ABSTRACT
Cellular immunotherapy with chimeric antigen receptor (CAR) T-cells has revolutionized the treatment of lymphoid malignancies. This review addresses the need for CAR expression in our endogenous T-cells to kill tumor cells with a focus on the basic principles of T-cell receptor recognition of major histocompatibility complex-peptide complexes.We review the factors associated with CAR T-cell outcomes and recent efforts to employ CAR T-cells in earlier lines of therapy. We also discuss the value of bispecific T-cell engagers as off-the-shelf products with better toxicity profiles. Finally, natural killer cells are discussed as an important cellular immunotherapy platform with the potential to broaden immunotherapeutic applications beyond lymphoid malignancies.
ABSTRACT
Purpose@#Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24. @*Materials and Methods@#Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24. @*Results@#Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001). @*Conclusion@#Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.
ABSTRACT
Background/Aims@#Although the use of surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is discouraged in patients with diffuse large B-cell lymphoma, its usefulness in different subtypes has not been thoroughly investigated. @*Methods@#We retrospectively evaluated 157 patients who showed positive results on surveillance FDG-PET/CT every 6 months following complete response for up to 5 years. All of the patients also underwent biopsies. @*Results@#Seventy-eight (49.6%) of 157 patients had true positive results; the remaining 79 (50.3%), including eight (5.1%) with secondary malignancies, were confirmed to yield false positive results. Among the 78 patients with true positive results, the disease in seven (8.9%) had transformed to a different subtype. The positive predictive value (PPV) of FDG-PET/CT for aggressive B-cell non-Hodgkin’s lymphoma (NHL) was lower than that for indolent B-cell or aggressive T-cell NHL (p = 0.003 and p = 0.018, respectively), especially in patients with a low/low-intermediate international prognostic index (IPI) upon a positive PET/CT finding. On the other hand, indolent B-cell and aggressive T-cell NHL patients showed PPVs of > 60%, including those with low/low-intermediate secondary IPIs. @*Conclusions@#The role of FDG-PET/CT surveillance is limited, and differs according to the lymphoma subtype. FDG-PET/CT may be useful in detecting early relapse in patients with aggressive T-cell NHL, including those with low/low-intermediate risk secondary IPI; as already known, FDG-PET/CT has no role in aggressive B-cell NHL. Repeat biopsy should be performed to discriminate relapse or transformation from false positive findings in patients with positive surveillance FDG-PET/CT results.
ABSTRACT
PURPOSE: Although hepatitis B surface antigen (HBsAg)–negative, hepatitis B core antibody (anti-HBc)–negative patients are not considered to be at risk for hepatitis B virus (HBV)–related hepatitis, the actual risk remains to be elucidated. This study aimed to evaluate the risk of HBV-related hepatitis in HBsAg-negative, anti-HBc–negative patients receiving autologous stem cell transplantation (ASCT) for multiple myeloma (MM) or malignant lymphoma. MATERIALS AND METHODS: We retrospectively reviewed data from 271 HBsAg-negative patients (161 anti-HBc–negative and 110 anti-HBc–positive at the time of ASCT) who received ASCT for MM or lymphoma. The risk of HBV-related hepatitis was analyzed according to the presence of anti-HBc. HBV serology results at the time of ASCT were compared with those at the time of diagnosis of MM or lymphoma. RESULTS: Three patients (two anti-HBc–negative MMs and one anti-HBc–positive MM) developed HBV-related hepatitis after ASCT. The rate of HBV-related hepatitis did not differ among patients with or without anti-HBc status (p=0.843). HBV-related hepatitis more frequently occurred in MM patients than in lymphoma patients (p=0.041). Overall, 9.1% of patients (16.7% with MM and 5.4% with lymphoma) who were HBsAg–negative and anti-HBc–positive at the time of diagnosis had lost anti-HBc positivity during chemotherapy prior to ASCT. CONCLUSION: Our data suggest that HBsAg-negative, anti-HBc–negative patients at the time of ASCT for MM or lymphoma still might be at a risk for HBV-related hepatitis.
Subject(s)
Humans , Diagnosis , Drug Therapy , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B , Hepatitis , Lymphoma , Multiple Myeloma , Retrospective Studies , Stem Cell Transplantation , Stem CellsABSTRACT
BACKGROUND: Isolated myeloid sarcoma (MS) is a rare extramedullary tumor mass composed of malignant myeloid precursor cells without any evidence of leukemia in the peripheral blood and bone marrow. We describe the clinical characteristics and outcomes of patients diagnosed with isolated MS at our institution. METHODS: We retrospectively reviewed 9 of 497 acute myeloid leukemia (AML) patients (1.8%) with isolated MS. Isolated MS patients were divided into 2 groups according to the first-line treatment strategy: systemic treatment only (S) or local treatment with or without systemic treatment (LS). RESULTS: The most common site of MS occurrence was the head and neck area (N=4, 44.4%), followed by the anterior mediastinum (N=2, 22.2%) and the gastrointestinal tract (N=2, 22.2%). The tumors of 4 patients (44.4%) eventually evolved to AML, in a median time of 13.4 months (range, 2.4–20.1 mo). The number of patients achieving complete remission after first-line treatment was higher in the LS group (N=5, 83.3%) than in the S group (N=1, 33.3%) (P =0.226). All patients in the LS group survived, but those in the S group died (P=0.012). CONCLUSION: Accurate and rapid diagnosis using various modalities and the early initiation of intensive combined treatment may be the optimal strategies to reduce the risk of isolated MS subsequently evolving to AML. To fully understand the characteristics of isolated MS, a larger number of patients from a multinational study is necessary.
Subject(s)
Humans , Bone Marrow , Diagnosis , Gastrointestinal Tract , Head , Leukemia , Leukemia, Myeloid, Acute , Mediastinum , Neck , Retrospective Studies , Sarcoma, MyeloidABSTRACT
PURPOSE: Doxorubicin/cyclophosphamide followed by docetaxel chemotherapy (AC-D) is an intermediate risk factor (incidence of 10%–20%) for febrile neutropenia (FN) in breast cancer. However, the reported incidence of FN while using this regimen was obtained mostly from Western breast cancer patients, with little data available from Asian patients. This study aimed to assess the incidence of FN in Korean breast cancer patients and to describe clinical variables related to FN. METHODS: From September 2010 to February 2013, data from the Yonsei Cancer Center registry of breast cancer patients who received neoadjuvant or adjuvant chemotherapy with four cycles of AC-D (60 mg/m2 doxorubicin, 600 mg/m2 cyclophosphamide every 3 weeks for four cycles followed by 75 mg/m2 or 100 mg/m2 docetaxel every 3 weeks for four cycles) were analyzed. The incidence of FN, FN associated complications, dose reduction/delays, and relative dose intensity (RDI) were investigated. RESULTS: Among the 254 patients reported to the registry, the FN incidence after AC-D chemotherapy was 29.5% (75/254), consisting of 25.2% (64/254) events during AC and 4.7% (12/254) during docetaxel chemotherapy. Dose reductions, delays, and RDI less than 85.0% during AC were observed in 16.5% (42/254), 19.5% (47/254), and 11.0% (28/254) of patients, respectively. Patients with FN events frequently experienced dose reduction/delays, which eventually led to a decreased RDI. CONCLUSION: The incidence of FN during AC-D neoadjuvant or adjuvant chemotherapy was higher than expected in Korean breast cancer patients. Whether these patients should be classified as a high-risk group for FN warrants future prospective studies.
Subject(s)
Female , Humans , Asian People , Breast Neoplasms , Breast , Chemotherapy, Adjuvant , Chemotherapy-Induced Febrile Neutropenia , Cyclophosphamide , Doxorubicin , Drug Therapy , Febrile Neutropenia , Incidence , Prospective Studies , Risk FactorsABSTRACT
The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bacterial Infections/complications , Bortezomib/administration & dosage , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Lymphocyte Count , Lymphopenia/therapy , Multiple Myeloma/complications , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Stem Cell Transplantation , Survival Rate , Transplantation, HomologousABSTRACT
A 60-year-old man visited the hospital after experiencing dyspnea after exertion for 2 weeks. An electrocardiogram showed sinus arrest with junctional escape rhythm at 40 beats/min. Transthoracic echocardiography showed that the right ventricular systolic pressure (RVSP) was approximately 71 mmHg and that the left ventricular ejection fraction was preserved. The ratio of peak early diastolic transmitral inflow velocity to early diastolic peak mitral annular velocity (E/E') was 29. Cardiac catheterization revealed a systolic pulmonary artery pressure (SPAP) of 63 mmHg, a mean pulmonary artery pressure of 27 mmHg, and a pulmonary capillary wedge pressure of 22 mmHg with a rhythm of 40 beats/min. The patient was diagnosed with pulmonary hypertension (group 2) due to sick sinus syndrome. SPAP decreased to 48 mmHg during atrial pacing at 60 beats/min. After permanent pacemaker insertion, RVSP decreased from 71 mmHg to 44 mmHg. In this case, passive group 2 pulmonary hypertension occurred due to sick sinus syndrome.
Subject(s)
Humans , Middle Aged , Blood Pressure , Cardiac Catheterization , Cardiac Catheters , Dyspnea , Echocardiography , Electrocardiography , Hypertension, Pulmonary , Pulmonary Artery , Pulmonary Wedge Pressure , Sick Sinus Syndrome , Stroke Volume , United NationsABSTRACT
Pacemaker lead endocarditis is treated with total removal of the infected device and proper antibiotics. The outcomes of patients undergoing percutaneous lead extraction for large vegetations (>2 cm) have not yet been shown. In this case report, we present two patients with pacemaker lead endocarditis with large vegetations of maximum diameter 2.4 cm and 3.2 cm. The first patient had multiple vegetations attached to the tricuspid and mitral valves and developed septic emboli to the brain, lung, and liver. The second patient had a large, persistent vegetation on the tricuspid valve, even two weeks after complete removal of the leads. Both patients were successfully treated with transvenous pacemaker lead removal and antibiotics.