Over a two-year period, immunophenotypic patterns of 266 acute leukemia cases were analyzed using a panel of tests including TdT, SmIg and 9 surface antigens by the immunofluorescence stains for the assessment of the incidence and grade of phenotypic ambiguity (lineage infidelity) and the possible clinical significance of unusual immunophenotypes. Immunophenotypes were classified into four groups according to the degree of ectopic antigen expression. We classified as Group A (91.7%, 244 of 266 cases) those expressing conventional pattern without ectopic antigen. Group B (3.0%, 8 of 266 cases) was defined to have at least two lineage specific markers and single ectopic antigen. Such a "low grade deviation" did not prevent a definite immunodiagnosis. Group C (4.2%, 11 of 266 cases) revealed a promiscuous coexpression of markers related to different lineages, including two cases (0.8%, 2 cases) of biphenotypic leukemia. Group D (1.1%, 3 cases) included unclassifiable immunophenotypes with no antigen or HLA-DR only expression. Both patients with biphenotypic leukemia and one patient with unclassifiable immunophenotypes failed to respond to induction chemotherapy, suggesting a poor prognosis in these patients. The incidence of acute myelogenous leukemia (AML) cases with one or more ectopic surface antigens was 10 (8.1%) of the 124 AML cases. Ectopic antigen expression was seen in 5 (4%) of the 125 B-lineage acute lymphoblastic leukemia (ALL) cases and 3 (25%) of the 12 T-ALL cases. It is concluded that nearly 95% of cases of acute leukemia cases can be diagnosed accurately with immunophenotyping alone including patients with a mild degree of deviation from expected antigenic patterns.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease ; Antigens, Differentiation/blood ; Burkitt Lymphoma/immunology ; Humans ; Immunophenotyping ; Leukemia/*immunology ; Leukemia, Myeloid/immunology ; Leukemia-Lymphoma, Adult T-Cell/immunology ; Retrospective Studies

The aim was to investigate the immunophenotypes of NK series leukemia. Immunophenotypes of 297 cases of acute leukemia (AL) were measured by flow cytometry, and these immucopenotypic features were analyzed. The results showed that 43 out of 297 cases of AL (14.5%) were CD56 positive. 6 cases were NK series leukemia and 37 cases were acute myelogenous leukemia with CD56 expressed. One patient has been diagnosed as myeloid/NK cell precursor acute leukemia, two patients were blastic NK cell leukemia, one was supposed to be NK-like T-cell lymphoma/leukemia, while another one was large granular lymphocyte leukemia (LGLL). It is concluded that almost all of CD56 positive leukemia were acute myelogenous leukemia with CD56 expressed. The immunophenotypes of NK series leukemia were antigens from hematopoietic stem cells to T/NK progenitor cells with meyloid antigen positive, and through NK progenitors to mature NK cells. The immunophenotypes of heterogeneous NK leukemia cells are different, that should be carefully distinguished.
Adolescent ; Adult ; Aged ; CD56 Antigen ; metabolism ; Female ; Humans ; Immunophenotyping ; Killer Cells, Natural ; immunology ; Leukemia, Myeloid, Acute ; immunology ; Lymphoma, T-Cell ; immunology ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology

This study was aimed to summarize and analyze the clinical features and biological characteristics of adult acute T-lymphoblastic leukemia (T-ALL), and compare the efficacy of chemotherapy and transplantation in order to explore the factors influencing the long term survival and prognosis. Twenty-two T-ALL patients, all of whom were initially diagnosed according to MICM classification criteria from May 2000 to May 2010, were enrolled in this study. All patients received VDCLP regimen as the induction chemotherapy. In consolidation stage, some of the patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the others underwent intensive chemotherapy. The clinical and laboratory parameters were summarized and the contribution to survival and efficacy was analyzed by using χ(2) test, Kaplan-Meier method, Cox regression analysis and log-rank test with the aid of SPSS13.0 software. The results showed that: (1) The median age of all 22 patients was 23.5 years (16 - 63 years). 15 patients with splenomegaly had much shorter event-free survival (EFS) period (P = 0.014) and overall survival (OS) period (P = 0.013). The median white blood cell (WBC) count was 148.82 (5.51-546.0) × 10(9)/L. 15 cases out of them had leucocytosis (WBC ≥ 80 × 10(9)/L), whose EFS period (P = 0.021) and OS time (P = 0.050) were reduced significantly. The similar condition was observed in 6 patients whose blood platelet (Plt) count was no more than 30 × 10(9)/L (P = 0.033 for EFS and P = 0.035 for OS, respectively); (2) Immunophenotypic analysis showed that from 22 cases 2 cases were of pro-T, 14 cases of pre-T, 3 cases of cortical-T and 3 cases of medullary-T. Supposing pro-T and pre-T as earlier period immunophenotype, cortical-T and medullary-T as advanced stage immunophenotype, there were significant differences between earlier period and advanced stage patients in terms of EFS and OS (P = 0.035 for EFS and P = 0.028 for OS, respectively); (3) Chromosome karyotype was analyzed in 19 cases at diagnosis, and among them 12 cases had normal karyotypes while abnormal karyotypes were observed in 7 cases. Correlation analysis showed that there were no significant differences between these two groups in time of EFS and OS; (4) The overall complete remission (CR) rate was 72.7 after the induction chemotherapy. The median CR period was 18.0 months. The EFS and OS rate were 57.9 and 67.1 for 1-year, and 23.0 EFS rate and 22.0 OS rate for 3-years, respectively. Six patients received allo-HSCT and the average EFS time and OS time were both 57.8 months, which were significantly longer than those of the intensive chemotherapy group (P = 0.001 and P = 0.002 for EFS and OS, respectively); (5) Cox regression analysis proved that allo-HSCT treatment was the independent favorable prognostic factor. It is concluded that higher CR rate can be achieved by using intensive induction chemotherapy in adult T-ALL, but the long term survival seems poor by chemotherapy only in consolidation treatment stage. Allo-HSCT is the optimal choice to improve the prognosis and the outcome.
Adolescent ; Adult ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Leukemia-Lymphoma, Adult T-Cell ; diagnosis ; immunology ; therapy ; Male ; Middle Aged ; Prognosis ; Remission Induction ; Young Adult

The aim of the study was to analyze the naive T cell level of thymic recent output in patients with B-cell malignancies, thereby to evaluate the potential T-cell function. Quantitative analysis of T-cell receptor rearrangement excision circles (TRECs) in DNA of peripheral blood mononuclear cells from 61 cases of B-cell lymphocytic malignancy (including 20 cases of adult B-ALL, 6 case of childhood B-ALL, 4 cases of B-CLL, 17 cases of B-NHL and 14 cases of MM) were preformed by real-time PCR (TaqMan), and TREC-level was detected according to the number of CD3-positive cells. 5 case of ALL-CR and 17 normal individuals were served as controls. The results showed a dramatic reduction of TREC values in all groups of patients. The mean value of TRECs was 0.53 +/- 1.52 copies/1000 PBMNC and 2.01 +/- 3.93 copies/1000 CD3+ cells in adult B-ALL (p = 0.0005, p = 0.0123), 0.11 +/- 0.15 copies/1000 PBMNC and 0.23 +/- 0.27 copies/1000 CD3+ cells in B-CLL (p = 0.0015, p = 0.0381), 0.71 +/- 1.34 copies/1000 PBMNC in B-NHL (p = 0.0017), 0.53 +/- 0.90 copies/1000 PBMNC in MM patients (p = 0.0018), as compared with 3.76 +/- 3.42 copies/1000 PBMNC and 5.87 +/- 4.96 copies/1000 CD3+ cells in normal individuals, the TREC level was significantly decreased in all groups of B-cell lymphocytic malignancy, as well as in ALL-CR group. However, the TREC level in childhood B-ALL was significant higher than those in adult B-ALL group. It is concluded that the function of thymic recent outputting naive T cells in B-cell malignancies significantly decreases, however, the individual difference of thymic output function is obvious. The thymic recent output function can not be recovered during CR phase in patients with B-cell malignancies, so that dynamic analysis of TREC level is necessary.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; B-Lymphocytes ; metabolism ; pathology ; Female ; Gene Rearrangement, T-Lymphocyte ; Humans ; Male ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; immunology ; pathology ; T-Lymphocytes ; immunology ; Thymus Gland ; immunology ; metabolism ; Young Adult

Interleukin-7 (IL-7) is known as a growth factor for pre B-cell and mature T-cells in human. But in leukemic cells, IL-7 effect is variously reported. To investigate the effect of IL-7 on the cells of childhood acute leukemia we used 3H-Thymidine assay. Twelve Acute lymphoblastic leukemia (ALL), seven T-ALL and three Acute myelogenous leukemia (AML) were involved in this study. Two out of twelve ALL and three out of seven T-ALL bone marrow (BM) cells were stimulated by IL-7 in 3H-Thymidine incorporation. In normal and AML BM cells, IL-7 had no stimulatory activity as in various leukemic cell lines. Two normal peripheral blood T-cells responded to IL-7 dose dependently. We have seen the effect of IL-7 to stimulate T-lineage cells but, for precise conclusion, further study using more purified samples will be needed.
Adolescent ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Humans ; Infant ; Interleukin-4/pharmacology ; Interleukin-7/*pharmacology ; Leukemia, Myeloid, Acute/*immunology ; Leukemia-Lymphoma, Adult T-Cell/*immunology ; Lymphocytes/drug effects/*immunology ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*immunology ; Tumor Cells, Cultured

OBJECTIVETo analyse the correlation between the cellular immunity and TCM Syndrome typing of patients with minimal residual leukemia (MRI).

METHODSThe analysis was performed by detecting cellular immunological parameters in 30 MRI patients, 55 healthy persons and 36 patients with acute leukemia (AL) using three fluoresceine-conjugated monoclonal antibodies and flow cytometer.

RESULTSAs compared with those in the healthy persons, universal reductions of various parameters were shown in the MRI patients, including WBC count, absolute value of total T-lymphocytes, T-helper lymphocyte (P < 0.05) and total lymphocytes; the percentage and absolute value of NK cells (P < 0.01); and the percentages of total T-lymphocytes, CD4+ CD29+, T-suppressor cells and T-memory cells (P < 0.05 or P < 0.01), but without any rising of absolute value. As compared with those in the patients with AL, parameters were similar in the two groups with insignificant difference. The disturbances, including the lowering on ratio of T-helper/T-suppressor lymphocytes, in MRI patients of Qi-blood insufficiency type was the severest, that in the patients of Qi-Yin deficiency type was the mildest, and that in patients of Yin-deficiency with excess Fire type located between them.

CONCLUSIONThe immune function of MRI patients is low, belonging to the TCM Syndrome of vital energy deficiency with evil-lingering. Since the degree of cellular immune disturbance is different in various TCM Syndrome types, therefore, they should be treated with different dosages of different drugs.

Adolescent ; Adult ; Aged ; CD4-CD8 Ratio ; Child ; Diagnosis, Differential ; Female ; Humans ; Immunity, Cellular ; Killer Cells, Natural ; immunology ; Leukemia, Myeloid, Acute ; immunology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasm, Residual ; immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; T-Lymphocyte Subsets ; immunology ; Yang Deficiency ; immunology ; Yin Deficiency ; immunology

OBJECTIVETo investigate the clinical efficacy of Shenqi Fuzheng Injection (SFI) combined with chemotherapy in treatment of patients with acute leukemia and its effect on the levels of T-lymphocyte subsets (CD4, CD8, CD4/CD8) and serum interferon-gamma(IFN-gamma), interleukin-10 (IL-10) and IL-2.

METHODSSixty-five patients with initial treating acute leukemia were randomly divided into 2 groups, the SFI group (n = 32) treated with SFI plus chemotherapy (CT), the control group (n = 33) treated with CT only. The remission rate, changes of peripheral mature neutrophilic granulocyte (PMNG) count, T-lymphocyte subsets, serum IL-10 and IL-2 before and after treatment were determined.

RESULTSThe remission rate in the two groups showed no obvious difference (P > 0.05). After CT for the 1st, 2nd and 3rd weeks, the PMNG count decreased in both groups, showing significant difference as compared with that before CT (P < 0.01 or P < 0.05). The PMNG count at the end of the 3rd and 4th week of CT remounted to higher than that at 1st and 2nd week, and the increment in the SFI group was significantly higher than that in the control group (P < 0.05). The levels of CD4, CD4 /CD8, IFN-gamma and IL-2 all increased in the two groups after treatment (P < 0.05, P < 0.01), however, that of IL-10 was significantly decreased (P < 0.01). The difference between the two groups in these criteria after treatment was also significant (P < 0.05).

CONCLUSIONSFI can improve and regulate the immune function of the patients with acute leukemia undergoing CT, it could promote bone marrow cells proliferation and enhance the efficacy.

Adolescent ; Adult ; Aged ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Leukemia, Myeloid, Acute ; drug therapy ; immunology ; Male ; Middle Aged ; Phytotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology ; T-Lymphocyte Subsets ; immunology

Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.
Allografts ; Axilla ; Breast Neoplasms/diagnosis/*etiology/immunology ; Diagnosis, Differential ; Fatal Outcome ; Female ; Humans ; Leukemia, Myeloid, Acute/surgery ; Lymph Nodes/pathology ; Lymphoma, T-Cell, Peripheral/*etiology/pathology/ultrasonography ; Peripheral Blood Stem Cell Transplantation/*adverse effects ; T-Lymphocytes/immunology/pathology ; Transplantation, Homologous ; Ultrasonography, Mammary/*methods ; Young Adult

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8 T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
Adult ; Antigens, CD19 ; metabolism ; Bone Marrow ; metabolism ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Gene Expression Regulation, Leukemic ; Gene Regulatory Networks ; Humans ; Immunotherapy, Adoptive ; Male ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; therapy ; RNA, Long Noncoding ; genetics ; metabolism ; Receptors, Antigen, T-Cell ; Transcription Factors ; metabolism ; Transcriptome ; genetics

OBJECTIVETo assess the value of histologic examination, immunohistochemistry and gene rearrangement studies in the diagnosis and subtyping of lymphoma with bone marrow involvement (BMI).

METHODSSixty-two formalin fixed, paraffin embedded bone marrow biopsy specimens were studied. Immunohistochemical and immunoglobulin heavy chain (IgH) and T-cell receptor gene rearrangement studies were performed in each case.

RESULTSChronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) demonstrated mainly and interstitial infiltration by dysplastic lymphocytes, with intertrabecular nodular arrangement or in dispersion. Sometimes, pseudofollicles may be noted. A predominantly para- or intertrabecular infiltration by nodules of lymphoma cells was characteristic of follicle center cell lymphoma (FCL) cases. In most lymphoplasmacytoid lymphoma (LPL) cases, there was infiltration by small lymphocytes and plasma cells between bony trabeculae. In marginal zone cell lymphoma (MZL), vague inter- or para-trabecular nodules of polymorphic lymphoma cells with clear cytoplasm might be noted. Small to medium-sized dysplastic lymphocytes, with absence of paraimmunoblasts or pseudofollicles, were the most frequent findings in mantle cell lymphoma (MCL). Hairy cell leukemia (HCL) might be identified by the presence of distinct cell membrane and abundant clear cytoplasm, resulting in a "fried-egg" appearance. Tumor cells with large nuclei and eosinophilic nucleoli were characteristically seen in lymphomatosis diffusa (Hodgkin's disease, HD). In T-cell non-Hodgkin lymphoma with BMI, dispersed or clusters of intertrabecular neoplastic lymphoid cells with clear cytoplasm and gyriform nuclei were often observed. In diffuse large B-cell lymphoma (DLBL), the tumor cells were large and isolated or arranged in diffuse pattern. Immunohistochemically, a panel of markers, including CD3 CD20, and CD79 are valuable for the differential diagnosis of T- and B-cell lymphomas. The neoplastic cells in MCL were cyclin D1- and CD5-positive, while BCL2- and CD10-positivity was characteristic for FCL. CLL/SLL cells might be stained with CD5 and CD23, in addition to CD20 and CD79. CD25 expression might be noted in HCL: the positivity for CD15, CD30 and fascin suggests HD. There was a higher positivity rate for IgH gene rearrangement in CLL/SLL, LPL MZL and DLBL (80%, 60%, 66.7%, 70% respectively) and for T- cell receptor gamma gene rearrangement in T-cell lymphoma (66.7%).

CONCLUSIONA combination of histopathology, immunohistochemistry and IgH / T-cell receptor gamma gene rearrangement studies may be of aid to the diagnosis and subtyping of lymphoma with BMI, especially if there is only a small number of tumor cells present in the specimen.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; chemistry ; pathology ; Diagnosis, Differential ; Female ; Gene Rearrangement ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; pathology ; Lymphoma ; classification ; immunology ; pathology ; Lymphoma, Follicular ; pathology ; Male ; Middle Aged