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)

We compared the results of Tc-99 evaluation of glomerular filtration rate (GFR) vs. the calculation of the creatinine clearance (CCrC) as a predictor for the development of renal insufficiency in pediatric patients following hematopoietic stem cell transplantation (HSCT). We reviewed 95 consecutive patients receiving autologous (n = 37) or allogeneic (n = 58) HSCT at Children's Memorial Hospital between January, 1995 and February, 1998. Diagnoses included leukemia (n = 43), solid tumor (n = 27), bone marrow failure syndrome (n = 12), non-malignant disease (n = 8), CNS tumors (n = 5) and immunodeficiency (n = 3). Tc-99 GFR was compared with a calculated creatinine clearance derived from the Schwartz formula (CCrC) prior to HSCT. These measures of renal function were compared with the patient's subsequent clinical course to determine if patients who developed renal insufficiency of sufficient magnitude as to require continuous veno-venous hemofiltration (CVVH) or dialysis, could have been identified. Overall comparison of the two methods of evaluation of renal function showed low correlation with values obtained by CCrC, which were consistently higher in most patients (r-value 0.01 in the regression analysis and a p = 0.08 95% CI -24.15 to 1.48). When stratified for age, correlation between the two methods was excellent only in children younger than 5 yr of age p = 0.02 95%, CI 0.032-0.49). Eleven patients required therapy with CVVH or dialysis but neither CCrC nor Tc-99 GFR prior to transplant predicted this event. Patients who received TBI were statistically more prone to develop renal insufficiency than those without TBI (p < 0.0001, 95% CI 0.25-0.008). Neither the Tc-99 GFR nor the CCrC was predictive of the development of renal insufficiency in HSCT patients as the majority of patients who required dialysis had normal Tc-99 GFR prior to transplant. The characteristics found in the patients who developed renal insufficiency and required dialysis include: the use of total body irradiation as part of the transplant-conditioning regimen (p < 0.0001) and the use of continuous infusion CSA (p = 0.04).
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PMID:Comparison of Tc-99 measurement of glomerular filtration rate vs. calculated creatinine clearance to assess renal function pretransplant in pediatric patients undergoing hematopoietic stem cell transplantation. 1617 14

Primary effusion lymphoma (PEL) is an unusual form of non-Hodgkin's lymphoma, which is characterized by lymphomatous effusion in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV). We describe a 54-year-old man with HIV-negative PEL, with a history of hepatitis B virus-related liver cirrhosis. Both abdominal and pleural cavities were involved; no solid tumor masses were found and bone marrow investigations were normal. The ascites and pleural effusion contained numerous pleomorphic lymphoid cells. Immunophenotyping was positive for CD138. Chromosome study showed complex cytogenetics. The genomic human herpesvirus-8 was detected in the lymphoma cells. It is postulated that the immunosuppressed state in this patient may have been caused by cirrhosis. The patient received four cycles of chemotherapy of CHOP and Picibanil (OK-432) intraperitoneal administration. However, no durable remission was achieved. Adefovir failed to halt the progressive liver failure after the development of YMDD mutant related to lamivudine. He died of sepsis and hepatic failure.
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PMID:Primary effusion lymphoma involving both pleural and abdominal cavities in a patient with hepatitis B virus-related liver cirrhosis. 1758 46

The recent advances in the investigation of tumor immunobiology have suggested that cancer chemotherapy, in addition to its well known cytotoxic activity, may play modulatory effects on the endogenous production of cytokines involved in the control of both tumor angiogenesis and antitumor immunity. Cancer chemotherapy constantly acts with inhibitory effects on anti-bacterial, anti-viral and anti- mycotic immune responses, whereas its action on anticancer immunity, which is mainly mediated by lymphocytes, has still to be better investigated and defined. The present study was carried out to evaluate the influence of chemotherapy on lymphocyte count and its relation to the clinical response in cancer patients suffering from the most commonly frequent tumor histotypes, including lung, colorectal, breast and prostate carcinomas. The study included 144 consecutive metastatic solid tumor patients. Lung cancer patients were treated with cisplatin plus gemcitabine, colorectal cancer patients received oxaliplatin plus 5-fluorouracil, while those affected by breast cancer or prostate carcinoma were treated with taxotere alone. An objective tumor regression was achieved in 66 out of 144 (46 percent) patients, whereas the remaining 78 patients had only a stable disease (SD)or a progressive disease. Independently of tumor histotype and chemotherapeutic regimen, a lymphocytosis occurred in patients who achieved an objective tumor regression in response to chemotherapy, and lymphocyte mean count observed at the end of the chemotherapeutic treatment was significantly higher with respect to the values seen before the onset of treatment. On the contrary, lymphocyte mean number decreased on chemotherapy in patients with SD or PD, even though the decline was statistically significant with respect to the pretreatment values in the only patients who had a PD in response to chemotherapy. This study would suggest that chemotherapy itself may paradoxically act, at least in part, as a cancer immunotherapy by inducing lymphocytosis, as well as previously demonstrated for the only immunotherapy with IL-2, probably by modulating the cytokine network and correcting the altered endogenous production of cytokines, responsible for cancer-related immunodeficiency.
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PMID:Cancer chemotherapy-induced lymphocytosis: a revolutionary discovery in the medical oncology. 1808 52

The Emu-TCL1 transgenic mouse spontaneously develops a CD5(+) B cell lymphoproliferative disorder similar to human chronic lymphocytic leukemia (CLL). Given the ineffectual T cell antitumor responses in this mouse model of CLL, we sought to determine whether combined treatment with anti-CD40 mAb (alphaCD40) and CpG-containing oligodeoxynucleotides (CpG) could exert immunotherapeutic effects. We have previously shown that macrophages activated by sequential ligation of CD40 and TLR9 could become cytotoxic against solid tumor cell lines both in vitro and in vivo. In the current study, we find that alphaCD40 plus CpG-activated macrophages induce tumor B cell apoptosis in vitro and that alphaCD40 plus CpG treatment markedly retards tumor growth in immunodeficient SCID/Beige mice following transplantation of primary tumor B cells. Our results suggest a novel immunotherapeutic strategy for CLL that may be effective even in the face of tumor or chemotherapy-induced T cell immunodeficiency.
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PMID:Tumoricidal effects of activated macrophages in a mouse model of chronic lymphocytic leukemia. 1945 72

The extensive use of bone marrow transplantation (BMT) in the treatment of a number of life threatening hematologic, oncologic and immunodeficiency disorders has come as a result of more than four decades of research and clinical experience. It is estimated that about 50,000 BMT per year are currently performed at more than 500 clinical centers all over the world. Total body irradiation (TBI) in combination with intensive chemotherapy (CT) proves to be a method without alternative in the preparation of patients with hematologic diseases for bone marrow or hematopoietic stem cells transplantation. Fractionated TBI is applied in myeloablative regimens where patients receive between 10 and 15 Gy. In the recent decade establishing the immunoreactivity of the graft lead to the introduction of nonmyeloablative conditioning regimens, including TBI, most often with a single dose of the order of 2 Gy received before transplantation. It is only in the last decade that the Bulgarian onco-radiologic community extended its knowledge and experience in the field of bone marrow transplantology. The first autologous BMT in Bulgaria was carried out in 1997, the first allogeneic BMT with conditioning TBI regimen--in 2002 and the first BMT with nonmyeloablative conditioning regimen including TBI with 2 Gy--in 2005. AIM OF The aim of the present review was to go over some aspects of the clinical experience that has been accumulated for the last ten years in the field of nonmyeloablative conditioning regimens and BMT. We also survey the basis for developing nonmyeloablative conditioning regimens, their aims and purposes, the main indications for their application, observed toxicity and therapeutic efficiency. The clinical experience gained in the last decade shows unambiguously that the BMT with conditioning "mini" TBI regimen, owing to the graft-versus-leukemia or graft-versus-tumor effect, is capable of achieving remission in patients with life threatening, conventional treatment-resistant hematologic, limphoproliferative disorders and some solid tumor.
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PMID:Nonmyeloablative conditioning regimens and bone marrow transplantation--some contemporary aspects. 2038 Feb 82

We describe the incidence of malignancy in patients with primary immunodeficiency disorders (PIDD) following hematopoietic cell transplantation (HCT). From the Center for International Blood and Marrow Transplant Research, 2266 PIDD patients who had undergone allogeneic HCT between 1968 and 2003 were identified. Patient, disease, and transplant factors for development of malignancy were examined and pathology reports for reported malignancies reviewed independently by a pathologist for confirmation. The incidence of malignancy was highest for Wiskott-Aldrich syndrome (3.3%), with an overall incidence of 2.3% for PIDD. Post-HCT malignancy was confirmed for 52 of 63 reported cases. Forty-five of 52 patients developed posttransplant lymphoproliferative disorders (PTLD) at a median of 3 months post-HCT. Of these, 26 had received T cell-depleted (TCD) bone marrow. Three patients who developed myelodysplastic syndrome had received TCD marrow and total body irradiation. Three patients developed a solid tumor. Patients with PIDD are at a relatively low risk of developing malignancies post-HCT compared with their historic risk of cancer. The most frequent malignancy or lymphoproliferative disorder was early-onset PTLD. As in other HCT recipients, TCD appears to correlate with PTLD development. Our results lend support to the hypothesis that immune reconstitution in PIDD following HCT leads to a decrease in cancer risk.
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PMID:Malignancies after hematopoietic cell transplantation for primary immune deficiencies: a report from the Center for International Blood and Marrow Transplant Research. 2165 61

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+) PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.
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PMID:Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL). 2458 36

Pleural effusion is a ubiquitous complication in hemodialysis (HD) patients. Common etiologies of pleural effusion in this patient group are heart failure, volume overload, parapneumonic effusion, tuberculotic pleuritis, and uremic pleuritis. Although thoracentesis is a useful diagnostic method of pleural effusion, empirical reduction of the dry weight is often attempted without thoracentesis because pleural effusion is commonly caused by volume overload and responds to the dry-weight reduction. However, this empiricism has a risk of overlooking or delaying the diagnosis of potentially fatal etiologies that need specific treatments. We report an 86-year-old human immunodeficiency virus (HIV)-negative male on HD with primary effusion lymphoma (PEL), a large-cell non-Hodgkin lymphoma presenting with characteristic lymphomatous effusions in the absence of solid tumor masses, which is in association with human herpes virus 8 (HHV8) infection in immunocompromised individuals. The patient presented with left-sided pleural effusion. This is the first case report of PEL developing in a patient receiving HD. Thoracentesis and cytological analysis of the effusion was key to the diagnosis. We also review the literature regarding pleural effusion in HD patients. Further, we examine Kaposi's sarcoma herpes virus/HHV8-negative effusion-based lymphoma, a newly proposed distinct lymphoma that clinically and cytomorphologically resembles PEL, because it can be cured without chemotherapy. This report may arouse clinicians' attention regarding the importance of evaluation for pleural effusion in HD patients, especially when the effusion or symptoms associated with pleural effusion are refractory to volume control.
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PMID:Primary Effusion Lymphoma in an Elderly HIV-Negative Patient with Hemodialysis: Importance of Evaluation for Pleural Effusion in Patients Receiving Hemodialysis. 2498 5

AMD3100, also known as plerixafor, was originally developed as an anti-human immunodeficiency virus (HIV) drug, and later characterized as a C-X-C chemokine receptor type 4 (CXCR4) antagonist. Previous reviews have focused on the application of AMD3100 in the treatment of HIV, but a comprehensive evaluation of AMD3100 in the treatment of leukemia, solid tumor, and diagnosis is lacking. In this review, we broadly describe AMD3100, including the background, functional mechanism and clinical applications. Until the late 1990s, CXCR4 was known as a crucial factor for hematopoietic stem and progenitor cell (HSPC) retention in bone marrow. Subsequently, the action and synergy of plerixafor with Granulocyte-colony stimulating factor (G-CSF) led to the clinical approval of plerixafor as the first compound for mobilization of HSPCs. The amount of HSPC mobilization and the rapid kinetics promoted additional clinical uses. Recently, CXCR4/CXCL12 (C-X-C motif chemokine 12) axis was found to be involved in a variety of roles in tumors, including leukemic stem cell (LSC) homing and signaling transduction. Thus, CXCR4 targeting has been a treatment strategy against leukemia and solid tumors. Understanding this mechanism will help shed light on therapeutic potential for HIV infection, inflammatory diseases, stem-cell mobilization, leukemia, and solid tumors. Clarifying the CXCR4/CXCL12 axis and role of AMD3100 will help remove malignant cells from the bone marrow niche, rendering them more accessible to targeted therapeutic agents.
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PMID:Effectiveness of AMD3100 in treatment of leukemia and solid tumors: from original discovery to use in current clinical practice. 2742 63

Immunodeficient mice engrafted with either normal or cancerous human cells are widely used in basic and translational research. In particular, NOD/SCID/IL2rg-/- mice can support the growth of various types of human cancer cells. However, the hairs of these mice interfere with the observation and imaging of engrafted tissues. Therefore, novel hairless strains exhibiting comparable immunodeficiency would be beneficial. Recently, the CRISPR/Cas9 system has been used for efficient multiplexed genome editing. In the present study, we generated a novel strain of nude NOD/SCID/IL2rg-/- (NSIN) mice by knocking out Foxn1 from NOD/SCID/IL2rg-/- (NSI) mice using the CRISPR/Cas9 system. The NSIN mice were deficient in B, T, and NK cells and not only showed impaired T cell reconstitution and thymus regeneration after allogeneic bone marrow nucleated cell transplantation but also exhibited improved capacity to graft both leukemic and solid tumor cells compared with NSI, NOG, and NDG mice. Moreover, the NSIN mice facilitated the monitoring and in vivo imaging of both leukemia and solid tumors. Therefore, our NSIN mice provide a new platform for xenograft mouse models in basic and translational research.
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PMID:CRISPR/Cas9-Mediated Deletion of Foxn1 in NOD/SCID/IL2rg-/- Mice Results in Severe Immunodeficiency. 2879 21


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