OBJECTIVE: To explore the relationship between serum complement levels at diagnosis and prognosis in patients with aggressive non-Hodgkin lymphoma(NHL). METHODS: The clinical data of 102 patients with aggressive non-Hodgkin lymphoma diagnosed in the First Hospital of Lanzhou University from February 2017 to March 2023 were selected to analyze the correlation between serum complement C3 and C4 levels and prognosis of patients with aggressive NHL at the time of initial diagnosis. The optimal cut-off point of C3 and C4 were obtained by calculating the Jorden index through the receiver operating characteristic（ROC） curve, and 102 patients were divided into low C3 group (C3< 1.07) and high C3 group (C3≥1.07), low C4 group (C4< 0.255) and high C4 group (C4≥0.255). The effects of serum C3 and C4 levels on the prognosis of these patients were analyzed. RESULTS: ROC curve analysis showed that the area under the curve (AUC) of C3 and C4 in predicting the prognosis of aggressive NHL patients was 0.634 (95%CI ：0.525-0.743；P =0.025) and 0.651 (95%CI ：0.541-0.761；P =0.012), respectively. The optimal cut-off points for C3 and C4 were 1.07 and 0.255, respectively. K-M survival analysis showed that groups with high C3 and C4 levels had shorter progression-free survival (PFS) (P =0.0079; P =0.0092) and overall survival (OS) (P =0.021; P =0.021). Multivariate Cox analysis showed that high level serum complement C3 (HR=2.37, 95%CI : 1.07-5.24, P =0.034) and age ≥60 years (HR=2.34, 95%CI : 1.11-4.95, P =0.025) were independent risk factors for PFS in patients with aggressive NHL. High level complement C3 (HR=2.37, 95%CI : 1.09-5.13, P =0.029) and age ≥60 years at diagnosis (HR=2.40, 95%CI : 1.13-5.13, P =0.024) were independent risk factors for OS in patients with aggressive NHL. CONCLUSION The level of serum complement C3 at diagnosis is one of the prognostic factors in patients with aggressive NHL.
Humans ; Lymphoma, Non-Hodgkin/blood* ; Prognosis ; Complement C3/metabolism* ; Complement C4/metabolism* ; ROC Curve ; Male ; Female ; Middle Aged ; Adult ; Aged

OBJECTIVE: To analyze the clinical characteristics, treatment effect and prognosis of patients with non-Hodgkin lymphoma (NHL) complicated by hypercalcemia. METHODS: The clinical features, treatment and prognosis of 47 patients with NHL complicated by hypercalcemia in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from January 2018 to January 2023 were retrospectively analyzed. RESULTS: Among the 47 lymphoma patients, 33 cases were T-cell NHL, 14 cases were B-cell NHL. The median serum calcium level of the 47 patients was 3.10 (2.77-4.86) mmol/L, with 27 cases (57.4%) experiencing mild hypercalcemia (2.75-3.00 mmol/L), 8 cases (17.0%) experiencing moderate hypercalcemia (3.00-3.50 mmol/L), and 12 cases (25.5%) experiencing severe hypercalcemia (>3.50 mmol/L). All 47 patients were treated with hydration, alkalization, diuresis, etc. 32 cases (68.1%) received combination chemotherapy, 21 cases (44.7%) received salmon calcitonin treatment, and 3 cases were treated with denosumab in 5 patients with renal insufficiency. After treatment, 38 patients' serum calcium gradually returned to normal, with a median recovery time of 6 (1-18) days, while 9 patients still failed to recover their serum calcium after treatment and all died within 1 month. 32 patients undergoing combination chemotherapy were evaluated for efficacy after 2-4 courses of chemotherapy. Among them, 8 cases (25.0%) achieved complete response (CR), 11 cases (34.4%) achieved partial response (PR), 7 cases (21.9%) showed stable disease (SD), and 6 cases (18.8%) showed progressive disease (PD). The median follow-up time was 10 months. There were 13 cases of disease progression after combination chemotherapy and a total of 28 deaths. The survival time ranged from 0.8 to 23.7 months, and the median progression time was 4.9 months. Multivariate Cox regression analysis showed that the T-cell NHL, blood calcium >3.5 mmol/L, and no decrease in blood calcium after treatment were independent risk factors for the OS, and the T-cell NHL was independent risk factors for the PFS. CONCLUSION NHL complicated by hypercalcemia has a poor prognosis, and hypercalcemia can be used as one of the indicators reflecting the tumor burden. Patients with NHL complicated by hypercalcemia should be given more clinical attention and treated actively.
Humans ; Hypercalcemia/complications* ; Lymphoma, Non-Hodgkin/diagnosis* ; Prognosis ; Retrospective Studies ; Female ; Male ; Middle Aged ; Adult ; Aged ; Calcium/blood*

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.
Acute Kidney Injury ; Bendamustine Hydrochloride ; Blood Platelets ; Carmustine ; Cytarabine ; Diarrhea ; Etoposide ; Follow-Up Studies ; Hodgkin Disease ; Humans ; Hyperbilirubinemia ; Kidney ; Liver ; Lymphoma ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell, Peripheral ; Melphalan ; Mortality ; Neutrophils ; Stem Cell Transplantation ; Stem Cells

BACKGROUND: Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. METHODS: This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m² IV d 1, 2), etoposide (200 mg/m² IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). RESULTS: We successfully collected stem cells from all patients, with a median of 7.9×10⁶/kg of body weight (range, 4.4 to 17.3×10⁶/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). CONCLUSION: For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.
Autografts* ; Bendamustine Hydrochloride* ; Blood Component Removal ; Body Weight ; Dexamethasone* ; Disease Progression ; Etoposide* ; Filgrastim ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cells* ; Humans ; Kinetics ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, Follicular ; Lymphoma, Non-Hodgkin* ; Prospective Studies ; Sepsis ; Stem Cells ; Transplantation, Autologous* ; Tumor Lysis Syndrome

BACKGROUND/AIMS: Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin’s lymphoma (NHL) is limited. METHODS: Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. RESULTS: Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. 6.1 × 106/kg, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ≥ 5.0 × 106/kg) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < 2.0 × 106/kg) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). CONCLUSIONS: The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.
Blood Component Removal ; Cisplatin* ; Cyclophosphamide ; Cytarabine* ; Dexamethasone* ; Doxorubicin ; Febrile Neutropenia ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cell Mobilization* ; Humans ; Lymphoma ; Lymphoma, Non-Hodgkin* ; Multivariate Analysis ; Prednisone ; Stem Cell Transplantation* ; Stem Cells* ; Vincristine

LW antigens are expressed in higher intensities in D-positive blood cells than D-negative cells, which can result in false identification of anti-D in pretransfusion testing. Although several cases of anti-LW have been reported abroad, to the best of our knowledge, none have been reported in Korea. Herein, we report a case of anti-LW in a 58 year-old RhD positive patient with non-Hodgkin's lymphoma with a positive direct Coombs test and a suspicion of the presence of passive anti-D antibodies because of a history of intravenous immunoglobulin administration. However, during a 5-month follow up, the antibody was confirmed as anti-LW on grounds that it showed weakened reaction in dithiothreitol treated cells and enforced reaction in cord O+ cells when compared to the results from antibody identification panel cells.
Antibodies ; Blood Cells ; Coombs Test ; Dithiothreitol ; Follow-Up Studies ; Humans ; Immunoglobulins ; Korea ; Lymphoma, Non-Hodgkin ; Sensitivity and Specificity*

Heavy proteinuria in the nephrotic range is an uncommon, often unrecognized manifestation of graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. A few isolated case reports have been published in the Korean literature involving a small number of patients who developed membranous nephropathy as GVHD after peripheral blood stem cell transplantation (PBSCT). A 17-year-old female was diagnosed with non-Hodgkin's lymphoma. Following remission, she underwent allogeneic PBSCT. Shortly thereafter, she developed acute GVHD, which was managed by medical therapy with prednisolone and cyclosporine. Approximately 13 months following PBSCT, the patient developed proteinuria without peripheral edema. Pulsed steroid therapy was initiated three times, but her condition did not improve. Twenty months after PBSCT, she developed nephrotic range proteinuria. A renal biopsy was performed, and the diagnosis was histologically consistent with membranous nephropathy. Because the response to steroids was not satisfactory, the dose of cyclosporine was increased. Approximately 3 months after renal biopsy, the proteinuria disappeared. Given the recent increase in the incidence of GVHD-mediated renal disease, in particular, renal biopsy is indispensable to the diagnosis of nephropathy and to the prevention of disease progression.
Adolescent ; Biopsy ; Cyclosporine ; Diagnosis ; Disease Progression ; Edema ; Female ; Glomerulonephritis, Membranous* ; Graft vs Host Disease* ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Lymphoma, Non-Hodgkin ; Peripheral Blood Stem Cell Transplantation ; Prednisolone ; Proteinuria ; Stem Cells* ; Steroids

Primary central nervous system lymphoma (PCNSL) is a type of highly invasive non-Hodgkin lymphoma. With a growing number of organ transplantation and immunosuppressant therapy, the incidence of PCNSL has been growing rapidly in recent years, which is attributed to the increased incidence of HIV/AIDS, a prominent risk factor for developing PCNSL. The rising rate of PCNSL incidence is the highest among the intracranial tumors. In the past 20 years, dozens of clinical trials related to PCNSL have been registered, but adequate therapeutics are still challenging. Currently, the chemotherapy regimens based on high-dose methotrexate and whole-brain radiotherapy are the two main therapeutic options; however, the toxicity associated with those is the main problem that challenges medical researchers. Novel agents and therapeutic strategies have been developed in recent years. In the current review, we describe advances in the treatment of PCNSL and discuss novel therapeutic approaches currently in development, such as the use of rituximab, disruption of the blood-brain barrier, and state-of-the-art radiotherapy.
Blood-Brain Barrier ; Central Nervous System* ; Drug Therapy ; Incidence ; Lymphoma* ; Lymphoma, Non-Hodgkin ; Methotrexate ; Organ Transplantation ; Radiotherapy ; Risk Factors ; Rituximab ; Transplants

BACKGROUND: Among pediatric non-Hodgkin lymphomas, there are 4 major subtypes: Burkitt lymphoma, lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma. Understanding of other rare subtypes derives only from small pediatric case series. We report our institutional experience with rare pediatric NHLs.METHODS: Thirty-six cases of rare NHL subtypes diagnosed at the Asan Medical Center from 1995 to 2015 were evaluated. We retrospectively reviewed the clinical and pathologic features and outcomes of these patients, excluding peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and extranodal NK/T-cell lymphoma (ENKL), on which we have previously reported.RESULTS: There were 23 cases of T-cell lineage (13 PTCL, 6 ENKL, 2 subcutaneous panniculitis-like T-cell lymphoma, 1 primary cutaneous CD4+2016-11-22 small/medium sized T-cell lymphoma, 1 enteropathy-associated T-cell lymphoma) and 13 cases of B-cell lineage lymphoma (5 marginal zone lymphoma, 6 primary mediastinal large B-cell lymphoma, 2 immunoblastic and plasmablastic lymphoma). All patients were treated with chemotherapy with or without surgery, except 4 out of 5 patients with marginal zone lymphoma who received surgery only. Two patients died and 6 patients relapsed. One patient with primary mediastinal large B-cell lymphoma received autologous peripheral blood stem cell transplantation. The 5-year overall survival and event-free survival rates of rare pediatric NHL excluding PTCL, NOS, and ENKL was 80.0% and 72.0%, respectively.CONCLUSION: Children diagnosed with rare pediatric NHL other than PTCL, NOS, and ENKL showed variable incidence and treatment outcomes. Multicenter studies in larger cohorts are needed for better understanding of these rare NHL subtypes in childhood.
B-Lymphocytes ; Burkitt Lymphoma ; Child ; Chungcheongnam-do ; Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Humans ; Incidence ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, Large-Cell, Anaplastic ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Peripheral ; Peripheral Blood Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; T-Lymphocytes

To determine expression of lactate dehydrogenase (LDH)-5 in non-Hodgkin lymphoma and its clinical significance.
 Methods: LDH-5 levels and LDH levels in NHL patients were examined by agarose gel electrophoresis and enzymatic method (n=63), respectively. Positive rates of LDH-5 and LDH were statistically analyzed.
 Results: The median age of NHL patients was 56(19-84) years old, including 36 males and 27 females. The positive numbers for LDH-5 and LDH in the initial treatment group (n=43) were significantly different (P<0.05). There was significant difference in 22 cases of diffuse large B cell lymphoma and in 9 cases of T cell lymphoma, whereas there was not significant difference in 12 cases of small B cell lymphoma (P>0.05). In 15 cases under the status of progress, the difference of LDH-5 and LDH expressions were not significant (P>0.05), whereas the difference in cases of small B cell lymphoma was significant (P<0.05).
 Conclusion: LDH-5 can be used as an index for NHL to judge the tumor load and to predict the recurrence.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; metabolism ; Female ; Humans ; Isoenzymes ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Lactate Dehydrogenase 5 ; Lymphoma, B-Cell ; genetics ; Lymphoma, Large B-Cell, Diffuse ; genetics ; Lymphoma, Non-Hodgkin ; genetics ; Lymphoma, T-Cell ; genetics ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; genetics ; Prognosis ; Tumor Burden