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Results for “hematologic malignancies”

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At least 865 records · Page 48Linked to original sources

PubMed1994

The role of fludarabine in hematological malignancies.

Fludarabine monophosphate, a synthetic nucleoside analog, has been shown to have considerable activity in a number of lymphoid malignancies. In chronic lymphocytic leukemia the response rates can exceed 70% with a considerable proportion of complete remissions being attained. These rates are markedly superior to earlier therapies with which complete remission was uncommon. It also has significant activity in previously treated patients for whom effective salvage regimens were unsatisfactory. In addition, fludarabine shows substantial activity in low grade non-Hodgkin's lymphoma, both as initial treatment and as salvage therapy. Fludarabine is effective in Waldenstrom's macroglobulinemia and is active in other low grade lymphoid malignancies. Major toxicities are reversible myelosuppression and depletion of T lymphocytes. The use of fludarabine in hematological malignancies will be reviewed, with reference to its mode of action and future use in combination therapies.

Adult↗

PubMed1989

Human T-cell leukemia virus-I and hematologic malignancies in Panama.

Serum samples were obtained in a 2-year period (November 1, 1984-December 31, 1986) from 136 Panamanian patients with hematologic malignancies identified by a population-based registry designed for studies investigating human T-cell lymphotropic virus (HTLV)-I. Only three patients had clinical and serologic findings of HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The authors conclude that although classical HTLV-I-associated ATLL occurs in the Panamanian population, it is not as prevalent as in other Caribbean populations.

Aged↗

PubMed2003

Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects.

Detection of minimal residual disease (MRD) has prognostic value in many hematologic malignancies, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, and multiple myeloma. Quantitative MRD data can be obtained with real-time quantitative PCR (RQ-PCR) analysis of immunoglobulin and T-cell receptor gene rearrangements, breakpoint fusion regions of chromosome aberrations, fusion-gene transcripts, aberrant genes, or aberrantly expressed genes, their application being dependent on the type of disease. RQ-PCR analysis can be performed with SYBR Green I, hydrolysis (TaqMan) probes, or hybridization (LightCycler) probes, as detection system in several RQ-PCR instruments. Dependent on the type of MRD-PCR target, different types of oligonucleotides can be used for specific detection, such as an allele-specific oligonucleotide (ASO) probe, an ASO forward primer, an ASO reverse primer, or germline probe and primers. To assess the quantity and quality of the RNA/DNA, one or more control genes must be included. Finally, the interpretation of RQ-PCR MRD data needs standardized criteria and reporting of MRD data needs international uniformity. Several European networks have now been established and common guidelines for data analysis and for reporting of MRD data are being developed. These networks also include standardization of technology as well as regular quality control rounds, both being essential for the introduction of RQ-PCR-based MRD detection in multicenter clinical treatment protocols.

Adult↗

PubMed1989

[Empiric therapy with aztreonam for febrile neutropenic patients with hematological malignancies].

Combination of aztreonam/amikacin/ticarcillin (AAT) and latamoxef/amikacin/ticarcillin (LAT) were compared in a prospective randomized trial of empiric therapy for febrile neutropenic patients with hematological malignancies. Low dose amphotericin B was also added to each regimen from the beginning. Of 45 evaluable episodes, 23 were treated with AAT and 22 with LAT. The response rates were 61 percent for AAT and 50 percent for LAT, statistically not significant. There was one infection-related death among patients assigned to AAT therapy and also one among those assigned to LAT therapy. Dose escalation of amphotericin B seemed to be effective for those patients who did not improve with initial therapy.

Aztreonam↗

PubMed1992

Prophylactic use of ofloxacin in granulocytopenic patients with hematological malignancies during post-remission chemotherapy.

The prophylactic efficacy of ofloxacin (OFLX) therapy was evaluated in 51 granulocytopenic episodes in 22 patients with hematological malignancies during post-remission chemotherapy in a prospective, randomized, controlled trial. Oral administration of OFLX plus amphotericin-B (AMPH) and polymyxin-B (PL) reduced episodes of fever and infection more than did the control regimen with PL and AMPH alone (p less than 0.01), and the reduction in the incidence of infection was evident even in patients showing severe granulocytopenia (p less than 0.01). Furthermore, the first fever after the onset of granulocytopenia in the OFLX regimen developed later than that in the control regimen (p less than 0.05). Clinically, the prophylactic efficacy was 92% for the OFLX regimen and 40% for the control regimen (p less than 0.01). These findings suggest that OFLX is a promising prophylactic agent following post-remission chemotherapy. Patient hemomyelogram findings similar to those of patients with other malignancies may imply that OFLX is widely effective in granulocytopenic patients taking aggressive chemotherapy.

Adolescent↗

PubMed2006

Identification of HLA-A*0201-presented T cell epitopes derived from the oncofetal antigen-immature laminin receptor protein in patients with hematological malignancies.

The oncofetal Ag immature laminin receptor (OFA-iLR) is a potential target molecule for immunotherapeutic studies in several tumor entities, including hematological malignancies. In the present study, we characterize two HLA-A*0201-presented epitopes eliciting strong OFA-iLR peptide-specific human cytotoxic T cell (CTLs) responses in vitro. Both allogeneic HLA-A*0201-matched and autologous CTLs recognized and killed endogenously OFA-iLR-expressing tumor cell lines and primary malignant cells from patients with hemopoietic malignancies in an MHC-restricted fashion but spared nonmalignant hemopoietic cells. Spontaneous OFA-iLR peptide-specific T cell reactivity was detectable in a significant proportion of leukemia patients. Interestingly, in patients with chronic lymphocytic leukemia and multiple myeloma but not in those with acute myeloid leukemia, significant frequencies of OFA peptide-specific CTLs could be detected in an early stage of disease but disappeared in patients with progressive disease. The identification of OFA-iLR-derived peptide epitopes provides a basis for tumor immunological studies and therapeutic vaccination strategies in patients with OFA-iLR-expressing malignancies.

Adult↗

PubMed1987

[Cancer chemotherapy combined with a calcium antagonist in patients with hematologic malignancies and solid tumors resistant to standard chemotherapy].

Cancer chemotherapy combined with calcium-channel blockers was administered to seventeen evaluable patients with hematologic malignancy and solid tumor who became resistant to standard chemotherapies between November 1981 and June 1986 in Saitama Cancer Center. Nicardipine and diltiazem were used as the calcium-channel blockers, which were given orally or intravenously. Adriamycin and/or vinca alkaloids were mainly used as a cancer chemotherapy. Partial remission was attained in 3 of 6 patients with malignant lymphoma. Remission was attained in 2 of 7 patients with acute leukemia including acute transformation of chronic myelogenous leukemia (CML/BC), one complete remission with acute lymphocytic leukemia and one cytoreductive effect with CML/BC. One partial response and one minor response were obtained among 4 patients with solid tumor. The remission of these responders was of short duration. The most serious side effect caused by calcium-channel blockers was hypotension, which was dose-limiting and induced oliguria in 6 of 23 courses. In conclusion, the clinical impression obtained with regard to the effectiveness against chemotherapy-resistant malignancies of cancer chemotherapy combined with calcium-channel blockers was not good even though the overall remission rate was 41%.

Acute Disease↗

PubMed1985

[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in hematological malignancies].

A Phase II study of recombinant leukocyte A interferon (rIFN-alpha A, Ro 22-8181) was performed in 121 patients with hematological malignancies at 33 institutions from July, 1982 to May, 1984. Patients received Ro 22-8181 by intramuscular injection daily for more than 4 weeks. Daily doses were escalated from 3 X 10(6) to 6X, 9X, 18X, 36X and 50X 10(6) units every 3-7 days. Among 70 evaluable cases, complete or partial responses were observed in 15 patients (21.4%). One complete and 10 partial responses (22.4%) were noted in 49 cases of multiple myeloma, 2 partial remissions (18.2%) in 11 cases of malignant lymphoma and 2 partial remissions (25.0%) in 8 cases of leukemia. Side effects included fever (57.0%), anorexia (34.2%), nausea-vomiting (22.8%), malaise (19.0%), leukopenia (44.3%), thrombocytopenia (45.6%) and increase of GOT or GPT (26.6% or 22.8%). They were all not serious and disappeared quickly after the discontinuation of Ro 22-8181.

Adolescent↗

PubMed1982

[Acute pulmonary infiltrates in hematologic malignancies in aplasia (author's transl)].

Extensive pneumonias are usually implicated as the sole cause for acute respiratory failure complicating severe neutropenia in hematologic malignancies and are often fatal. We report study of 11 patients investigated and treated in intensive care unit, using transtracheal aspiration, continuous positive airway pressure (CPAP) via face mask and granulocyte transfusions Two groups of patients emerged from this study. The first group with immediately diffuse pulmonary infiltrates, positive blood cultures, negative tracheal cultures, marked improvement in hypoxemia during CPAP, benefits from granulocyte transfusion without impairment in ventilatory status and may be considered as non-hemodynamic pulmonary oedema. The second group with localized pulmonary infiltrates, negative blood cultures and positive tracheal culture, slight improvement in hypoxemia during CPAP, gets no benefit from granulocyte transfusion, with additional impairment in ventilatory status and may be considered as acute extensive pneumonias.

Acute Disease↗

PubMedDate not supplied

Rhabdomyosarcoma presenting as acute hematologic malignancy: case report and review of the literature.

The authors describe a case of undifferentiated rhabdomyosarcoma from unknown primary site, presenting as an acute hematologic malignancy with generalized lymphadenopathy, extensive bone marrow involvement and clinical and laboratory features of disseminated intravascular coagulation. Such a peculiar behaviour is known for rhabdomyosarcoma but is rare and can be a serious diagnostic problem for the clinician and the pathologist. The importance of a large spectrum immunohistochemistry as first diagnostic approach to any undifferentiated small-cell malignant tumor is stressed, together with the knowledge of the different immunoreactivity patterns. Desmin, MS-actin and myoglobin are the most reliable markers of this type of myogenic sarcoma.

Actins↗

PubMed2000

[Total hematological analysis system as a screening test for hematological malignancy].

Measurement of complete blood cell count and white blood cell differentiation is an essential laboratory test and the most important screening test for hematological malignancy. Recently, several automated blood cell analyzers have been developed to improve accuracy and precision. When flag messages generated in the presence of morphological abnormalities of the samples are displayed, manual revision is necessary. In our laboratory, the manual revision rate has been 35-40%. Therefore blood cell analyzers are useful in screening for abnormalities as well as greatly reducing expensive and time-consuming manual differential procedures. In addition, automated blood cell analyzers can provide several types of useful information including the leukocyte distribution scattergram. However, most such information is not utilized in the clinical field. In the future, a total hematological analysis system will be constructed so that all information provided by automated blood cell analyzer and by manual methods are available.

Blood Cell Count↗

PubMed1999

Supportive care in hematological malignancies: hematopoietic growth factors, infections, transfusion therapy.

This article focuses on a selected number of topics among recent developments in the supportive care of hematological malignancies. The first section focuses on the role of hematopoietic growth factors, such as granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, thrombopoietin, interleukin-11, and keratinocyte growth factor. The following sections discuss the management of fungal and viral infections as well as changes in the current policies of platelet transfusion. The focus of this review is on the clinical utility and economic feasibility of the published findings.

Anti-Infective Agents↗

PubMed2004

The soluble form of CD83 is present at elevated levels in a number of hematological malignancies.

Recombinant forms of soluble CD83 (sCD83) inhibit anti-tumor responses. In this analysis of circulating sCD83 levels we report that although >95% of acute myeloid leukemia (AML) and multiple myeloma (MM) patients have normal or only weakly elevated sCD83 levels, 20% of chronic lymphocytic leukemia (CLL) and 5/7 mantle cell lymphoma (MCL) patients have significantly elevated levels (>1 ng/ml). Isolated CLL cells both weakly expressed membrane CD83 (mCD83), and released sCD83 during in vitro culture. We conclude that malignant cells are a potential source of sCD83 and that it may have functional and/or prognostic significance in hematological malignancies, particularly CLL and MCL.

Acute Disease↗

PubMed1990

Serum transferrin receptor measurements in hematologic malignancies.

An enzyme-linked immunosorbent assay using specific monoclonal antibodies was used to measure circulating transferrin receptor (TR) in 87 patients with various hematologic malignancies. The mean serum TR was significantly elevated in patients with myeloproliferative disorders (15.47 +/- 12.54 micrograms/ml), whereas there were no differences in chronic granulocytic leukemia (7.89 +/- 3.56 micrograms/ml), myelodysplastic disorders (9.25 +/- 4.73 micrograms/ml), and acute nonlymphocytic leukemia (3.85 +/- 3.50 micrograms/ml) as compared to normal (5.63 +/- 1.42 micrograms/ml). Among patients with lymphoproliferative disorders, the mean level was normal in lymphoma (5.73 +/- 2.59 micrograms/ml), multiple myeloma (5.47 +/- 1.31 micrograms/ml), and hairy cell leukemia (7.04 +/- 3.69 micrograms/ml). The serum TR was significantly elevated in chronic lymphocytic leukemia (CLL; 14.17 +/- 12.29 micrograms/ml), and the serum levels reflected the clinical stage of the disease. These findings suggest that serum TR measurement may provide a useful laboratory index of disease activity in certain disorders such as CLL, whereas it most likely reflects the intensity of erythropoiesis in the remaining hematological disorders that were evaluated in this study.

Adult↗

PubMed2006

Nucleic acid therapeutics for hematologic malignancies--theoretical considerations.

Our work is motivated by the belief that RNA targeted gene silencing agents can be developed into effective drugs for treating hematologic malignancies. In many experimental systems, antisense nucleic acids of various composition, including antisense oligodeoxynucleotides (AS ODNs) and short interfering RNA (siRNA), have been shown to perturb gene expression in a sequence specific manner. Nevertheless, our clinical experience, and those of others, have led us to conclude that the antisense nucleic acids (ASNAs) we, and others, employ need to be optimized with regard to intracellular delivery, targeting, chemical composition, and efficiency of mRNA destruction. We have hypothesized that addressing these critical issues will lead to the development of practical and effective nucleic acid drugs. An overview of our recent work which seeks to addresses these core issues is contained within this review.

Hematologic Neoplasms↗

PubMed2004

NF-kappaB/Rel-mediated regulation of apoptosis in hematologic malignancies and normal hematopoietic progenitors.

The activity of NF-kappaB/Rel transcription factors can downmodulate apoptosis in normal and neoplastic cells of the hematologic and other compartments, contributing in maintaining neoplastic clone survival and impairing response to therapy. Alterations in nfkappab or ikappaB genes are documented in some hematologic neoplasias, while in others dysfunction in NF-kappaB/Rel-activating signaling pathways can be recognized. The prosurvival properties of NF-kappaB/Rel appear to rely on the induced expression of molecules (caspase inhibitors, Bcl2 protein family members, etc.), which interfere with the apoptosis pathway. Constitutive NF-kappaB/Rel activity in some hematologic malignancies could be advantageous for neoplastic clone expansion by counteracting stress stimuli (consumption of growth factors and metabolites) and immune system-triggered apoptosis; it is furthermore likely to play a central role in determining resistance to therapy. Based on this evidence, NF-kappaB/Rel-blocking approaches have been introduced in antineoplastic strategies. The identification of NF-kappaB/Rel target genes relevant for survival in specific neoplasias is required in order to address tailored therapies and avoid possible detrimental effects due to widespread NF-kappaB/Rel inhibition. Moreover, comparative analyses of normal hematopoietic progenitors and neoplastic cell sensitivities to inhibitors of NF-kappaB/Rel and their target genes will allow to evaluate the impact of these tools on normal bone marrow.

Animals↗

PubMed2000

Early detection of relapse and evaluation of treatment for mixed chimerism using fluorescence in situ hybridization following allogeneic hematopoietic cell transplant for hematological malignancies.

In order to detect chimerism, fluorescence in situ hybridization (FISH) and cytogenetic analyses were performed on bone marrow cells from 47 patients with hematological malignancies following allogeneic hematopoietic cell transplant (HCT). The dual-color XY, major Bcr-Abl (M-Bcr-Abl), and specific alpha-satellite probes were used for sex-mismatched HCT, chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) cases with karyotypic abnormalities before HCT, respectively. Donor cells were found using FISH analysis in all 32 cases examined within 2 months following HCT, confirming engraftment. In six cases, however, cytogenetic analysis failed to detect donor cells due to lack of metaphases. Relapse occurred in four of the six cases in which mixed chimerism was detected using FISH analysis after 6 months of HCT. In contrast, after 12 months of HCT, no relapse was found in 24 patients without host cells. For two patients with mixed chimerism, gradual reduction of immunosuppressants or donor lymphocyte infusion resulted in the disappearance of host cells as analyzed using FISH analysis. In three extramedullary relapse cases, however, cytogenetic relapse preceded morphological and FISH relapse. These findings suggest that FISH analysis is more useful for detecting residual host cells after HCT, and the combination of FISH and cytogenetic analyses provide a more detailed evaluation for HCT patients. The results also indicate that monitoring of mixed chimerism using FISH analysis after 6 months of HCT is important for allowing the early detection of hematological relapse.

Female↗

PubMedDate not supplied

Development of autoimmune thyroid diseases during long-term treatment of hematological malignancies with alpha-interferons.

In recent years recombinant alpha-interferons (alpha-IFNs) have been widely used in the treatment of several hematological malignancies. Prolonged courses of IFN have been shown to induce autoantibodies and to support the exacerbation or even the development of autoimmune diseases. In this report we describe the development of symptomatic autoimmune thyroid diseases in 4 (7.4%) out of 54 patients in chronic treatment with recombinant alpha-IFNs in our department. Two patients developed a disease resembling Hashimoto's thyroiditis after 17 and 49 months of continuous IFN treatment, while the other two developed a typical Graves' disease after 41 and 52 months of therapy. The mechanism by which IFN induces autoimmune thyroid diseases, the choice of searching for anti-thyroid autoantibodies before starting long-term IFN treatment, the option of discontinuing IFN therapy in the presence of overt thyroid diseases, and the management of these diseases are discussed.

Autoimmune Diseases↗