1.Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma.
Xin-Yue JI ; Da-Peng SHENG ; Yu-Qiong YANG ; Yuan-Feng WEI ; Xi HUANG ; Qiong LIU ; Dan-Ning YU ; Yu-Xin GUO ; He-Sheng HE
Journal of Experimental Hematology 2023;31(2):396-402
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*
2.Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology.
Zhihang HU ; Modan YANG ; Hao CHEN ; Chiyu HE ; Zuyuan LIN ; Xinyu YANG ; Huigang LI ; Wei SHEN ; Di LU ; Xiao XU
Journal of Zhejiang University. Science. B 2023;24(5):387-396
Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).
Humans
;
T-Lymphocytes
;
Immunotherapy, Adoptive
;
Neoplasm Recurrence, Local
;
Transplantation, Homologous
;
Cell- and Tissue-Based Therapy
3.A single-center, retrospective analysis of relapse and progression patterns of primary central nervous system lymphoma: can whole brain radiotherapy be replaced?.
Yue QIN ; Rongping LIU ; Xiaonan ZHANG ; Wan ZHANG ; Chen REN ; Dehua WU
Journal of Southern Medical University 2023;43(4):499-506
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
5.Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant.
Yong Qiang ZHAO ; Yan Zhi SONG ; Zhi Hui LI ; Fan YANG ; Teng XU ; Fei Fei LI ; Dong Fang YANG ; Tong WU
Chinese Journal of Hematology 2023;44(6):465-471
Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.
Humans
;
Adult
;
Retrospective Studies
;
Neoplasm Recurrence, Local
;
Hematologic Neoplasms/therapy*
;
Busulfan/therapeutic use*
;
Graft vs Host Disease/prevention & control*
;
Chronic Disease
;
Unrelated Donors
;
Hematopoietic Stem Cell Transplantation
;
Transplantation, Homologous
;
Transplantation Conditioning
7.A case of pancreatic cancer treated with chemotherapy combined with immunotherapy and targeted therapy.
Bo ZHANG ; Kezhong TANG ; Xin DONG
Journal of Zhejiang University. Medical sciences 2023;52(5):578-582
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
8.Clinical Analysis of Autologous Peripheral Blood Hematopoietic Stem Cells Mobilization and Collection in Lymphoma Patients.
Heng LIU ; Rui XI ; Hai BAI ; Tao WU
Journal of Experimental Hematology 2023;31(6):1845-1851
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
9.Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review.
Xueli JIN ; Hui LIU ; Jing LI ; Xibin XIAO ; Xianggui YUAN ; Panpan CHEN ; Boxiao CHEN ; Yun LIANG ; Fengbo HUANG
Journal of Zhejiang University. Science. B 2023;24(8):711-722
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*

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