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

The T cell chronic leukemias encompass a broad spectrum of diseases involving mature post-thymic T cells. With the development of highly specific marker studies, clear patterns of immunophenotypic and functional characteristics of the involved cells have emerged. These studies, along with the development of molecular probes for the T cell receptor gene loci, have helped to elucidate the pathogenetic basis for the highly variable clinical course which has been described for patients with these disorders. The T gamma lymphocytosis syndrome has been identified as a benign chronic illness which is nevertheless usually a monoclonal neoplastic proliferation of large granular lymphocytes. These patients represent a distinct clinical entity characterized by splenomegaly, neutropenia, and peripheral blood lymphocytosis. The cells of TGLS are large granular lymphocytes and display many of the immunophenotypic and functional characteristics of NK and K cells. These cells have been implicated pathogenetically in the associated cytopenias seen in the illness, but a clear link has not been established. Although the lymphoproliferative manifestations of the disease are usually easily controlled with low-dose alkylating agents, therapy of the neutropenia has been relatively unsuccessful. Separating these patients from the rest of the spectrum of the T cell chronic leukemias has provided insight into the other disorders as well. It has established that T-CLL and T-PLL are, in fact, extremely rare. T-CLL is similar to its B cell counterpart, except that patients have a higher incidence of skin infiltration. Available data suggest that the prognosis in T-CLL is actually less variable, and somewhat worse, than generally believed when those patients were viewed in conjunction with the patients with the more benign TGLS. T-PLL is an extremely aggressive disease characterized by massive splenomegaly, lymphadenopathy, and skin infiltration. It is refractory to most forms of therapy. These illnesses are again phenotypically distinct from the retrovirus-associated ATLL. Most of the early cases of T-CLL reported from Japan were probably ATLL; this disease is characterized by pronounced splenomegaly, hepatomegaly, lymphadenopathy, and skin infiltration. It has an extremely aggressive natural history, and survival is usually less than 1 year from diagnosis. The rapid development of sophisticated immunologic and molecular techniques for analyzing T cell proliferations has allowed highly specific distinctions to be made among the cells of origin of the different T cell chronic leukemias. It is hoped that increased understanding of the immunologic and functional characteristics of these diverse T lymphoid populations will provide further insights which will have an impact on directed therapeutic interventions in the future.
 ...
PMID:T gamma lymphocytosis and T cell chronic leukemias. 218 3

In this short review we discuss two clinical entities characterized by the accumulation in the blood of mature lymphocytes bearing T-cell markers (formerly T-cell chronic lymphocytic leukemia or T-CLL). The lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the expansion of granular lymphocytes (GL). Clinically most patients have a benign clinical course, while some have neutropenia. The neoplastic or reactive nature of the disease is discussed. T-CLL with a T-helper phenotype is, on the other hand, an aggressive disease with poor survival. Patients may be classified into two subgroups according to the presence of serum antibodies against HTLV-I. The possible etiological role of HTLV-I in the disease is discussed.
 ...
PMID:Relevance of monoclonal antibody phenotyping and of genetic studies in the classification of T-cell leukemia/lymphoma. 295 37

The expanded T cell populations of 10 patients with either T gamma lymphocytosis (five patients) or proven chronic T cell malignancy (five patients) were analyzed with respect to functional activity in vitro, including proliferative responses to mitogens, cytotoxic activity (killer [K] and natural killer [NK] cell activity), and regulatory activity on pokeweed mitogen- (PWM) induced immunoglobulin (Ig) synthesis (help and suppression) in comparison with marker phenotypes. In each of the five patients with T gamma lymphocytosis, only one out of three functionally distinct cell types was found: T gamma-K cells, T gamma-S cells, or T gamma-NK/K cells, which mediated K-cell activity, suppressive activity, and both NK and K cell activity, respectively. An expanded T gamma-K cell population was demonstrated in three patients with neutropenia with or without recurrent infections. T gamma-S cells were found in a patient with severe hypogammaglobulinemia, and T gamma-NK/K cells in one patient with asymptomatic lymphocytosis. T gamma-K and T gamma-S cells had a similar surface-marker profile (E+ or E-, Fc gamma+, OKT1-3+4-8+I1-M1-), whereas that of T gamma-NK/K cells was different (E+, Fc gamma+, OKT1-3-4-8-I1+M1+). Longitudinal studies of three untreated patients with T gamma-K lymphocytosis showed that the abnormalities were persistent but not progressive. In contrast, five patients with chronic T cell malignancy (two with T-CLL, two with cutaneous T cell lymphoma [CTCL], and one with T-PLL) all had progressive disease. The neoplastic cells in these cases were E+, Fc gamma-OKT1+4+6- with variable expression of the OKT3 and OKT8 markers. The only functional activity observed in these cells was suppressive activity by OKT3-4+8- cells from a patient with CTCL.
 ...
PMID:Functional properties of T cells in patients with chronic T gamma lymphocytosis and chronic T cell neoplasia. 621 84

Twenty-one patients are described with a proliferation of morphologically mature T lymphocytes. The clinical course was chronic in most, and splenic enlargement the main clinical finding; skin involvement and lymphadenopathy were rare. The mean lymphocyte count at presentation was 8 X 10(9)/1 (range 0.75-24 X 10(9)/1). Nineteen of these patients showed some form of cytopenia (18 neutropenia, two red cell aplasia, eight thrombocytopenia) and one had hypogammaglobulinaemia. Seven patients had long-standing arthropathy serologically proven to be rheumatoid arthritis and these had previously been considered to have Felty's syndrome. Five of the group have died (three with an aggressive course), but most have remained stable for prolonged periods with a slow increase in peripheral lymphocyte count and marrow infiltration. Spontaneous regression was never observed but in two patients a prolonged remission was achieved by chemotherapy. The lymphocytes were morphologically and phenotypically homogeneous at presentation and remained so post-splenectomy; they contained azurophilic granules, stained with acid phosphatase but weakly or not at all with alpha napthyl acetate esterase. Membrane phenotyping shows the majority of the cells to be E+, Fc gamma+, OKT3+, OKT8+. Most cells do not stain with OKT1-like reagents and a significant number express HLA-Dr. From these and other reported cases it is clear that this condition represents a distinct entity resulting from the expansion of a subset of cytotoxic/suppressor T cells--the question of the benign or neoplastic nature of the disease remains open. Using T cell-specific antisera and E-rosetting techniques, a small percentage of CLL cases have been shown to be of T-cell origin (TCLL) (Dickler et al, 1973; Lille et al, 1973). Estimates of the percentage vary but in most series T-CLL has been diagnosed in less than 5% (Brouet & Seligmann, 1981), and this is supported by date from the M.R.C. Leukaemia Unit which found T-CLL in only 1.5% of 600 cases of CLL examined by marker studies (D. Catovsky, unpublished). Amongst the published reports of T-CLL a variety of clinical and morphological entities have been described including T prolymphocytic leukaemia (TPLL) (Brouet et al. 1975) and adult T cell disease in Japanese (Uchiyama et al, 1977) and West Indian Caribbean groups (ATLL) (Catovsky et al, 1982). In the original series of Brouet & Seligmann (1981) the group was defined as presenting in middle age with marked hepatosplenomegaly, some lymphadenopathy, skin involvement and with an aggressive disease course; peripheral blood and marrow lymphocytosis were variable.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Chronic T cell lymphocytosis: a review of 21 cases. 633 88

We studied the peripheral blood of 37 patients with hairy cell leukemia (HCL) prior to (n = 24) or following (n = 19) splenectomy, in the Hemalog D multi-channel white cell differential counter, to investigate whether the apparatus could contribute to the (early) diagnosis of this entity and to the differential diagnosis of HCL from atypical hairy cell leukemia (AHCL; n = 9), chronic lymphocytic leukemia (CLL; n = 21) and leukemic non-Hodgkin lymphoma of low-grade malignancy (LNHL; n = 19). HCL showed almost invariably monocytopenia, neutropenia and an increased percentage of LUC, with a rather typical picture of the X-Y display of the peroxidase channel. The percentage of hairy cells closely correlated with the percentage of the LUC from the Hemalog D. Discriminant analysis using several parameters of the Hemalog D differential count resulted in a complete separation of HCL from CLL, and a fair, although not complete, distinction of HCL from AHCL and LNHL. It was impossible to discriminate between AHCL and LNHL. The most important discriminating (single or combined) parameters were the absolute monocyte count, the TWBC and the absolute neutrophil number. It is concluded that the Hemalog D is a valuable tool in the (early) diagnosis of HCL and in the discrimination between HCL and other leukemic lymphoproliferative disorders.
 ...
PMID:The Hemalog D automated differential counter in the diagnosis of hairy cell leukemia. 685 71

The nucleoside analogs fludarabine monophosphate, 2-chlorodeoxyadenosine, and 2-deoxycoformycin (pentostatin) all have activity in chronic lymphocytic leukemia. The most widely studied drug is fludarabine which is able to obtain complete or partial responses in more than 50% of previously treated patients. The response rate is 44% for 2-CDA and approximately 25% for pentostatin. Fludarabine has also been used to treat patients as initial therapy, and has resulted in overall response rate of 79% with 75% of the patients achieving complete remission. The NCI and International Working Group for CLL criteria for complete remission allow for persistent nodules or lymphoid infiltrates in the bone marrow biopsy. Studies have now demonstrated persistent lymphoid aggregates are associated with a shorter time to progression for responders but no survival disadvantage. There is a strong association of documented refractoriness to alkylating agents with probability of response to fludarabine and also survival. The major morbidity associated with the use of these drugs are infections, which, in some circumstances, are associated with neutropenia but in other circumstances are probably related to the hypogammaglobulinemia and T-cell immunodeficiency which are part of the disease. The T-cell immunodeficiency is aggravated by the nucleoside analogs. Even after discontinuation of therapy the immunodeficiency as measured by CD4 cell number is sustained for 12 to 24 months. Opportunistic organisms such as herpes simplex, herpes zoster, Listeria monocytogenes, and pneumocystis carinii are being noted in patients treated with these agents. The potency of these drugs and low incidence of toxicities to other organs suggests that they will be effectively combined with other agents.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nucleoside analogs in treatment of chronic lymphocytic leukemia. 809 53

We report a case where life threatening gram negative sepsis developed in a patient with CLL in association with post chemotherapy neutropenia on three occasions. Bacterial typhlitis or neutropenic enterocolitis, which is a well described entity of bowel necrosis seen in immunosuppressed patients, was demonstrated at colonoscopy and was the probable portal of entry of micro-organisms. After spontaneous resolution of the typhlitis, further chemotherapy has been given without recurrent sepsis. Typhlitis should be considered as a cause of recurrent septicaemia in neutropenic patients.
 ...
PMID:Recurrent septicaemia in a neutropenic patient with typhlitis. 893 93

T cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) and large granular lymphocyte leukemia of T or NK cell type (T-LGL or NK-LGL leukemia) are chronic lymphoproliferative diseases derived from post-thymic immunocompetent lymphoid cells. T-PLL is morphologically characterized by a prominent central nucleolus in a medium-sized cell expressing a mature T cell immunophenotype. Clonal genetic changes involving chromosome 14 and T cell receptor gene rearrangements are characteristics of these diseases. They are usually progressive and there is no efficient treatment available. The classification of some cases presenting with a morphological picture similar to B-CLL, but with immunophenotypic and clinical features resembling T-PLL, as T-CLL is still controversial. The phenotypic profiles and the establishment of clonality are the hallmarks of defining T-LGL leukemia and NK-LGL leukemia. The CD3+/CD57+/CD56- immunophenotype and the clonal rearrangement of the T cell receptor genes characterize T-LGL leukemia, which presents clinically with a rather indolent course of disease, complicated by frequent infections secondary to neutropenia. NK-LGL leukemia cells express CD3-/CD56+/CD57-, but in most cases clonality cannot easily be established. Clinically the patient may either present with constitutional symptoms and suffer a short and aggressive course of disease or may have a more chronic disease similar to T-LGL leukemia. Therefore, it may be reasonable to subdivide NK-LGL proliferation into the more aggressive 'NK-LGL leukemia/lymphoma' and 'chronic NK cell lymphocytosis'.
 ...
PMID:Chronic lymphatic leukemias of T and NK cell type. 917 39

The aim of our study was to determine the efficacy and toxicity of 2-chlorodeoxyadenosine (2-CdA) in 2-hour infusions in the treatment of elderly patients with B-cell chronic lymphocytic leukemia (B-CLL). Forty three patients aged 70 years and older received 1 to 6 courses of 2-CdA (median 3) in a dose of 0.12 mg/kg daily for 5 consecutive days. Thirty three of them were untreated and 10 had relapsed or refractory to disease after prior therapy with chlorambucil, COP and CHOP. Complete response (CR) was achieved in 13 (30.2%) and partial response (PR) in 17 (39.6%) patients, giving an overall response rate of 69.8%. The difference in overall response rate between both groups were not statistically significant (69.8% and 50%, respectively). The most frequent side effects of 2-CdA treatment were thrombocytopenia observed in 18 (41.9%) and infections in 7 (16.3%) patients. Drug related neutropenia was observed in 6 (13.9%) and allergic dermatitis in 2 patients. Six (13.9%) patients died, one because of drug related thrombocytopenia resulting in a central nervous system hemorrhage, two because of pneumonia and two of cardiovascular complications. In conclusion, our results suggest that 2-CdA is also effective treatment for elderly patients with CLL. The drug toxicity is acceptable and seems to be similar for that observed in younger patients.
 ...
PMID:2-Chlorodeoxyadenosine (cladribine) in the treatment of elderly patients with B-cell chronic lymphocytic leukemia. 1035 Mar 43

Interleukin 4 (IL-4) is a pleiotropic type II cytokine which has been shown to have a direct killing effect on lymphoma and B-cell chronic lymphocytic leukaemia (B-CLL) cells in vitro. The clinical effects and toxicity of IL-4 treatment in patients with B-CLL were evaluated. Fourteen patients with B-CLL who were in partial remission after chemotherapy received one, two or three 8-week cycles of escalating doses (2, 4 or 6 microg/kg/d s.c.) of IL-4 for 3 d/week. Clinical response was analysed after each treatment cycle and toxicity was monitored continuously. Ten patients (71%) had progressive disease (PD) during IL-4 treatment. This was mainly attributable to an increase (two- to fourfold) of the blood lymphocyte count during IL-4 therapy. After cessation of IL-4 treatment, the lymphocytosis decreased spontaneously in 8 out of 12 evaluable patients. Splenomegaly remained unchanged in 7/7 patients, whereas enlarged lymph nodes were reduced by > 50% in 1/13 patients and by 25-50% in 4/13 patients. None of the patients achieved an objective tumour regression (complete or partial remission). A temporary increase (16-60%) of the platelet count was observed during IL-4 treatment. The platelet count decreased in 8/11 patients after the end of IL-4 therapy. World Health Organization (WHO) grade I/II fever, arthralgia and fatigue was observed in one-third of the patients and was more commonly seen with the highest dose (6 microg/kg/d). One patient developed pulmonary oedema and WHO grade III neutropenia was recorded in three patients. IL-4 was well tolerated by most patients in an outpatient setting. The anti-tumour activity observed in previous in vitro studies was not verified by the present in vivo trial which showed that IL-4 may instead increase the number of CLL cells in blood, indicating that IL-4 may have induced a stimulatory or antiapoptotic effect on the CLL cells in blood. These results may have important implications for the development of immunotherapy of CLL. In addition, the potential platelet-stimulatory effect of IL-4 warrants further studies.
 ...
PMID:Interleukin 4 therapy for patients with chronic lymphocytic leukaemia: a phase I/II study. 1116 96


1 2 3 4 Next >>