OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL). METHODS: The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively. RESULTS: Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×10⁹ /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 ⁺ CD4^- CD8 ⁺), 6 cases were CD57 ⁺, 3 cases were TCRα/β ⁺, and 3 cases were TCRγ/δ ⁺. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving. CONCLUSION The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Male ; Middle Aged ; Female ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; Retrospective Studies

Humans ; Anemia, Aplastic ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Immunophenotyping

OBJECTIVETo analyze the clinical manifestations and laboratory features of patients with T large granular lymphocytic leukemia (T-LGLL), so as to improve the understanding of this disease.

METHODSThe clinical data of 10 patients with T-LGLL in General Hospital of Chinese PLA from October 2015 to March 2010 were analyzed retrospectively.

RESULTSTheir median age at diagnosis was 51 years old. 9/10 (90%) patients showed symptoms of anemia, with a median Hb level of 82.5 g/L, 5/10 (50%) patients combined with autoimmune disorders and with a median Hb level of 77 g/L. 7/10 (70%) patients had splenomegaly, 2/10 (20%) patients had complex karyotype, 2/10 (20%) patients had gene mutations, the median age of 4 patients with complex karyotype and gene mutation was 49 years old, all of them suffered from splenomegaly. The immunophenotype of 6/10 patients was CD3+ CD4- CD8+ and that of 2/10 patients (20%) was CD3+ CD4- CD8-, that of another 2/10 (20%) was CD3+ CD4+ CD8-, the clinical features between different types of immunization were not statistically different.

CONCLUSIONT-LGLL patients often are old men, combined with anemia and splenomegaly, often associated with autoimmune diseases; the patients with complex karyotype and gene mutation are younger and they are more with hepatosplenomegaly; the guide role of different immunotypes for clinical strategy is no significant.

Anemia ; pathology ; Autoimmune Diseases ; pathology ; Chromosome Aberrations ; Hemoglobins ; analysis ; Humans ; Immunophenotyping ; Leukemia, Large Granular Lymphocytic ; diagnosis ; pathology ; Middle Aged ; Retrospective Studies ; Spleen ; pathology

OBJECTIVEPresenting the clinical features of one patient with CD4⁺/CD8⁻ T-cell large granular lymphocytic leukemia, to improve the understanding of the disease.

METHODSClinical data of one patient hospitalized for skin rush and leukocytosis were analyzed, and the related literatures were reviewed.

RESULTSThe patient was hospitalized for skin rush and leukocytosis. Routine blood test showed remarkable elevated white blood cell counts and mild anemia. Subsequent hematological examination led to a diagnosis of T- cell large granular lymphocytic leukemia with CD4⁺/CD8⁻ immunophenontype.

CONCLUSIONCD3⁺/CD4⁺/CD8⁻ T- cell large granular lymphocytic leukemia is a kind of variant subtype, and is relatively rare, it has different clinical features with classic CD3⁺/CD4⁻/CD8⁺/TCRαβ⁺T- cell large granular lymphocytic leukemia, so differentiating diagnosis is of great importance.

Anemia ; Humans ; Immunophenotyping ; Leukemia, Large Granular Lymphocytic ; classification ; diagnosis

Large granular lymphocytic (LGL) leukaemia is an uncommon clonal lymphoproliferative disorder. The WHO classification recognizes three distinct disorders of LGLs: T-cell large granular lymphocytic leukaemia (T-LGL), chronic lymphoproliferative disorders of NK-cells (CLPD-NK) and aggressive NK-cell leukaemia. Despite the different origin of cells, there is considerable overlap between T-LGL and CLPD-NK in terms of clinical presentation and treatment. Majority of these patients are asymptomatic and may not need treatment. When significant cytopenias occur, the application of immunosuppressive therapy often should be considered. In contrast, aggressive NK cell leukemia and the rare CD56(+) aggressive T-LGL leukemia have a fulminant clinical course and an earlier age of onset, therefore, more intensive combination chemotherapy is required, followed by allogeneic hematopoietic stem cell transplantation. However, these diseases are relatively rare, there are few clinical trials to guide management. In this review, the pathogenesis, diagnosis, treatment and prognosis of this leukemia are summarized and discussed.
Humans ; Leukemia, Large Granular Lymphocytic ; classification ; diagnosis ; pathology ; therapy

In order to improve the recognition of myeloid/natural killer cell acute leukemia and to reduce misdiagnosis, one case of myeloid/natural killer cell acute leukemia resembling acute promyelocytic leukemia(APL) was reported and the related articles published were reviewed. A series of clinical tests, the morphologic and immunophenotypic analysis of leukemia cells, cytogenetic and molecular biological examinations were performed. The results indicated that the patient had anemia, thrombocytopenia and leucocytosis, but no evidence of lymphadenopathy and hepatosplenomegaly. The morphology of leukemia cells was similar to that of abnormal promyelocytic cells, especially the variant of M3 (M3v) leukemia cells. The leukemia cells expressed CD117, CD33, CD15, CD56 and cMPO, but did not express CD34, HLA-DR, CD13 and CD16. Abnormal cytogenetics with del (7) (q22q32) was found. Neither t(15;17) nor PML/RARα gene rearrangement was detected. The patient failed to show a differentiation-induction response to all-trans retinoic acid(ATRA). In conclusion, the myeloid/natural killer cell leukemia is extremely rare. It is very important to distinguish the disorder from APL/M3v. The patient with myeloid/natural kill cell acute leukemia should be treated with chemotherapy as acute myeloid leukemia.
Aged, 80 and over ; Female ; Humans ; Leukemia, Large Granular Lymphocytic ; diagnosis ; Leukemia, Promyelocytic, Acute ; diagnosis ; etiology

We report here a case of a 59-yr-old man with CD4+ T-cell large granular lymphocytic leukemia (T-LGL). Peripheral blood examination indicated leukocytosis (45x10(9) cells/L) that consisted of 34% neoplastic lymphoid cells. Other laboratory results indicated no specific abnormalities except for serum antinuclear antibody titer (1:640), glucose (1.39 g/L), and hemoglobin A1c (7.7%) levels. Computed tomography indicated multiple small enlarged lymph nodes (<1 cm in diameter) in both the axillary and inguinal areas, a cutaneous nodule (1.5 cm in diameter) in the left suboccipital area, and mild hepatosplenomegaly. Bone marrow examination revealed hypercellular marrow that consisted of 2.4% neoplastic lymphoid cells. The neoplastic lymphoid cells exhibited a medium size, irregularly shaped nuclei, a moderate amount of cytoplasm, and large granules in the cytoplasm. Immunohistochemical analysis indicated CD3+, CD4+, T-cell receptor betaF1+, granzyme B+, and TIA1+. Flow cytometric analysis of the neoplastic lymphoid cells revealed CD3+, cytoplasmic CD3+, CD4+, and CD7+. Cytogenetic analysis indicated an abnormal karyotype of 46,XY,inv(3)(p21q27),t(12;17)(q24.1;q21),del(13)(q14q22)[2]/46,XY[28]. The patient was diagnosed with CD4+ T-LGL and received chemotherapy (10.0 mg methotrexate). This is the second case of CD4+ T-LGL that has been reported in Korea.
Antibodies, Antinuclear/analysis ; Blood Glucose/analysis ; Bone Marrow Cells/metabolism/pathology ; Hemoglobin A, Glycosylated/metabolism ; Humans ; Immunohistochemistry ; Immunophenotyping ; Karyotyping ; Leukemia, Large Granular Lymphocytic/*diagnosis/pathology/radiography ; Lymph Nodes/pathology ; Male ; Middle Aged ; Neoplastic Cells, Circulating/metabolism/pathology ; Tomography, X-Ray Computed

We report here a case of a 59-yr-old man with CD4+ T-cell large granular lymphocytic leukemia (T-LGL). Peripheral blood examination indicated leukocytosis (45x10(9) cells/L) that consisted of 34% neoplastic lymphoid cells. Other laboratory results indicated no specific abnormalities except for serum antinuclear antibody titer (1:640), glucose (1.39 g/L), and hemoglobin A1c (7.7%) levels. Computed tomography indicated multiple small enlarged lymph nodes (<1 cm in diameter) in both the axillary and inguinal areas, a cutaneous nodule (1.5 cm in diameter) in the left suboccipital area, and mild hepatosplenomegaly. Bone marrow examination revealed hypercellular marrow that consisted of 2.4% neoplastic lymphoid cells. The neoplastic lymphoid cells exhibited a medium size, irregularly shaped nuclei, a moderate amount of cytoplasm, and large granules in the cytoplasm. Immunohistochemical analysis indicated CD3+, CD4+, T-cell receptor betaF1+, granzyme B+, and TIA1+. Flow cytometric analysis of the neoplastic lymphoid cells revealed CD3+, cytoplasmic CD3+, CD4+, and CD7+. Cytogenetic analysis indicated an abnormal karyotype of 46,XY,inv(3)(p21q27),t(12;17)(q24.1;q21),del(13)(q14q22)[2]/46,XY[28]. The patient was diagnosed with CD4+ T-LGL and received chemotherapy (10.0 mg methotrexate). This is the second case of CD4+ T-LGL that has been reported in Korea.
Antibodies, Antinuclear/analysis ; Blood Glucose/analysis ; Bone Marrow Cells/metabolism/pathology ; Hemoglobin A, Glycosylated/metabolism ; Humans ; Immunohistochemistry ; Immunophenotyping ; Karyotyping ; Leukemia, Large Granular Lymphocytic/*diagnosis/pathology/radiography ; Lymph Nodes/pathology ; Male ; Middle Aged ; Neoplastic Cells, Circulating/metabolism/pathology ; Tomography, X-Ray Computed

OBJECTIVETo explore the hematopathologic features of T-cell large granular lymphocytic leukemia (T-LGLL).

METHODSA retrospective analysis of the clinical presentation, bone marrow morphology, immunophenotyping and T-cell receptor gene rearrangement status were performed in 19 patients with T-LGLL.

RESULTSOf 19 patients, the most frequent hematological abnormalities were anemia and neutropenia (16/19 and 17/19 patients, respectively). Large granular lymphocytes (LGLs) were observed in 17 of 19 peripheral blood smears and 15 of 19 bone marrow aspirate specimens. Lymphocytosis (> 0.2) was present in 17 of 19 patients in their bone marrow aspirate specimens. Bone marrow biopsy specimens revealed lymphocytosis in 16 cases, with a mild to moderate increase of lymphocytes observed in 12 cases (12/16). The pattern of lymphoid distribution was interstitial in bone marrow sections. Intravascular distribution was seen in 8 cases. Lymphoid nodules were present in 4 cases. Flow cytometery showed an immunophenotype of CD3(+) CD4(-) CD8(+) CD56(-) CD57(+) of the tumor cells in 13 cases. Of the other 6 cases, the immunophenotypes included CD8(-) (1 case), CD56(+) (2 cases) and CD57(-) (3 cases). Immunohistochemistry showed CD3+ (10/10), CD57+ (3/3), CD8+ (6/7), TIA-1+ (6/7), granzyme B+ (4/7), perforin + (1/7), CD4- (4/4) and CD56- (9/9). Clonal T-cell receptor γ gene rearrangement by PCR was detected in 12 cases (12/17).

CONCLUSIONSHematopathologic features of most T-LGLL are distinct. Morphologic, immunophenotypic and molecular analysis of both peripheral blood and bone marrow specimens are essential and complementary in the diagnosis and differential diagnosis of T-LGLL.

Adult ; Aged ; Anemia ; metabolism ; pathology ; Bone Marrow ; pathology ; CD3 Complex ; metabolism ; CD57 Antigens ; metabolism ; CD8 Antigens ; metabolism ; Diagnosis, Differential ; Female ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Granzymes ; metabolism ; Humans ; Immunophenotyping ; Leukemia, Large Granular Lymphocytic ; metabolism ; pathology ; Lymphocytosis ; metabolism ; pathology ; Male ; Middle Aged ; Neutropenia ; metabolism ; pathology ; Poly(A)-Binding Proteins ; metabolism ; Retrospective Studies ; T-Cell Intracellular Antigen-1

This study was aimed to investigate the immunogenetic diagnosis of large granular lymphocytic leukemia (LGLL) and therapeutic efficacy of sirolimus, and to analysis 256 cases of LGLL reported at home and abroad within 2000 - 2010. Besides the routine examination of peripheral blood and classification of bone marrow cell morphology, the expression of T cell receptor variable region of β-chain (TCR BV), CD3, CD4 and CD8, as well as TCRαβ, TCRγδ were detected by flow cytometry; the RT-PCR was used to amplify and determine the TCR gene spectrotypes, and to analyze the clonality of abnormal cells. Sirolimus was first given to patients who did not gain efficacy from common agents. The results showed that lymphocytosis happened in all LGLL patients, but patients from West countries always displayed neutropenia while Chinese patients always displayed anemia. In 2 out of 4 patients from our hospital, the large granular lymphocytes (LGL) were difficult to be distinguished. In all 4 patients, almost all lymphocytes were CD3(+), CD8(+), and TCRα/β(+). TCR BV 24 gene family clones showed monoclonal TRBV 23, TRBV 20, TRBV 13.6, and TRBV 13.6, respectively. FCM results were consistent with those of RT-PCR. When 4 patients had been given sirolimus (6 mg first dose, 2 mg once a day) for about 1 week, hemoglobin level and reticulocyte count increased significantly without any serious side effects. It is concluded that the detection of specific lymphocyte monoclonal TCR BV 24 gene family by FCM contributes to the diagnosis of LGLL. Sirolimus is an effective agent without serious side effect for LGLL patients, especially for patients who cannot tolerate common drugs.
Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Immunogenetics ; Leukemia, Large Granular Lymphocytic ; diagnosis ; drug therapy ; Male ; Middle Aged ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; Receptors, Antigen, T-Cell, gamma-delta ; genetics ; Sirolimus ; therapeutic use ; Treatment Outcome