Clinical Characteristics of Aggressive NK-Cell Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore and summarize the clinical characteristics and treatment of aggressive NK-cell leukemia (ANKL), and provide new insights for clinical diagnosis and treatment of this disease.@*METHODS@#The clinical data of 7 patients with ANKL admitted to the First Affiliated Hospital of Wannan Medical College from March 2014 to July 2021 were retrospectively analyzed, and their clinical characteristics, laboratory and imaging results, treatment and outcomes were analyzed.@*RESULTS@#Among the 7 patients, 5 were males and 2 were females, with a median age of 47 (33-69) years old. The morphology of bone marrow cells in 7 patients showed similar large granular lymphocytes. Immunophenotyping revealed abnormal NK cells in 5 cases. By the end of follow-up, 6 cases died and 1 case survived, with a median survival time of 76.9 (4-347) days.@*CONCLUSION@#ANKL is a rare disease with short course and poor prognosis. If combined with hemophagocytic syndrome (HPS), the prognosis is even worse. There is no unified treatment method at present, and the use of PD-1 inhibitors may prolong the survival in some patients.

Clinical and Pathological Characteristics of Aggressive Natural Killer Cell Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinicopathologic characteristics, diagnosis and therapy of aggressive natural killer cell leukemia (ANKL) patients.@*METHODS@#Clinical manifestations, cellular morphology, immunophenotypic analysis by flow cytometry (FCM), TCR gene rearrangement, pathology and Immunohistochemical analysis of bone marrow (BM) were combined to diagnose the six patients with ANKL.@*RESULTS@#The median age of the patients were 35.5 years old. All the patients with fever, cytopenia and liver dysfunction. Imageological examination presented hepatosplenomegaly (6/6), and PET/CT presented diffusely increased metabolism in liver, spleen and BM (3/3). BM cytologic examination presented increased hematophagocyte at the early stage and 1%-42% leukemic cell were detected in BM with the progression of diseases. FCM showed the leukemic cells were positive for CD2(6/6), CD56(5/6), CD16(2/6), CD94(3/6), CD38(3/6), cCD3(1/5), CD8(1/6), CD7(2/6), CD57(1/6) and negative for CD3, CD4, TdT, cMPO, TCR α/β, TCR γ/δ. The neoplastic cells were negative for TCR gene rearrangement. Five cases showed increased quantitation of whole blood Epstein-Barr virus (EBV) DNA.@*CONCLUSION@#ANKL is a highly aggressive disease. Prompt and repeating BM examination is important to patient with fever, cytopenia and liver dysfunction. The diagnosis of ANKL relies mainly on the integration of clinical, morphologic, immunophenotypic finding and EBV-DNA increasement.

Clinical and laboratory analysis of 17 patients with γδT-cell large granular lymphocyte leukemia / 中华血液学杂志

Objective: To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αβ T-cell large granular lymphocyte leukemia (αβT-LGLL) . Methods: The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αβT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed. Results: The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αβT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4(-)/CD8(-) phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%. Conclusion: γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αβT-LGLL. γδT-LGLL predominantly expressed a CD4(-)/CD8(-) phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.

Large Granular Lymphocytic Leukemia and JAK/STAT Signaling Pathway--Review / 中国实验血液学杂志

Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow, and often associated with autoimmune disorders. According to the current WHO classification of the hematopoietic and lymphoid tissue tumors, the clonal LGL expansions are further classified as T-cell large granular lymphocytic leukemia (T-LGLL), chronic lymphoproliferative disorders of NK cells (CLPD-NK) and aggressive NK cell leukemia. Since there is a general lack of awareness of this disease, some patients may be misdiagnosed or some cases may be missed when diagnosis was done. At present, the pathogenesis of LGLL remains incomplete and unclear, and the therapeutic effects are unsatisfactory. For this reason, it is necessary to find prognostic marks and therapeutic targets of this disease. The constitutive activation of JAK/STAT pathway has been claimed to be involved in the development of LGLL. Recently, the somatic mutations in the SH2 domain of STAT3 in LGLL are frequently observed, which lead to the activation of JAK/STAT pathway. STAT3 is the first molecular markers that are highly specific for LGLL, and STAT3 mutations have been rarely detected in other tumor types studied, thus the STAT3 mutations can be used as molecular markers for LGLL diagnosis and can provide a novel therapeutic target for patients with LGLL.

Analysis of Clinical Characteristics in 10 Patietns with T Large Granular Lymphocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>The clinical data of 10 patients with T-LGLL in General Hospital of Chinese PLA from October 2015 to March 2010 were analyzed retrospectively.</p><p><b>RESULTS</b>Their 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.</p><p><b>CONCLUSION</b>T-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.</p>

CD4⁺/CD8⁻ T- cell large granular lymphocytic leukemia: one case report and literatures reviews / 中华血液学杂志

<p><b>OBJECTIVE</b>Presenting the clinical features of one patient with CD4⁺/CD8⁻ T-cell large granular lymphocytic leukemia, to improve the understanding of the disease.</p><p><b>METHODS</b>Clinical data of one patient hospitalized for skin rush and leukocytosis were analyzed, and the related literatures were reviewed.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>CD3⁺/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.</p>

Large granular lymphocyte leukemia / 中国实验血液学杂志

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.

T-cell large granular lymphocytic leukemia: 4 cases

No abstract available.

Pure red cell aplasia with thymoma/T-cell large granular lymphocyte leukemia: two cases report and literatures review / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory features of 2 cases of pure red cell aplasia (PRCA) with thymoma/T-cell large granular lymphocyte leukemia (T-LGLL), and to improve the recognition of the disease and the role of lymphocyte in its mechanism.</p><p><b>METHODS</b>Two cases of PRCA with thymoma/T-LGLL were reported and the related literatures were reviewed.</p><p><b>RESULTS</b>Case 1 was a 63-years old male with hemoglobin level of 54 g/L at admission. Case 2 was a 52-years old female with hemoglobin level of 79 g/L at admission. They were both diagnosed as PRCA with thymoma before admission to our hospital and had no benefit from their thymectomy. Further examinations in our hospital showed that CD3⁺CD4⁻CD8⁺CD57⁺ large granular lymphocytes amplified with clonal TCR rearrangement in their peripheral blood. The diagnosis of PRCA with thymoma/T-LGLL was clarified. Case 1 did not respond to any of the frontline therapies while case 2 responded completely to cyclosporine.</p><p><b>CONCLUSION</b>Both thymoma and T-LGLL could be the cause of secondary PRCA, lymphocyte proliferation may play critical role in the pathogenesis.</p>

A Case of CD4+T-Cell Large Granular Lymphocytic Leukemia

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.

A Case of CD4+T-Cell Large Granular Lymphocytic Leukemia

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.

Myeloid/natural killer cell acute leukemia resembling acute promyelocytic leukemia / 中国实验血液学杂志

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.

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4x10(9)/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment dueto liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

Immunogenetic diagnosis of large granular lymphocytic leukemia and therapy by sirolimus / 中国实验血液学杂志

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.

Hematopathologic features of T-cell large granular lymphocytic leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the hematopathologic features of T-cell large granular lymphocytic leukemia (T-LGLL).</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>Of 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).</p><p><b>CONCLUSIONS</b>Hematopathologic 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.</p>

An unusual child case of myeloid/natural killer cell precursor acute leukemia treated successfully with acute myeloid leukemia-oriented chemotherapy / 中国实验血液学杂志

This study was aimed to identify the characteristics of childhood myeloid/natural killer cell precursor acute leukemia (M/NKPAL), and to summarize the therapeutical experiences of this rare hematologic malignancy. A child case of M/NKPAL accompanied by CNS leukemia was enrolled in this study, the therapeutic regiments and the results of long time following up were analysed and evaluated. The results showed that the unusual child case of M/NKPAL with CNS infiltration was diagnosed, showing immunophenotype of CD7(+), CD33(+), CD34(+), CD56(+), HLA-DR(+), MPO(-) and negative for other NK cell, T and B cell differentiation antigens; the chromosomal abnormalities were trisomy 8 and deletion of chromosome 12p. The child case was treated with daunorubicin and cytarabine, and achieved complete remission. Then, 5 courses of acute myeloid leukemia-oriented chemotherapy were given as consolidation chemotherapy, all of the 5 courses contained high dose cytarabine. This child case was given 9 times of lumbar puncture and intrathecal injection, besides these, this case was also given cranial radiotherapy with a dose of 36 Gy. After treated with these methods, the child case achieved long-term complete remission. It is concluded that the M/NKPAL is a rare disease with distinctive immunophenotypic characteristics, acute myeloid leukemia-oriented chemotherapy regimen with high dose of cytarabine may be able to induce long-term remission.

Clinicopathologic features of aggressive natural killer cell leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of aggressive natural killer cell leukemia (ANKL).</p><p><b>METHODS</b>The clinical and pathologic features were analyzed in 10 patients with ANKL. The complete blood count, peripheral blood smears, bone marrow aspirates and bone marrow biopsies were studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. T-cell receptor (TCR) γ gene rearrangement was studied by PCR method.</p><p><b>RESULTS</b>The most frequent hematologic abnormalities observed were anemia (7 cases) and thrombocytopenia (9 cases). Large granular lymphocytes were found on peripheral blood smears of 6 patients. In bone marrow aspirates, lymphocytosis (> 20.0%) was demonstrated in 8 cases and large granular lymphocytes in 6 cases. Bone marrow biopsies revealed various degrees of neoplastic infiltration, as follows: mild (5 cases), moderate (3 cases) and severe (2 cases). The neoplastic cells were mainly interstitial in distribution in 8 cases and diffuse in 2 cases. Hemophagocytosis was observed in 4 cases. Flow cytometry showed CD2+ sCD3- CD4- CD56+ CD57- in all cases, CD7+ in 9 cases, CD16+ in 5 cases, CD8+ in 4 cases and CD5+ in 1 case. Immunohistochemistry performed in 8 cases showed the following results: cCD3+ in 4 cases, CD56+ in 6 cases, TIA-1+ in 6 cases, granzyme B+ in 4 cases and perforin+ in 2 cases. PCR study revealed germline TCRγ gene configuration in all cases.</p><p><b>CONCLUSIONS</b>ANKL is a highly aggressive NK cell-derived lymphoid neoplasm. Comprehensive morphologic, immunophenotypic and molecular analysis are essential in arriving at a correct diagnosis. ANKL needs to be distinguished from other types of NK-cell and T-cell lymphomas.</p>

Angioimmunoblastic T-cell lymphoma with large granular lymphocytosis / 中国实验血液学杂志

To improve the recognition of angioimmunoblastic T-cell lymphoma (AITL) and to reduce misdiagnosis, a case diagnosed as AITL with large granular lymphocytosis was reported and the related articles were reviewed. A series of clinical tests, pathologic examination and immunohistochemical test, TCR gene rearrangement detection by multiple PCR and assay of lymphocyte immunophenotypes were carried out. The results indicated that the patient was characterized by fever, skin rash, generalized lymphadenopathy, splenomegaly, pleural effusion, ascites, anemia and thrombocytopenia, increase of circulating large granular lymphocytes with CD3(-) and CD16(+), CD56(+) were detected, T-cell receptor γ-chain gene was rearranged. More large granular lymphocytes with abnormal mitosis were found in ascites. The histological and immunohistochemical changes observed by the lymph node biopsy were compatible with AITL, some cells of which were CD56-positive. In conclusion, AITL is characterized by aggressive progress and generally occurs in elderly patients, its clinical prognosis is poor, the large granular lymphocytosis may be an autoimmune response to the tumor cells or originate from tumor stem/progenitor cells.

Frequent CD7 Antigen Loss in Aggressive Natural Killer-Cell Leukemia: A Useful Diagnostic Marker / 대한진단검사의학회지

BACKGROUND: Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells. However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for ANKL, we analyzed the clinical data and laboratory findings obtained for 20 patients with ANKL. METHODS: From January 2000 to July 2007, 20 patients were diagnosed with ANKL on the basis of bone marrow studies. We retrospectively analyzed the clinical features and laboratory findings, including the complete blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic results. RESULTS: The subjects included 6 women and 14 men (median age, 44 yr; range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and karyotypic abnormalities were observed in 9 patients (50%). None of the cytogenetic abnormalities were constantly observed in all the patients. However, 6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of the leukemic NK-cells was cytoplasmic CD3+, surface CD3-, CD16/56+, CD2+, and CD5-. Notably, the CD7 antigen was absent in 10 patients (50%). When the CD7 loss was combined with cytogenetic abnormalities, clonal markers could be identified in 75% of the ANKL cases. CONCLUSIONS: The CD7 antigen loss was frequently observed in our series of ANKL patients. In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.

The clinical and laboratory characteristics of T cell large granular lymphocyte leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of T-cell large granular lymphocyte leukemia (T-LGLL).</p><p><b>METHODS</b>Retrospectively analyze the clinical and laboratory data of 27 patients with T-LGLL diagnosed between 1999 and 2007 in our hospital.</p><p><b>RESULTS</b>The median age at diagnosis was 48 years. All patients were symptomatic, mainly complaining of fatigue. Of the 27 patients, 14 (51.9%) had splenomegaly, and 4(14.8%) hepatomegaly. Rheumatoid arthritis was not present in any patients. The most frequent hematological abnormality was anemia (24 patients, 88.9%) with a median Hb level of 57.5 g/L. Pure red cell aplasia was found in 18 patients (66.67%). The median WBC count was 4.24 x 10(9)/L and 19 cases were neutropenia (ANC < 1.5 x 10(9)/L). The median LGL count in peripheral blood was 1.45 x 10(9)/L and most of them (77.8%) were less than 2.0 x 10(9)/L. Twenty-two patients (81.5%) showed the CD3+ CD8+ CD57+ CD56(-) LGL phenotype. With immunosuppressive therapy, 91.3% of patients responded and complete hematological remission rate was 65.2%.</p><p><b>CONCLUSION</b>T-LGLL mainly presented with anemia and complete hematological remission rate was 65.2%. Pure red cell aplasia was commonly associated with the disease. The patients had a good response to immunosuppressive therapy.</p>