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PubMed1998

A nosocomial cluster of Candida inconspicua infections in patients with hematological malignancies.

Candida inconspicua was recovered from three patients with hematological malignancies. Two patients had intravenous-catheter-associated fungemia, whereas the third had fungal hepatitis. The three cases of infection occurred over a period of 1 month in patients staying in adjacent single rooms. In vitro susceptibility testing of fungal strains showed all isolates to be resistant to fluconazole, with MICs greater than 32 microg/ml. All of the strains had identical DNA restriction profiles and randomly amplified polymorphic DNA fingerprints. These data suggest a nosocomially acquired infection emanating from a common source within the hospital environment.

Adult↗

PubMed1995

Dicentric (9;12) in acute lymphocytic leukemia and other hematological malignancies: report from a dic(9;12) study group.

Fourteen cases of dic(9;12)(p11-13;p11-12) in early B-lineage acute lymphoblastic leukemia (ALL) and other hematological malignancies are reported with a review of the literature. Altogether 36 cases were collected for analysis: ALL at diagnosis (31 cases) or in relapse (one case), chronic myeloid leukemia in lymphoid blast crisis (two cases), T-cell lymphoblastic lymphoma (one case) and T-cell non-Hodgkin's lymphoma (one case). We report the first cases of dic(9;12) with a T-cell phenotype. Dic(9;12) occurs predominantly in B-progenitor ALL of childhood and young adults (age range, 1-47 years, median 12 years) but not of infancy. One or more adverse clinical features, age > 10 years, WBC > 100 x 10(9)/l, pre-B immunophenotype, platelets < 100 x 10(9)/l, were found in over 90% of cases. Additional structural chromosomal changes or trisomy 8 were frequently present. Nevertheless with a median follow-up of 5 years, 29/31 cases (94%) remain in first remission conferring an excellent prognosis to this leukemia. Additional cases are being sought to confirm the prognostic value of this cytogenetic aberration in various hematological malignancies.

Adolescent↗

PubMed2006

Anthracycline-induced cardiotoxicity in adult hematologic malignancies.

Anthracyclines are a highly efficacious treatment for adult hematologic malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphoma. The consequences of anthracycline-induced cardiotoxicity have obliged hematologists to set empirical dose limits, above which the cardiotoxic risk is deemed unacceptable. However, subclinical (and also clinical) cardiotoxicity occurs below these empirical doses and may begin to induce cardiac damage in an unpredictable and progressive manner after the first dose of treatment. As a result, treatment with anthracyclines may be withdrawn from patients prematurely or substituted with less efficacious alternative therapies. Through discontinuing further use of anthracyclines, relapsed patients previously treated with these agents may consequently be treated with second-line therapy that is less effective and possibly less well tolerated. Anthracycline-induced cardiotoxicity is potentially fatal and can significantly impair patients' quality of life, while also substantially increasing health care costs.

Adult↗

PubMed2003

Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies.

PRAME (Preferentially expressed antigen of melanoma), highly expressed in various solid tumor cells and normal testis, was first isolated as a human melanoma antigen recognized by cytotoxic T cells (CTL). This gene was also expressed in some of the hematological malignancies, including acute myelogenous leukemia (AML) and multiple myeloma. We and others have extensively evaluated the PRAME expression in various hematological malignancies and demonstrated high expression of the PRAME gene in subsets of AML, chronic myelogenous leukemia, acute lymphocytic leukemia, lymphoma and multiple myeloma. In addition, we have demonstrated that PRAME was a useful marker for detection of minimal residual disease (MRD) in patients with leukemia, particularly those leukemias in which tumor specific markers are currently unavailable. Since PRAME was first identified as a tumor antigen recognized by T cells, the possibility that PRAME is a leukemia antigen recognized by T cells was evaluated, and it was found that PRAME-positive leukemia cell lines and fresh leukemia cells were susceptible to lysis by the PRAME-specific CTL. Five CTL epitopes associated with either HLA-A*0201 or HLA-A*2402 have recently been identified. It is, therefore, an attractive strategy to apply PRAME specific immunotherapy on patients with PRAME positive leukemia in MRD condition.

Antigens, Neoplasm↗

PubMed2002

Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies.

Ribonucleotide reductases catalyze the de novo biosynthesis of deoxyribonucleosides for DNA synthesis. Increased ribonucleotide reductases activity has been associated with malignant transformation and tumor cell growth. The ribonucleotide reductases inhibitors may bind with the R1 subunit of the enzyme (Class 1) or the nonheme iron (Class 2). This review focuses on the therapeutic use of ribonucleotide reductases inhibitors in hematologic malignancies. Hydroxyurea, fludarabine and cladribine have established roles in the management of hematologic malignancies, while other ribonucleotide reductases inhibitors, such as gemcitabine, tezacitabine and heterocyclic carboxaldehyde thiosemicarbazones (e.g., triapine) are being evaluated in clinical trials.

Antineoplastic Agents↗

PubMedDate not supplied

Management of infections during intensive treatment of hematologic malignancies.

In febrile neutropenic patients with high-grade hematologic malignancies, empirical antimicrobial intervention is mandatory. Large randomized clinical trials have elucidated the benefit of broad-spectrum beta lactam antibiotics used as single drugs or in combination with aminoglycosides in order to provide activity against gram-negative aerobes as well as against streptococci and Staphylococcus aureus. As a result, infection-related mortality was reduced to less than 10% also in patients undergoing intensified remission induction or consolidation therapy for acute leukemias. Distinct subgroups of patients have been identified who need an empirical modification of antimicrobial treatment i.e., patients with catheter-related infections, patients with pulmonary infiltrates, and patients with unexplained fever not responding to first-line antibiotics. In two consecutive, prospectively randomized trials conducted by the Paul Ehrlich Society it was demonstrated that empirical antifungal therapy is beneficial for second-line treatment in patients with persistent unexplained fever and should be part of the first-line approach in patients with lung infiltrates. The empirical addition of glycopeptides, however, should be restricted to patients with catheter-related infections due to coagulase-negative staphylococci.

Aminoglycosides↗

PubMed2002

Pathogenic molds (including Aspergillus species) in hospital water distribution systems: a 3-year prospective study and clinical implications for patients with hematologic malignancies.

The incidence of mold infections in patients with hematologic malignancies continues to increase despite the widespread use of air filtration systems, suggesting the presence of other hospital sources for these molds. Water sources are known to harbor pathogenic molds. We examined samples from water, water surfaces, air, and other environment sources from a bone marrow transplantation unit with optimal air precautions. Molds (Aspergillus species, others) were recovered in 70% of 398 water samples, in 22% of 1311 swabs from plumbing structures and environmental surfaces, and in 83% of 274 indoor air samples. Microscopic examination of the water plumbing lines revealed hyphal forms compatible with molds. Four findings suggest that indoor airborne molds were aerosolized from the water: (1) higher mean airborne concentrations of molds in bathrooms (16.1 colony-forming units [CFU]/m(3)) than in patient rooms (7 CFU/m(3)) and hallways (8.6 CFU/m(3); P =.00005); (2) a strong type and rank correlation between molds isolated from hospital water and those recovered from indoor hospital; (3) lack of seasonal correlation between the airborne mold concentration in outdoor and indoor air; and (4) molecular relatedness between a clinical strain and a water-related strain (previously reported). Hospital water distribution systems may serve as a potential indoor reservoir of Aspergillus and other molds leading to aerosolization of fungal spores and potential exposure for patients.

Air Microbiology↗

PubMed2004

Residential proximity to high-voltage power lines and risk of childhood hematological malignancies.

BACKGROUND: Epidemiologic studies of electromagnetic fields and childhood cancers have focused on home exposure. The authors investigated whether residence in districts near high-voltage power lines is associated with childhood hematological malignancies, using small area analysis. METHODS: Among 50,000 children in a city in Japan, 14 cases aged younger than 15 years were diagnosed with these malignancies in the period from 1992 through 2001. A total of 294 districts constituting this city were classified according to their proximity to high-voltage power lines (either 66 kV or 220 kV). Mantel-Haenszel rate ratio is used to calculate incidence rate ratio and its 95% confidence interval (CI). RESULTS: Compared to districts of which no area fell within 300 m of high-voltage power lines, districts in which at least 50% of the area fell within 300 m of high-voltage power lines demonstrated an increased risk (incidence rate ratio: 2.2; 95% CI: 0.5-9.0). The association was strengthened for homes in which patients had resided for the longest interval of their lives (incidence rate ratio: 3.4; 95% CI: 0.9-13.2). Point-in-time measurements showed no increase in magnetic field levels for patient homes in districts near the lines. CONCLUSION: An increased, albeit nonsignificant, risk of childhood hematological malignancies associated with residential proximity to high-voltage power lines warrants further investigations.

Adolescent↗

PubMed1998

Cell cycle dependency of 67gallium uptake and cytotoxicity in human cell lines of hematological malignancies.

67Gallium (67Ga) is a radionuclide which accumulates in hematological malignancies and is used for diagnostic imaging. We investigated in this in vitro study the cell cycle dependency of cellular uptake and cytotoxicity of 67Ga. Cell cycle synchronization of cells was achieved by counterflow centrifugal elutriation and the use of cytostatic drugs. The human lymphoma cell lines U-937 and U-715 were used and in elutriation experiments we also used the leukemic cell line HL-60. The transferrin receptor (CD71) expression, 67Ga uptake and cell proliferation inhibition were the parameters measured. We also studied cytotoxicity in various schedules for combination of 67Ga and drugs and the residual proliferative capacity was measured. The CD71 expression in the three cell lines increased from 106-177% on S phase cells and from 118-233% on G2M cells, as compared to the G0/G1 cell fraction. The 67Ga uptake varied from 108-127% for S cells and 128-139% for G2M cells. The drugs chosen induced cell cycle phase accumulation in S and/or G2M phase during preincubation. 67Ga preincubation induced accumulation in the G2M phase. Almost all combinations of 67Ga and drugs resulted in a non-interactive effect, except for methotrexate which resulted in an antagonistic effect. No preferential effect of any of the incubation schemes was seen. CD71 expression and 67Ga uptake were increased in S and G2M cells. Combination of 67Ga with drugs which arrest cells in these cell cycle phases did not result in a change in cytotoxicity. However, these results implicate that 67Ga and the cytostatic drugs tested except for methotrexate might be used together or sequentially in therapy.

Antineoplastic Agents↗

PubMed1993

Cladribine for the treatment of hematologic malignancies.

The mechanism of action, pharmacokinetics, efficacy, adverse effects, storage, dosage and administration, and cost of cladribine are reviewed. Cladribine (2-chloro-2'-deoxyadenosine) is a synthetic purine nucleoside developed for the treatment of hematologic malignancies. It appears that cladribine interferes with lymphocyte proliferation by inhibiting DNA repair. The pharmacokinetics of cladribine best fit a two-compartment, first-order-elimination model. Of the conditions that have been treated with cladribine, hairy cell leukemia (HCL) has shown the most dramatic response. Overall response rates in clinical studies have ranged from 80% to 100%, with a large majority of these being complete remissions; median durations of responses have ranged from about 9 to 16 months. Other conditions that have responded to cladribine are chronic lymphocytic leukemia (CLL), acute leukemia, chronic myeloid leukemia, low-grade lymphomas, Waldenström's macroglobulinemia, and cutaneous T-cell lymphoma. The drug is inactive against solid tumors. The principal dose-limiting adverse effect of cladribine is bone marrow suppression; fever, immunosuppression, renal and neurologic effects, and local skin reactions have also been reported. The drug is typically administered as an extended continuous i.v. infusion. The usual dosage for treating HCL is 0.1 mg/kg/day for seven days. The estimated cost of cladribine for treating an average patient with HCL is $3500. Cladribine has shown efficacy against a variety of hematologic malignancies, notably HCL and CLL.

Cladribine↗

PubMed2006

[High-dose etoposide with granulocyte colony-stimulating factor for mobilization of autologous peripheral blood stem/progenitor cells in patients with hematologic malignancies].

To explore the efficacy and safety of high-dose of etoposide with granulocyte colony-stimulating factor (G-CSF) for mobilization of peripheral blood stem cells, 10 patients with hematologic malignancies including 6 patients with multiple myeloma and 4 with non Hodgkin' s lymphoma received an etoposide dose of 1.6 g/m2. The total dose of undiluted etoposide was given on day 1 as a continuous intravenous infusion via a central vein for 10 hours. G-CSF 5 microg/kg was used on day 3 and given daily subcutaneously until leukopheresis was completed. The results showed that leukopheresis was started at days 11 (range 9-13 days) following etoposide therapy, the mean number of CD34+ cells collected in all 10 patients was 9.4 x 10(6)/kg (range 4.2 - 17.3 x 10(6)/kg), by an average of 2.6 leukophereses (range 1-4) times. Mobilization procedure that produced yields of greater than 4.0 x 10(6)/kg were achieved in every patient. Toxicity showed oropharyngeal mucositis, faucitis and urethritis respectively in 3 patients. It is concluded that high-dose etoposide with G-CSF is an effective and safe mobilizing regimen for autologous peripheral blood stem progenitor cells in patients with hematologic malignancies.

Adolescent↗

PubMed1987

Compliance with oral drug therapy in patients with hematologic malignancy.

Compliance with oral self-administered allopurinol (daily medication) and prednisone (intermittent medication) as well as compliance with monthly scheduled clinic appointments, were examined in 108 patients with newly diagnosed hematologic malignancy. Baseline levels of compliance (control group) were compared to results obtained after implementation of three intervention packages, whose aim was to increase compliance. The packages included combinations of education, home psychologic support and restructuring, and training in pill taking. A 24-hour profile of the two drugs and their metabolites was first determined. Serum samples were then obtained monthly over 6 months and analyzed for presence of the drugs. Control patients were fully compliant with allopurinol only 16.8% of the time. This rate increased significantly (44% to 48% of the time) for those who received any one of the intervention programs. With respect to prednisone, control patients were compliant 26.8% of the time, with no real improvement after interventions. Finally, self reports overestimated compliance by a factor of two when compared to drug analysis. The results indicated that full compliance with oral medications was remarkably low among our patients who have treatable and in some cases curable hematologic malignancy. However, compliance can be significantly improved by the use of various intervention packages.

Administration, Oral↗

PubMed1980

Serum ferritin in hematologic malignancies.

Serum ferritin was measured in a variety of hematologic malignancies at presentation, in remission following therapy, and in relapse. Ferritin was strikingly increased in all acute leukemias at presentation and in relapse, in the blastic crisis of CML, and in smouldering leukemia. Remission in both ALL and ANLL was associated with a reduction of serum ferritin, and this normalization was a function of remission duration. In the malignant lymphomas serum ferritin was related to tumor histology. Highest levels were found in Hodgkin disease and histiocytic lymphoma, normal levels in lymphocytic lymphoma, and intermediate levels in mixed histiocytic-lymphocytic lymphoma. In all cases, remission was associated with normalization of serum ferritin. These correlations suggest that serum ferritin measurements may be of clinical usefulness in the initial evaluation and in the assessment of response to therapy in patients with acute leukemia and malignant lymphoma.

Acute Disease↗

PubMed1989

Pharmacokinetics of amikacin in hematologic malignancies.

The pharmacokinetics of amikacin in 10 patients with hematologic malignancies and 1 patient with aplastic anemia were investigated. At an administered dose of 7 mg/kg of body weight, a volume of distribution of 0.4 liters/kg, an elimination half-life of 3.0 h, and a total body clearance of 2.1 ml/min per kg, amikacin achieved a peak level in blood of 21 micrograms/ml. Results of the study revealed that there was a marked increase in volume of distribution of amikacin in these patients compared with normal.

Adult↗

PubMed2001

Hematologic malignancies.

This article reviews highlights in the field of hematologic malignancies presented at the 2001 annual meeting of the American Society of Clinical Oncology. Targeted therapies continue to proceed from the laboratory to the clinic. Monoclonal antibody-based therapies predominate, and further data on radioimmunoconjugates (RICs) (tositumomab and Iodine 131 tositumomab [Bexxar] and ibritumomab tiuxetan [Zevalin]) are presented. Both agents have high response rates in relapsed B-cell non-Hodgkin's lymphoma (NHL). Results from the first trial directly comparing an RIC (Zevalin) to an unconjugated antibody (rituximab) are presented. A novel application of RIC therapy as part of high-dose therapy for mantle cell NHL is described. A new fusion toxin, BL22, targets the CD22 antigen and shows marked activity in the treatment of hairy cell leukemia. Similarly, the Hu1D10 monoclonal antibody has activity in B-cell NHL and might have a relatively unique mechanism of action. Finally, advances in the treatment of mucositis are described. These abstracts all describe therapies derived from our enhanced understanding of tumor immunology and molecular biology.

Antibodies, Monoclonal↗

PubMed1992

[Clinical evaluation of imipenem/cilastatin sodium against infections in compromised children (malignancy, hematological disease, collagen disease)].

Eighteen immuno-compromised children (malignancies, hematological diseases, collagen diseases) with neutropenia and infections were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and the safety of the drug were evaluated. 1. Responses to IPM/CS were excellent in 13 patients, good in 1, and fair in 4. None of the patients displayed a poor response to the treatment thus the efficacy rate was 77.8%. 2. Of 5 patients with sepsis, 4 had excellent or good responses. IPM/CS was effective against sepsis caused by Enterococcus faecalis and Pseudomonas aeruginosa. 3. In patients with severe neutropenia (WBC less than 100/mm3), the efficacy rate was 70%. 4. As for side effects, elevations of GOT and GPT were observed in 1 patient with liver cirrhosis. These results indicate that IPM/CS is safe and effective in immuno-compromised children with neutropenia and infections.

Adolescent↗

PubMed1992

Familial occurrence of hematologic malignancies and other diseases in multiple myeloma: a case-control study.

In a population-based case-control study in Sweden on multiple myeloma, the occurrence of different diseases in relatives, particularly hematologic malignancies and different types of cancer, was investigated. Through a questionnaire mailed to all living subjects, i.e. cases and controls, and to the next-of-kin for deceased subjects, information was obtained on malignant and certain other diseases among relatives. All malignant diseases reported among first-degree relatives were verified, if possible, through parochial authorities and the Swedish Cancer Register. In total, data from 239 cases with myeloma and 220 controls were analyzed. An increased risk was found for persons with first-degree relatives with hematologic malignancies (relative risk [RR] = 2.36, 90 percent confidence interval [CI ) = 0.90-6.15), and also with multiple myeloma specifically (RR = 5.64, CI = 1.16-27.51). An increased risk also was seen if the close relatives had experienced another tumor disease (RR = 1.21, CI = 0.86-1.71). Particularly, occurrence of prostatic cancer (RR = 3.11, CI = 1.25-7.71) or brain tumor (RR = 6.61, CI = 1.42-30.67) in relatives increased the risk for multiple myeloma.

Brain Neoplasms↗

PubMed1994

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies.

PURPOSE: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies. PATIENTS AND METHODS: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0. RESULTS: Patients with early leukemia had a disease-free survival rate of 53% +/- 9% and an overall survival rate of 57% +/- 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% +/- 5% and overall survival rate of 17% +/- 5%. The actuarial relapse rate for the early-leukemia group is 33% +/- 9% versus 69% +/- 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early-leukemia group was 10% versus 50% for patients with more advanced disease. CONCLUSION: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.

Adolescent↗