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Frontiers in Oncology 2021Epstein-Barr virus (EBV)-associated lymph nodal T/NK cell lymphoma (nodal TNKL) is a rare and aggressive malignancy with an extremely poor prognosis. Although treatments...
Epstein-Barr virus (EBV)-associated lymph nodal T/NK cell lymphoma (nodal TNKL) is a rare and aggressive malignancy with an extremely poor prognosis. Although treatments of extranodal NK/T cell lymphoma are frequently reported, the characteristics and pathogenesis of EBV-associated nodal TNKL are different. However, there is no known effective therapy regimen at present. Here, we reported the clinical efficacy and feasibility of the programmed death 1 (PD-1) blockade therapy regimen in an elderly female patient with EBV-associated nodal TNKL. The patient failed to respond to cyclophosphamide, doxorubicin, vindesine, and prednisone regimen but achieved complete response after three cycles of anti-PD-1 antibody (tislelizumab) combined with gemcitabine and oxaliplatin (GemOx) regimen. The finding indicated that tislelizumab combined with the GemOx regimen may be a potent salvage regimen for EBV-associated nodal TNKL.
PubMed: 34277451
DOI: 10.3389/fonc.2021.706865 -
Frontiers in Pediatrics 2021To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG). Clinical data of children with JXG who...
To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG). Clinical data of children with JXG who were hospitalized in Beijing Children's Hospital, Capital Medical University, from January 2012 to December 2019 were retrospectively analyzed, including clinical manifestations, laboratory determinations, treatment, and prognosis of the children. Patients were treated with vindesine + prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone ± cladribine as the second-line treatment. Ten patients, including 8 males and 2 females, with a median of onset age of 1.95 (0.80-7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30-12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 29 (3-115) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. At the end of follow-up, 7 patients were in active disease (AD)/regression state (AD-better), and 2 patients were in an AD/stable state (AD-stable). Three patients had permanent sequelae, mainly central diabetes insipidus. The rates of response to the first-line treatment and the second-line treatment were 40.0 and 66.7% respectively. The chemotherapy protocol for Langerhans cell histiocytosis (LCH) may be effective for patients with systemic JXG. Central nervous system involvement may not impact overall survival, but serious permanent sequelae may occur.
PubMed: 34178890
DOI: 10.3389/fped.2021.672547 -
Medicine Jun 2021To investigate the relationship between the changes in circulating CD45RO+T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally...
To investigate the relationship between the changes in circulating CD45RO+T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO+T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO+ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO+ratio.Circulating CD45RO+ratio of 1.07 was determined as the optimal cut-off point and CD45RO+ratio-high was associated with lower tumor regression grade grading (P = .031), T stage (P = .001), and tumor node metastasis (TNM) stage (P = .012). The 3-year DFS and OS rate in the CD45RO+ratio-high group was significantly higher than that in the CD45RO+ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO+ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153-0.752; P = .008) and OS (OR, 0.244; 95% CI,0.082-0.726; P = .011).Circulating CD45RO+ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Separation; Chemoradiotherapy, Adjuvant; Colonoscopy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Flow Cytometry; Follow-Up Studies; Humans; Leukocyte Common Antigens; Lymphocyte Count; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxaliplatin; Prednisone; Preoperative Period; Proctectomy; Prognosis; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Rectum; Retrospective Studies; Survival Rate; T-Lymphocyte Subsets; Vindesine
PubMed: 34160385
DOI: 10.1097/MD.0000000000026214 -
Frontiers in Oncology 2021Although pegylated liposomal doxorubicin (PLD) has been approved in combination with bortezomib for relapsed/refractory multiple myeloma (MM), the antitumor efficacy and...
Pegylated Liposomal Doxorubicin in Vindesine-Based and Bortezomib-Based Regimens for Patients With Newly Diagnosed Multiple Myeloma: A Retrospective Study of Efficacy and Safety.
PURPOSE
Although pegylated liposomal doxorubicin (PLD) has been approved in combination with bortezomib for relapsed/refractory multiple myeloma (MM), the antitumor efficacy and tolerability of PLD in different regimens for patients with newly diagnosed MM (NDMM) have not been fully defined.
METHODS
A total of 249 NDMM patients diagnosed between January 2008 and October 2019 were included in this retrospective study. Among them, 112 patients received vindesine-based chemotherapy (35 vDD and 77 vAD) and 137 received bortezomib-based chemotherapy (58 VDD and 79 VD).
RESULTS
In bortezomib-containing regimens, the complete response rate (48.3 30.4%, p = 0.033) and very good partial response or better rate (74.1 . 57.0%, p = 0.038) of VDD were significantly higher than those of VD subgroup. While no superior survival was found between VDD and VD subgroup. In vindesine-containing regimens, no statistical significance was identified between vDD and vAD in terms of response rate and survival. The occurrence rates of all cardiac AEs were similar between VDD and VD.
CONCLUSIONS
The vDD regimen was similar with vAD in the aspect of response rate, survival, and toxicity in NDMM patients. The addition of PLD to VD brought deeper response without increased toxicity, while no superior survival was found.
PubMed: 33842312
DOI: 10.3389/fonc.2021.597453 -
JAMA Oncology Jun 2021Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial.
IMPORTANCE
Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer.
OBJECTIVE
To evaluate survival and late toxic effects 10 years after patients were treated with curative CRT.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, phase 3 West Japan Thoracic Oncology Group (WJTOG) 0105 randomized clinical trial was conducted between September 2001 and September 2005 in Japan. Patients with histologically or cytologically confirmed non-small-cell lung cancer with unresectable stage III disease were assessed for eligibility. Additional data were analyzed from January 2018 to December 2019.
INTERVENTIONS
A total of 440 eligible patients were randomly assigned to groups as follows: A (control), 4 cycles of mitomycin/vindesine/cisplatin plus thoracic radiotherapy (TRT) of 60 Gy; B, weekly irinotecan/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of irinotecan/carboplatin consolidation; or C, weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of paclitaxel/carboplatin consolidation.
MAIN OUTCOMES AND MEASURES
The primary outcome was 10-year survival probability after CRT. The secondary outcome was late toxic effects that occurred more than 90 days after initiating CRT.
RESULTS
From September 2001 to September 2005, 440 patients (group A, n = 146 [33.2%; median (range) age, 63 (31-74) years; 18 women (12.3%)]; group B, n = 147 [33.4%; median (range) age, 63 (30-75) years; 22 women (15.0%)]; group C, n = 147 [33.4%; median (range) age, 63 (38-74) years; 19 women (12.9%)]) were enrolled. The median (range) follow-up was 11.9 (7.6-13.3) years. In groups A, B, and C, median (range) overall survival times were 20.5 (17.5-26.0), 19.8 (16.7-23.5), and 22.0 (18.7-26.2) months, respectively, and 10-year survival probabilities were 13.6%, 7.5%, and 15.2%, respectively. There were no significant differences in overall survival among treatment groups. The 10-year progression-free survival probabilities were 8.5%, 6.5%, and 11.1% in groups A, B, and C, respectively. Grade 3 or 4 late toxic effect rates were 3.4% (heart, 0.7%; lung, 2.7%) in group A, and those only affecting the lung represented 3.4% and 4.1% in groups B and C, respectively. No other cases of late toxic effects (grades 3/4) were observed since the initial report.
CONCLUSION AND RELEVANCE
In this 10-year follow-up of a phase 3 randomized clinical trial, group C achieved similar efficacy and toxic effect profiles as group A 10 years after initiating treatment. These results serve as a historical control for the long-term comparisons of outcomes of future clinical trials of CRT.
TRIAL REGISTRATION
UMIN Clinical Trial Registry: UMIN000030811.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Female; Follow-Up Studies; Humans; Lung Neoplasms; Neoplasm Staging; Paclitaxel
PubMed: 33734289
DOI: 10.1001/jamaoncol.2021.0113 -
Annals of Hematology Apr 2021High-dose methotrexate (HD-MTX) at 3 g/m is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas,...
High-dose methotrexate (HD-MTX) at 3 g/m is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.
Topics: Adolescent; Adult; Ambulatory Care; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Doxorubicin; Female; Hematologic Diseases; Humans; Infusions, Intravenous; Kidney Diseases; Kidney Function Tests; Leucovorin; Liver Function Tests; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasm Invasiveness; Outpatient Clinics, Hospital; Prednisone; Retrospective Studies; Rituximab; Vincristine; Vindesine; Young Adult
PubMed: 33608849
DOI: 10.1007/s00277-020-04341-7 -
Oncology Reports Mar 2021Non‑Hodgkin lymphoma (NHL) is a form of lymphoid malignancy, with diffuse large B cell lymphoma (DLBCL) being the most common NHL isoform. Approximately half of... (Observational Study)
Observational Study
Non‑Hodgkin lymphoma (NHL) is a form of lymphoid malignancy, with diffuse large B cell lymphoma (DLBCL) being the most common NHL isoform. Approximately half of patients with DLBCL are successfully cured via first‑line Rituximab, Cyclophosphamide, Epirubicin, Vindesine, Prednisolone (R‑CHOP) treatment. However, 30‑40% of patients with DLBCL ultimately suffer from treatment‑refractory or relapsed disease. These patients often suffer from high mortality rates owing to a lack of suitable therapeutic options, and all patients are at a high risk of serious treatment‑associated dose‑dependent toxicity. As such, it is essential to develop novel treatments for NHL that are less toxic and more efficacious. Oncolytic Vaccinia virus (OVV) has shown promise as a means of treating numerous types of cancer. Gene therapy strategies further enhance OVV‑based therapy by improving tumor cell recognition and immune evasion. Beclin1 is an autophagy‑associated gene that, when upregulated, induces excess autophagy and cell death. The present study aimed to develop an OVV‑Beclin1 therapy capable of inducing autophagic tumor cell death. OVV‑Beclin1 was able to efficiently kill NHL cells and to increase the sensitivity of these cells to R‑CHOP, thereby decreasing the dose‑dependent toxic side effects associated with this chemotherapeutic regimen. The combination of OVV‑Beclin1 and R‑CHOP also significantly improved tumor growth inhibition and survival in a BALB/c murine model system owing to the synergistic induction of autophagic cell death. Together, these findings suggest that OVV‑Beclin1 infection can induce significant autophagic cell death in NHL, highlighting this as a novel means of inducing tumor cell death via a mechanism that is distinct from apoptosis and necrosis.
Topics: Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; Autophagic Cell Death; Beclin-1; Biopsy; Cell Line, Tumor; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Genetic Engineering; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Mice; Middle Aged; Oncolytic Virotherapy; Oncolytic Viruses; Prednisone; Rituximab; Tumor Escape; Vaccinia virus; Vincristine; Vindesine; Xenograft Model Antitumor Assays
PubMed: 33469679
DOI: 10.3892/or.2021.7942 -
Frontiers in Immunology 2020CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of...
Case Report: Humanized Selective CD19CAR-T Treatment Induces MRD-Negative Remission in a Pediatric B-ALL Patient With Primary Resistance to Murine-Based CD19CAR-T Therapy.
BACKGROUND
CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10-20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem.
CASE DESCRIPTION
A 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020.
CONCLUSION
CD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cytokine Release Syndrome; Cytokines; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Male; Mice; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Chimeric Antigen; Remission Induction; Salvage Therapy
PubMed: 33424835
DOI: 10.3389/fimmu.2020.581116 -
Medicine Dec 2020The rarity of adult T cell leukemia/lymphoma (ATLL) in China, coupled with its clinicopathologic mimicry of primary skin disease, poses a diagnostic challenge. The...
RATIONALE
The rarity of adult T cell leukemia/lymphoma (ATLL) in China, coupled with its clinicopathologic mimicry of primary skin disease, poses a diagnostic challenge. The method of diagnosis and mechanism of immune regulation in ATLL are discussed in the present report.
PATIENT CONCERNS
A 51-year-old Chinese man was admitted to the hospital with 2-years history of systemic plaque lesions and 1-year history of left ankle joint pain.
DIAGNOSES
The patient was diagnosed with ATLL based on the results of flow cytometry immunophenotype and human T-cell lymphotropic virus type 1 (HTLV-1) serology.
INTERVENTIONS
The patient received 3 cycles of cyclophosphamide, epirubicin/ vinorelbine, and dexamethasone (CHOP) chemotherapy. However, he relapsed and did not respond to epirubicin, vindesine, etoposide, dexamethasone (EPOCH) chemotherapy.
OUTCOMES
His family discontinued the treatment and opted for hospice care.
LESSONS
Patch and plaque ATLL types exhibits a better survival rate, but atypical skin patches delays the diagnosis of ATLL and negatively affects the patient survival. Based on the present findings, we suggest that patients with petal-like nuclear lymphocytes in blood smears, a high CD4: CD8 ratio, and strong CD25 expression should undergo HTLV-1 serology testing.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Etoposide; Flow Cytometry; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Prednisolone; Prednisone; Skin Diseases; Vincristine
PubMed: 33327284
DOI: 10.1097/MD.0000000000023491 -
Blood Apr 2021Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab....
Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2-/PET4-) received immunochemotherapy. Responders after only cycle 4 (PET2+/4-) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2-/4- and PET2+/4- had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Positron-Emission Tomography; Prednisone; Rituximab; Vincristine
PubMed: 33211799
DOI: 10.1182/blood.2020008750