Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and laboratory findings as well as the immunological cell phenotype of nine patients with chronic T-cell lymphocytosis (T-CL) are presented. The clinical course was stable in most patients and only one patient died. Splenic enlargement was the main clinical finding and in contrast to B-CLL the age at presentation was lower; T-CL predominated in females and lymphadenopathy was rare. The lymphocyte count was moderate (range 4.1-23.8 X 10(9)/L). Six patients displayed neutropenia; in contrast, anaemia was only observed in one patient and thrombopenia in another. The immunological cell phenotype was heterogeneous: four cases exhibited a cytotoxic/suppressor phenotype, two a helper phenotype and in the remaining three cases mixed OKT4+ and OKT8+ lymphocytes were observed; these results suggest that T-CL may originate from different T-cell subsets. Although the question of the benign or neoplastic nature of the T-CL remains open, some of the characteristics of the immunological phenotype could provide additional evidence to demonstrate the malignant condition of the process: in contrast to normal lymphocytes (CD5+, CD7+) the lymphocytes in T-CL were generally CD5 +/-, CD7-, and one patient showed an aberrant phenotype (OKT3+, OKT6+), an occasional finding in other T lymphoproliferative disorders.
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PMID:Heterogeneity of chronic T-cell lymphocytosis: immunological and clinical aspects. 349 59

This study reports the clinical, haematological and immunophenotypic features of a series of 25 patients with clonal expansions of large granular lymphocytes (LGL)/NK-associated (NKa) cells. These showed a male predominance (16:9) with a median age of 67 (range 38-91) years; four had a documented history of rheumatoid arthritis, a further 18 had diverse clinical disorders, and the remaining three were clinically well. Mild anaemia was found in approximately half the patients and a lymphocytosis (seen in approximately 70% of the cases) was usually modest (< 10.0 x 10(9)/l). Neutropenia was the most frequently observed feature, and this was typically persistent in nature. Serum studies revealed few consistent features although positive rheumatoid factor and increased soluble CD8 levels were noted in 67% and 87% of those cases tested. Phenotypically, all cases were CD2+CD3+CD8+ and expressed membrane TCR alpha beta chains; most (17/22) were additionally CD5+ and (19/22) CD7+. The staining intensities of CD5 and CD7 antigens were however lower than that of normal CD4+ and CD8+ blood lymphocytes. Expression of NKa antigens was variable although 16/22 cases were CD16+CD56- and 19/22 were CD57+. Clonal CD3+CD8+ LGL/NKa expansions with a CD16+CD56+ composite phenotype were not seen in this patient series. Analyses of 'activation' antigens showed a consistent lack of CD25 expression by CD3+ cells, but increased CD3/Ia co-expression was found in a high proportion (19/25) of cases. Studies of CD45R isoform expression by CD8+ LGL/NKa cell fractions revealed a consistent CD45RA+RO- profile for all cases tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clonal CD3+CD8+ large granular lymphocyte (LGL)/NK-associated (NKa) expansions: primary malignancies or secondary reactive phenomena? 858 Aug

The clinical application of recombinant human G-CSF in patients with acute myeloid leukemia (AML) has been controversial because it stimulates the in vitro proliferation of leukemic cells. In order to explore the possibility of predicting in vivo leukemic proliferation after G-CSF administration to AML patients by using in vitro assays, we investigated the leukemic blasts of 30 AML patients, including 14 patients who received G-CSF for severe infection associated with neutropenia following chemotherapy (G-CSF group) and 16 patients who did not (control group). Of the 14 patients in the G-CSF group, 9 showed an increase of leukemic blasts in the peripheral blood during G-CSF administration, while 11 of the 16 control patients developed leukemic resurgence. In the G-CSF group, the frequency of leukemic resurgence among patients whose blasts showed dose-dependent proliferation after addition of G-CSF to cultures was similar to that among patients whose blasts did not. In addition, there were no significant differences between the G-CSF and control groups in [3H]thymidine incorporation by leukemic cells and leukemic colony formation after the addition of G-CSF to cultures. The G-CSF receptor affinity of leukemic blasts was significantly higher in the patients with leukemic resurgence (mean dissociation constant [Kd]: 55 pM in the G-CSF group and 63 pM in the control group) than in those without it (101 pM and 96 pM, respectively), and the number of G-CSF receptors per cell was significantly lower when leukemic resurgence occurred (200 in the G-CSF group and 260 in the control group) than when it did not (3400 and 3030, respectively). Immunophenotyping (for CD2, CD7, CD10, CD13, CD19, CD33, CD34, CD71, HLA-DR, glycophorin A and the G-CSF receptor) revealed no significant differences between blasts from the patients with and without leukemic resurgence in the G-CSF group. Thus, we conclude that the in vivo leukemic resurgence during G-CSF administration after chemotherapy for AML was not correlated with the in vitro responsiveness of leukemic blasts to this cytokine or with blast phenotyping data. Leukemic resurgence is likely to occur in patients whose leukemic blasts have fewer numbers of G-CSF receptors with a high affinity irrespective of whether patients receive G-CSF.
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PMID:Granulocyte colony-stimulating factor in acute myeloid leukemia. 859 Aug 66

It has been suggested that some cases of nonimmune chronic idiopathic neutropenia of adults (NI-CINA) may be considered preleukemic disorders. This paper describes two patients with NI-CINA who developed acute myeloid leukemia (AML) 34 and 64 months, respectively, following NI-CINA diagnosis. Patient 1 presented erythema nodosum and patient 2 polyarthritis of the large joints 9 and 2 months, respectively, before AML. Patient 1 had AML M4 disease associated with aberrant expression of CD7 and CD19 cell surface markers and one abnormal clone in bone marrow karyotype. Patient 2 had myeloid/natural killer (NK) cell leukemia with expression of CD7 and CD56 molecules and four derivative abnormal clones in the karyotype. Both patients had del(5)(q22q35) in common. No mutations in the transmembrane or the intracytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor were found. The first patient had disease resistant to chemotherapy from the beginning of the treatment and the second following a brief complete hematological remission. On the basis of these observations, we concluded that a causal link of AML with the underlying NI-CINA cannot be presently justified, but the unusual findings noted in our patients prompt the description of additional cases for a further investigation of the relationships, if any, between these two granulocytic disorders.
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PMID:Two patients with nonimmune chronic idiopathic neutropenia of adults developing acute myeloid leukemia with aberrant phenotype and complex karyotype but no mutations in granulocyte colony-stimulating factor receptor. 1180 37

This article describes a rare case of bone marrow transplantation (BMT) from an unrelated donor (URD) in an adult Japanese male with Down syndrome (DS) diagnosed as having acute mixed lineage leukemia. Examination of peripheral blood demonstrated WBC 6.2 x 10(9)/l with 45.5% blasts at admission. Leukemic blasts with positive peroxidase stain, but negative periodic acid-Schiff stain comprised 91.6% on bone marrow specimen. Surface marker analysis of these blasts showed the following: CD3(-), CD5(-), CD7(-), CD10(+), CD19(+), CD13(+), CD14(-), CD33(+), CD34(+), CD41a(-), and CD56(-). Based on these data, he was diagnosed as having acute mixed lineage (myeloid and B-lymphoid lineage) leukemia. He achieved complete remission (CR) by lymphoid-oriented chemotherapy performed after ineffective myeloid-oriented therapy. After four courses of consolidation chemotherapy for lymphoid lineage blasts, recurrence due to proliferation of myeloblasts had occurred. Thereafter, a second CR was obtained by low dose cytosine arabinoside (AraC) therapy. As this patient was considered to have a high risk of relapse, we selected allogeneic BMT from URD. Severe stomatitis due to methotrexate (MTX) occurred probably due to altered pharmacokinetics usually observed in DS patients. Though acute graft-versus-host disease (GVHD) of systemic skin (grade II) and pneumonia were observed during neutropenia due to the post-conditioning regimen, he could be discharged from our hospital on the 135th day after BMT. On day 205 post-BMT, however, bronchiolitis obliterans (BO) occurred as a chronic GVHD disorder. Despite therapy with prednisolone and FK506, he died on day 400 post-BMT because of respiratory failure due to BO. In DS patients, superfluous toxicities due to MTX and AraC treatment have been reported, and these toxicities have been considered due to altered pharmacokinetics in patients with DS. This patient could tolerate the transplant conditioning regimen commonly used in patients without DS.
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PMID:Unrelated donor bone marrow transplantation for acute mixed lineage (myeloid and B-lymphoid lineage) leukemia in an adult with Down syndrome. 1270 27

T-cell large granular lymphocytes (LGL) proliferations range from reactive expansions of activated T cells to T-cell leukemias and show variable clinical presentation and disease course. The vast majority of T-LGL proliferations express TCRalphabeta. Much less is known about the characteristics and pathogenesis of TCRgammadelta+ cases. We evaluated 44 patients with clonal TCRgammadelta+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRgammadelta+ T-LGL leukemia patients had similar clinical presentations as TCRalphabeta+ T-LGL leukemia patients. Their course was indolent and 61% of patients were symptomatic. The most common clinical manifestations were chronic cytopenias - neutropenia (48%), anemia (23%), thrombocytopenia (9%), pancytopenia (2%) - and to a lesser extent splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2, CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56, CD11b, and CD11c. The Vgamma9/Vdelta2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vdelta1, reflecting the TCR-spectrum of normal TCRgammadelta+ T-cells in adult PB. Identification of the well-defined post-thymic Vdelta2-Jdelta1 selection determinant in all evaluable Vgamma9+/Vdelta2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRgammadelta+ T-LGL leukemia patients.
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PMID:TCRgammadelta+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRgammadelta+ T-cells. 1643 45

We describe here two cases of myelodysplastic syndrome (MDS) with a novel unbalanced translocation der(5;19)(p10;q10). Both patients had complex karyotypes including der(5;19) accompanied by an extra chromosome 19, resulting in deletion of the whole long arm of chromosome 5. Furthermore, these patients presented several common clinical and hematological characteristics: MDS subtypes as refractory anemia with excess of blasts (RAEB)-1 or RAEB-2, marked anemia and thrombocytopenia without neutropenia, leukoerythroblastosis, trilineage dysplasia with prominent dyserythropoiesis, CD7 expression in blasts, and association with abnormalities of chromosomes 6, 17 and 18. These findings indicate that der(5;19)(p10;q10) may play a crucial role in the pathogenesis of high-risk MDS as a rare but recurrent translocation.
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PMID:Unbalanced whole-arm translocation der(5;19)(p10;q10) is a novel and recurrent cytogenetic aberration in myelodysplastic syndrome. 1882 9

This study was aimed to investigate the characteristics of immunophenotypes in the patients with myelodysplastic syndrome (MDS) without an increase of marrow blasts, and to confirm their diagnostic significance. Marrow cells from 222 patients with pancytopenia, dysplastic changes in one or more hematopoietic lineages and blast cells less than 5% were analyzed by multiparametric flow cytometry(FCM). The abnormal immunophenotypes were evaluated in asynchronous antigen expression (CD34 or CD117 in mature granulocytes or mature monocytes, HLA-DR in mature granulocytes), in cross-lineage antigen expression (CD7 or CD56 in granulocytes or monocytes), in aberrant light-scatter (CD45/SSC in mature granulocyte or monocyte) and in abnormal expression of differentiation antigen (CD13/CD16 pattern in granulocytes and HLA-DR under-expression in monocytes). The sensitivity and specificity of abnormal immunophenotypes were determined on diagnosis. Among 222 cases, 127 cases were diagnosed as MDS by traditional diagnostic method and 95 cases were non-MDS (drug-related neutropenia, autoimmune cytopenia and idiopathic thrombocytopenia). In mature granulocyte gate, the sensitivity of asynchronous, cross-lineage antigen expression, aberrant light-scatter of CD45/SSC and abnormal expression of differentiation antigen were 31.5%, 30.7%, 49.6% and 60.6% respectively, and the specificity were 100%, 100%, 88.4% and 52.6% respectively. In monocyte gate, the sensitivity of asynchronous, cross-lineage antigen expression, aberrant light-scatter of CD45/SSC and abnormal expression of differentiation antigen were 2.3%, 11%, 37% and 12.6% respectively. The specificity was 100% in all of them. Among 8 above mentioned items, sensitivity of more than 2 abnormalities was 77.9%, and specificity was 95.8%. The positive predictive value was 96.1%. It is concluded that the abnormal expression of asynchronous, cross-lineage antigen expression, aberrant light-scatter of CD45/SSC have a high specificity and a low sensitivity for diagnosis of MDS. The abnormal expressions of differentiation antigens have a high sensitivity and a low specificity; however, the detection of multiple expression abnormalities possesses the high sensitivity and specificity for diagnosis of MDS.
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PMID:[Diagnostic significance of immunophenotyping of bone marrow cells in myelodysplastic syndrome without an increase of marrow blasts]. 2003 Sep 30

A 71-year-old man presented to our dermatological clinic with a 3-month history of a wound on his leg. He complained of weakness for the past few months. On his dermatological examination he had a 3x3-cm necrotic ulcer on his left tibia (Figure 1). On physical examination, there was 1 x 1-cm axillary lymphadenopathy. There was no other lymph node enlargement, hepatosplenomegaly, or gingival hypertrophy. Peripheral blood results showed 2.4x103/mm3 leukocytes (normal range 4-11 x 103/mm3) with 66% neutrophils. The hemoglobin value was 10.1 g/dL (13-18 g/dL), and the platelet count was 63x103/mm3 (150-440 x 103/mm3). No blasts were detected in a peripheral blood smear. His lactate dehydrogenase level was 567 U/L (240-480 U/L). All other results of blood chemistry were within normal limits. Punch biopsy of the skin lesion showed ulceration and dense dermal acute and chronic inflammation. There was a superficial and deep perivascular and periadnexal infiltrate of neoplastic cells composed of relatively abundant eosinophilic cytoplasm and large nuclei with blastic chromatin and occasional small nucleoli (Figure 2). Mitotic figures were prominent. Immunohistochemical stains were performed, and the neoplastic cells were CD3, CD20, CD138, and S100 protein negative. Myeloperoxidase and CD68 were positive. The histopathological findings were consistent with leukemic infiltration. Examination of bone marrow biopsy revealed that the blastic cells constituted more than 20% of the bone marrow cellularity. Cytogenetic analysis of bone marrow aspiration with fluorescence in situ hybridization was negative for inversion 16, t(8;21) and t(15;7). Histochemical stains for myeloperoxidase, sudan black, periodic acid-Schiff, and alpha naphthyl acetate were also negative. Blastic cells were DR, CD13, CD117, and CD34 positive and CD5, CD7, CD10, CD14, CD19, CD20, CD33, CD41, CD56, CD64, and CD79 negative according to flow cytometry immunophenotyping. Blastic cells were 35% in the bone marrow. Based on the findings of bone marrow examination, the patient was diagnosed as having acute myeloblastic leukeamia (AML) with minimal differentiation (subtype MO) according to French-American-British and World Health Organization classification. The examination of abdominal ultrasonography and thorocic and abominal computed tomography revealed no metastases. The patient was treated with chemotherapy that consisted of cytarabin and daunorubicin. After chemotherapy, the lesion regressed. One month after chemotherapy, the patient presented to the hospital with a complaint of fever. He was diagnosed with febrile neutropenia. He died of cardiac failure 12 months after appearance of skin infiltration.
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PMID:Necrotic ulcer: a manifestation of leukemia cutis. 2254 28

We report a 38-year-old woman presenting with febrile neutropenia, acute myeloid leukemia (AML) and invasive mucormycosis. Bone marrow aspirate was characteristic of AML minimally differentiated (WHO classification 2008). Flow cytometric immunophenotyping analysis showed blasts positive for CD7, CD33, CD34, CD71, CD117, HLA-DR, MPO, and TdT, with normal karyotype (46, XX), and the absence of the FLT3-ITD and NPM1 mutations. The patient's management included chemotherapy with cytarabine and idarubicin, and treatment with liposomal amphotericin B, deferasirox, hyperbaric oxygen therapy, and antibiotics. Nowadays, she is in complete hematological remission, and CT images of control are normal. Invasive mucormycosis is an uncommon and severe condition, which involves diagnosis and treatment challenges. Clinical features and predisposing factors should be highlighted in order to enhance the suspicion index, contributing to early diagnosis and disease control. Our aim is to report classical features of this uncommon condition and to emphasize usual management challenges.
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PMID:Mucormycosis in a patient with acute myeloid leukemia successfully treated with liposomal amphotericin B associated with deferasirox and hyperbaric oxygen. 2344 51


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