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PubMed1983

Fluorescence polarization as a parameter of plasma lipids in patients with hematologic malignancies.

Abnormal diphenylhexatriene fluorescence polarization measurements (FP values) of plasma have previously been reported in patients with hematologic malignancies. However, the biological significance of this measurement is unclear. We have prospectively studied plasma from 39 patients with leukemia and lymphoma as well as normal donors for total cholesterol, total triglyceride, and lipoprotein-cholesterol fractions, and correlated these values with measured FP values. Total triglyceride, very low density lipoproteins (VLDL), high density lipoprotein (HDL) levels, and FP values were all strongly correlated with clinical and biochemical measures of tumor burden and varied directly with the presence of malignancy. Although the presence of abnormal FP values was confirmed in patients with leukemia and lymphoma, it was not a particularly sensitive measure for minimal tumor and it appeared to correlate directly with other measures of lipids and cholesterol, particularly triglyceride. It is suggested that further studies of conventional plasma lipids and lipoproteins be pursued in order to elucidate the apparently pervasive alterations in lipid metabolism present in these patients.

Adolescent↗

PubMed1988

Non-caseating granulomas in patients with hematologic malignancies. A report of three cases.

Sarcoidosis or sarcoid-like lesions occurred in three patients with hematologic malignancies. In one patient, an overlap syndrome sarcoidosis/polycythemia vera was the most probable diagnosis. In the other two cases, the granulomas were probably secondary to myelofibrosis and Waldenström's disease, respectively. Recent epidemiological studies have failed to show a causal relationship between sarcoidosis and malignancy. The co-existence of sarcoidosis and malignancy is probably fortuitous, but non-caseating granulomas may occur secondary to malignant diseases.

Aged↗

PubMed1994

Alterations of the putative tumor suppressor gene p16/MTS1 in human hematological malignancies.

The chromosome band 9p21-22 is frequently rearranged or deleted in a variety of tumors including hematological malignancies. This supports the notion of a tumor suppressor gene in this chromosome region. Indeed, the p16/MTS1 gene encoding a cyclin-dependent kinase (CDK) inhibitor has been shown to be frequently deleted and/or inactivated by nonsense mutations in a number of tumors. We have examined 98 DNA samples from blood, bone marrow cells and lymph node biopsies of patients with leukemia (ALL and AML) or lymphoma (follicular lymphoma and T-cell lymphoma), using Southern blot hybridization and a p16/MTS1-specific probe. Molecular abnormalities, mainly homozygous deletions, were found principally in ALL (8 out of 22 patients), much less frequently in AML (2/32) and lymphoma (2/32). While these data argue in favor of a large involvement of p16/MTS1 in ALL, AML and lymphomas appear to be less frequently implicated.

Adult↗

PubMed1994

Immunohistochemical evaluation of hematologic malignancies.

This article summarizes the most recent developments and current practice of immunohistochemistry in the diagnosis of hematologic malignancy. Increased availability of monoclonal antibodies applicable in formaldehyde-fixed and paraffin-embedded tissue is discussed as are immunohistochemical definitions for many small cell lymphoma entities. Evaluation is made of the biologic potential of lymphomas and leukemias by the use of antibodies to proliferation antigens, such as Ki-67 and products of tumor suppressor genes (p53).

B-Lymphocytes↗

PubMedDate not supplied

Chemiluminescent detection of gene rearrangements in hematologic malignancy.

A chemiluminescent based Southern blot assay is described for the detection of gene rearrangements in human hematologic malignancies. The DNA probes for regions of rearrangements within the immunoglobulin genes were labeled with digoxigenin-11-dUTP and detected by an antibody conjugated to alkaline phosphatase with Lumiphos 530 as a substrate. This assay has proven more sensitive than colorimetric assays and provides rapid turn-around times without the hazards of radioactive isotopes.

Blotting, Southern↗

PubMed1998

[Advantages of CD45 vs. side scatter based gating in the course of flow cytometric immuno-phenotyping in malignant hematologic diseases].

The application of the CD45 vs. side scatter gating in the flow cytometric immunophenotyping of malignant haematological disorders was investigated. In the course of the conventional double labeling the light scatter based gating is the method of choice, which allows the immunophenotypic characterization of the subpopulations of interest. Using this gating strategy one can separate the lymphocytes, monocytes, neutrophil granulocytes, eosinophils and platelets as distinct cell populations in normal blood samples. The blastic cells present in different malignant hematological disorders might, however, represent an overlapping population with the lymphocytes, NK-cells, monocytes, and nucleated erytroid elements on the FSC vs. SSC histogram, making it difficult or impossible to separate them from the residual reactive cells. This will impart false mixed immunophenotypic property to the blastic cells. The authors found definitive advantages of CD45 vs. SSC gating in contrast to the FSC vs. SSC analysis due to the reliable separation of lymphoblasts, myeloblasts, nucleated erytroblasts as well as the debris from the reactive cell populations. The most plausible application of this method is shown in the course of three-color labeling, applying CD45 as a constant marker. Furthermore, the authors demonstrated that the CD45 vs. SSC gating strategy will result in considerable increase in resolution of blastic population also in the course of the most conventional dual-color labeling method.

Flow Cytometry↗

PubMed2002

Noninvasive detection of multidrug resistance in patients with hematological malignancies: are we there yet?

The success of chemotherapy in the treatment of malignancies may be limited by cellular mechanisms leading to drug resistance. In hematological malignancies, mechanisms leading to the development of multidrug resistance (MDR) include overexpression of the membrane-based export pump P-glycoprotein (Pgp) and the MDR-associated protein (MRP). Recently, the overexpression of the lung-resistance protein (LRP) has also been associated with reduced intracellular drug accumulation. A major problem in assessing the significance of the expression of these resistance proteins in clinical MDR has been the variability of detection techniques either at the mRNA or protein level. Currently, the detection of resistance proteins relies heavily on antibody and cDNA probes, and these methods may not be informative about the in vivo function of Pgp, MRP, or LRP. Nuclear medicine imaging techniques such as single-photon emission tomography (SPECT) and positron emission tomography (PET) have been evaluated for noninvasive determination of the presence and the function of Pgp- and MRP-mediated transport systems. Technetium 99m ((99m)Tc)-sestamibi, an agent in clinical use for myocardial perfusion and tumor imaging, is recognized as a substrate for Pgp and MRP, and has been used to visualize Pgp expression. (99m)Tc-tetrofosmin is also a substrate for the Pgp efflux pump mechanism and is used to evaluate Pgp function in in vitro and in vivo studies. Recently, radiopharmaceuticals including carbon 11-labeled colchicine, verapamil, and daunorubicin have been used in cell line and animal studies for the evaluation of Pgp-mediated transport functions using PET technology. Preliminary results suggest that the potential to detect MDR in tumors prior to or after exposure to chemotherapeutic agents exists in imaging using either (99m)Tc-labeled compounds and SPECT or positron emitting compounds and PET.

Biopsy, Needle↗

PubMed1984

[Phase II study of etoposide (NK 171) in advanced hematological malignancies].

A clinical study of a new semisynthetic podophyllotoxin etoposide (NK 171) was performed in patients with various hematological malignancies refractory to standard chemotherapies. The drug was given intravenously in a dose of 100-130 mg/m2/day for five days or orally in a dose of 130-170 mg/m2/day for five days. Out of 9 patients with non-Hodgkin's lymphoma, 2 CR and 4 PR were obtained; out of 4 acute nonlymphoblastic leukemias, 1 CR, and out of 4 chronic myerogenous leukemias 2 CR and 1 PR, were obtained. The dose limiting factor was leukopenia, and alopecia was frequent while other hematologic and gastrointestinal toxicities were mild. Etoposide (NK 171) had no clinical cross resistance to other antitumor agents, thus warranting further clinical trials, in combination chemotherapy against NHL, ANLL and CML-BC.

Administration, Oral↗

PubMed2002

Emerging fungal pathogens in patients with hematologic malignancies and marrow/stem-cell transplant recipients.

Fungal infections are a major cause of morbidity and mortality among patients with hematologic malignancies and recipients of bone-marrow/hematopoietic stem-cell transplants. Although Candida and Aspergillus species remain the most common fungal pathogens, multiple unusual fungal pathogens are being increasingly recognized as a cause of infection in these patients. Many of these rare fungal infections have a characteristic clinical disease spectrum. Early diagnosis and prompt treatment of these infections is the key to a successful outcome. In this article, we summarize the epidemiology, pathogenesis, clinical features, and approach to the management of infections caused by Fusarium, Zygomycetes, Scedosporium, Trichosporon, Malassezia, Alternaria, Paecilomyces, and Penicillium.

Bone Marrow Transplantation↗

PubMed2000

Nonrandom rearrangements of 6p in malignant hematological disorders.

It is very uncommon to observe nontranslocation abnormalities (NTAs) involving the short arm of chromosome 6 (6p) in malignant hematological disorders (MHDs). By using conventional cytogenetics and fluorescence in situ hybridization (FISH) with chromosome-microdissection probes specific for 6p21 and 6p25, we observed five patients with myeloid malignancies and two patients with lymphoid malignancies to have 6p NTAs. On the basis of our data and those in the literature, it is possible to divide 6p NTAs into the following three groups in MHD: The first group presents with 6p NTAs as a sole or primary change in myeloid malignancies. There are only two cases reported in this group, including one case with del(6)(p23) and the present case with ins(6)(q23p23p25) identified by FISH only. The second group presents with 6p deletions as a sole or primary change in lymphoid malignancies. Three cases have been reported in this group, including one case with del(6)(p21p23), one with del(6)(p21), and the present case 2 with del(6)(p21). The third group has 6p deletions in addition to other known primary changes, present in both myeloid and lymphoid disorders, with 36 cases reported, including five cases from our series. Deletions involving 6p21, 6p22, or 6p23 have been observed in both myeloid and lymphoid disorders. The present data provide cogent information for further molecular characterization of 6p anomalies in MHD.

Adult↗

PubMed2003

Ifosfamide in hematological malignancies of adults.

Ifosfamide is an alkylating agent with a broad spectrum of activity in solid tumors and hematological malignancies. In this review we will illustrate its use in the treatment of lymphomas and Hodgkin's disease and the results of the principal studies which have investigated ifosfamide-containing regimens. Ifosfamide has been mainly used, in combination with other drugs, as a component of salvage regimens for relapsed or primarily refractory lymphoma. These regimens induced a variable clinical response rate (complete remissions ranging from 6 up to 73% and overall response rate from 24 to 72%). High-dose ifosfamide, in combination with etoposide or mitoxantrone, showed a good potential for mobilization of peripheral stem cells while reducing the tumor burden. Ifosfamide-based regimens are also being evaluated in the treatment of newly diagnosed patients in sequential, response-based protocols, using many non-cross-resistant drugs.

Adult↗

PubMed1986

The intraventricular reservoir in the treatment of neurological disease secondary to hematological malignancy: an eight year experience.

Between 1974 and 1982, 17 patients with central nervous system disease secondary to hematological malignancy had an intraventricular reservoir inserted to monitor their disease and to instill cytotoxic chemotherapy. Two other patients with acute lymphoblastic leukemia and difficult access to the cerebrospinal fluid had a reservoir inserted to facilitate intrathecal chemotherapy. All 17 patients with established disease showed clinical improvement. Thirteen patients had complete elimination of malignant cells from the cerebrospinal fluid with cytotoxic chemotherapy, and the other four had a reduction in the concentration of malignant cells. Infection and neurotoxicity were found in a significant number of cases, and therefore the good clinical response associated with the procedure must be weighed carefully against the associated toxicity.

Adolescent↗

PubMedDate not supplied

Central venous catheter clots: incidence, clinical significance and catheter care in patients with hematologic malignancies.

In a 7-month period we studied 38 Hickman central venous catheters (CVCs) positioned in children with hematologic malignancies with the aim of evaluating the incidence and clinical impact of CVC clots. Clots were found in 74% of the CVCs. Three methods of catheter care were developed for flushing the clotted CVCs: (a) use of a heparinized solution (400 IU/mL) on alternate days, (b) use of a heparinized solution (400 IU/mL) and saline solution containing urokinase (10,000 IU/mL) on alternate days, and (c) use of a saline solution containing urokinase (10,000 IU/mL) daily. Only method b decreased clot formation (33% success rate). There were no major mechanical complications in any of the CVCs with clots. Eighteen percent of patients with clots in their CVCs presented with CVC-related infections while no infective complications were observed in the patients without clots in their CVCs. In conclusion, CVC clots may predispose the patient to infections, which must be correctly treated.

Adolescent↗

PubMed1992

[Analysis of T-cell receptor delta chain gene in hematological malignancies].

We analyzed the rearrangement of T-cell receptor (TcR) delta chain gene in 196 cases of hematological malignancies. This rearranged band (s) was observed in 15% of the total cases investigated. All T-ALL patients and cell lines, except for P30/Okubo, had a new band (s) or deletion of J delta 1 gene locus, indicating the gamma delta T-cell type or the alpha beta T-cell type. In the other T-cell malignancies, the delta rearranged band (s) was recognized in 5% of T-cell lymphomas, 20% of AILD but not in ATL, Hodgkin's disease, T-CLL. Inappropriate delta rearrangement was frequently recognized in 63% of B-ALL and 50% of CML-BC but none or few (5% less) in B-CLL, B-lymphoma and AML. Southern blotting, using J delta 1 and V delta gene probes or Pst I enzyme digestion, indicated that the inappropriate delta rearranged band in B-ALL and CML-BC is V delta 2D or DD without a J delta locus. The rearranged band (s) involved J delta locus, was mostly recognized in 5/6 cases of CD7 (+) stem cell leukemia. Therefore, the TcR delta gene is useful in evaluating clonality for the most immature T-cell neoplasms, not showing rearrangement of the other TcR genes. Moreover, this delta gene may be a useful tool for distinguishing T-lineage from the other lineages, using the characteristic rearrangement pattern (V delta 2D as a inappropriate pattern, or (D) DJ and V (D) DJ as the T-lineage pattern (s)).

Chromosome Deletion↗

PubMed1990

[Comparison among three preconditioning regimens for allogeneic bone marrow transplantation in hematological malignancies].

We analysed probability of disease free survival (DFS) and remaining in remission (POR) in evaluable patients with hematological malignancies undergoing allogeneic bone marrow transplantation by Nagoya BMT groups between 1976 and August 1989 according to conditioning regimens retrospectively. Patients were divided into good risk patients with acute leukemia in first remission or CML in chronic phase and high risk patients with advanced disease. The results are as follows: 1. DSF and POR in good risk patients was 45% and 68% at 7 1/2 years for thirty nine patients treated by CY + TBI, 63% and 78% at 5 2/3 years for thirty nine patients treated by CA + CY + TBI, 84% and 84% at 2 years for sixteen patients treated by preconditioning regimens without TBI respectively. 2. DFS and POR in high risk patients was 21% and 45% at 6 years for twenty nine patients treated by CY + TBI, 23% and 48% at 4 5/6 years for forty patients treated by CA + CY + TBI, 64% and 74% at 2 years for eight patients treated by preconditioning regimens without TBI respectively. 3. There were no statistical differences among these conditioning regimens in good and high risk patients. These results show that more effective and stronger preconditioning regimens are needed especially for high risk patients for prevention of posttransplant leukemia relapses.

Acute Disease↗

PubMed1990

[Invasive fungal infections in hematologic malignancies--a retrospective study of 61 autopsied cases].

In a review of 61 consecutive autopsy cases with a hematologic malignancy, said cases extending from April, 1984 to August, 1989, 34 cases were documented to have had an invasive fungal infection. The highest rate of incidence was found in various leukemia cases (69 to 100%), followed by those who had had a malignant lymphoma (50%) and a multiple myeloma (33%). Cultures from autopsy materials that determined the presence of a fungus were positive in 21 cases, including 13 cases of candidiasis, 8 cases of aspergillosis, and 2 cases of geotrichosis. The most frequent site of the fungal infection was in the lungs (76%), followed by the GI tract, the kidneys, the liver, and the spleen. Of 36 cases that had been treated with an empiric antifungal therapy, an invasive fungal infection was documented in 22 cases, half of them being fatal. In contrast, of 20 cases that had not received any antifungal treatment prior to death, an invasive fungal infection was found in 8 cases and three of these were fatal.

Aspergillosis↗

PubMed1989

Application of polymerase chain reaction to detect activated oncogenes in hematological malignancies.

Polymerase chain reaction (PCR) was applied to detect the structural change accompanying the activation of oncogenes in hematological malignancies and preleukemic states. Point mutation of N-ras oncogene was examined by oligonucleotide differential hybridization coupled with PCR. Five out of 17 AML patients were shown to have mutated N-ras gene. These mutations could be used as a genetic marker to diagnose the residual malignant cells. Philadelphia chromosome in CML was examined by cDNA synthesis and PCR with successful results. PCR was shown to be a highly versatile and sensitive method which would be invaluable in clinical diagnosis.

Base Sequence↗

PubMed1983

[Phase II study of Vindesine in patients with hematological malignancy].

At Saitama Cancer Center a Phase II study of Vindesine was carried out in 18 patients with hematological malignancy being refractory to standard chemotherapies. Vindesine (VDS) was given weekly at a dose of 3 mg/m2 as single-agent chemotherapy. One cytoreduction effect (CE) in 5 patients with acute lympho blastic leukemia, two CEs in 2 patients with acute non-lymphocytic leukemia, one PR and one CE in 4 patients with CML/BC, three PRs in 3 patients with diffuse non-Hodgkin's lymphoma (NHL) of large cell type, one CR in 2 patients with lymphoblastic lymphoma and one PR in 2 patients with Burkitt's lymphoma were obtained. VDS was discontinued in two patients because of neurologic toxicities such as incontinence of urine, abdominal distension, and severe constipation.

Adult↗