Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fludarabine is a highly effective chemotherapeutic agent for chronic lymphocytic leukemia/small lymphocytic lymphoma and is also active in other B-cell lymphoproliferative disorders. Although highly efficacious in destroying the malignant B-cells, fludarabine also causes T-cell lymphopenia and immunosuppression. We present five patients given fludarabine for low-grade B-cell lymphoproliferative disorders who showed transformation of the primary neoplasm to a higher grade tumor. Immunohistologic antibody studies were performed on paraffin-embedded tissue sections of the initial tissue (when available) and on the follow-up biopsy specimens for CD20, CD3, CD45RO, CD43, CD30, CD15, and latent membrane protein (LMP-1) for Epstein-Barr virus (EBV). The initial diagnoses in these five patients included chronic lymphocytic leukemia/small lymphocytic lymphoma (three cases), follicle center lymphoma (one case), and Waldenstrom's macroglobulinemia (one case). All of the follow-up biopsy specimens showed scattered Hodgkin's-like cells, and two of the five also showed foci of large-cell transformation. The Hodgkin's-like cells showed CD30 immunoreactivity in four of the five cases and CD15 immunoreactivity in three of the five. Strong immunoreactivity of the large, atypical, Hodgkin's-like cells for LMP-1 of EBV was noted in four cases; in the remaining case, this finding was equivocal. In situ hybridization for EBV-encoded RNA was positive in four of the five cases. Molecular studies by polymerase chain reaction (PCR) showed the presence of EBV in three of the five cases. PCR for detection of immunoglobulin heavy chain demonstrated identical monoclonal rearrangements in the original lymphoma and transformation in one case with available material. The CD4 lymphocyte count in each patient was less than 550/microL, indicating cellular dysfunction. Transformation of low-grade non-Hodgkin's lymphomas after fludarabine therapy might be associated with EBV and severe immunosuppression.
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PMID:Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment. 938 67

Protease inhibitors are an important new class of agents for the treatment of human immunodeficiency virus (HIV) infection. The purpose of our trial was to determine the feasibility of combining the protease inhibitor saquinavir with a 96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M2), doxorubicin (50 mg/M2, and etoposide (240 mg/M2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE every 28 or more days. All patients received saquinavir (600mg PO TID), filgrastim and Pneumocystis carinii and fungal prophylaxis. Patients also received either stavudine (n = 2) or both stavudine and didanosine (n = 10). Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and the data were compared with the data from our prior study of CDE plus didanosine. An interim analysis was performed after accrual of the first 12 patients in order to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12 patients (67%) treated with CDE plus saquinavir compared with three of 25 patients (12%) in our prior study treated with CDE without saquinavir (P < 0.001). In logistic regression analysis, saquinavir use was the only factor associated with a significantly greater risk of severe mucositis (relative risk 7.9; P = 0.03). Saquinavir use was not associated with a significant difference in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes for patients treated with saquinavir (absolute decrease of 23/microL, or a 26% decrease from baseline) was significantly less than for patients treated without saquinavir in the prior study (absolute decrease of 91/microL, or 42% decrease from baseline; P = 0.05). Four of 10 patients (40%) treated with saquinavir had an increase in CD4 lymphocytes of > or = 10/microL compared with none of 25 patients (0%) treated without saquinavir (P < 0.001). Combination of the protease inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma was associated with a significant increase in the incidence of severe mucositis. This finding suggests that saquinavir may alter the metabolism of one of more of the cytotoxic agents in the CDE regimen, and underscores the need for careful investigation regarding the use of the protease inhibitors in patients receiving chemotherapy.
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PMID:Saquinavir enhances the mucosal toxicity of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma. 964 31

We analyzed 33 patients with AILD T-NHL in a retrospective multicentric study. The median age was 62 yr (35-84 yr) (19 patients over 60 yr). Advanced disease (n = 31) and B-symptoms were consistently found (n = 29) and 20 patients had bone marrow involvement. The main laboratory abnormalities were: anemia (n = 13), hypereosinophilia (n = 13), lymphopenia (n = 14), hypergammaglobulinemia (n = 17), elevated lactate dehydrogenase (LDH) level (n = 24). First-line therapy was chemotherapy (ChT) alone (n = 25) or ChT after steroids (n = 8). Most patients received a CHOP-like regimen for a median number of 6 cycles and 3 patients received interferon alpha (IFN alpha) as consolidation after chemotherapy. With a median follow-up of 46 mo, 60% achieved a complete response but the outcome was poor with a relapse rate at 56%, a median survival referring to the total population was of 36 mo (2-108+ mo) and an overall survival at 5 yr of 36%. Two patients received high-dose chemotherapy (with total body irradiation) and autologous progenitor-cell transplantation for chemosensitive relapse and were free of disease at, respectively, 76 and 24 mo+. In conclusion AILD T-NHL still has a poor prognosis compared to other NHL. The role of intensive therapy and IFN alpha still remains to be evaluated.
Leuk Lymphoma 1999 Feb
PMID:Angioimmunoblastic-like T-cell non Hodgkin's lymphoma: outcome after chemotherapy in 33 patients and review of the literature. 1004 27

The prognosis of patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) after primary therapy is poor and multi-drug salvage treatments are associated with less than 60% response rates, usually of short duration. Here we report the results of a phase II study using a fludarabine-cyclophosphamide (FAMP-Cy) combination as a salvage failure regimen in refractory and relapsing low-grade (6) and intermediate-grade (9) NHL patients. Fifteen patients, who had received up to 4 regimens prior to therapy with FAMP-Cy were treated with fludarabine (25 mg/m2) and cyclophosphamide (300 mg/m2) for 3 consecutive days followed by G-CSF (5 microg/kg). The overall response was 74%, 4 achieving complete responses (CR) and 7 partial responses (PR). All patients with low-grade NHL responded (4 CR, 2 PR); 5 patients with intermediate-grade NHL achieved PR lasting for a median of 5 months. The main toxicity encountered was moderate myelosuppression. Three patients had febrile neutropenia, one had drug-induced fever and a single patient developed severe neurotoxicity. Opportunistic infections due to lymphopenia were not seen. The combination of fludarabine and cyclophosphamide used as a salvage regimen showed an impressive response in a small group of heavily pretreated low-grade NHL patients who had previously received a large number of prior regimens. FAMP-Cy had limited effect in a similar group of intermediate-grade NHL patients. Results with this "failure" regimen are encouraging, however further studies are needed in order to confirm these observations in a larger series of patients.
Leuk Lymphoma 1999 Mar
PMID:Salvage chemotherapy using a combination of fludarabine and cyclophosphamide for refractory or relapsing indolent and aggressive non-Hodgkin's lymphomas. 1019 33

We present a case of tuberculous meningitis in a patient with acute myelogenous leukemia. The patient was in complete remission; he had persistent lymphopenia and CD4+ T lymphocytopenia. Diagnosis was complicated by the chronic and subacute nature of symptoms; some originally thought to be secondary to depression and chemotherapy related toxicity. Treatment was further complicated by the unusual phenomenon of paradoxical progression of disease while on appropriate therapy. This case illustrates the importance of consideration of mycobacteriosis in the differential diagnosis of chronic unexplained fever complicating treatment for acute leukemia. The natural history and essential aspects of diagnosis and treatment of CNS tuberculosis are reviewed. The clinical significance of unexplained CD4+ T lymphocytopenia and chronic lymphopenia in patients with leukemia is also discussed.
Leuk Lymphoma 1999 Mar
PMID:Tuberculosis meningitis in a patient with acute myelogenous leukemia. 1019 37

Patients with Hodgkin's disease (HD) are known to have peripheral blood lymphopenia, but the prognostic significance of this observation and its implication on immune therapy remain controversial. We determined the peripheral blood lymphocyte (PBL) counts and their subsets of 238 newly diagnosed patients with HD referred to our institution, and the quantitative changes of B, T, and natural killer cells were correlated with the patients' clinical variables. The mean white blood cell count increased steadily with advancing disease stage. In contrast, the mean absolute PBL count and its CD4, CD8, and CD3-/CD56+/CD16+ subsets, after an initial increase in stage I, steadily decreased with advanced HD stages. The mean CD20 lymphocyte count decreased steadily with advancing stage without an initial increase. Prognostic factor analysis was determined in 196 patients adequately treated with modern therapies. Neither the absolute PBL count, nor CD4, CD8, or CD20 counts correlated with shorter disease free survival. In this study, the decline in total PBL count or in its subsets in HD patients did not correlate with shorter disease free survival. Because peripheral blood lymphopenia of HD correlated with advanced clinical stage but had no independent prognostic significance, we propose that this peripheral blood lymphopenia is likely to be due to lymphocyte trafficking and homing to the diseased nodes rather than due to an absolute quantitative deficiency. Thus, strategies to improve lymphocyte functions in HD patients should continue to be explored therapeutically.
Leuk Lymphoma 1999 Aug
PMID:Therapeutic and prognostic implications of peripheral blood lymphopenia in patients with Hodgkin's disease. 1049 75

Between March 1992 and August 1993, thirty patients with hairy cell leukemia (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2-CdA) for one course (N=27) or two courses at six month interval (N=3). Sixteen patients were previously untreated, 14 had been treated with alpha interferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy, alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable patients were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients relapsed after 18, 24 months and five years. Two were retreated successfully. Two CR patients relapsed after five years. Careful clinical survey, sequential bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of response and detection of residual disease and serially evaluation of lymphocyte subsets counts were performed. Results of bone marrow biopsies study show 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44+ cells (80% of BMB). There was a correlation between the presence of > 5% DBA44 positive cells on 6th month BMB and relapse. 60% had an absolute CD4+ lymphocyte count less than 0.2 10(9)/l at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymphopenia was less marked in splenectomized patients: 7/7 splenectomized patients tested have recovered a CD4+ lymphocyte count equal to pretherapy level compared to 3/11 non splenectomized patients (p: 0.004). Three opportunistic infections were observed early (first 6 months) after 2CdA therapy: pneumocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infection while in second CR. At five years, overall survival is 83% and progression free survival is 66%. Our study shows 1) long-lasting response in the majority of patients after 2-CdA, 2) a correlation between persistent minimal residual disease detected with DBA44 immunostaining and occurrence of relapse and 3) a profound and persistent CD4+ lymphopenia more marked in non splenectomized patients.
Leuk Lymphoma 1999 Nov
PMID:Five years follow-up after 2-chloro deoxyadenosine treatment in thirty patients with hairy cell leukemia: evaluation of minimal residual disease and CD4+ lymphocytopenia after treatment. 1060 93

Emerging evidence suggests that apoptosis is an important mechanism of tumor cell death from antineoplastic therapy. 7-hydroxystaurosporine (UCN-01) is a novel protein kinase inhibitor that increases chemotherapy-induced apoptosis in vitro and is in early phases of clinical development. In this report, we present a 68-year-old patient with chemotherapy-resistant lymphoma treated with UCN-01 and chemotherapy. He had a stage IV plasmacytoid lymphoma that failed to enter remission with high-dose EPOCH II (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) chemotherapy. Due to disease progression and transformation to large cell lymphoma in the liver and bone marrow, he received UCN-01. Four weeks later, he received "standard-dose" EPOCH because of progression, developed severe neutropenia for 9 days, and expired from Candida sepsis on day 23. At autopsy, there was no histological evidence of residual lymphoma, although PCR for immunoglobulin gene rearrangement analysis revealed a faint clonal band in two of six nodes but none in the liver. Significantly, no B cells were detected by immunohistochemistry in lymph nodes, and a polyclonal ladder pattern associated with the presence of normal B cells was not seen in the immunoglobulin gene rearrangement PCR assay. Profound peripheral lymphopenia (50 cells/microliter) was also observed. Pharmacokinetics showed UCN-01 salivary concentrations, a surrogate for free drug concentrations, to be within an effective range in vitro (45 nmol/L) as a modulator of DNA-damaging agent cytotoxicity. In vitro, UCN-01 is synergistic with multiple cytotoxic agents and increases fludarabine-induced apoptosis in a human breast cell line. These results suggest that UCN-01 sensitized the lymphoma to the cytotoxic effects of EPOCH, possibly by modulating the "threshold" for apoptosis, and may illustrate a new paradigm for reversal of drug resistance.
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PMID:Modulation of clinical drug resistance in a B cell lymphoma patient by the protein kinase inhibitor 7-hydroxystaurosporine: presentation of a novel therapeutic paradigm. 1069 May 18

We experienced a case of adult T cell leukemia/lymphoma (ATLL) in a 48-year-old Korean female, who has never been abroad since birth and no history of blood transfusion. The patient had hypercalcemia and multiple lymphadenopathy. Histopathologic study of left cervical lymph node (LN) and bone marrow (BM) revealed that infiltrates of malignant lymphoid cells were composed of small, medium and large cells with pleomorphic nuclei. Smears of peripheral blood (PB) showed lymphopenia (16%) with the appearance of a few atypical lymphoid cells (less than 2%), but not the typical clover leaf cells seen in ATLL. Immunophenotypic study of LN and BM revealed T cell phenotype. PB showed increased CD4+ T cell (T(H), CD3/CD4+, 57%) and decreased CD8+ T cell counts (T(S), CD3/CD8+, 6.7%). The sera of the patient and her family were reactive for HTLV-I antibody. The specific sequences of pol, env, and tax of HTLV-I DNA were detected in the lymphoma cells and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction. Ultrastructural examination of PBMC confirmed numerous type c virus particles in extracellular space. This case was an acute type of ATLL without overt leukemic features in PB. Despite chemotherapy and intensive conservative treatment, she died 3 months after admission.
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PMID:Adult T cell leukemia/lymphoma with lymphopenia in a Korean. 1080 4

Anemia, thrombocytopenia, and neutropenia are common manifestations in patients with human immunodeficiency virus infection that become more frequent and severe with progression from the asymptomatic state to acquired immunodeficiency syndrome (AIDS). Causes of anemia in AIDS include nutritional deficiencies, infection, and marrow suppression by antiretroviral drugs and by the disease itself. Autoimmune hemolysis and blood loss from gastrointestinal lymphoma or Kaposi sarcoma may also contribute. Granulocytopenia may be due to infection, autoimmunity, or bone marrow suppression by drugs or the immunodeficiency virus. Lymphopenia, the classic hallmark of the disease, typically affects T-helper cells first and worsens as the disease advances. Lymphopenia is a result of the direct cytopathic effects of the virus. Thrombocytopenia can occur from antibodies causing an idiopathic thrombocytopenic purpura-like state from bone marrow suppression or from thrombotic thrombocytopenic purpura. A prolonged partial thromboplastin time due to a coagulopathy caused by lupus anticoagulant causing has been described. A variety of malignancies occurs.
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PMID:Hematological Effects of Human Immunodeficiency Virus Infection. 1088 19


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