Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with hairy cell leukemia who developed mediastinal mass and fever is described. A CT-guided aspiration of the mass yielded Salmonella tiphymurium. Granulocyte response to infection was intact and could explain the favorable course of this unusual Salmonella infection. Although several reports deal with salmonellosis as a complication of immunodeficiency states, this type of infection is of rare occurrence in hairy cell leukemia.
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PMID:Salmonella infection in hairy cell leukemia: report of a case. 402 17

Cell surface marker analyses conducted on human peripheral blood lymphoid cells have proven extremely useful in the diagnosis of immunodeficiency and the diagnosis and staging of malignancies. In this paper we have focused on the ratio of helper to suppressor cells in patients with the acquired immune deficiency syndrome and in patients with malignancy. In thirty-three patients with the acquired immune deficiency syndrome, the majority showed an inverted helper:suppressor ratio, elevated serum thymosin alpha 1, and elevated serum lysozyme levels. The inverted ratio was due to a deficiency in T-helper cells. The inverted helper:suppressor ratio was associated with functional suppressor cell activity that was seen in 12 out of 21 patients examined. Patients' lymphocytes were found to suppress the PHA, pokeweed mitogen, and concanavalin-A responses of normal subjects' lymphocytes. The suppression also correlated with impaired lymphocyte proliferative responses among the patients' cells themselves. Because of these findings, the helper:suppressor ratio was studied in patients with solid tumors, lymphoma, acute leukemia, chronic lymphocytic leukemia, and hairy cell leukemia. Approximately 30% of these patients have an inverted helper:suppressor ratio. However, in ten out of 30 patients with chronic lymphocytic leukemia and in three out of 45 patients with lymphoma, the helper:suppressor ratio was elevated, being greater than 3.0. The significance of these findings is as yet to be explored, but it is suggested that an inverted helper:suppressor ratio in patients with malignancy may relate to an advanced stage of disease or a poor prognosis. Documentation of this point will require further study.
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PMID:Leukocyte subset analysis and related immunological findings in acquired immunodeficiency disease syndrome (AIDS) and malignancies. 623 50

Recent evidence of cell membrane expression of interleukin-2 receptors (IL-2R) by malignant B cells in hairy cell leukemia (HCL) and B-chronic lymphocytic leukemia (B-CLL) has lead to speculation that growth factors, such as IL-2, may play a role in the pathophysiology of these diseases. However, to date, it is not clear that IL-2 is a consistent growth factor in vitro or in vivo for malignant B cells. What then is the potential significance of membrane IL-2R on the malignant B-cell membrane? Laboratory analysis indicates that the malignant cells are the source of elevated serum levels of soluble Tac protein (sIL-2r alpha) in both diseases. Indeed, these cells spontaneously secrete sIL-2R alpha into culture medium. We speculate that the presence of an expanding mass of malignant B cells possessing high and low affinity membrane IL-2R may contribute significantly to the associated immunodeficiency seen in B-CLL. In particular, it is the cell associated high affinity IL-2R that have the greatest potential for reducing the levels of free IL-2 available to normal immune cells.
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PMID:Does IL-2 receptor expression and secretion in chronic B-cell leukemia have a role in down-regulation of the immune system? 828 5

The expression of the apoptosis-regulating genes Bcl-2, Bcl-x, Bax, Mcl-1, and p53 analyzed in 4 cases of human immunodeficiency virus (HIV)-associated Hodgkin's disease, in 36 cases of HIV-related non-Hodgkin's lymphomas (NHLs), and in 109 cases of non-HIV-related NHLs by using immunohistochemistry. HIV-associated Hodgkin's disease samples were positive for all markers. For the HIV-related NHL samples, 36, 66, 88, 100, and 94% of the cases were Bcl-2, Bcl-x, Bax, Mcl-1, and p53 were found to be expressed in 69, 65, 82, 83, and 42%, respectively. No significant differences were observed in Bax and Mcl-1 staining between HIV-unrelated NHLs of B cell and T cell types. In contrast, Bcl-2 was positive in 66/79 (83%) and 10/30 (33%) of B cell and T cell HIV-unrelated NHLs, respectively (P2 < 0.001). Peculiar patterns were observed for hairy cell leukemia (Bax+, Bcl-2+, Mcl-1-) and for anaplastic large cell lymphoma (Bax+, Mcl-1+, Bcl-2-) in HIV-unrelated NHLs. Of interest, all cases with a positive expression of Bax were also found to express either Mcl-1 and/or Bcl-2, suggesting that Mcl-1 and Bcl-2 may counteract the pro-apoptosis function of Bax in vivo by protein-protein interaction within the tumor cell, as demonstrated previously in vitro. These results suggest that apoptosis regulation may have a role in the pathogenesis of some HIV-related and HIV-unrelated NHLs.
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PMID:Immunodetection of apoptosis-regulating proteins in lymphomas from patients with and without human immunodeficiency virus infection. 868 41

The long-term outcome of patients with hairy cell leukemia resistant to interferon-alpha (IFN-alpha) following treatment with deoxycoformycin (DCF) was examined, and the kinetics of recovery of lymphocyte subsets and factors influencing the rate of recovery investigated. Between May 1986 and May 1989, 15 patients with histologically confirmed hairy cell leukemia resistant to IFN-alpha received DCF 4 mg/m2 every 2 weeks with 12 cycles planned. All 15 patients were evaluable for response and have been followed for a median of 88 months (range, 72 to 106 months) from the start of therapy. Fourteen patients responded to DCF, all attaining complete remission (CR) (response rate 93%; 95% confidence interval, 69% to 100%). Seven patients have developed recurrent disease after 45 to 74 months. Using the method of Kaplan and Meier, the median remission duration is 74 months and, at 8 years, 46% (95% confidence interval, 33% to 59%) of patients are projected to be in ongoing CR. The seven relapsing patients have responded to treatment with 2-chlorodeoxyadenosine (2-CdA) and all 15 patients remain alive. After DCF, nadir CD4+ and CD8+ lymphocyte counts were significantly lower than prior to therapy (P < 0.0001 and P = 0.05, respectively), but returned to baseline levels during follow-up. Median times to attainment of the lower limit of the normal range of CD4+ and CD8+ lymphocytes were 54 and 36 months, respectively. Those patients who had previously undergone splenectomy (n=7) had higher baseline CD4+ (P= 0.073) and CD8+ (P= 0.043) lymphocyte counts and more rapid recovery of both CD4+ (P= 0.027) and CD8+ lymphocyte counts (P = 0.016) than non-splenectomized patients. One elderly patient (age, 78 years) was diagnosed with subsequent malignancy. No late opportunistic infections were observed. Resistance to IFN-alpha does not impair subsequent responsiveness of patients with hairy cell leukemia to treatment with DCF. Responses are durable and without evidence of long-term sequelae. CD4+ and CD8+ lymphocyte subsets recover slowly without clinical manifestations of immunodeficiency. Splenectomized patients appear to have higher baseline lymphocyte counts and more rapid lymphocyte recovery following treatment with DCF.
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PMID:Response duration and recovery of CD4+ lymphocytes following deoxycoformycin in interferon-alpha-resistant hairy cell leukemia: 7-year follow-up. 900 17

The rationale for antileukemic therapy in hairy cell leukemia is to reduce the significant risk of infection and other potential serious complications. Corticosteroids have limited value; both corticosteroids and chemotherapy are associated with substantial risks of infection. The mainstay of therapy has been splenectomy. Improvement is seen in 50% to 70% of patients with cytopenias; although the impact of splenectomy on survival has not been clearly demonstrated, prolonged hematologic improvement can occur. Splenectomy presumably alleviates the pancytopenic effect of hypersplenism by removing the preferred site of leukemic cell proliferation. Human interferon represents a major advance in management. Favorable results with natural leukocyte alpha interferon have been confirmed by data with biosynthetic (recombinant) alpha interferon. Importantly, the incidence of infection has been clearly shown to decrease, suggesting improved survival in patients with advanced hairy cell leukemia. Many questions regarding interferon therapy remain unanswered, including optimal dose, optimal duration, and maintenance therapy after maximal response. The mechanism of action is unclear, but possibly interferon modulates as yet unidentified lymphokines or growth factors. In vitro evidence suggests a direct antiproliferative effect of type I interferon on hairy cells. Preliminary data suggest that although toxicity issues, including induction of immunodeficiency and renal insufficiency require further clarification, deoxycoformycin, an adenosine deaminase inhibitor, is also highly effective and holds substantial promise as an important therapeutic modality.
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PMID:Evolving therapy of hairy cell leukemia. 1082 65

Interferons are agents with antiviral, antiproliferative, and immunomodulatory properties. Interferon-alfa (IFN-alpha) is used in the treatment of hematologic malignancies and solid tumors. IFN-alpha has shown antitumor and antiviral efficacy that are not correlated, one with another. Approval by the US Food and Drug Administration was granted early for the treatment of patients with hairy cell leukemia, acquired immune deficiency syndrome-related Kaposi's sarcoma, and condylomata acuminata. Although IFNs are effective as single agents in certain clinical pathologic entities, increasing experience with these cytokines suggests that their greatest therapeutic potential may be realized in combination with other biological response modifiers, cytotoxics, or antiviral agents. For example, trials combining IFN-alpha with 5-fluorouracil to treat colorectal carcinoma or IFN-alpha with zidovudine to treat acquired immune deficiency disorder showed increased efficacy over IFN-alpha alone. While IFN-alpha appears to be moderately effective in certain diseases, the flu-like syndrome associated with its use is a major limiting factor for its clinical application. Further studies are needed to determine the underlying mechanism of action for IFNs and the most effective combinations and appropriate preclinical models, or intermediate endpoints that will then facilitate the rational use of this agent in combinations based on the mechanisms of action of IFN-alpha.
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PMID:Cancer immunotherapy: the interferon-alpha experience. 1206 84

We describe the case of a patient treated with 2-chloro-2'-deoxyadenosine, CdA or Cladribine for hairy cell leukemia who subsequently developed an Epstein Barr virus (EBV)-positive polymorphous large B-cell lymphoma (p-LBCL). The time interval between Cladribine therapy and development of p-BCL was 11 months and morphologically resembled an EBV-positive post transplant lymphoproliferative disorder (PTLD). Molecular genetic studies for EBV-clonality by Southern blot hybridization showed a clonal population of infected cells, implying that this was an EBV induced lesion. The chronology of events suggest that Cladribine, a purine analog which has been previously described to induce long-lasting immunodeficiency, can, in some cases, weaken the host defense mechanism to a level at which an innocuous EBV infection may transform the normal lymphoid cells into an aggressive neoplasm. Unlike most methotrexate-related lymphoproliferative disorders (LPDs), which undergo spontaneous remission after discontinuation of therapy, LPDs secondary to purine analogs often fails to resolve after discontinuation of therapy and requires additional therapy. Our patient was treated with rituximab following the diagnosis of p-LBCL, with the goal of improving the pancytopenia to permit chemotherapy. However, the patient failed to show any dramatic improvements in counts, developed systemic symptoms and progressive ascites. He expired 3 weeks after a second dose of rituximab. Cladribine is a potent immunosuppressive agent and should be included with the list of immunosuppressive agents that may be associated with EBV-related B-cell lymphoproliferative disorders.
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PMID:Epstein-Barr virus positive large B-cell lymphoma arising in a patient previously treated with Cladribine for hairy cell leukemia. 1529 65

The natural history of hairy cell leukemia (HCL) includes frequent and potentially life-threatening infections. Prior to the development of effective therapy, the incidence in patients followed for several years was as high as 60%, with infection as a prime cause of death in patients. Studies of the immune system of patients with HCL identified several potential reasons, including profound neutropenia and monocytopenia. In addition, treatment including chemotherapy and splenectomy further compromised the immune system. The success of new therapies has changed the frequency and severity of infections in patients with HCL. During the initial phase of treatment, however, infection risk remains high, with incidence ranging from 30 to 50%. Attempts to ameliorate the risk with growth factors in conjunction with treatment have not been successful, but lower doses of drugs and/or combination therapy have been tried with reported success. In the majority of patients, successful therapy results in normalization of the neutrophil count and marked reduction in the severity and frequency of infections. Interestingly, after purine nucleoside treatment, there is profound depression of CD4+ cells without development of the opportunistic infections seen with patients with human immunodeficiency virus (HIV). Studies to reduce morbidity and mortality should focus on initial induction regimens, as well as confirming the long-term benefit of treatment on risk of infection.
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PMID:Infectious complications in hairy cell leukemia. 2150 85

Abstract Pancytopenia is regularly encountered in hematology practice, yet there exist few published assessments of the frequencies of various etiologies, and these frequencies exhibit substantial geographic variation. We reviewed bone marrow specimens from pancytopenic adults to determine the most common etiologies and to identify associations with clinical and laboratory findings. Of 132 patients with no history of hematolymphoid neoplasia, no prior bone marrow study for pancytopenia and no recent cytotoxic chemotherapy, 64% had clonal hematopoietic disorders. Most common were myeloid processes: 26% of patients had acute myeloid leukemia, and 17% had myelodysplasia. Less common were lymphoid neoplasms such as non-Hodgkin lymphoma (6%), hairy cell leukemia (5%) and precursor B acute lymphoblastic leukemia (4%). Among non-clonal cases, the most common specific diagnoses were aplastic anemia (5%), megaloblastic anemia (2%) and human immunodeficiency virus (HIV)-related changes (2%). Clonal diagnoses were associated with more severe cytopenias than non-clonal cases. Circulating nucleated erythroid precursors, immature granulocytes and blasts were seen more frequently in clonal cases. Nearly two-thirds of cases of new onset pancytopenia in adults in our North American practice setting have a clonal etiology, with myeloid neoplasms being most common. Blood counts and peripheral smear findings can provide insights into the likelihood of a clonal etiology.
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PMID:New onset pancytopenia in adults: a review of underlying pathologies and their associated clinical and laboratory findings. 2382 6


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