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PubMed2006

[Detection of promoter methylation of p16 gene in hematological malignant cell lines by nested methylation specific polymerase chain reaction].

This study was aimed to investigate the efficiency of modified methylation-specific polymerase chain reaction i.e. nested methylation-specific polymerase chain reaction, used to detect the promoter methylation of p16 gene in six hematological malignant cell lines, and to explore the application in selection of hematological malignant cell lines with promoter hypermethylation, and make them to be an idel cell models for studying the relationship between gene methylation and expression. DNAs were denatured by NaOH and then were subjected to bisulfite modification and a nested-MSP was used to amplify the promoter region, nested MSP product of p16 gene promoter was analyzed and sequenced. The results showed that the hypermethylation of p16 gene was detected in CA46 and U266, however, Molt4, K562, HL-60 and Jurkat cell lines were unmethylated. In conclusion, p16 gene methylation in hematological malignant cell lines can be perfectly detected by nested-MSP method, which is simple, sensitive and specific for screening all kinds of hematological malignant cell lines with p16 gene methylated.

Base Sequence↗

PubMed1991

Hemodialysis for acute renal failure in patients with hematologic malignancies.

OBJECTIVE: To assess the prognosis of patients with hematologic malignancies in acute renal failure who require hemodialysis. DESIGN: Retrospective study. SETTING: ICU. PATIENTS: Forty-three consecutive patients. METHODS: Prognostic analysis using both univariate and multivariate (stepwise regression) methods. RESULTS: Fifteen (35%) patients recovered from acute renal failure and 12 (28%) were discharged from the ICU. The prognosis of patients with acute renal failure linked to sepsis is poorer than the prognosis of the patients with acute renal failure from other etiologies. Only one patient survived in the former group (n = 26) and 11 in the latter group (n = 17); p less than .0001 in multivariate analysis. When accompanied by associated respiratory failure, mortality rate was higher (93% vs. 33%; p less than .0001). The Simplified Acute Physiology Score (SAPS) calculated within the first 24 hr of admission was significantly (p less than .001) related to mortality when the SAPS was greater than or equal to 13. The presence of neutropenia and the type of hematologic malignancy were not related to a worse prognosis. Tolerance to hemodialysis appeared good, and complications were rare.

Acute Kidney Injury↗

PubMed2000

Impact of malignant hematological disorders on cardiac surgery.

BACKGROUND: Patients suffering from malignant hematological disorders may be at increased risk, when undergoing cardiac surgery. We report on our experiences with ten cardiac procedures in nine patients (3 males, 6 females, 19-85 yr old, mean age 61 yr). METHODS AND RESULTS: There were two patients with Hodgkin's lymphoma and one patient each with Waldenstrom's syndrome, multiple myeloma, polycythemia, myelodysplasia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma and idiopathic aplastic anemia. Cardiac diseases included coronary artery disease in six, aortic stenosis in two, and mitral insufficiency in one patient. Consecutively, cardiac procedures were coronary artery bypass grafting in six, aortic valve replacement in two, and mitral valve replacement in one patient. No patient died. Postoperatively, one patient suffered from a pericardial tamponade requiring surgical removal and 5 months later from a prosthetic endocarditis necessitating change of the bioprosthesis. One patient developed a superficial wound infection, which was treated conservatively. Four patients received no blood products. Altogether, we transfused 32 packed red blood cells, seven units of fresh frozen plasma and 16 platelet concentrates. Total drainage loss was 883 ml (250-1510 ml). CONCLUSIONS: Cardiac surgery in patients suffering from malignant hematological disorders may be performed, but carries an increased morbidity. Therefore, indications for cardiac procedures must be carefully considered.

Adult↗

PubMedDate not supplied

Qualitative findings on the experience of end-of-life care for hematological malignancies.

There is a loud silence in the literature on the issues related to palliative care for hematological malignancies. This article presents information that begins to address that silence. The limited research that is available indicates that, to date, patients with a hematological malignancy and their families received scant attention with regards to the provision of palliative care. The findings presented in this article demonstrates that families are enduring considerable hardship and are left with much emotional pain and many unresolved issues when such care is not offered. It is hoped that the findings presented in this article will be used for developing effective strategies to ensure that patients with hematological malignancies and their families, no less than any others, can be afforded the dignity and respect that the appropriate provision of palliative services ensures.

Adolescent↗

PubMed2002

Endemic mycoses in patients with hematologic malignancies.

Histoplasmosis, blastomycosis, and coccidioidomycosis are uncommon, but often life-threatening infections in patients who have hematologic malignancies. Disease occurs either as a result of new infection after an environmental exposure or as a result of reactivation of a remote infection. Among patients who have hematologic malignancies, the greatest risk appears to be in those who have cellular immune deficiencies. Severe pulmonary infection and widespread disseminated infection are the most common manifestations of these infections in patients with hematologic malignancies. Early diagnosis is best accomplished by tissue biopsy with histopathologic evaluation for the distinctive tissue forms characteristic of these fungi; confirmation by growth in culture is essential, but slow for histoplasmosis and blastomycosis. Initial treatment in the immunosuppressed host should almost always be with amphotericin B rather than an azole. Azole antifungal agents can be used in those patients who respond quickly to amphotericin B and for those requiring long-term suppressive therapy.

Blastomycosis↗

PubMed2001

Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies.

Hepatitis virus infection through virus reactivation has a high risk of mortality in patients with hematological malignancies receiving chemotherapy. We examined the incidence of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and severe liver dysfunction (alanine aminotransferase >ten times the normal upper limit and total bilirubin >5 mg/dl) during chemotherapy in 268 patients with hematological malignancies. Eight patients (3.0%) were infected with HBV and 22 patients (8.2%) were infected with HCV. One patient (0.4%) was infected with both HBV and HCV. HBV- or HCV-infected patients showed severe liver dysfunction at a significantly higher incidence than non-infected patients (11/31 (35.5%) vs. 0/237 (0%), p<0.0001). Furthermore, the incidence of severe liver dysfunction in HBV-infected patients was significantly higher than in HCV-infected patients (6/8 (75.0%) vs. 4/22 (18.2%), p<0.01). Three of eight HBV-infected patients were initially negative for hepatitis B surface antigen (HBsAg) by latex agglutination and became positive for HBsAg during chemotherapy. Furthermore, all three patients developed severe liver dysfunction and two developed fatal fulminant hepatitis. From an examination of the original stock of serum samples before chemotherapy, two patients were found to be positive for HBV-DNA by polymerase chain reaction (PCR). Although post-transfusion HBV infection was suspected in the one remaining patient, the cause of HBV infection could not be clarified due to the impossibility of examination in blood donors. Since HBV-infected patients develop severe liver dysfunction at a higher incidence than either patients not infected with virus or HCV-infected patients before chemotherapy for hematological malignancies, it is recommended that HBV-DNA should be tested by PCR to detect HBV marker-negative carriers and liver function tests should be carefully monitored.

Adolescent↗

PubMed1997

Ambulatory mediastinal biopsy for hematologic malignancies.

OBJECTIVE: We retrospectively evaluated our experience with outpatient surgical biopsy of mediastinal lesions in patients with hematologic malignancies, its cost-effectiveness and ability to allow diagnosis. METHODS: Eighty patients underwent outpatient surgical biopsy of mediastinal lesions related to hematologic malignancies (50 cervical mediastinoscopies, 24 anterior mediastinotomies and six video-assisted thoracoscopies). Eight patients had a superior vena cava syndrome, five had lesions residuing or relapsing after chemo-radiotherapy and six and had been treated with steroids before diagnosis; in five cases the biopsy had been previously performed at other hospitals without achieving a positive diagnosis. RESULTS: Ambulatory mediastinal biopsy allowed diagnosis in all cases. Fifty-one patients had Hodgkin disease, 28 had non-Hodgkin lymphoma and one had chronic lymphatic leukemia. There was no operative mortality. Complications were: pneumothorax and bleeding during mediastinoscopy and wound infection after anterior mediastinotomy. CONCLUSIONS: Mediastinal biopsy can be safely performed on an outpatient basis in selected patients with mediastinal involvement due to hematologic malignancies. Costs were markedly reduced with respect to in-hospital procedures.

Adolescent↗

PubMed1998

Single-chain immunotoxins targeted to CD40 for the treatment of human B-lineage hematologic malignancies.

Immunotoxins, in chemical conjugate form, have shown limited efficacy in clinical trials in patients with hematologic malignancies. Single-chain immunotoxins (SCIT) provide for enhanced therapeutic efficacy over chemical conjugate forms without additional toxicity and thus may result in improved antitumor activity. We have evaluated two SCITs targeted to CD40, a receptor expressed on most B-lineage hematologic malignancies, for the treatment of non-Hodgkin's lymphoma and multiple myeloma. Both SCITs, G28-5 sFv-PE40 and BD1-G28-5 sFv, were highly potent and specifically cytotoxic against non-Hodgkin's lymphoma and multiple myeloma cell lines. G28-5 sFv-PE40 has proven to be efficacious in SCID mice bearing human non-Hodgkin's lymphoma and multiple myeloma xenografts. Antitumor activity has also been noted in preliminary studies using BD1-G28-5 sFv in non-Hodgkin's lymphoma models. The data presented here indicate that these agents should be considered for use in clinical trials in patients with refractive non-Hodgkin's lymphoma, multiple myeloma and other CD40-expressing hematologic malignancies.

Animals↗

PubMed1996

Trisomy 15 in hematological malignancies: six cases and review of the literature.

We report six cases of trisomy 15 in patients with hematological malignancy. In four cases trisomy 15 was the sole abnormality and in two cases it was associated with sex chromosome loss. The patient age range was 6-91 years, and three patients were male. Four patients had myelodysplasia (refractory anemia), one patient each had acute myeloid leukemia and acute lymphoblastic leukemia. A literature review identified ten other cases of trisomy 15 as the sole abnormality in hematological malignancies. Trisomy 15 as the sole autosomal abnormality in hematological malignancy is uncommon, but can occur in both myeloid and lymphoid malignancies. It appears to occur most frequently in myelodysplasia.

Adult↗

PubMed2002

TNF-alpha targeted therapeutic approaches in patients with hematologic malignancies.

Tumor necrosis factor (TNF)-alpha is a major effector and regulatory cytokine with a pleiotropic role in the pathogenesis of several immune-regulated diseases, including graft versus host disease (GVHD) and hematologic malignancies, such as multiple myeloma (MM), myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Curative treatment for the above diseases are not currently available for most patients. Therapeutic approaches inactivating or blocking TNF-alpha are being evaluated in clinical trials. This review describes the development of the soluble TNF-alpha receptor (p75 TNF-R: Fc; etanercept) and other agents inactivating or blocking TNF-alpha in the management of patients with hematologic malignancies. The satisfactory safety profile of etanercept--as demonstrated in patients with autoimmune diseases--has been confirmed in patients with hematologic malignancies and GVHD. Studies to assess whether etanercept, either as a single agent or in combination with cytotoxic and/or immune therapy, may increase response rates and/or survival in patients with MM, MDS, AML and other hematologic malignancies are now warranted.

Antineoplastic Agents↗

PubMed1987

Constitutional translocation t(3;6)(p14;p11) in a family with hematologic malignancies.

We describe a family with an inherited constitutional balanced translocation t(3;6)(p14;p11) and hematologic malignancies. Of two proven translocation carriers, one had acute myeloid leukemia and the other had myelofibrosis. A third member who had died of acute leukemia was a possible translocation carrier (chromosome analysis had not been performed). Five healthy translocation carriers were detected. Neither the translocation nor additional hematologic malignancies were found outside the nuclear family. It could not be definitely clarified if this constitutional translocation predisposes to hematologic malignancies. Breakpoint 3p14 has previously been implicated in recurrent cancer-associated rearrangements but 6p11 has not. We suggest that other investigators look for involvement of these breakpoints in cancer patients.

Acute Disease↗

PubMed1997

Interleukin-2 therapy after bone marrow or stem cell transplantation for hematologic malignancies.

PURPOSE: Autologous or allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT) for advanced hematologic malignancies is associated with a high relapse rate. It has been postulated that recombinant interleukin-2 (rIL-2) administered as consolidative immunotherapy early after BMT or SCT, at a time of minimal residual disease, might reduce the relapse rate. We review here preliminary results from a series of studies designed to investigate the safety, immunomodulatory effects, and clinical benefits of rIL-2 therapy following autologous and allogeneic BMT and SCT. PATIENTS AND METHODS: Patients with hematologic malignancies underwent autologous or allogeneic BMT or SCT and received rIL-2 by continuous intravenous infusion a median of 33 to 56 days later. In all trials, the rIL-2 regimen consisted of a moderate induction dose for 4 to 5 days in the hospital, 4 to 6 days of rest, and a low maintenance dose for 10 days in the outpatient setting. A phase I trial of Roche rIL-2 after autoBMT, a feasibility trial of autologous lymphokine-activated killer cells with rIL-2, and another phase I/II trial of Chiron rIL-2 after autoBMT were performed. A similar phase I trial of IL-2 after alloBMT was also performed in children with acute leukemia beyond first complete remission. RESULTS: An rIL-2 regimen has been identified that can be tolerated early after transplantation. Administration of this rIL-2 regimen induces marked increases in CD3+CD8+ T lymphocytes and CD3-CD56+ natural killer cells and enhances their antitumor cytolytic activity. Encouraging but somewhat inconsistent clinical outcomes were noted in phase I/II trials in patients with lymphoma and acute myeloid leukemia. CONCLUSIONS: The results of phase I/II trials are sufficiently encouraging to justify prospectively randomized phase III trials to determine whether rIL-2 after autologous SCT will reduce the rate of posttransplantation relapse and improve survival in patients with advanced hematologic malignancies.

Adolescent↗

PubMed1997

Mechanisms of drug resistance in hematologic malignancies.

Multiple cellular mechanisms contribute to the overall clinical drug-resistant phenotype of malignant cells. A major mechanism of drug resistance documented to occur in hematologic malignancies is overexprssion of the MDR-1 gene product, P-glycoprotein (P-gp). Drugs, called chemosensitizers, have been designed to overcome P-gp-mediated drug resistance, and these agents are now being tested in the clinic. Overcoming P-gp-mediated resistance may select for alternative mechanisms of resistance that are not affected by chemosensitizing agents. Alternative mechanisms are now being described, and the clinical relevance of these mechanisms is being investigated in hematologic malignancies. The exact mechanisms involved in the overall drug-resistant phenotype will likely depend on the type of malignancy and its exposure to anticancer drugs. A major challenge in improving the treatment of patients with hematologic malignancies will be to determine if and when these various cellular mechanisms contribute to clinical drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Physical performance, depression, immune status and fatigue in patients with hematological malignancies after treatment.

BACKGROUND: Fatigue is a frequent and severe problem after treatment of patients with hematological malignancies. This symptom has been associated with anemia, reduced physical performance, mood, endocrine disorders and impaired nutritional status. Recently, it has been suggested that fatigue can be related to a persistent activation of the immune system with increased production of proinflammatory cytokines. However, there is no conclusive evidence regarding the role of the immune system in the origin of fatigue in cancer patients. PATIENTS AND METHODS: We evaluated the correlation of fatigue with thyroid function, markers of immune activity [interleukin (IL)-1alpha, IL-1 soluble receptor, IL-6, C-reactive protein and neopterin], liver and kidney function, mood and physical ability in 71 patients with hematological malignancies. All patients had been free of relapse and not received treatment (chemotherapy, radiotherapy or immune modulators) for at least 3 months. RESULTS: Fatigue was related to depression (r=0.84; P<0.0001) and reduced performance status (r=-0.61; P<0.0001). However, there was no correlation between fatigue and thyroid, liver and kidney function, anemia, albumin concentration or markers of immune activity (all r-values <0.20; P>0.05). CONCLUSIONS: We conclude that fatigue in relapse-free patients with hematological malignancies is associated with depressive mood and reduced physical performance, but not with impairment of thyroid function, anemia or persistent activation of the immune system.

Adult↗

PubMed1991

Effect of ubenimex on the immune system of patients with hematological malignancies.

The effect of in vivo administration of ubenimex (Bestatin) on the immune status of patients with hematological malignancies in remission was studied. Natural killer (NK) cell activities, lymphokine activated killer (LAK) cell activities, production of interferon-gamma (gamma-IFN) and surface antigens of peripheral lymphocytes were examined before and after administration of ubenimex. Analysis of the T, B and NK cell compartment ax conducted by assessing expression of the following antigens: CD3+CD19- (T), CD3-CD19+ (B), CD8+CD11b- (Tc), CD8+CD11b+ (Ts), CD4+Leu8-(Th), CD4+Leu8+(Ti), CD16CD57 (NK) using a 2-color flow cytometric analysis. NK and LAK activity was significantly lower in patients with hematological malignancies as compared to normal subjects. The absolute numbers of lymphocytes and NK cells were also lower than those in healthy controls. The reduced NK and LAK activity, however, was elevated after ubenimex administration. The absolute numbers of helper T cells, cytotoxic T cells and NK cells were also increased after administration of the drug. These findings were not observed in patients treated without ubenimex. Serum levels of IFN-gamma were not markedly changed after ubenimex administration. But peripheral blood mononuclear cells cultured with rIL2 showed appreciable levels of IFN-gamma production, and production increased after ubenimex administration. These results shows that ubenimex is a powerful immunomodulator that augments or restores some immune functions in patients with hematological malignancies.

Antibiotics, Antineoplastic↗

PubMed2002

The emerging role of angiogenesis inhibitors in hematologic malignancies.

Angiogenesis is an important component of the pathogenesis of hematologic malignancies. A negative prognostic implication of increased angiogenesis has been established for acute and chronic myeloid and lymphocytic leukemias, myeloproliferative diseases, multiple myeloma, non-Hodgkin's lymphoma (NHL), and hairy cell leukemia. An association between the return of increased marrow vascularity to normal levels and durability of response has been established in some of these diseases. Elevated levels ofproangiogenic factors have been associated with a poor prognosis in the acute and chronic leukemias, multiple myeloma, and NHL. These data lend support to the reduction of activity of proangiogenic factors as a therapeutic modality. Vascular endothelial growth factor (VEGF) has been implicated as the major proangiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. A direct relationship between VEGF and leukemic blasts and malignant plasma cells has been established, but VEGF may have a function distinct from its role in angiogenesis. Current protocols with anti- VEGF agents in patients with hematologic malignancies involve the use of monoclonal antibody, blockers of the VEGF-receptor tyrosine kinase pathway, thalidomide (Thalomid) and its analogs, and cyclooxygenase inhibitors. The receptor tyrosine kinase inhibitors also affect platelet-derived growthfactor, c-kit, and Flt-3 to varying degrees, considerably broadening their potential efficacy. This review will summarize several angiogenesis inhibitors in clinical development.

Angiogenesis Inhibitors↗

PubMed1999

Quality of life and treatment value in the management of hematologic malignancies.

This report is an overview of quality-of-life (QOL) concerns among people living with hematologic malignancies, and attempts to place these concerns in the context of overall therapeutic benefit and treatment value. There are two general categories of potential benefit offered by any treatment: time and QOL. If time can be added by a treatment, either by cure or prolonging survival, the value of that time makes toxicity more tolerable to patients, providers, payers, and society. If QOL can be improved, this will also make toxicity more acceptable. However, in the absence of time extension, this trade-off must demonstrate that the QOL benefit clearly outweighs the toxicity. In other words, the acceptability of toxicity increases as the likelihood of benefit improves. The range of possible symptoms and functional problems associated with hematologic malignancies is diverse, characterized by site and degree of involvement. Uncertainty of prognosis and the need to tolerate ambiguity frame many of the emotional challenges that face patients who must make difficult treatment and follow-up decisions. As more QOL data become available from clinical trials in hematologic malignancies, treatment decisions, while still difficult, can be made with more information about risk, type of improvements, toxicities, and probability of overall clinical benefit.

Antibodies, Monoclonal↗

PubMed2002

Expression of B7 costimulator in eight human malignant hematological cell lines and its significance.

OBJECTIVE: To explore the expression of B7 co-stimulator in human malignant hematological cell lines and its significance. METHODS: Amplified and purified plasmid DNA was transfected by liposome and detection of B7 gene expression by flow cytometry and RT-PCR. RESULT: Eight human malignant hematological cell lines U937, K562, CEM, Daudi, GM, PEER, Jurkat, Raji express high level of HLA molecules, low or undetectable level of B7-1 gene, and high level of B7-2 gene. Expression level of B7-1 gene was enhanced after B7-1 transfection. T cell expressed high level of IL-2 mRNA after B7-1 transfection. CONCLUSION: Multiple human malignant hematological cell lines express low or undetectable level of B7-1 gene, suggesting that B7-1 plays a critical role in tumor immunity.

B7-1 Antigen↗