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World Journal of Hepatology Sep 2018To systematically review liver disease associated with hemophagocytic lymphohistiocytosis (HLH), propose reasonable contraindications for liver transplantation for liver...
AIM
To systematically review liver disease associated with hemophagocytic lymphohistiocytosis (HLH), propose reasonable contraindications for liver transplantation for liver failure in HLH, and report an illustrative case.
METHODS
Systematic review according to PRISMA guidelines of hepatic manifestations of HLH using computerized literature search PubMed of articles published since 1980 with keywords ("hemophagocytic lymphohistiocytosis" or "HLH") AND ("liver" or "hepatic"). Two authors independently performed literature search and incorporated articles into this review by consensus. Illustrative case report presented based on review of medical chart, and expert re-review of endoscopic photographs, radiologic images, and pathologic slides.
RESULTS
A 47-year-old Caucasian male, was hospitalized with high-grade pyrexia, rash, total bilirubin = 45 g/dL, moderately elevated hepatic transaminases, ferritin of 3300 ng/dL, leukopenia, and profound neutropenia (absolute neutrophil count < 100 cells/mm³). Viral serologies for hepatitis A, B, and C were negative. Abdominal computed tomography scan and magnetic resonance imaging revealed no hepatic or biliary abnormalities. Pathologic analysis of liver biopsy revealed relatively well-preserved hepatic parenchyma without lymphocytic infiltrates or macrophage invasion, except for sparse, focal hepatocyte necrosis. Bone marrow biopsy and aspirate revealed foamy macrophages engulfing mature and precursor erythrocytes, consistent with HLH. Interleukin-2 receptor (CD25) was highly elevated, confirming diagnosis of HLH according to Histiocytic Society criteria. Patient initially improved after high-dose prednisone therapy. Patient was judged not to be a liver transplant candidate despite model for end stage liver disease (MELD) score = 33 because liver failure was secondary to severe systemic disease from HLH, including septic shock, focal centrilobular hepatocyte necrosis from hypotension, bone marrow failure, and explosive immune activation from HLH. The patient eventually succumbed to overwhelming sepsis, progressive liver failure, and disseminated intravascular coagulopathy. Systematic review reveals liver injury is very common in HLH, and liver failure can sometimes occur. Data on liver transplantation for patients with HLH are very limited, and so far the results have shown a generally much worse prognosis than for other liver transplant indications. Liver transplantation should not be guided solely by MELD score, but should include liver biopsy results and determination whether liver failure is from intrinsic liver injury multisystem (extrahepatic) organ failure from HLH.
CONCLUSION
This case report illustrates that liver transplantation may not be warranted when liver failure associated with HLH is primarily from multisystem failure from HLH. Liver biopsy may be very helpful in determining the severity and pathophysiology of the liver disease.
PubMed: 30310541
DOI: 10.4254/wjh.v10.i9.629 -
Cancer Treatment Reviews Feb 2017Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to... (Meta-Analysis)
Meta-Analysis Review
Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.
Topics: Aged; Dose Fractionation, Radiation; Hematologic Neoplasms; Humans; Middle Aged; Patient Selection; Radiotherapy; Spleen; Splenomegaly; Treatment Outcome
PubMed: 28063304
DOI: 10.1016/j.ctrv.2016.11.016 -
Seminars in Arthritis and Rheumatism Jun 2015Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic... (Review)
Review
OBJECTIVE
Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic infection whose hallmarks may mimic SLE symptoms. Here, we report a case series and evaluate the published, scientific evidence of the relationship between SLE and VL infection.
METHODS
To assess original studies reporting cases of VL-infected patients presenting manifestations that are capable of leading to inappropriate suspicions of SLE or mimicking an SLE flare, we performed an extensive search in several scientific databases (MEDLINE, LILACS, SciELO, and Scopus). Two authors independently screened all citations and abstracts identified by the search strategy to identify eligible studies. Secondary references were additionally obtained from the selected articles.
RESULTS
The literature search identified 53 eligible studies, but only 17 articles met our criteria. Among these, 10 lupus patients with VL mimicking an SLE flare and 18 cases of VL leading to unappropriated suspicions of SLE were described. The most common manifestations in patients infected with VL were intermittent fever, pancytopenia, visceromegaly, and increased serum level of acute phase reactants. The most frequent autoantibodies were antinuclear antibodies, rheumatoid factor, and direct Coombs' test.
CONCLUSION
In endemic areas for VL, the diagnosis of SLE or its exacerbation may be a clinical dilemma. Hepatosplenomegaly or isolated splenomegaly was identified in the majority of the reported cases where VL occurred, leading to unappropriated suspicions of SLE or mimicking an SLE flare. Furthermore, the lack of response to steroids, the normal levels of complement proteins C3 and C4, and the increased level of transaminases suggest a possible infectious origin.
Topics: Adolescent; Adult; Antibodies, Antinuclear; Coombs Test; Diagnosis, Differential; Female; Fever; Humans; Leishmaniasis, Visceral; Lupus Erythematosus, Systemic; Pancytopenia; Rheumatoid Factor
PubMed: 25704907
DOI: 10.1016/j.semarthrit.2014.12.004 -
Biomedical Papers of the Medical... Mar 2015The treatment of malignancies like acute myeloid leukemia (AML) is often complicated by the heterogeneity of the disease and the mechanisms of the disease progression.... (Review)
Review
BACKGROUND
The treatment of malignancies like acute myeloid leukemia (AML) is often complicated by the heterogeneity of the disease and the mechanisms of the disease progression. This heterogeneity is often not reflected in standard treatment approaches which provide predictable outcomes in the majority of patients but fail in individual cases even with high-dose multi-agent chemotherapy regimens and allogeneic stem cell transplantation. Further, the unselective effect of chemotherapy causes high treatment-related toxicity and accelerates the risk of infection during prolonged pancytopenia, preventing further dose escalation. Despite rapid progress in therapeutic strategies, the fatality of high-grade malignancies remains enormous.
OBJECTIVES
Adhesive interactions trigger signal transduction pathway activation and this prevents the apoptosis of both normal and malignant cells. A correlation between expression of defined adhesion molecules and patient outcome has been found for several malignant diseases including AML. We aim to describe how disruption of these signalling pathways can overcome the high resistance to treatment and increase the selectivity of targeting malignant cells. This could effectively reduce the overall treatment-related toxicity and improve the general outcome.
CONCLUSIONS
Adhesion molecules facilitate growth of malignant diseases. This review provides a deeper insight into these processes. Modulation of adhesion molecules-mediated interactions is an innovative and feasible approach in treatment of AML and many other malignancies. Due to expected low toxicity it is an acceptable addition to standard chemotherapeutical regimens for all age groups of patients. This approach could improve the overall treatment outcome in the future.
Topics: Cell Adhesion Molecules; Combined Modality Therapy; Humans; Leukemia, Myeloid, Acute; Prognosis
PubMed: 25270108
DOI: 10.5507/bp.2014.049 -
The Cochrane Database of Systematic... Jul 2013Acquired severe aplastic anemia is a rare and potentially fatal disease, which is characterized by hypocellular bone marrow and pancytopenia. The major signs and... (Meta-Analysis)
Meta-Analysis Review
First-line allogeneic hematopoietic stem cell transplantation of HLA-matched sibling donors compared with first-line ciclosporin and/or antithymocyte or antilymphocyte globulin for acquired severe aplastic anemia.
BACKGROUND
Acquired severe aplastic anemia is a rare and potentially fatal disease, which is characterized by hypocellular bone marrow and pancytopenia. The major signs and symptoms are severe infections, bleeding, and exhaustion. First-line allogeneic hematopoietic stem cell transplantation (HSCT) of a human leukocyte antigen (HLA)-matched sibling donor (MSD) is a treatment for newly diagnosed patients with severe aplastic anemia. First-line treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin (as first-line immunosuppressive therapy) is an alternative to MSD-HSCT and is indicated for patients where no MSD is found.
OBJECTIVES
To evaluate the effectiveness and adverse events of first-line allogeneic hematopoietic stem cell transplantation of HLA-matched sibling donors compared to first-line immunosuppressive therapy including ciclosporin and/or antithymocyte or antilymphocyte globulin in patients with acquired severe aplastic anemia.
SEARCH METHODS
We searched the electronic databases MEDLINE (Ovid), EMBASE (Ovid), and The Cochrane Library CENTRAL (Wiley) for published articles from 1946 to 22 April 2013. Further searches included trial registries, reference lists of recent reviews, and author contacts.
SELECTION CRITERIA
The following prospective study designs were eligible for inclusion: randomized controlled trials (RCTs) and non-randomized controlled trials if the allocation of patients to treatment groups was consistent with 'Mendelian randomization'. We included participants with newly diagnosed severe aplastic anemia who received MSD-HSCT or immunosuppressive therapy without prior HSCT or immunosuppressive therapy, and with a minimum of five participants per treatment group. We did not apply limits on publication year or languages.
DATA COLLECTION AND ANALYSIS
Two review authors abstracted the data on study and patient characteristics and assessed the risk of bias independently. We resolved differences by discussion or by appeal to a third review author. The primary outcome was overall mortality. Secondary outcomes were treatment-related mortality, graft failure, no response to first-line immunosuppressive therapy, graft-versus-host-disease (GVHD), relapse after initial successful treatment, secondary clonal and malignant disease, health-related quality of life, and performance score.
MAIN RESULTS
We identified three trials that met the inclusion criteria. None of these trials was a RCT. 302 participants are included in this review. The three included studies were prospectively conducted and had features consistent with the principle of 'Mendelian randomization' as defined in the present review. All studies had a high risk of bias due to the study design. All studies were conducted more than 10 years ago and may not be applicable to the standard of care of today. Primary and secondary outcome data showed no statistically significant difference between treatment groups. We present results for first-line allogeneic hematopoietic stem cell transplantation of an HLA-matched sibling donor, which we denote as the MSD-HSCT group, versus first-line treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin, which we denote as the immunosuppressive therapy group in the following section.The pooled hazard ratio for overall mortality for the MSD-HSCT group versus the immunosuppressive therapy group was 0.95 (95% confidence interval 0.43 to 2.12, P = 0.90, low quality evidence). Therefore, overall mortality was not statistically significantly different between the groups. Treatment-related mortality ranged from 20% to 42% for the MSD-HSCT group and was not reported for the immunosuppressive therapy group (very low quality evidence). The authors reported graft failure from 3% to 16% for the MSD-HSCT group and GVHD from 26% to 51% (both endpoints not applicable for the immunosuppressive therapy group, very low quality evidence). The authors did not report any data on response and relapse for the MSD-HSCT group. For the immunosuppressive therapy group, the studies reported no response from 15% (not time point stated) to 64% (three months) and relapse in one of eight responders after immunosuppressive therapy at 5.5 years (very low quality evidence). The authors reported secondary clonal disease or malignancies for the MSD-HSCT group versus the immunosuppressive therapy group in 1 of 34 versus 0 of 22 patients in one study and in 0 of 28 versus 4 of 86 patients in the other study (low quality evidence). None of the included studies addressed health-related quality of life. The percentage of the evaluated patients with a Karnofsky performance status score in the range of 71% to 100% was 92% in the MSD-HSCT group and 46% in the immunosuppressive therapy group.
AUTHORS' CONCLUSIONS
There are insufficient and biased data that do not allow any conclusions to be made about the comparative effectiveness of first-line allogeneic hematopoietic stem cell transplantation of an HLA-matched sibling donor and first-line treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin (as first-line immunosuppressive therapy). We are unable to make firm recommendations regarding the choice of intervention for treatment of acquired severe aplastic anemia.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Cyclosporine; Graft Rejection; Graft vs Host Disease; HLA Antigens; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Immunosuppressive Agents; Mendelian Randomization Analysis; Siblings; T-Lymphocytes; Transplantation, Homologous
PubMed: 23881658
DOI: 10.1002/14651858.CD006407.pub2 -
Methotrexate and trimethoprim-sulphamethoxazole: extremely serious and life-threatening combination.Journal of Clinical Pharmacy and... Jun 2013Combining methotrexate (MTX) with trimethoprim-sulfamethoxazole (TS) is associated with a potential drug interaction that increases MTX toxicity. The aim of this article... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Combining methotrexate (MTX) with trimethoprim-sulfamethoxazole (TS) is associated with a potential drug interaction that increases MTX toxicity. The aim of this article is to review the current literature about the potential drug interaction resulting from combining MTX with TS, and to establish therapeutic recommendations regarding their use together.
METHODS
Literature for relevant evidence was searched by Medline (through PubMed), Cochrane library and a manual search through major journals for articles referenced in those located through PubMed.
RESULTS AND DISCUSSION
One systematic review, three studies and 17 case reports were found to be relevant to the topic. Results from the current available literature clearly indicate a major drug interaction between MTX and TS, which increases the risk of MTX toxicity, like severe pancytopenia, which was fatal in some cases. Recommendations to prevent this serious interaction should be developed and implemented in the currently available therapeutic guidelines related to MTX therapy.
WHAT IS NEW AND CONCLUSION
MTX and TS is an extremely serious and life-threatening combination that should be avoided. Practical recommendations regarding MTX use can be established to prevent harm from drug interactions. Increasing awareness of physicians, pharmacist and patients is essential to assure safe and effective MTX therapy.
Topics: Anti-Infective Agents; Antirheumatic Agents; Drug Interactions; Humans; Methotrexate; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 23521709
DOI: 10.1111/jcpt.12060 -
Biomedical Papers of the Medical... Dec 2012Acute myeloid leukemia (AML) shows a high degree of heterogeneity owing to a variety of mutations and the mechanisms of leukemogenesis. This heterogeneity is often not... (Review)
Review
BACKGROUND
Acute myeloid leukemia (AML) shows a high degree of heterogeneity owing to a variety of mutations and the mechanisms of leukemogenesis. This heterogeneity is often not reflected in standard treatment approaches which while providing predictable outcomes in the majority of patients fail in particular cases even with high-dose multiagent chemotherapy regimens. Further, the unselective effect of chemotherapy leads to high treatment-related toxicity and the enormous risk of infection during prolonged pancytopenia, preventing further dose escalation.
OBJECTIVES
Cytokines play a role in leukemogenesis, AML cell persistence and treatment outcome. In this review we highlight cytokine dependent mechanisms essential for AML cell survival and the role of single cytokines in leukemogenesis and allogeneic transplantation-related phenomena. Cytokine-related mechanisms of leukemogenesis, AML cell persistence and resistance to chemotherapy are complex. Modulation of the cytokine network can disrupt signalling pathway activation and overcome the high resistance to treatment. It may also increase the selectivity of AML treatment, reduce the overall treatment-related toxicity and improve outcomes of AML treatment in all age groups of patients.
CONCLUSIONS
This review provides a deeper insight into these processes with focus on the most vulnerable step. Special attention is paid to the possibility of selective influence on defined cell populations for therapeutic target. We believe that modulating cytokine-dependent processes in AML is an approach that could be included in standard chemotherapeutic regimens for improving overall treatment outcome.
Topics: Cytokines; Humans; Leukemia, Myeloid, Acute
PubMed: 23223353
DOI: 10.5507/bp.2012.108 -
Rheumatology International Aug 2008Polyarteritis nodosa (PAN) is not commonly associated with hematologic abnormalities. We report the first case of pancytopenia as the presenting symptom of PAN. There... (Review)
Review
Polyarteritis nodosa (PAN) is not commonly associated with hematologic abnormalities. We report the first case of pancytopenia as the presenting symptom of PAN. There was no associated malignancy or reactive hemophagocytic syndrome (RHS) to explain the findings. The patient, after successful treatment of PAN, subsequently developed RHS a few years later. He is the fourth reported case of RHS in a patient with PAN. In addition to describing the patient's presentation and clinical course, a systematic review of the literature was performed examining the association between hematologic conditions, including RHS, and PAN.
Topics: Adult; Humans; Male; Pancytopenia; Polyarteritis Nodosa
PubMed: 18368407
DOI: 10.1007/s00296-008-0572-1 -
Neurological Sciences : Official... Dec 2007Azathioprine (Aza) has been proposed in the treatment of multiple sclerosis (MS) since 1971 and continues to be used in MS Clinical Centres. Recent data, suggesting its... (Review)
Review
Azathioprine (Aza) has been proposed in the treatment of multiple sclerosis (MS) since 1971 and continues to be used in MS Clinical Centres. Recent data, suggesting its efficacy in reducing MRI lesion load and in refractory IFN-treated MS patients, has renewed interest in this drug. Its therapeutic index over other immunosuppressive agents is generally considered favourable, but concerns about a possible risk of malignancy have limited its use. On the other hand, the occurrence of unexpected adverse events (AEs) in clinical trials in recent years has aroused the interest in the safety profile of the drugs. No systematic review of AEs in patients affected by MS is available. The aim of this study is to review the safety profile of the drug in patients affected by MS, in order to support a correct management of these patients in the clinical practice. The controlled and observational clinical studies published between 1971 and 2007 have been included. The AEs have been registered in ad hoc form and the frequency has been calculated. The risk of cancer and toxicity on reproductive function has been also considered. Gastrointestinal complaints and leukopenia are the most frequent AEs of Aza therapy in MS, occurring in more than 10% of the patients, while infections, allergy, anaemia, thrombocytopenia and pancytopenia are common (>1%-<10%). Pancreatitis is not common (>0.1%-<1%). Most of them are easily managed by dosage adjustment or therapy interruption. The cancer risk increases with the treatment duration and cumulative dose. No data on reproductive toxicity in MS treated with Aza are available. The safety profile of Aza is acceptable, if strategies for management of expected AEs are adopted, following dosage and treatment duration indications, and if long-term monitoring to evaluate the risk of cancer is warranted.
Topics: Azathioprine; Databases, Factual; Drug Evaluation; Humans; Immunosuppressive Agents; Longitudinal Studies; Magnetic Resonance Imaging; Multiple Sclerosis; Retrospective Studies
PubMed: 18175075
DOI: 10.1007/s10072-007-0842-9