BACKGROUND T-cell large granular lymphocytic leukemia(T-LGLL)is a rare type of aplastic anemia with diverse clinical manifestations.Concomitant diseases are often present at the first manifestation.We describe the tre...BACKGROUND T-cell large granular lymphocytic leukemia(T-LGLL)is a rare type of aplastic anemia with diverse clinical manifestations.Concomitant diseases are often present at the first manifestation.We describe the treatment of a patient with CD57-negativeγδT-LGLL with pure red cell aplasia(PRCA).CASE SUMMARY A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted.Her condition was diagnosed as CD57-negativeγδT-LGLL with PRCA through bone marrow cytology,bone marrow pathology,bone marrow flow cytometry,bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis,and other tests.Treatment with prednisone,methotrexate,and subcutaneous erythropoietin did not significantly change her hemoglobin level.After treatment with oral cyclophosphamide for 3 mo,her hemoglobin level increased to approximately 100 g/L.After 5 mo of treatment,the patient could perform activities of daily living independently.CONCLUSION The treatment of CD57-negativeγδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.展开更多
Large granular lymphocytic leukemia(LGLL)is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells.Standard first-line immunosuppressive treatments have limitations,achieving complete remissi...Large granular lymphocytic leukemia(LGLL)is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells.Standard first-line immunosuppressive treatments have limitations,achieving complete remission(CR)rates of up to 50%.Immune system dysregulation is implicated in LGLL.Promising results for thalidomide,an immunomodulatory drug,combined with prednisone and methotrexate(TPM),were observed in our pilot study.This multicenter study evaluated the effcacy and safety of a thalidomide,prednisone,and methotrexate(TPM)regimen in 52 symptomatic,methotrexate-and thalidomide-naive LGLL patients from June 2020 to August 2022.Thalidomide(100 mg daily for up to 24 months),prednisone(0.5-1.0 mg/kg every other day,tapered after 3 months),and methotrexate(10 mg/m^(2) weekly for up to 12 months)were administered.The primary objective was to determine the CR rate.The median follow-up duration was 29.0 months(range:4.0-42.0).Forty-seven patients(90.4%)achieved hematological and symptomatic responses.Thirty-nine patients(75.0%)achieved CR.The median time to response was 3.0 months(range:3.0-9.0).The median progression-free survival was 40.0 months(95%confidence interval(Cl):38.0-42.0),and the median duration of response was 39.0 months(95%Cl:36.1-41.9).The most common adverse event was peripheral neuropathy(24.1%),most of which(84.6%)were grades 1-2.Four patients experienced grade≥3 adverse events.In conclusion,the TPM regimen was an effective and safe treatment for symptomatic LGLL patients,with a particularly high CR rate.This trial was registered at www.clinicaltrials.gov(#NCT04453345).展开更多
Large granular lymphocytic leukemia(LGLL)is a relatively uncommon malignancy of the blood system,marked by the clonal expansion of cytotoxic lymphocytes,particularly CD8+T cells(T-LGLL),and in some cases,natural kille...Large granular lymphocytic leukemia(LGLL)is a relatively uncommon malignancy of the blood system,marked by the clonal expansion of cytotoxic lymphocytes,particularly CD8+T cells(T-LGLL),and in some cases,natural killer(NK)cells(NK-LGLL).1 Though rare,LGLL is clinically significant,representing approximately 2%to 6%of all chronic lymphopro-liferative diseases,with a somewhat higher incidence in Asian populations.展开更多
Variants in the solute carrier family 40 member 1(SLC40A1)gene are the molecular basis of ferroportin disease,which is an autosomal dominant hereditary hemochromatosis.Here,we present a patient with pure red cell apla...Variants in the solute carrier family 40 member 1(SLC40A1)gene are the molecular basis of ferroportin disease,which is an autosomal dominant hereditary hemochromatosis.Here,we present a patient with pure red cell aplasia(PRCA)and large granular lymphocytic leukemia(LGLL)associated with an extremely high levels of serum ferritin and iron overload syndrome.Whole exon sequencing revealed a novel heterozygous variant in SLC40A1(p.T419I),which was found in his daughter as well.A series of functional studies in vitro of the T419I variant in ferroportin were conducted and the results revealed a reduced capacity of iron export from cells without changes in protein localization and its sensitivity to hepcidin.Intracellular iron storage in mutated cells was significantly higher than that of wild-type.These findings suggest that the novel variant p.T419I can cause the classical form of ferroportin disease and an elevated intracellular iron level indicates a potential novel pathogenic mechanism underlying PRCA and LGLL.展开更多
基金Supported by Xiamen Medical and Health Guidance Project,No.3502Z20199137Fujian Medical and Health Training Project for Young and Middle-aged Backbone Talents,No.2020GGB068Educational and Scientific Research Program for Young and Middle-Aged Teachers of Fujian Province,No.JAT190838.
文摘BACKGROUND T-cell large granular lymphocytic leukemia(T-LGLL)is a rare type of aplastic anemia with diverse clinical manifestations.Concomitant diseases are often present at the first manifestation.We describe the treatment of a patient with CD57-negativeγδT-LGLL with pure red cell aplasia(PRCA).CASE SUMMARY A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted.Her condition was diagnosed as CD57-negativeγδT-LGLL with PRCA through bone marrow cytology,bone marrow pathology,bone marrow flow cytometry,bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis,and other tests.Treatment with prednisone,methotrexate,and subcutaneous erythropoietin did not significantly change her hemoglobin level.After treatment with oral cyclophosphamide for 3 mo,her hemoglobin level increased to approximately 100 g/L.After 5 mo of treatment,the patient could perform activities of daily living independently.CONCLUSION The treatment of CD57-negativeγδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.
基金supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-12M-C&T-B-081 and 2022-I2M-1-022)the National Nature Science Foundation of China(82170193,82370197,82200215)+1 种基金the Tianjin Health Science and Technology Project(TJWJ2022XK021)the Tianjin Health Research Project(TJSQNYXXR-D2-152).
文摘Large granular lymphocytic leukemia(LGLL)is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells.Standard first-line immunosuppressive treatments have limitations,achieving complete remission(CR)rates of up to 50%.Immune system dysregulation is implicated in LGLL.Promising results for thalidomide,an immunomodulatory drug,combined with prednisone and methotrexate(TPM),were observed in our pilot study.This multicenter study evaluated the effcacy and safety of a thalidomide,prednisone,and methotrexate(TPM)regimen in 52 symptomatic,methotrexate-and thalidomide-naive LGLL patients from June 2020 to August 2022.Thalidomide(100 mg daily for up to 24 months),prednisone(0.5-1.0 mg/kg every other day,tapered after 3 months),and methotrexate(10 mg/m^(2) weekly for up to 12 months)were administered.The primary objective was to determine the CR rate.The median follow-up duration was 29.0 months(range:4.0-42.0).Forty-seven patients(90.4%)achieved hematological and symptomatic responses.Thirty-nine patients(75.0%)achieved CR.The median time to response was 3.0 months(range:3.0-9.0).The median progression-free survival was 40.0 months(95%confidence interval(Cl):38.0-42.0),and the median duration of response was 39.0 months(95%Cl:36.1-41.9).The most common adverse event was peripheral neuropathy(24.1%),most of which(84.6%)were grades 1-2.Four patients experienced grade≥3 adverse events.In conclusion,the TPM regimen was an effective and safe treatment for symptomatic LGLL patients,with a particularly high CR rate.This trial was registered at www.clinicaltrials.gov(#NCT04453345).
文摘Large granular lymphocytic leukemia(LGLL)is a relatively uncommon malignancy of the blood system,marked by the clonal expansion of cytotoxic lymphocytes,particularly CD8+T cells(T-LGLL),and in some cases,natural killer(NK)cells(NK-LGLL).1 Though rare,LGLL is clinically significant,representing approximately 2%to 6%of all chronic lymphopro-liferative diseases,with a somewhat higher incidence in Asian populations.
基金was supported by grants from the National Natural Science Foundation of China under grant numbers 81770119&81700120。
文摘Variants in the solute carrier family 40 member 1(SLC40A1)gene are the molecular basis of ferroportin disease,which is an autosomal dominant hereditary hemochromatosis.Here,we present a patient with pure red cell aplasia(PRCA)and large granular lymphocytic leukemia(LGLL)associated with an extremely high levels of serum ferritin and iron overload syndrome.Whole exon sequencing revealed a novel heterozygous variant in SLC40A1(p.T419I),which was found in his daughter as well.A series of functional studies in vitro of the T419I variant in ferroportin were conducted and the results revealed a reduced capacity of iron export from cells without changes in protein localization and its sensitivity to hepcidin.Intracellular iron storage in mutated cells was significantly higher than that of wild-type.These findings suggest that the novel variant p.T419I can cause the classical form of ferroportin disease and an elevated intracellular iron level indicates a potential novel pathogenic mechanism underlying PRCA and LGLL.
