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PubMed1989

Cytogenetically unrelated clones in hematological neoplasms.

We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.

Chromosome Aberrations↗

PubMed2001

[Use of central venous catheters in children with hematologic neoplasms from the viewpoint of the pediatric surgeon].

Venous access by cannulation of the central vein is a necessary prerequisite of the oncological treatment. Within the period 1998-2001 there 395 CVCs (Central Venous Catheters) were introduced using a subcutaneous tunnel in 335 hospitalised patients at the Clinic of the Child Surgery, Orthopaedics and Traumatology FN Brno. In 310 patients Hickman CVC was used and in 25 Groshong CVC. Using the vena subclavia 1. dx., 131 CVCs were introduced, via the vena subclavia 1. sin. 264 CVCs. The average period of CVCs introduction was 3 months. In 78 introduced CVCs infectious complication developed. A local infection was noticed only 8 times, general infection at 70 cases. In 13 patients CVCs had to be removed. The authors present their experience with the introduction of tunneled CVCs in oncological patients and the options for solving the infectious complications when using CVCs.

Adolescent↗

PubMedDate not supplied

Interphase cytogenetics of hematological neoplasms under the perspective of the novel WHO classification.

The novel WHO classification of tumors of hematopoietic and lymphoid tissues highlights the importance of genetic aberrations for the proper diagnosis of these malignancies. Among those techniques allowing detection of chromosomal changes, we have shown repeatedly that interphase fluorescence in situ hybridization (FISH) is currently the most robust and reliable technique for the diagnosis of lymphoma-associated translocations. Interphase FISH assays for the detection of the most frequent chromosomal alterations in myeloid and lymphoid disorders have become commercially available during the recent past. The sensitivity of some of these assays reaches levels below 1% providing valuable tools not only for diagnosis but also for follow-up and detection of minimal residual disease. Improvements of interphase FISH include the development of multicolor interphase FISH assays to detect several of the diagnostic changes in a single cell and of simultaneous fluorescence immunophenotyping (FICTION technique) to correlate phenotypic and genotypic cell features.

Hematologic Neoplasms↗

PubMed2000

[Resistance of hematologic neoplasm cells to cytostatics. Part II].

Resistance to cytotoxic drugs is a serious drawback in the treatment of patients with tumours, both of the haemopoietic and non-haemopoietic origin. The cytotoxic effect of drugs on the malignant cells manifests as the process of apoptosis. In the resistant malignant cells, apoptosis becomes prevented by several mechanisms. The multidrug resistance (MDR) is one of the principal mechanisms when the cancer cells develop resistance to multiple chemically and functionally unrelated cytotoxic compounds. The decrease of the cytotoxic drug concentration at the molecular target site may come from activation of some efflux membrane systems participating in the transport of cytotoxic drugs out of the cell (e.g. Pgp, MDR, and LRP). Another mechanism of resistance is the increased enzymatic detoxification of the drug by glutathion-s-transferase system. Changes in the molecular target of the cytotoxic drug such as topoisomerase molecule can be also responsible for the resistance. At least two additional mechanisms of resistance of tumour cells were identified. Resistance can come from either deregulation of proapoptotic mechanisms in tumour cells or by increased activity of reparation processes which control the damaged molecule of DNA. Several methods that detect the cause of resistance in distinct cell populations have been developed. The great effort is now focused on both the detection of mechanisms of the resistance and on the clinical procedures of overcoming the resistance to cytotoxic drugs.

Antineoplastic Agents↗

PubMed1997

[Hypocholesterolemia in hematologic neoplasms].

PURPOSE: To evaluate the cholesterol metabolism in oncohaematologic patients and its inclusion as a biochemical marker as well as other parameters in the diagnostic period (leukocytes, deshidrogenase lactate, erithrosedimentation, haptoglobine). Many different epidemiological studies discuss the relation between the high risk for cancer mortality and low blood cholesterol in patients with colon, rectum, ovary and brain cancer as well as in chronic myeloid leukaemia, acute leukaemia and policytemia vera. PATIENTS AND METHODS: Two groups were studied: a normal group (n = 32) was confronted to a group of oncohaematologic patients (n = 37) (15 lymphoma, 4 acute leukaemia, 7 chronic myeloid leukaemia, 1 chronic myelomonocytic leukaemia, 3 policytemia vera, 5 myeloma and 2 chronic lymphoid leukaemia). In all the cases we determinated the total cholesterol, HDL cholesterol, LDL cholesterol, A1 y B apolipoproteins. RESULTS: The means obtained in the normal group were 184.63 mg/dL, 50.34 mg/dL, 116.38 mg/dL, 140.93 mg/dL, 79.57 mg/dL while in the pathologic group were 163.43 mg/dL, 38.19 mg/dL, 106.60 mg/dL, 102.81 mg/dL and 101.23 mg/dL, respectively. There was a significant difference in the total cholesterol, HDL cholesterol and apolipoprotein A1. These values were lower for leukocytes higher than 10.0 x 10(9)/L. Furthermore the lowest total cholesterol value was seen in myeloma patients. CONCLUSION: The cholesterol, its fractions and the apolipoproteins determinations might be considered as a biochemical marker while diagnostic is being made, since they are known to play an important role in the tumoral cell metabolism.

Adult↗

PubMed2000

[Autologous transplantation of peripheral blood stem cells in the framework of treatment for hematologic neoplasms. II. Determination of CD34+ cells and progenitor colonies].

119 collections of peripheral blood stem cells were performed in 60 patients suffering from various haematological malignancies. One patient was transplanted twice. Peripheral blood stem cell mobilisation was performed using various regimens. A correlation (r = 0.732) was found between the number of peripheral CD34+ cells and the number of CD34+ cells that were collected by apheresis. Furthermore, the number of collected peripheral blood stem cells correlated with the number of colony-forming units (CFU-GM) identified after cell culture (r = 0.607). After transplantation, the duration of neutropenia (> 0.5 x 10(9)/l) was 11.7 days (SD = 3.3) and of thrombocytopenia (> 20 x 10(9)/l) 12.7 days (SD = 6.8). For the whole group, no correlation was observed between the number of CD34+ cells infused and the length of the aplasia. However, when the patients were separated into two groups, according to the amount of CD34+ cells transplanted (< 10 x 10(6)/kg, n = 48 and > 10 x 10(6)/kg, n = 13), a statistically significant but moderate decrease in the duration of neutropenia and thrombocytopenia was observed in patients who received the highest doses of CD34+ cells. Our results confirm the utility of measuring the number of the CD34+ cells in peripheral blood as well as in the product collected by apheresis, but they challenge the place of cultures of progenitor haematopoietic cells. Moreover, the infusion of large amounts of CD34+ cells shortens the duration of the aplasia.

Antigens, CD↗

PubMed1999

[Complications associated with central venous catheters in patient with hematologic neoplasms or hematopoietic transplants].

OBJECTIVE: Nontunneled central venous catheters (CVCs) have been found an excellent cost-effective alternative to tunneled CVCs with comparable durability and safety when managed by a specialized team. The objective of this study was to evaluate the complications related with a nontunneled polyurethane CVC in a medium-size hospital without such dedicated services. PATIENTS AND METHODS: A representative sample of 82 cancer patients with 123 nontunneled CVCs inserted at our centre were followed up and evaluated clinically and microbiologically. Insertion and care were performed by the medical and nursing teams. RESULTS: The mean duration of the catheters in place was 28.2 days. Eleven mechanic complications (8.9%) were observed. We had a total of 3,380 days of catheter use with an infection rate of 0.86 per 100 catheter-days. Staphylococcus coagulase-negative was the most common microorganism isolated. Local and systemic infection showed a different pattern of incidence, early after insertion and a month later respectively. Male sex and neutropenia at catheter removal were the only risk factors for bacteremia while receiving antibiotics at insertion date was a protecting factor. Age, number of lumens, insertion difficulty or patient diagnosis were not related with infection risk. CONCLUSIONS: Contamination at catheter insertion clinical or manipulation must be avoided especially when a neutropenia period is expected. A highly trained team working under rigorous guidelines is an important factor for optimal clinical and economic results with nontunneled CVCs. The cost of a specialized infusion team may well be below the price of poorly maintained catheters.

Adolescent↗

PubMed2003

[Infections with Van B phenotype Enterococcus faecium and E. faecalis in patients with immune deficiency during the course of hematologic neoplasms].

In this work, we have analyzed the second outbreak of VRE with the VanB phenotype to be identified in the country. The aim of this study was to characteristics of the types of resistance to glycopeptide antibiotic and to check the resistance patterns of these pathogens. A trial of monitoring the risk factors for colonization or infection with VRE as well as epidemiological investigation were undertaken. Genus identification of the isolates was performed according to the method of Facklam and Collins, and species were identified using the API 20 Strep test. MICs of different antimicrobial agents were determined by the E-test method. The isolates collected during the investigation demonstrated resistance to multiple antimicrobials, which is a common characteristic of VRE. Isolates were found to be uniformly resistant to penicillin, fluoroquinolones, tetracycline and to high concentrations of aminoglycosides. The only drugs with in vitro activity against the isolates were ampicillin (VRES), linezolid (VRES, VREM) and quinupristin-dalfopristin (VREM). Except for a single VREM isolate, they all revealed the typical VanB phenotype with resistance to vancomycin and susceptibility to teicoplanin. One of the VREM isolates turned out to be resistant to teicoplanin, which coincided with the use of this antibiotic in the patient's therapy. Its vanB gene variant differed by a single mutation from that found in other isolates; however, it also lacked a large part of the vanB gene claster, including the regulatory genes vanRB and -SB, and the vancomycin--inducible promoter PYB. Our studies have found an association between colonization or infection with VRE and the mean duration of hospital stay, previously administration of glycopeptide, cephalosporins and imipenem. These organisms were a common cause of monoethiological bloodstream infections.

Adult↗

PubMed1996

[Cytogenetic study of 121 patients suffering from various hematologic neoplasms using the in situ hybridization technique].

PURPOSE: In situ hybridization (ISH) is an efficient tool for detecting chromosomal abnormalities in haemopoietic malignancies. Structural and numerical changes typical of most pathological entities can be detected using chromosome-specific probes on interphase or metaphase cells by means of this technique. PATIENTS AND METHODS: In this report we present chromosome analysis combining conventional cytogenetics with ISH in 121 patients affected with different haematological diseases. We have studied 92 patients with B-chronic lymphoproliferative disorders (B-CLPD), 11 myelodysplastic syndromes (MDS), 17 acute nonlymphocytic leukaemias (ANLL), 1 acute lymphocytic leukaemia and 1 aplastic anaemia. The ISH was carried out with two kind of biotin-labeled probes: a) 8 and 12 centromeric alpha satellite probes and b) whole painting chromosome (WPC) library probes from all the chromosomes except numbers 10, 16, 21, X and Y. RESULTS: The cytogenetic analysis of B-CLPD has been hampered by several problems. These leukaemic cells have very low spontaneous mitotic activity and the cell response to mitogens is often poor, unpredictable and variable. Even so, an extra chromosome 12 (+ 12) is one of the most frequent abnormal karyotypes reported. ISH and chromosome 12 specific biotinylated alpha satellite DNA probe was applied in 84 patients with B-CLPD. Among 50 patients with typical chronic lymphocytic leukaemia (CLL) the ISH studies showed two signals of hybridization in the 50 cases. By conventional cytogenetics 9 out of 18 atypical CLL showed chromosomal abnormalities and 7 of them trisomy 12. ISH detected trisomy 12 in 11 of these cases. Trisomy 8 is the most frequent karyotypic change in MDS and ANLL. Cytogenetic results revealed a clear extra copy of chromosome 8 in 13 cases. In all of these trisomic cases, the presence of trisomy 8 clone was confirmed by ISH. ISH revealed trisomy 8 not detected by conventional cytogenetics in 7 cases. The yield of trisomy is much higher with the ISH technique than with conventional cytogenetics. Finally, conventional cytogenetics combined with CISS (chromosomal in situ suppression) hybridization was performed in 15 patients affected with different haematological diseases showing structural aberrations, complex karyotypes or marker chromosomes. CONCLUSIONS: Our results show that ISH can detect both numerical and structural chromosome changes with high specificity and reliability. The fact that chromosome spreads of very poor quality can now be included in such analysis is the decisive advantage of this approach.

Biotin↗

PubMed1989

Infection of human T-cell leukemia virus type I and development of human T-cell leukemia lymphoma in patients with hematologic neoplasms: a possible linkage to blood transfusion.

Among 354 adult patients with either hematological malignancy or aplastic anemia, eight were positive for anti-HTLV-I antibodies; six of eight had received multiple transfusions. There was an approximately 3.5-fold increase (P less than .001) of HTLV-I seropositivity in the patients with hematologic disease (8 of 354, 2.23%) compared to the healthy adults older than 20 years (34 of 5252, .65%). Two hematological patients, one with Hodgkin's disease and one with acute promyelocytic leukemia, were found to be positive for HTLV-I, and developed and died of adult T-cell leukemia/lymphoma (ATL) subsequently. Both were long-term survivors of the primary disease and had received multiple transfusions. The latent period from blood transfusion to onset of ATL was 6 months and 11 years, respectively. Immunocompromised patients, who were seropositive for HTLV-I, may be at increased risk for ATL compared to healthy carriers of HTLV-I, and the latent period may be shorter.

Antibodies, Viral↗

PubMedDate not supplied

[Psychiatric disorders in hospitalized patients with hematologic neoplasms].

We report the results of a year of regular psychiatric support in the Hematology Department (UTI-DH) at Santa Maria Hospital. During a six-month period, the total group of hospital inpatients suffering from leukemia, Hodgkin's disease or non-Hodgkin's lymphoma, were assessed, using a semi-structured interview. A prevalence of 30% of adjustment disorders (depression and/or anxiety) and 2% of organic mental syndromes was found employing the DSM-III-R diagnostic system. In the second six-month period only patients referred by their doctor and/or nurse were observed. The two rates are discussed. A lower prevalence was found if compared with other studies in cancer patients in general. Possible causes will be focussed. General problems related to the nature of the cancer were identified. The consequences of the omission of cancer diagnosis to patients are analysed. The communication between physician and patient which is often neglected irrespectively of the culture or country, is stressed.

Adolescent↗

PubMedDate not supplied

Terminal deoxynucleotidyl transferase activity in non-hematologic and hematologic neoplasms.

The presence of terminal deoxynucleotidyl transferase (TdT) has been determined in neoplastic cells from 50 patients with non-hematologic tumors as well as neoplastic cells from 85 patients with hematologic malignancies. The results indicate that TdT is not present in cells from non-hematologic tumors, Hodgkin's lymphoma, B cell lymphoproliferative disorders, peripheral T cell neoplasms, reactive lymphadenopathy, and acute non-lymphocytic leukemia. In contrast, TdT activity is present in non-T non-B cell acute lymphocytic leukemia, T cell acute lymphocytic leukemia, T cell lymphoblastic lymphoma and chronic granulocytic leukemia in blast crisis. It is concluded that the TdT assay is a measurement useful in the differential diagnosis of some hematologic malignancies.

Acute Disease↗

PubMed1990

Secondary hematologic neoplasm after intravesical chemotherapy for superficial bladder carcinoma.

Two cases are reported of patients who developed a hematologic malignancy several years after intravesical chemotherapy of superficial bladder cancer with etoglucid, doxorubicin, and mitomycin C. In one patient, karyotypic abnormalities (-5, 7q-) typical of a therapy induced malignancy were associated with rapid progression of a refractory anemia with excess blasts in transformation to an acute non-lymphocytic leukemia. Intravesical chemotherapy may be associated with a risk of secondary malignancy.

Aged↗

PubMed2003

Profiling aberrant DNA methylation in hematologic neoplasms: a view from the tip of the iceberg.

Cancer is also an epigenetic disease. The main epigenetic modification in humans is DNA methylation. Transformed cells undergo a dramatic change in their DNA methylation patterns: certain CpG islands located in the promoter regions of tumor-suppressor genes become hypermethylated and the contiguous gene rests silenced and this phenomenon occurs in an overall genomic environment of DNA hypomethylation. The profile of CpG island hypermethylation in hematologic malignancies is an epigenetic signature unique for each subtype of leukemia or lymphoma. Although the most widely studied genes are the cell-cycle inhibitors p15INK4b and p16INK4a (specially in AML and ALL), the list of methylation-repressed genes in these neoplasms is expanding very rapidly, including MGMT, RARB2, CRBP1, SOCS-1, CDH1, DAPK1, and others. A necessary cross-talk between genetic alterations and DNA methylation exists: certain chromosomal translocations may induce hypermethylation, such as the PML-RARa, or attract methylation, such as BCR-ABL, but DNA hypomethylation can be the culprit behind the genesis of certain abnormal recombination events. From a translational standpoint, hypermethylation can be used as a marker of recurrent disease or progression, for example, in MDS, or response to chemotherapy, such as MGMT methylation in B-cell non-Hodgkin's lymphoma. Furthermore, promising studies using DNA demethylating agents and histone deacetylase inhibitors are underway to awake these dormant tumor-suppressor genes for a better treatment of the patient with a hematologic malignancy.

CpG Islands↗

PubMed1982

Carboquone therapy for hematologic neoplasms.

A daily oral dose of 1-2 mg of Carboquone was administered for remission induction to 38 patients with hematologic malignancy, and the following results were obtained: 2 of the 3 patients with malignant lymphoma, 1 of the 12 patients with multiple myeloma, 13 of the 14 patients with chronic myelogenous leukemia, and all 9 patients with polycythemia vera attained complete remission.

Administration, Oral↗

PubMed1983

[Systemic mycoses in hematologic neoplasms].

Between July 1973 and June 1981 systemic fungal infections were found in 27 of 270 autopsies of patients with hematologic malignancies: in 16 aspergillosis, in 6 candidiasis, in one aspergillosis and candidiasis, and in 4 mucormycosis. The frequency increased from 6% during the first 6 years to 25% during the last 2 years (p = 0.025). Fever despite antibiotics and new pulmonary infiltrates were the major symptoms. In only 6 of 16 patients did microbiological findings support the clinically suspected diagnosis. Systemic fungal infections were the principal cause of death in 12 patients. Because of the difficulty of establishing the diagnosis, empiric antimycotic therapy should be started promptly on clinical suspicion in patients with neutropenia and fever despite antibiotics.

Amphotericin B↗

PubMed1994

[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors].

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).

Adolescent↗

PubMed1990

[Minimal residual disease in hematological neoplasms].

The existence of neoplastic cells with low or no sensibility to antiblastic drugs represents the most important cause of relapse in hematological malignancies. The amount of leukemic cells that remains after antiblastic chemotherapy represents the minimal residual disease. These cells can re-expand at any moment, even after months or years, causing short-term or long-term relapse. The minimal residual disease is not always detectable with morphological examination. The recent utilization of techniques such as cell culture by stimulation with growth factors and genetic amplification have made it possible to reach resolutions of more than 1-10(5) cells. The therapeutic strategies for total eradication of residual neoplastic cells are currently under investigation. The combined use of biological responder modifiers with chemotherapy or the use of immunotherapy with Interleukin-2 or LAK cells has provided one possible solution to this problem.

Antineoplastic Agents↗