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Results for “hematologic malignancies”

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PubMed2002

Cytotoxic effect of nitric oxide on human hematological malignant cells.

We investigated the cytotoxic effect of nitric oxide (NO) on primary culture of human hematological malignant cells. Sodium nitroprusside (SNP), an NO donor, had cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma. Cultured cells from the ML patient remained sensitive to SNP after the cells became resistant to anti-cancer drugs. In contrast, the cells from the patients with AML and CMMoL became resistant to SNP while anti-cancer drugs remained effective. In samples of the cells of the patients with ML and AML, the number of CD3 positive lymphoma cell was decreased by SNP and the number of CD33 negative cells and normal B lymphocytes (CD19 positive cells) were increased. In the cells of the patient with ML, apoptosis was induced by SNP. SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP had an anti-tumor effect on human hematological malignant cells.

Adolescent↗

PubMed2006

Expression and functional significance of osteocalcin splicing in disease progression of hematological malignancies.

The aim of this study was to investigate the expression of osteocalcin (OCN) splicing variants in hematological malignancies. We analysed bone marrow obtained from two patients with chronic myeloid leukemia (CML), seven patients with other myeloproliferative diseases (MPD) and four patients with acute myeloid leukemia (AML). RT-PCR analyses were performed in order to assess and quantify spliced (OCNs) and unspliced (OCNu) mRNA, the associated transcription factors (AML1 and AML3) as well as c-KIT which is a marker for activated stem cells. Our data indicate that OCNs mRNA and OCN protein is expressed in c-KIT positive neoplastic stem cells in hematological malignancies.

Alternative Splicing↗

PubMed2002

[Allogeneic peripheral blood stem cell transplantation in the treatment of hematologic malignancies].

OBJECTIVE: To investigate the application of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in the treatment of hematologic malignancies. METHODS: Between October 1995 and August 2001, fifty-one patients with hematologic malignancies (median age 34 years, range 5.5 approximately 52 years) received allo-PBSCT from HLA-identical (50) or 1-antigen mismatched sibling donors with conditioning regimens of TBI + CY or modified BU/CY2. Thirty-one patients were acute leukemia (AL) (15 in CR(1), 7 in CR(2) or greater, 10 in relapse including 2 relapse after allo-BMT and the other one never achieved remission); 12 chronic myeloid leukemia (CML) (CP 5, AP 2, BC 4 and relapse after allo-BMT 1); 7 MDS (RAEB 1, RAEB-T 1, AL secondary to MDS 5); Burkitt's lymphoma 1. A combination of cyclosporine and methotrexate was administered for GVHD prophylaxis. RESULT: All patients were engrafted. The median time (range) to neutrophil >/= 0.5 x 10(9)/L and platelet >/= 20 x 10(9)/L was 14 (10 approximately 20) and 11 (7 approximately 45) days post-transplant, respectively. Grade II approximately IV acute GVHD occurred in 20/51 (39%) and grade III approximately IV aGVHD in 2 patients. Clinical chronic GVHD was diagnosed in 23 of 44 (52%) evaluable patients. Fourteen patients died: 8 died of transplant related complications, 6 of relapse. Thirty-seven patients are alive with a median follow-up of 399 (75 approximately 2 176) days, and among them 34 are in continuous complete remission, the other 3 relapsed. The 2-year probability of overall survival, disease-free survival (DFS) and relapse is 64%, 61% and 24%, respectively. CONCLUSION: Allogeneic PBSCT is safe for both donors and recipients, and results in a rapid and stable engraftment without increase in incidence or severity of acute GVHD.

Acute Disease↗

PubMed2004

Lamivudine facilitates optimal chemotherapy in hepatitis B virus-infected children with hematological malignancies: a preliminary report.

Hepatitis B virus (HBV) reactivation is well documented in infected patients who have hematologic malignancies, precluding appropriate chemotherapy courses and, therefore, increasing the possibility of relapse of malignancies. The objective of this study was to evaluate lamivudine treatment to prevent hepatitis B reactivation in children with cancer who acquired infection with HBV and so allow completion of optimal chemotherapy. Ten children (7:3 M:F; median age: 9.8 years), undergoing chemotherapy for hematological malignancies and suffering from immunosuppressive-induced hepatitis B virus reactivation, were treated concurrently with lamivudine (3 mg/kg bw, od) for up to 18 months. All were HBsAg+ve, HBsAb-ve, HBV-DNA+ve. Serology markers (HBsAg/Ab, HBeAg/Ab, HBV-DNA) and ALT were tested 3 monthly. Histological assessments were performed pre- and 18 months post-lamivudine therapy. During lamivudine therapy chemotherapy courses were completed for all children, and none of the patients suffered reactivation of hepatitis. After a median follow-up of 10 months, remission of malignancy was maintained in 7/10 patients while 3 patients relapsed. HBeAg+ve seroconversion occurred in 4/9 HBeAg+ve children within 3 months. After 9 months of therapy, 8/10 were HBV-DNA-ve. Six out of 7 children with histological evidence of chronic hepatitis showed marked improvement post-therapy. Lamivudine therapy for up to 18 months in children receiving chemotherapy helped prevent recurrence of hepatitis B exacerbations and improved the underlying chronic hepatitis, while facilitating completion of appropriate chemotherapy regimens without compromise.

Adolescent↗

PubMed2001

[Amphotericin B for treatment of fungal infections in 40 patients with malignant hematologic diseases].

OBJECTIVE: To observe the therapeutic effect and side effects of amphotericin B for fungal infections in patients with malignant hematologic diseases. METHODS: 40 patients (male 27, female 13; average age 35.5 years) with malignant hematologic diseases were given amphotericin B, 5-50 mg/d per day for 5-85 days (average time 21 days). RESULTS: The clinical efficacy rate of amphotericin B was 52.5%, and the fungal elimination rate was 56.2%. Among the side effects, rigor and fever were present in 2.5% of the patients. Hypokalaemia was found in 12.5%, hepatotoxicity in 15.0% and nephrotoxicity in 15.0%. CONCLUSION: As amphotericin B has a broad anti-fungal spectrum and relatively good efficacy, it is still a high-efficiency drug in treatment of systematical fungal infections. However, the use of drug is limited because of its many side effects. Our study indicates that if it is used properly and hepatic and renal function tests are carried out regularly, amphotericin B is a relatively safe and effective drug.

Adolescent↗

PubMed2002

[Clinical and cytogenetic studies of hematological malignancies with isolated trisomy 11].

OBJECTIVE: To evaluate the association between isolated trisomy 11 and the clinical, hematological, immunological, prognostic aspects in hematological malignancies. METHODS: Bone marrow cell cytogenetic analysis was performed by direct method and/or 24 h culture method. RHG banding was used for karyotype analysis. Immunophenotype analysis was carried out by flow cytometry. Ten patients with acute myeloid leukemia (AML) were treated with HA regimen chemotherapy and followed up. RESULTS: The isolated trisomy 11 was found in 11 of 1 * ! 763 hematological malignancies cases (0.6%). The diagnoses included 10 AML (6 M(2), 2 M(5), 1 M(1), 1 M(4)), and 1 myelodysplastic syndromes. Ten of them have no hepatosplenomegaly. The immunophenotypical analysis of leukemia cells showed positive for CD(13), CD(33) and CD(34) in 5 cases. Follow-up data were available in 10 cases. The complete remission rate was 40% with a median survival of 10 months. CONCLUSION: The isolated trisomy 11 was mainly seen in AML, especially in M(2) subtype. Their prognosis was poor.

Adult↗

PubMed1988

Outcome of children with hematologic malignancy who are admitted to an intensive care unit.

Sixty-four (48%) of 133 children with hematologic malignancy who were admitted to three pediatric ICUs died. Children who required management because of airway obstruction or after general anesthesia had the best outlook (mortality rate of 7% or less); those children who required major circulatory support or mechanical ventilation for hypoxemia did poorly (mortality rate of 84% or greater). Certain conditions in children with hematologic malignancy that require intensive care are associated with a mortality rate of approximately 75%. These include the following: suspected sepsis, interstitial pneumonitis, encephalopathy due to sepsis or hemorrhage. In children with these life-threatening conditions, therapy must be improved because at this stage, the patients do not benefit from admission to the ICU.

Anemia, Aplastic↗

PubMed1997

[Utility of daily oral administration of etoposide in 25 cases of refractory hematological malignancies].

We estimated the utility of daily oral administration of etoposide (ETOP) in 25 cases of refractory hematological malignancies who had been admitted to our hospital between February, 1988 and October, 1995. Patients were 9 cases of malignant lymphoma, 7 cases of adult T cell leukemia (ATL), 7 cases of acute leukemia, 1 case of primary macroglobulinemia, and 1 case of chronic lymphocytic leukemia (CLL). Eight cases were elderly patients over 65 years old, 7 cases were refractory to previous chemotherapies, and 13 cases were relapsed cases. ETOP was administered at 25 or 50 mg per day for at least more than 3 consecutive weeks, if the peripheral white blood cell count exceeded 1,000/microliter. Complete and partial responses were obtained in 64% of all cases, especially in 81% of malignant lymphoma and ATL. Probability of survival for 3 years of malignant lymphoma and ATL was 36.7%. As mild toxicities, 2 cases (8%) had nausea and vomiting, 2 cases (8%) had diarrhea, and 3 cases (12%) had stomatitis. Grade 3 leukocytopenia was observed in 16% of cases. Twelve out of 16 evaluable patients recovered in performance status (PS) after this therapy. Daily oral administration of ETOP might be an effective therapy for refractory hematological malignancies, especially for malignant lymphoma.

Administration, Oral↗

PubMed1998

Tetanus immunity in patients with hematological malignancies.

The aim of this study was to investigate long-term immunity to tetanus toxoid among patients with hematological disease who had been treated with conventional doses of chemotherapy. Altogether 206 patients with different hematological malignancies were included in the study. There were marked differences between the rates of seronegativity against tetanus, varying from 20% to 70% in different groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of 80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2 of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005) and advanced disease stage (P = 0.0001) were independent risk factors for loss of tetanus immunity in patients with hematological malignancies.

Adolescent↗

PubMed2005

Outcome in severely ill patients with hematological malignancies who received intravenous chemotherapy in the intensive care unit.

OBJECTIVE: To assess the outcome in severely ill patients with hematological malignancies who receive intravenous chemotherapy in an intensive care unit (ICU) for a life-threatening malignancy-related complication. DESIGN: Retrospective observational study of prospectively collected data. PATIENTS: All 37 critically ill patients with hematological malignancies who received intravenous chemotherapy in the ICU between January 1997 and March 2005 (mean age 46+/-19 years; mean APACHE II 23+/-7). MEASUREMENTS AND RESULTS: Thirty-seven (69%) patients received chemotherapy because of extensive disease with organ involvement (54%), extensive disease without organ involvement (19%), severe disseminated intravascular coagulation (11%), and other reasons (16%). In 41% there was concomitant infection when chemotherapy was initiated, in 86% a high-grade malignancy, and 30% relapsing disease. Twenty-three (62%) patients received mechanical ventilation at the moment of or soon after initiation of chemotherapy for a median duration of 5 days (1-67), and 24% underwent renal replacement therapy during ICU stay. Only ventilation was associated with in-hospital mortality (odds ratio 9.3). ICU, in-hospital, and 6-month mortality rates in nonventilated vs. ventilated patients were 7% and 48%, 14% and 61%, and 54% and 74%, respectively. CONCLUSIONS: Starting chemotherapy in the ICU for a life-threatening malignancy related complication can be lifesaving even when infection or organ failure is present.

Adolescent↗

PubMed2003

Mutational analysis of IkappaBalpha in hematologic malignancies.

The activation of the NF-kappaB family of transcription factors plays a crucial role in oncogenesis. The IkappaB family has the ability to retain the NF-kappaB in an inactive complex in the cytoplasm. Recently, mutations of the IkappaBalpha gene were found in Hodgkin's lymphoma, which allows NF-kappaB proteins to translocate into the nucleus in an active form. In this report, we describe a mutational analysis of IkappaBalpha for primary tumor cells obtained from patients with a variety of hematologic malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, hairy cell leukemia, adult T-cell leukemia, and mantle cell lymphoma) as well as 15 leukemia, lymphoma, and myeloma cell lines (HL60, U937, HEL, K562, NALM1, Jurkat, JM, MOLT4, Raji, KS1, OKM2T, OKM3T, F6T, Su9T01, and C2-2). RT-PCR, followed by direct sequencing, was performed and all samples expressed IkappaBalpha. One missense mutation was identified in a primary effusion lymphoma cell line, KS1. However, NF-kappaB (p65) protein was absent from the nucleus of KS1 immunohistochemically, suggesting that the mutation did not alter the function of IkappaBalpha in this case. Taken together, although it is not clear whether normal IkappaBalpha protein was expressed in hematologic malignancies, mutations of IkappaBalpha could be rare events in these diseases, except for Hodgkin's lymphoma. Alterations of other members of NF-kappaB/ IkappaB family proteins might act on the development of hematologic malignancies.

DNA Mutational Analysis↗

PubMed1996

Inactivation of the p15INK4B and p16INK4 genes in hematologic malignancies.

The recently discovered p15INK4B and p16INK4 genes encoding cell cycle regulating proteins, map to a region on chromosome 9p21 that is commonly deleted in a variety of malignant diseases. The p16INK4 gene has now been shown to be a tumor suppressor gene. It is frequently inactivated in cancer and is possibly the second most often mutated gene in human malignant disease after p53. The role of the p15INK4B and p16INK4 genes in hematologic malignancies has been the subject of intense investigation since their discovery. In this review we address the function and possible role in tumorigenesis of the p15INK4B and p16INK4 genes and discuss their significance as prognostic markers in hematologic malignancies.

Carrier Proteins↗

PubMed2003

Effects of endurance training on the physical performance of patients with hematological malignancies during chemotherapy.

Fatigue and impaired physical performance are common and sometimes serious problems of cancer patients during and after treatment. To avoid fatigue, cancer patients are often advised to rest and downregulate their daily activities. However, these recommendations can cause paradoxical results. Since inactivity induces muscular wasting, prolonged rest can result in further loss of endurance. Recent studies suggest that exercise, as well as behavioral and some psychosocial interventions, may reduce fatigue and improve the performance status of cancer patients. In this paper, we review interventions proposed for the treatment of cancer-related fatigue and present the results of a study about the effects of exercise on the physical performance of patients with hematological malignancies. Sixty-six inpatients (34 men, 32 women) undergoing conventional ( n=45) or high-dose chemotherapy with stem cell rescue ( n=21) for the treatment of a hematological malignancy exercised daily on a treadmill. Physical performance was assessed on admission and once a week during hospitalization (30+/-10 days, range 10-49). Physical performance remained unchanged in a submaximal standard stress test (on admission: 5.5+/-1.4 km/h; midhospitalization: 5.3+/-1.3 km/h; at discharge: 5.5+/-1.3 km/h; p=0.60) despite chemotherapy and its related complications. A significant decrease in the mean hemoglobin concentration (from 10.3+/-2.0 g/dl on admission to 9.6+/-1.2 g/dl at discharge; p=0.03). We conclude that a daily endurance-training program reduces the treatment-related loss of physical performance in patients with hematological malignancies undergoing chemotherapy.

Adult↗

PubMed1997

Phase I/II trial of cure-oriented high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method for refractory hematological malignancies. Nagoya CD34+ PBSCT Study Group.

A multicenter phase I/II clinical trial was conducted to evaluate the safety of a device (Isolex System; Baxter Health Corporation, Irvine, Calif., USA) using the immunomagnetic bead method to purify CD34+ stem cells from peripheral blood and to assess the efficacy and toxicity of high-dose chemoradiotherapy with peripheral blood stem-cell transplantation (PBSCT) using purified CD34+ stem cells in patients with refractory hematological malignancies. Patients eligible for the study included those who had T-cell acute lymphoblastic leukemia (T-ALL), lymphoblastic lymphoma (LBL), mantle-cell lymphoma (MCL), high-risk aggressive non-Hodgkin's lymphoma (NHL), and adult T-cell leukemia/lymphoma (ATLL) in first complete remission (CR) and those who had standard-risk aggressive NHL, indolent lymphoma, Hodgkin's disease, or acute promyelocytic leukemia (APL) in second CR or first partial remission (PR) after the completion of first-line chemotherapy and were chemosensitive to salvage chemotherapy, in whom tumor contamination of harvested peripheral blood stem cells (PBSCs) was possible due to bone marrow or peripheral blood involvement. Lack of CD34 expression by tumor cells was an important selection factor. Eight patients with hematological malignancies (six NHL patients, one ATLL patients, and one APL patient) were enrolled; their median age was 41 years (range 26-49 years). After consolidation and mobilization chemotherapy, two or three courses of apheresis were performed in each patient. After high-dose chemo(radio)therapy, in each patient a median of 1.8 x 10(6) cells/kg (range 8.2 x 10(5)-5.1 x 10(6) cells/kg) purified CD34+ PBSCs were infused; granulocyte colony-stimulating factor was given from day 1. Median times to hematopoietic recovery were as follows: WBC of > or = 1,000/microliter, day 11; platelet count of > or = 50,000/microliter, day 19; and reticulocyte count of > or = 10/1000, day 15. Two NHL patients relapsed at 23 and 9 months after PBSCT, respectively; the remaining six patients are alive and in CR. No severe toxicity was observed in any patient. Tumor contamination as measured using a polymerase chain reaction-mediated RNase protection assay at the 10-4 level was detected in the CD34(+)-purified fractions of 2 of the 5 samples analyzed; however, a reduction in contaminating lymphoma cells from the autograft of at least 1,000 to 10,000 orders of magnitude was achieved by CD34+ selection using the immunomagnetic bead method. High-dose chemoradiotherapy with transplantation of CD34+ PBSCs purified by the immunomagnetic bead method was thus shown to be an active and safe therapy for refractory hematological malignancies with bone marrow or peripheral blood involvement. However, it is too early for evaluation of the long-term survival benefit.

Adolescent↗

PubMed1989

Herpes simplex virus in oral mucosal ulcers in patients with hematological malignancy.

Developments of oral mucosal ulcers induced by herpes simplex virus (HSV) were studied in patients with hematologic malignancy. Herpes simplex virus type-1 (HSV-1) was identified by immunological staining using virus-specific monoclonal antibodies in the epithelial cells of such ulcers from two patients with malignant lymphoma (ML), three with acute myeloblastic leukemia (AML), one with refractomy anemia with excess blasts, two with chronic myelocytic leukemia (CML), one with acute lymphoblastic leukemia (ALL) and one with aplastic anemia (AA). Herpes simplex virus type-2 (HSV-2) was also identified in an ulcer from a patient with AML. Isolation of HSV-1 was successful in the two patients with ML, one with CML, one with AML, the one with ALL and the one with AA. The ulcers developed on the tongue (four cases), buccal membrane (five cases), hard palate (one case), soft palate (one case), soft palate (one case) and gingiva (two cases). Only one patient with CML and one with AML had accompanying labial vesicular lesions. All patients except the one with AA had previously been given combination chemotherapy with anti-neoplastic agents. The results indicate that HSV may have an important role to play in the development of chemotherapy-related oral mucosal ulcers in patients with hematological malignancy.

Adult↗

PubMed2001

Ramosetron for the management of chemotherapy-induced gastrointestinal events in patients with hematological malignancies.

The objective of this study was to evaluate the efficacy and safety of ramosetron hydrochloride for the management of nausea and vomiting induced by chemotherapy in patients with hematological malignancies. A total of 30 patients with hematological malignancies were included in the ramosetron group. Ramosetron (0.3 mg i.v.) was administered 0.5 h before chemotherapy. The impact of ramosetron on anorexia, nausea and vomiting as well as other adverse effects were assessed. Meanwhile, another 39 patients received tropisetron (o.d. for 3 days). As compared to the tropisetron group, the response rate of the ramosetron group in controlling anorexia within 18-24 h after chemotherapy was higher (p < 0.05); within 18-24 h after chemotherapy, the complete response rate and effective rate in controlling nausea was higher (p < 0.05); within 12-18 h and 18-24 h after chemotherapy, the complete response rate and effective rate in controlling vomiting was higher (p < 0.05). The incidence of adverse effects was similar in both groups. We conclude that ramosetron belongs to a new generation of 5-HT3 receptor antagonists and that it is a safe, economic and effective antiemetic drug.

Adolescent↗

PubMed1991

Use of ofloxacin in prevention and treatment of secondary infections in hematological malignancies.

We evaluated the effectiveness of ofloxacin (OFX) administered for prophylactic purposes during 77 episodes of neutropenia (less than 500/mm3) in 54 patients with hematological malignancies and to combat infection in 17 patients with both hematological malignancies and secondary infections. The prophylactic effect of OFX was demonstrated by the absence of febrile episodes in 73.3% of patients during the neutropenic phase. Of 16 patients who developed secondary infections, 13 showed good responses with other antibiotics. The overall efficacy rate of OFX in secondary infections was 64.7%. Although 4 patients developed elevated SGOT and SGPT levels and 1 showed an elevated BUN level, OFX was generally well tolerated.

Adolescent↗

PubMed2004

Moderate increase of secondary hematologic malignancies after myeloablative radiochemotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group.

PURPOSE: An increased risk of therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) after high-dose therapy and autologous stem-cell transplantation (ASCT) for malignant lymphoma has been described by several studies, reporting a highly variable incidence ranging from 1% to 12%. To assess this risk more precisely, the German Low Grade Lymphoma Study Group investigated the incidence of t-MDS/t-AML after ASCT on the basis of a randomized comparison of ASCT versus interferon alfa (IFN-alpha) maintenance in indolent lymphoma. PATIENTS AND METHODS: Between 1996 and 2002, 440 patients with indolent lymphoma were randomly assigned after a cyclophosphamide, doxorubicin, vincristine, and prednisone-like induction therapy regimen to myeloablative radiochemotherapy followed by ASCT or IFN-alpha. The incidence of secondary hematologic malignancies was determined by standardized follow-up of all study patients. Bone marrow samples from patients with proven or suspected t-MDS/t-AML were centrally reviewed. RESULTS: After a median follow-up of 44 months, 431 patients were assessable. Five of 195 patients developed a secondary hematologic malignancy after ASCT. Two of these patients developed a secondary AML. Accordingly, the estimated 5-year risk for secondary hematologic neoplasias after ASCT was 3.8%. In contrast, in the IFN-alpha arm, the 5-year risk of hematologic neoplasias was 0.0% (P = .0248). CONCLUSION: The data of this randomized trial demonstrate an increased risk of secondary hematologic malignancies after myeloablative radiochemotherapy and ASCT compared with conventional chemotherapy. However, as ASCT significantly improves progression-free survival, it is currently not evident to what extent the higher rate of t-MDS/t-AML will diminish the benefit of ASCT in indolent lymphoma.

Acute Disease↗