A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).
Male ; Humans ; Aged ; Pancreatic Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adenocarcinoma ; Neoplasm Recurrence, Local/surgery* ; Immunotherapy ; Liver Neoplasms/therapy* ; Pancreatectomy

OBJECTIVE: To analyze the factors influencing collection of autologous peripheral blood hematopoietic stem cells in lymphoma patients. METHODS: Clinical data of 74 patients who received autologous peripheral blood hematopoietic stem cells mobilization and collection in the 940th Hospital of Joint Logistic Support Force of PLA from April 2009 to April 2021 were collected. The effects of gender, age, disease type, stage, course of disease, chemotherapy cycle number, relapse, radiotherapy, disease status and blood routine indexes on the day of collection on peripheral blood hematopoietic stem cell collection were analyzed. RESULTS: The success rate of collection was 95.9%(71/74), and the excellent rate of collection was 71.6%(53/74). There was a significantly statistical differentce in the number of CD34⁺ cells in grafts collected from patients with chemotherapy cycle ≤6 and >6 ［(9.1±5.2)×10⁶/kg vs (6.4±3.7)×10⁶/kg, P=0.031］. The number of CD34⁺ cells in the first collection was positively correlated with WBC count, hemoglobin, platelet count, neutrophil count, lymphocyte count, monocyte count and hematocrit value on the day of collection ( r value was 0.424,0.486,0.306,0.289,0.353,0.428,0.528, respectively). WBC count, hemoglobin, monocyte count and hematocrit value have higher predictive value for the first collection of CD34⁺ cells. The area under the receiver operating characteristic was 0.7061,0.7845,0.7319,0.7848, respectively. CONCLUSION Low dose CTX and VP16 chemotherapy combined with G-CSF can effectively mobilize autologous peripheral blood stem cells. The cycle number of chemotherapy relates to the collection of autologous peripheral blood stem cells. After mobilization, the success of the first collection can be better predicted by the blood routine indexes.
Humans ; Antigens, CD34/metabolism* ; Neoplasm Recurrence, Local/drug therapy* ; Hematopoietic Stem Cell Mobilization ; Lymphoma/drug therapy* ; Granulocyte Colony-Stimulating Factor/pharmacology* ; Hematopoietic Stem Cells ; Hemoglobins ; Transplantation, Autologous ; Hematopoietic Stem Cell Transplantation

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.
Humans ; Rituximab/therapeutic use* ; Vincristine/therapeutic use* ; Prednisone/therapeutic use* ; Epstein-Barr Virus Infections/drug therapy* ; Herpesvirus 4, Human ; Neoplasm Recurrence, Local ; Lymphoma, T-Cell/drug therapy* ; Cyclophosphamide/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Doxorubicin/therapeutic use* ; Lymphadenopathy/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

OBJECTIVE: To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed. RESULTS: Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m² d1 + oxaliplatin 100 mg/m² d 1 + etoposide 60 mg/m² d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later. CONCLUSION PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.
Humans ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies ; Etoposide ; Neoplasm Recurrence, Local/drug therapy* ; Asparaginase ; Deoxycytidine ; Lymphoma, T-Cell, Peripheral/drug therapy* ; Lymphoma, Extranodal NK-T-Cell/therapy* ; Oxaliplatin/therapeutic use*

OBJECTIVE: To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment. METHODS: This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions. RESULTS: MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area. CONCLUSIONS Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.
Humans ; Lymphoma/radiotherapy* ; Central Nervous System Neoplasms/pathology* ; Retrospective Studies ; Prospective Studies ; Neoplasm Recurrence, Local/drug therapy* ; Combined Modality Therapy ; Brain/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Methotrexate

Humans ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Neoplasm Recurrence, Local/drug therapy* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.
Antigens, Neoplasm/chemistry* ; Biomarkers, Tumor/metabolism* ; Glycosylation ; Hematologic Neoplasms/drug therapy* ; Humans ; Immunotherapy, Adoptive/methods* ; Male ; Neoplasm Recurrence, Local/metabolism* ; Receptors, Chimeric Antigen ; T-Lymphocytes ; United States

Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Dexamethasone/therapeutic use* ; Humans ; Multiple Myeloma/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Proto-Oncogene Proteins c-bcl-2

INTRODUCTION: Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes. METHODS: Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS). RESULTS: At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression. CONCLUSION Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.
Adjuvants, Immunologic/therapeutic use* ; Administration, Intravesical ; BCG Vaccine/therapeutic use* ; Diabetes Mellitus ; Disease Progression ; Humans ; Male ; Metformin/therapeutic use* ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; Urinary Bladder Neoplasms/drug therapy*