as advanced ovarian cancer and underwent TAHBSO. Grossly, both ovaries were enlarged and nodular. Histology showed a round cell neoplasm composed predominantly of medium-sized, cleaved lymphocytes, admixed with scattered larger atypical cells. Initial immunohistochemistry panel demonstrated diffuse CD45 positivity and negativity for AE1/AE3, Inhibin, SALL4, Desmin, and Calretinin. Subsequently, CD20 and PAX5 showed diffuse reactivity. CD10, BCL2, and BCL6 highlighted neoplastic follicles. CD3 was negative. High-grade B-cell lymphoma was considered; however, the Ki-67 proliferative index was 38%, and c-MYC expression was low (5%). A final diagnosis of follicular lymphoma involving both ovaries was rendered. Discussion: The clinical presentation strongly suggested advanced ovarian carcinoma. However, histologic and immunophenotypic evaluation established lymphoma. Although aggressive subtypes are more common in advanced cases, indolent entities such as follicular lymphoma should also be considered, particularly in resource-limited settings where delays in diagnosis occur. Distinguishing lymphoma from carcinoma is critical, as management differs significantly and misclassification may lead to overtreatment. Conclusion Recognition of ovarian lymphoma is critical, as accurate diagnosis alters management and prevents unnecessary radical surgery.
CA-125 Antigen ; Immunohistochemistry ; Lymphoma, Follicular ; Ovarian Neoplasms

BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

BACKGROUND

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). Classification of DLBCL is often based on the cell of origin (COO), distinguishing between germinal center B-cell (GCB) and non-GCB subtypes. Although not yet recognized as a distinct entity by the World Health Organization (WHO), double expressor lymphoma (DEL), characterized by the co-expression of c-MYC and BCL2, carries an unfavorable prognosis for a subgroup of DLBCL patients. Another entity is the so-called high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit/triple-hit lymphomas) diagnosed through fluorescent in-situ hybridization (FISH) analysis.

This study aimed to determine the clinicopathologic profile and survival outcomes of Filipino DLBCL patients at the Philippine General Hospital (2016-2021), comparing double-hit versus non-double-hit and doubleexpressor versus non-double-expressor lymphomas, and assessing concordance between FISH-measured double-hit and IHC-measured double-expressor statuses.

This is a single-arm, retrospective cohort study involving all surgical pathology cases signed out, with the aid of immunohistochemistry (IHC) studies, as NHL DLBCL, GCB, or non-GCB subtype, from 2016 to 2021. A second panel of IHC studies and FISH analysis using tissue microarray was subsequently done. Most cases exhibited a nonGCB subtype and were classified as DEL on second IHC panel. Five out of eleven DEL cases were reclassified as double hit lymphoma (DHL).

Clinically, most patients with these lymphomas present at age 60 years and below, exhibit B symptoms, with elevated serum lactate dehydrogenase (LDH) levels, at least stage III-IV disease at diagnosis, and possess a high International Prognostic Index (IPI) score, collectively indicating a poor prognosis.

Survival outcomes for patients with DLBCL ranges from three to 37 months. All cases of mortality were associated with DEL, contrasting with DHL cases which had variable outcomes. Due to limited sampling, statistical significance of the results cannot be determined. A comprehensive evaluation is essential to the diagnosis of DLBCL and DHL to include a complete immunohistochemistry panel and molecular testing, notably with FISH studies.

INTRODUCTION

Parotid lymphoma is a rare occurrence, let alone a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Salivary gland tumors commonly affect the parotid gland, although a primary malignant lesion rarely occurs, with an incidence of 0.5 to 3.0/100,000 population/year worldwide. This case report describes the presentation of this rare lymphoma. This also demonstrates the efficacy of standard of care chemotherapy with doxorubicin, vincristine, bleomycin, and dacarbazine with an anti-CD20 monoclonal antibody, rituximab (R-ABVD).

This is a case of a 44-year-old male with a gradually enlarging right preauricular mass. Biopsy and immunohistochemical staining confirmed a diagnosis of NLPHL Stage IIA. A total of six cycles of chemotherapy with R-ABVD was given. Follow-up PET CT showed resolution of FDG avid nodes localized near the surgically removed parotid gland, confirming complete remission.

Parotid malignancy only accounts for 5% of all head and neck tumors. NLPHL is even more rare, with an incidence of 1.5/1,000,000 population per year. The rarity of the case limits clinical trials for its treatment. Because of this, R-ABVD has been employed as a treatment of choice for intermediate-staged NLPHL. Overall response showed an 85% five-year progression-free survival and 99% overall survival.

This case report highlights the significance of early lymphoma detection despite its rarity among parotid tumors and prompt initiation of chemotherapy.