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At least 19 recordsLinked to original sources
PubMed2004

Proteasome inhibition in hematologic malignancies.

Hematologic malignancies, including multiple myeloma (MM), will account for more than 100,000 new cases of cancer and over 57,000 deaths in the United States in 2003. Treatment of MM is a serious challenge, because despite a variety of available therapies, median survival is short. A new therapeutic area focuses on inhibiting the activity of the proteasome, a 26S protease complex involved in cell cycle regulation, cell adhesion, inflammation, and protein turnover. The novel proteasome inhibitor, bortezomib (Velcade), was recently approved for use in patients with refractory and relapsed MM and to date is the only proteasome inhibitor to have entered clinical trials. Bortezomib has demonstrated activity with manageable toxicity in a variety of hematologic malignancies in addition to MM, including leukemia and non-Hodgkin's lymphoma. This article reviews clinical information on bortezomib in hematologic malignancies both as monotherapy and in combination with dexamethasone. Preliminary reports of bortezomib in combination with Doxil (pegylated liposomal doxorubicin), melphalan, and thalidomide are discussed, and current trials are described. Available data suggest that bortezomib will be useful in the treatment of a variety of hematologic malignancies.

Asthenia↗
PubMed2000

Manipulation of the stem cell as a target for hematologic malignancies.

Hematologic malignancies affect more than 80,000 patients in the United States each year. Some patients with lymphoma and leukemia are cured with conventional chemotherapy treatments. For others, autologous or allogeneic bone marrow transplantation may be the best therapeutic option. This chapter will explore novel therapies for the hematologic malignancies, using the stem cell as a target. We review work in the murine model looking at (1) the phenotype of the engrafting cells, (2) stem cell competition and host stem cells, (3) allochimerism with low-dose total body irradiation, and (4) the tolerance approach with costimulator blockade. Human data, including stem cell migration, adhesion receptor expression, and manipulations for gene therapy, are reviewed. The NOD/scid mouse model serves as a bridge between the basic bench work and human clinical trials, and we discuss applications related to umbilical cord blood and gene therapy, as well as discuss the inherent variability of this system. Finally, we address unique clinical applications in gene therapy, high-dose cell transplants, minimal myeloablation, and cellular immune therapy as approaches to treatment of for patients with hematologic malignancies.

Animals↗
PubMed1987

[Significance of tumor markers in the treatment of cancer: hematologic malignancy].

Hematologic malignancies, such as acute leukemia and malignant lymphoma. Respond well to cancer chemotherapy. Therefore, it is important to monitor the state of response to chemotherapy as well as to determine the complete disappearance of the tumor and to predict early detection of recurrence in routine clinical work by estimation of tumor marker levels. Although changes in the levels of paraprotein in multiple myeloma have been utilized for monitoring the responsiveness to chemotherapy, since the amounts of paraprotein are directly proportional to the number of myeloma cells, in other hematologic malignancies there are no tumor markers for monitoring the clinical course, for detecting the presence of minimal residual disease, or for predicting disease recurrence. In the future it is expected that developments in biotechnology create a large number of reagents including 'oncogene'-related markers or 'oncogene' products for application to the diagnosis and treatment of cancer patients.

Acute Disease↗
PubMed2001

[Clinical application of metabolic bone markers in hematologic malignancies].

Hematologic malignancies such as multiple myeloma, adult T cell leukemia and malignant lymphoma are often complicated with bone lesions and/or hypercalcemia. The abnormal bone metabolism in these diseases are modified by co-existing cachexia, malnutrition, sex hormone deficiency and abnormal parathyroid function or by chemotherapy in a complex manner. Metabolic bone markers are not only clinically useful for evaluation and diagnosis of such bone abnormalities but may also be used to monitor the disease activity itself, particularly in multiple myeloma which almost inevitably involves bone destructive lesions.

English Abstract↗
PubMed2006

[Home care of hematological malignancies].

Hematological malignancies such as leukemia or lymphoma are mainly treated by hospitalization or in outpatient clinics. Therefore, home care and home nursing are not so intensively done in the treatment of these malignancies. However, G-CSF administration against neutropenia after chemotherapy and administration of narcotics or opioids against severe pain have been performed sometimes during home care, and have been contributing to better QOL of the patients.

Analgesics, Opioid↗
PubMed1991

Decision making in critically ill patients with hematologic malignancy.

Hematologic neoplasms that were previously considered fatal are now potentially curable with techniques such as bone marrow transplantation. Such therapies also carry significant morbidity and mortality. With the increasing application of these therapies, a growing number of physicians are using medical decision making regarding critical care for these patients. The process by which ethical decisions are reached for these critically ill patients may be baffling because of several factors: rapidly evolving treatments, uncertain probabilities of the cure of the malignant disorder, the relatively young age of many of these patients, and the poor prognosis with critical illness. I discuss a process to reach acceptable decisions, providing a case example of the application of the process. This process is derived from the ethical principles that drive decision making in general medicine and attempts to maximize patients' autonomy. It involves a consideration of accurate information regarding the disease process and the prognosis, a clear delineation of the goals of the medical care, and communication with patients. Appropriate, ethical, and consistent decisions regarding the critical care of patients with hematologic malignancy can be reached when these considerations are addressed.

Adult↗
PubMed2001

[Occurrence of bacteriuria in malignant hematologic diseases].

BACKGROUND: Infection risk with patients suffering from hematological malignant diseases is a result of an interaction between a patient and a host and of a dysfunction of organs. During the evolution, human beings have developed an effective defense mechanism. It was defined with functioning of: 1) skin and mucus membranes, 2) phagocyte cells and 3) humoral and cellular immunity. The patients with malignant hematological diseases are exposed to complex pathogenic processes that disturb their balance, which leads to the occurrence of an infective syndrome. METHODS: In the retrospective study of 422 patients with malign hematological disease, epidemiological-clinical analysis of the infectious syndrome has been carried out. Patients were hospitalized at the Clinic for Hematology--Clinical Center of Sarajevo University, in the period from January 1, 1993 to January 1, 2000. diagnostic protocol included the following procedures: anamnesis, clinical picture, biochemical, cytomorphological, pathohistological, microbiological and radiological test. The goal of work was to determine bacteriuria in case of malign hematological diseases as an accompanying, combined complication during the treatment of these patients. RESULTS: In case of patients that were hospitalized in 1994, bacteriuria was present in the percentage of 56, which is over expected trend line whereas in 2000 it was registered in 20.65% of patients had bacteriuria while 17% of patients had have infection, 28% of patients had bacteriuria while 17% of patients had other infections. In case of patients up to 65 age, bacteriuria was more frequent in female population while in the age of over 65 it was more frequent in male population. Through microbiological analysis of urinary flora, monomicrobial bacteriuria was found in case of 58% patients, and patients were mainly in the initial phase of disease. In case of patients with long treatment with antineoplastic drugs or in the phase of advanced basic process, bacteriurias with polymicrobial character were dominant, which is characteristic of recurrent infections of urinary tract. CONCLUSIONS: The authors came to the conclusion that it is necessary to monitor urine flora with malignant hematological disease patients and by using an adequate treatment to minimize initial infection, relapse and reinfection of urinary tract. Still, it is not clear which is the basic factor initiating the infection of urinary tract--whether it is the prevailing intensity and pathogenic aggressiveness of an agent, or the exposure intensity or a supportive condition of the patient.

Aged↗
PubMed2004

Renal insufficiency in patients with hematologic malignancies undergoing total body irradiation and bone marrow transplantation: a prospective assessment.

PURPOSE: Patients with malignant hematologic disorders undergoing bone marrow transplantation (BMT) may develop renal insufficiency. A study was undertaken to assess prospectively the subclinical renal function changes with radioisotopic methods in patients undergoing BMT for hematologic malignancies. METHODS AND MATERIALS: We studied 71 patients with normal renal function undergoing BMT for various hematologic malignancies, mostly leukemias. Conditioning included chemotherapy and 12 Gy (45 patients) or 13.5 Gy (26 patients) fractionated total-body irradiation (TBI). In 21 patients receiving 12 Gy TBI, the kidney dose was limited to 10 Gy using partial transmission blocks fabricated after renal opacification with nonionic, hypo-osmolar contrast medium. The glomerular filtration rate (GFR) and effective renal plasmatic flow (ERPF) were determined radioisotopically before conditioning and at 4, 12, and 18 months, using (51)Cr ethylene-diamine-tetra-acetic acid and (131)I ortho-iodo-hippurate, respectively. Renal insufficiency was defined as a decrease of >/=30% in GFR or ERPF compared with the baseline values. The potential influence of patient- and treatment-related variables on renal dysfunction was assessed. RESULTS: At 4 (early) and 12-18 (late) months, a >/=30% GFR drop was observed in 54% and 49% of patients and a >/=30% ERPF drop in 44% and 34% of patients, respectively. After stepwise logistic analysis, a GFR reduction at 4 months correlated significantly with age (<40 years old, worse), TBI using kidney blocks (partial kidney shielding to 10 Gy was associated with a higher rate of renal dysfunction at 4 months compared with the full TBI dose), and days of aminoglycoside/vancomycin use. An ERPF drop at 4 months was independently related with the days of amphotericin use and days of prostaglandin E(1) use (prophylaxis against hepatic venoocclusive disease). A GFR and ERPF reduction at 12-18 months correlated with days of amphotericin use and days of prostaglandin E(1) use, respectively. CONCLUSION: Early post-BMT renal dysfunction is associated with the administration of potentially nephrotoxic drugs. An inverse correlation with the prescribed TBI dose was observed; patients whose kidneys received 10 Gy through the use of partial shielding blocks had significantly greater renal dysfunction at 4 months. The administration of potentially nephrotoxic contrast agents used in radiotherapy treatment planning may be responsible for the latter observation. Prostaglandin E(1) use correlated with a significant reduction in ERPF at both 4 and 12-18 months.

Adolescent↗
PubMed1985

Hematologic malignancies associated with primary mediastinal germ-cell tumors.

Three men with primary mediastinal germ-cell tumors subsequently developed a malignant hematologic disorder characterized by pancytopenia and marrow infiltration with hematopoietic blast cells. Two of these patients were classified as having acute megakaryocytic leukemia and the third was believed to have a myelodysplastic syndrome with a prominent megakaryocytic component. Analysis of clinical characteristics of these patients and review of the literature suggest that the proximate association of mediastinal germ-cell tumors with malignant hematologic disorders is neither a coincidence nor a consequence of chemotherapy given for the germ-cell tumor. We believe this association represents the evolution of a neoplastic disorder that initially involves a totipotent germ cell. These germ cells, when located in the mediastinum, apparently acquire hematologic phenotypes and are manifested clinically as a hematologic malignancy.

Acute Disease↗
PubMed2001

Killing activity of human umbilical cord blood-derived TCRValpha24(+) NKT cells against normal and malignant hematological cells in vitro: a comparative study with NK cells or OKT3 activated T lymphocytes or with adult peripheral blood NKT cells.

PURPOSE: We aimed to determine the effects of human umbilical cord blood (UCB)-derived natural killer T (NKT) cells as immunological effectors against hematological malignancies, as well as auto- or allo-dendritic cells (DCs) or EB transformed cell lines (EBCLs). MATERIALS: TCRValpha24(+) Vbeta11(+) UCB- or PB-NKT cells were isolated by sorting and activated by alpha-galactosylceramide-pulsed autologous DCs. UCB-NK cells were induced from CD34(+) cells by stem cell factor plus IL-15. UCB-T cells were primarily activated by anti-CD3 monoclonal antibody. All those effectors were cultured with IL-2 (100 U/ml), and their cytotoxic activities were evaluated by (51)Cr-release assay. UCB-NKT cells were cultured with IL-12, IL-18 or higher dose of IL-2 (1000 U/ml), and again tested for the cytotoxicity against selected targets. RESULTS: UCB-NKT cells exhibited a pattern of killing activity against various hematological malignancies similar to that of UCB-NK cells, but could not kill K562, which was a vulnerable target for NK cells. The level of activity was quite similar to that of PB-NKT cells. In contrast, OKT-3-activated UCB-T lymphocytes showed a stronger and wider spectrum of killing compared with UCB-NK or NKT cells. IL-12, IL-18 or a higher dose of IL-2 upregulated the activity; however several targets, including fresh leukemic cells, still remained resistant. NKT cells killed auto- or allo-DCs at a level similar to that of T cells, but could not kill allo-EBCLs, which were efficiently killed by T cells. While NK cells showed only marginal or no killing against DC or EBCLs. DISCUSSION: The anti-cancer activity of human NKT cells depends on the concentrations or the combination of Th1-cytokines. Basically, those cells might not be contributing to the immune surveillance of hematological malignancies, as shown by a relatively low cytotoxicity against malignant cells, together with the quite strong killing against auto-DCs.

Antigens, CD1↗
PubMed2005

[Pulmonary fungal infection in malignant hematological diseases: an analysis of 14 cases].

The objective of this study was to evaluate the etiological factors, diagnosis and therapy of pulmonary fungal infection in hematological malignancies, 14 cases of malignant hematological disease with pulmonary fungal infection were collected and analyzed. The results showed that 11 out of 14 cases had the respiratory manifestations, sputum was sticky and difficult to be expectorated in 7 cases, X rays in chests showed shadows with features of stigma and sheet in 11 cases, Candida albicans and aspergillus infection were observed in 10 and 2 cases respectively, the numbers of neutrophil were below 0.5 x 10(9)/L in 8 cases and below 1.0 x 10(9)/L in 3 cases respectively, fluconazole was used for 12 cases and clinical symptoms of 11 cases were improved within two weeks. In conclusion, the occurrence of pulmonary fungal infection in malignant hematological diseases is associated with intensive chemotherapy, decrease of neutrophil counts and using of broad-spectrum antibiotics, the diagnosis at early stage is difficult and clinicians should pay more attention to its clinical and laboratory examinations, and give them therapy in time.

Adolescent↗
PubMed1994

Emotional states of patients with hematological malignancies: preliminary study.

We conducted a study to demonstrate the kinds and frequencies of psychiatric symptoms among 31 inpatients with malignant hematological diseases. The DSM-III-R (Diagnostic and Statistical Manual for Mental Disorders, third edition-revised, 1987) structured interview and three psychological tests, such as the Self-rating Anxiety Scale, Self-rating Depression Scale and Profile of Mood States, were administered. The structured interview demonstrated 29.0% of the patients to have met the criteria for some form of psychiatric disorder, i.e., two for major depression and seven for adjustment disorder (three with depressed mood, two with anxious mood and two with mixed emotional features). Of the remaining 22 patients (71.0%) none met the criteria for psychiatric disorders. Of the five patients who knew their true diagnoses, three were assessed as having adjustment disorder with depressed mood and one as having major depression. Also, among the five patients on chemotherapy, four met the criteria for psychiatric disorders. Adjustment disorders were fewer among Japanese patients with malignant hematological diseases than among patients from previous studies in western countries, which can be explained by the patients' defense mechanism such as 'denial' and/or the less frequent 'truth-telling' in Japan. In addition, since the diagnostic criteria or psychological scales contain physical symptoms, they should be arranged or revised if applied to patients with life-threatening diseases such as hematological malignancies.

Adult↗
PubMed1986

[Secondary malignancies associated with hematological malignancies following anticancer treatment].

We have investigated the present status of secondary malignancies throughout the country following anticancer treatment for the initial cancers. We recorded by questionnaire 272 patients with multiple primary cancers associated with hematological malignancies from 64 among 1487 main institutes. Of them, we analyzed 131 patients who developed hematological malignancies from carcinomas metachronously and 101 patients who developed metachronous malignancies from hematological malignancies. Comparison of patients with a history of chemotherapy or radiotherapy for the initial cancer (treated group) and patients without (untreated group) showed that the incidence of secondary acute leukemias seemed to be higher than expected in the treated group. The characteristics of secondary acute leukemias were similar to those from the untreated group in age, types of leukemia, and hematological findings at diagnosis. However, patients from the treated group with secondary acute leukemias showed a tendency to have a higher frequency of antecedent hematological abnormalities and a poorer prognosis than those from the untreated group.

Acute Disease↗
PubMed1998

[Invasive fungal infection in malignant hematologic diseases].

In patients with hematological malignancies invasive mycoses occur frequently. In this retrospective study autopsy and histopathology material of 171 patients with hematological malignancy who had died between 1994 and 1996 at the 1st Department of Internal Medicine (Hematology), St. László Hospital, Budapest was analysed. In cases with invasive fungal infection post mortem results were compared to clinical and microbiological data. Through the three years' period an invasive mycosis could be confirmed in 33 patients by autopsy. Aspergillosis occurred in 21, candidiasis in 11, other fungal infections in 2 cases, a double infection was seen in 1 patient. The incidence was 19.2% (in invasive candidiasis: 6.4%, in aspergillosis 12.2%). Invasive aspergillosis most frequently was seen in the lung (71%), while candidiasis occurred mainly in the intestinal tract (42%). Cultures for mycology were collected from the autopsy material of 9 patients, of which 8 gave positive results. A previous fungal colonisation results was confirmed in 23 patients, but based on colonisation conclusions rarely could be driven concerning the species causing invasive infection. Sensitivity of Aspergillus antigen and antibody tests was 45 and 50%, respectively. Predisposing factors for invasive aspergillosis and candidiasis were similar, except for duration of neutropenia (24 vs. 12 days, p < 0.004). The antifungal drug most frequently used was amphotericin B. We observed a persisting infection in invasive pulmonary aspergillosis and chronic disseminated candidiasis in spite of the administration of a cumulative dosis of 1-2 g. Most frequently Aspergillus infections--primarily that of the lung--can be seen. Presence of invasive mycoses can usually be confirmed in vivo, but an early diagnosis still remains unsolved.

Aspergillosis↗
PubMed1998

Detection of RB1 deletions by fluorescence in situ hybridization in malignant hematologic disorders.

We evaluated the usefulness of fluorescence in situ hybridization (FISH) using different-colored commercial RB1 and 13qter DNA probes to identify RB1 deletions in interphase nuclei of bone marrow from 24 patients with agnogenic myeloid metaplasia (AMM), 20 patients with multiple myeloma (MM), 21 patients with other hematologic malignancies, and 25 normal bone marrow transplant (BMT) donors. Based on the 25 normal BMT donors, the upper boundary for the normal percentage of nuclei with one RB1 signal was 6.5%. Based on eight specimens known to have a deletion of 13q14 by cytogenetic studies, the lower limit of abnormal for the percentage of nuclei with one RB1 signal was 12.5%. More than 12.5% of nuclei had a single RB1 signal in 7/24 (29%) patients with AMM and 3/20 (15%) patients with MM. None of the 21 patients with hematologic malignancies other than AMM or MM had more than 12.5% nuclei with loss of RB1. The results of this study suggest that FISH with RB1 probes is useful to detect loss of RB1 in interphase nuclei from patients with hematologic disorders who have chromosome abnormalities involving 13q14. Thus, FISH with probes for RB1 is efficacious to investigate the pathogenesis of RB1 in malignant neoplasms and is a useful adjunct to conventional cytogenetic studies in clinical practice when abnormalities of 13q14 are involved.

Adult↗
PubMed2003

Caspase-mediated cell death in hematological malignancies: theoretical considerations, methods of assessment, and clinical implications.

Apoptosis, the caspase-mediated cell death, plays an important role in the etiology, pathogenesis and therapy of a variety of diseases. Abnormalities of apoptosis regulation, resulting in either its inhibition or enhancement, play a key role in the development of various malignant hematological disorders. Several routine and new therapeutic strategies in Oncohematology are based on apoptosis modulation. Cytotoxic effects of most antineoplastic drugs are based on induction of apoptosis. The accurate estimate of incidence of apoptosis, therefore, is of importance in Oncohematology. In this review we provide an overview of the methods designed to measure the incidence of apoptosis, including the recently developed assays that are based on detection of caspases activation. We also review recent findings on the role of caspase-mediated cell death in hematological malignancies and discuss their clinical implications, including new therapeutical strategies that evolve from these findings.

Animals↗
PubMed1996

[Indications for bone marrow and peripheral stem cell transplantation in malignant hematological diseases].

Transplantation of hematopoietic precursor cells is an established therapy today in the treatment of hematological malignancies. Cells from different sources [bone marrow, peripheral blood, cord blood] and from different donor types [autologous, syngeneic or allogeneic] are used for transplantation. The aim of autologous transplantation is to apply intensive high-dose chemo-radiotherapy and to shorten the duration of aplasia. Allogeneic cells, in addition, are free of potentially contaminating precursor cells and provide a graft-versus-leukemia effect. For all patients, transplantation should be considered at diagnosis as an integral part of treatment strategy and, depending on risk factors, be performed early in the course of disease. Preferred time for patients with high-risk acute leukemias is first complete remission, second complete remission for standard or low-risk acute leukemias. For chronic myeloid leukemia, allogeneic transplantation should be performed within one year of diagnosis, preferably still in first chronic phase. Autologous transplantation can be considered in a protocol setting. For patients with myelodysplastic syndromes of the FAB subtype refractory anemia or refractory anemia with sideroblasts, allogeneic transplantation is the treatment of choice as initial therapy. For patients with refractory anemia and excess of blasts with or without transformation, remission induction should be attempted before transplantation. Autologous transplantation is the preferred treatment strategy for patients with Hodgkin's and non-Hodgkin's lymphoma, for high-risk patients in first complete remission, for other patients in chemotherapy-sensitive first relapse. For patients with myeloma, transplantation should be considered after first line therapy. Age is the main individual patient's risk factor, transplant-related mortality immediately increases in parallel to increasing age. Autologous transplants are limited to patients below 60 to 65 years, allogeneic HLA-identical sibling transplants to patients below 50 to 55 years, and unrelated transplants to patients below 40 to 45 years. Prerequisites for transplant are availability of a donor, access to a transplant bed, informed consent of patient and donor, as well as financial guarantee. Indications for the different hematological malignancies and the major risk factors are discussed.

Bone Marrow Transplantation↗