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

Humans ; Leukemia, Myelomonocytic, Chronic/therapy* ; Mutation ; Myelodysplastic Syndromes

Humans ; Leukemia, Myelomonocytic, Chronic/drug therapy* ; Nitriles ; Pyrazoles/therapeutic use* ; Pyrimidines

Spontaneous chronic subdural hematoma (SDH) is a rare condition that could develop in association with hematologic disease. A 66-year-old male developed a chronic SDH as an initial manifestation of chronic myelomonocytic leukemia (CMML). He experienced recurrent chronic subdural hemorrhage and newly developed intracerebral hemorrhage. Considering the scheduled long-term chemotherapy, bilateral middle meningeal artery (MMA) embolization was performed to prevent recurrence of subdural hemorrhage. Although pancytopenia occurred during the 7 months' follow-up period, residual chronic subdural hemorrhage was absorbed without recurrence. To our best knowledge, this is the first report of CMML with spontaneous chronic SDH. MMA embolization is potentially a useful and safe treatment option in the challenging clinical situations with underlying pathologies.
Aged ; Cerebral Hemorrhage ; Drug Therapy ; Follow-Up Studies ; Hematologic Diseases ; Hematoma, Subdural* ; Hematoma, Subdural, Chronic ; Humans ; Leukemia ; Leukemia, Myelomonocytic, Chronic ; Male ; Meningeal Arteries ; Pancytopenia ; Pathology ; Recurrence

No abstract available.
Adult ; Bone Marrow/pathology ; DNA Mutational Analysis ; Humans ; Leukemia, Myelomonocytic, Chronic/*diagnosis/genetics/therapy ; Leukemia, Neutrophilic, Chronic/*diagnosis/genetics/therapy ; Leukocyte Disorders/diagnosis ; Male ; Middle Aged ; Mutation ; Prognosis ; Receptors, Colony-Stimulating Factor/*genetics ; Recurrence ; *Stem Cell Transplantation ; Transplantation, Homologous

This study was purposed to explore the therapeutic efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) and in patients with juvenile myelomonocytic leukemia (JMML). The clinical data of 3 cases of CMML and 2 cases of JMML underwent allo-HSCT were analysed in term of multiparameter. The results showed that the hematopoietic stem cells in 5 patients grafted successfully. One case of JMML died of pulmonary disease, other 4 cases survive without disease. The analysis found that the disease burden before transplant, chromosome karyotype, acute GVHD II-IV and poor risk cytogenetics all associated with the relapse rate and disease-free survival rate of CMML. The low intensity conditioning regimen was better than myeloablative conditioning regimen. Type of donor and source of stem cells did not statistically and significantly affect OS and RFS. The splenectomy before allo-HSCT as well as spleen size at time of the alloHSCT did not influence on posttransplantation outcome of JMML. However, cord blood HSCT for JMML patients delayed hematologic recovery as compared to that of bone marrow or peripheral blood HSCT. The age, GVHD, HbF level played an important role in leukemia replace. It is concluded that the allogeneic hematopoietic stem cell transplantation is a curative regimen for CMML and JMML, but there also is a serial problems to be resolved.
Adult ; Child, Preschool ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myelomonocytic, Chronic ; therapy ; Leukemia, Myelomonocytic, Juvenile ; therapy ; Male ; Middle Aged ; Transplantation, Homologous ; Treatment Outcome

Aged ; Antimetabolites, Antineoplastic ; therapeutic use ; Azacitidine ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Leukemia, Myelomonocytic, Chronic ; drug therapy

Aged ; Echinocandins ; administration & dosage ; therapeutic use ; Humans ; Leukemia, Myelomonocytic, Chronic ; pathology ; Lipopeptides ; Male ; Pneumonia, Pneumocystis ; diagnosis ; drug therapy ; pathology ; Trimethoprim, Sulfamethoxazole Drug Combination ; administration & dosage ; therapeutic use ; Uremia ; pathology

Antigens, CD ; metabolism ; Antigens, CD20 ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Axilla ; Histiocytic Sarcoma ; drug therapy ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, IgE ; metabolism

We report herein two cases of leukemia cutis. One case is a 54-year-old woman who came to our department with complaints of a solitary ulcerating nodule on her left leg that had been present for 2 months since prior to her visit. Through histopathological studies, the diagnosis of myelocytic leukemia cutis was made before the final diagnosis of acute myelocytic leukemia was made by hematological studies. When combined chemotherapy was finished, she was in a partial remission state and the nodule disappeared after 1 month of chemotherapy. The other case is a 77-year-old man having multiple infiltrative nodules on the right forearm and right thigh for 1 month prior his visit. He was diagnosed as having leukemia cutis for his skin lesions histopathologically. This was redefined as chronic myelomonocytic leukemia of the myelodysplastic syndrome with blastic transfor- mation by hematological examination. He developed septicemia and died 3 weeks after the dermato- logical diagnosis.
Aged ; Diagnosis ; Drug Therapy ; Female ; Forearm ; Humans ; Leg ; Leukemia* ; Leukemia, Myeloid ; Leukemia, Myeloid, Acute ; Leukemia, Myelomonocytic, Chronic ; Logic ; Middle Aged ; Myelodysplastic Syndromes ; Sepsis ; Skin ; Thigh ; Ulcer