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Results for “hematologic malignancies”

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PubMed1983

[Phase II study of a new anthraquinone antineoplastic agent, mitoxantrone, in hematological malignancies].

At Saitama Cancer Center a phase II study of mitoxantrone was carried out in 18 patients with hematological malignancy. Mitoxantrone was given at either doses of 3, 5, or 6 mg/m2 daily X 5 in 8 patients with acute leukemia, while 10 patients with NHL were given intravenously at a dose of 10, 12, or 14 mg/m2 every 3 to 4 weeks. Although remission was not obtained in patients with acute leukemia, severe hypoplastic marrow was induced in 3 patients. Of 10 patients with NHL, one achieved CR, and 4 had a PR which lasted 31 weeks, 27 weeks, 19 weeks, 12 weeks +, and 9 weeks+. These patients had previous exposure to anthracyclines. Gastrointestinal toxicity and alopecia were less frequently seen and less severe with mitoxantrone.

Adolescent↗

PubMed1998

Unrelated mismatched cord blood transplantation in patients with hematological malignancies: a single institution experience.

We report on six cases of unrelated UCB transplant in adult patients with hematological malignancies: three chronic myelocytic leukemias and three acute leukemias. Their median age and body weight were respectively: 28 years (range 15.5-40) and 55.5 kg (range 46-90). The cord blood units were from the New York Blood Center. The median number of nuclear cells provided, evaluated before thawing, was 2.1 x 10(7)/kg (range 1 x 10(7)/kg-4.7 x 10(7)/kg). The degree of HLA disparity was 1/6: two patients, 2/6: three patients, 3/6: one patient. The patients received a pretransplant regimen including total body irradiation. They were given graft-versus-host disease prophylaxis which consisted of cyclosporin A and corticosteroids. They were all given a combination of G-CSF and erythropoietin. The median time of white blood cell and platelet reconstitution were respectively 24 days (range 12-43) and 60 days (range 23-90). All the patients had a full chimerism. A grade I acute GVHD was observed in four patients and two patients do not have any GVHD. No chronic GVHD has been observed yet. Three patients died from toxicity. Three patients are alive and well in complete remission at 2 years, 1 year and 11 months post-graft.

Adolescent↗

PubMed2004

Addition of teicoplanin or vancomycin for the treatment of documented bacteremia due to gram-positive cocci in neutropenic patients with hematological malignancies: microbiological, clinical and economic evaluation.

A prospective, randomized, double-blind trial was conducted on 124 febrile patients with hematological malignancies to compare teicoplanin with vancomycin as an addition to the initial empiric amikacin-ceftazidime regimen after documented bacteremia due to gram-positive cocci. At enrollment, patients in both groups were comparable with respect to age, sex, underlying hematologic disorders and duration of neutropenia. Rates of therapeutic success were 55/63 (87.3%) in the teicoplanin group and 56/61 (91.8%) in the vancomycin group (p = 0.560). The mean duration of treatment was similar, being 12.2 and 11.4 days, respectively (p = 0.216). Patients treated with teicoplanin remained febrile for slightly longer than those treated with vancomycin (4.9 vs. 4.0 days) (p = 0.013). Thirteen patients experienced an adverse drug reaction, but without any significant difference in the two arms. Isolated staphylococci showed a progressive and significant decrease in susceptibility to both glycopeptides during the 8 study years. The economic analysis performed showed that the addition of vancomycin is cost-saving.

Adult↗

PubMed2003

Gene therapy for hematological malignancies.

Since cancer is the result of genetic mutations, it should be well suited for correction through gene therapy. Hematological malignancies in which human gene transfer has been performed are leukemias, lymphomas, graft-versus host disease after allogeneic bone marrow transplantation in leukemia, and multiple myeloma. Gene therapy may be used to induce or enhance an antitumor immunological reaction, to correct a genetic defect in the tumor cells, to render the malignant disease more susceptible to conventional therapies, to make the normal host cells more resistant to conventional therapies, or to track cells used for therapy. Gene therapy will probably be most valuable for the eradication of minimal residual disease after the use of conventional therapies.

Apoptosis↗

PubMed2002

Advancing the treatment of hematologic malignancies through the development of targeted interventions.

Significant advances have been made in the development of targeted interventions for hematologic malignancies. Progress has been made in defining the molecular pathogenesis of human leukemias. Data indicate that nonrandom, somatically acquired translocations, inversions, and other abnormalities occur in many acute leukemias. In the treatment of acute promyelocytic leukemia (APL), targeted therapy with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy leads to dramatic improvements in disease-free survival. Imatinib mesylate, a signal transduction inhibitor that inhibits tyrosine kinase activity, the protein product of the ABL proto-oncogene, has remarkable activity in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL). Farnesyltransferase inhibitors (FTIs), a promising class of agents that target multiple pathways including Ras proteins, are potential anticancer therapy for a wide range of malignancies, including leukemias and myelodysplastic syndromes (MDS). There also is evidence that recombinant human erythropoietin therapy (r-HuEPO) can benefit patients with chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. This supplement will discuss advances in our understanding of human leukemias, including the use of unconjugated monoclonal antibodies such as Campath-1H (Wellcome, Beckenham, UK, and Ilex Oncology, San Antonio, TX) and rituximab and immunoconjugates such as gemtuzumab ozogamicin and BL-22. Although these novel therapies are beginning to fulfill their promise, continued research efforts are needed to determine the optimal role of targeted therapy in acute and chronic leukemias.

Antineoplastic Agents↗

PubMed2004

Thrombosis in children with hematologic malignancies.

This review is based on pediatric reports (- January 2004) on the presence of symptomatic thrombosis in children with hematologic malignancies, mainly acute lymphoblastic leukemia, treated with different treatment protocols and associated with acquired and inherited prothrombotic risk factors (factor V G1691A, factor G20210A, MTHFR C677T genotypes, protein C, protein S, antithrombin, elevated levels of lipoprotein(a), and homocysteine). The interactions of treatment modalities, study designs, ethnical backgrounds and associated central lines are discussed. Based on the data presented here, we suggest the use of prednisone and E. coli asparaginase concomitantly administered in a leukemic patient suffering a prothrombotic risk factor to be responsible for the onset of venous thrombosis in the majority of cases. In addition, primary preventive anticoagulant/antithrombotic strategies are discussed.

Antineoplastic Agents↗

PubMed1991

p53 gene alterations in human hematological malignancies: a review.

Mutations of the tumor suppressor gene p53 are found in a wide variety of human tumors. In hematological malignancies, p53 alterations are involved in the evolution of chronic phase CML to myeloid blast crisis. p53 mutations were also found associated with Burkitt lymphoma (35%) and its leukemic counterpart, L3 type B-cell acute lymphoblastic leukemia (60%). These observations suggest that several common mechanisms are involved in the transformation process of these two hematological disorders.

Gene Rearrangement↗

PubMed1993

Cloning and characterization of the human t(3;6)(p14;p11) translocation breakpoint associated with hematologic malignancies.

The t(3;6)(p14;p11) chromosome translocation was identified in a family in which three members developed hematologic malignancies. To help characterize the region on chromosome 3 surrounding this translocation breakpoint, two flanking lambda clones, MS156 and MJ1525, were linked by pulsed-field gel electrophoresis to the same 510-kb NotI fragment on chromosome 3. MS156 was localized to a region proximal to the breakpoint of a der(3) chromosome somatic cell hybrid (derived from the t(3;6) cell line), and MJ1525 localized distal to the breakpoint. MJ1525 was used to screen the CEPH yeast artificial chromosome (YAC) library, which revealed a YAC, 195F3, that spanned the breakpoint. Subcloning into Lambda DASH II and production of a contiguous array of overlapping lambda clones revealed a clone, L17, that spanned the breakpoint. A rare restriction endonuclease map for the YAC 195F3 was constructed, and multiple clusters of rare restriction sites within the YAC were identified, possibly indicating the disruption of a gene by the t(3;6) translocation breakpoint.

Animals↗

PubMed2005

Cytoprotection by amifostine during autologous stem cell transplantation for advanced refractory hematologic malignancies.

This study evaluated whether amifostine protects against mucositis and other toxicities in patients with advanced, refractory, or recurrent hematologic malignancies undergoing high-dose chemotherapy and total body irradiation. Thirty-five patients (20 with non-Hodgkin lymphoma, 12 with Hodgkin disease, and 3 with acute myelogenous leukemia) who underwent autologous stem cell transplantation were conditioned with total body irradiation 2 Gy twice daily on days -8 through -6; cyclophosphamide 6 g/m(2), etoposide 1.8 g/m(2), and carboplatin 1 g/m(2) on days -5 through -3; and amifostine 500 mg/m(2) on days -8 through -2. Prior institutional experience in patients treated without amifostine was used as a historical comparison (no-amifostine group). Severe mucositis occurred in 14 (40%) of 35 patients in the amifostine group, compared with 33 (94%) of 35 in the no-amifostine group (P < .0001). Total parenteral nutrition was used by 4 (11%) of 35 amifostine-treated patients and 34 (97%) of 35 no-amifostine patients (P < .0001). The median duration of narcotic use decreased from 15.5 days with no amifostine to 11 days with amifostine (P = .002). Granulocyte and platelet engraftment times were similar. Prospective trials with innovative designs and clearly defined stopping rules are warranted to confirm whether amifostine reduces the toxicities of a myelosuppressive conditioning regimen before autologous stem cell transplantation without compromising therapeutic response.

Acute Disease↗

PubMed1991

alpha-Interferon in hematological malignancies.

Recent studies have generated data demonstrating significant clinical activity of alpha-interferon therapy in each of six hematological malignancies, chronic myeloid leukaemia, essential thrombocythemia, polycythemia rubra vera, non-Hodgkin's lymphomas, multiple myelomatosis and hairy cell leukaemia.

Humans↗

PubMed1992

Large-volume leukapheresis for peripheral blood stem cell collection in patients with hematologic malignancies.

Large-volume leukapheresis (LVL, 15-35 L) was performed in two groups of patients (n = 10) with hematologic malignancies to obtain peripheral blood stem cells for bone marrow rescue following high-dose chemotherapy. The target cell count was 7 x 10(8) mononuclear cells (MNCs = lymphocytes and monocytes) per kg of body weight. Group A patients (n = 4) were studied on Day 1 of LVL, and components were collected from them as four sequential samples. Total MNCs collected averaged 1.29 x 10(10), total colony-forming-units granulocyte-macrophage (CFU-GM) averaged 12.1 x 10(6), and a 1.8-fold mobilization of CFU-GM was observed (p < 0.05, Sample 1 vs. Sample 4). Group B patients (n = 6) were studied throughout the three consecutive planned days of 5-hour LVL. An average of three LVL procedures per patient was performed (range, 1.25-4), and an average of 27 L (range, 24-33) of blood per LVL was processed. The blood:ACD-A ratio was 24:1 with 3000 units of heparin per 500 mL of ACD-A; heparin was also added to the collection bags. The component had an average hematocrit (Hct) of 0.02 and MNC content of 93 percent. The patients' pre-LVL and post-LVL average Hct varied significantly (before Day 1, 0.36 +/- 0.08; after Day 3, 0.28 +/- 0.06; p < 0.05). Platelet counts also decreased, with post-Day 3 counts averaging 19 percent of the average pre-Day 1 counts (p < 0.05). A decrease in the average MNC count after LVL was significant on Day 1 only (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Preservation↗

PubMed2006

Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions.

BACKGROUND: Conventional amphotericin B-based antifungal therapy for invasive fusariosis in patients with a hematologic malignancy results in a > or = 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species. METHODS: In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis. Twenty-one patients with proven or probable invasive fusariosis who had disease refractory to or who were intolerant of standard antifungal therapy received oral posaconazole suspension (800 mg per day in divided doses) as salvage therapy. RESULTS: Successful outcome occurred in 10 (48%) of all 21 patients. Among patients with leukemia who received posaconazole therapy for >3 days, the overall success rate was 50%; for patients who recovered from myelosuppression, the success rate was 67%, compared with 20% for those with persistent neutropenia. CONCLUSION: These results suggest that posaconazole is useful for the treatment of invasive fusariosis.

Adult↗

PubMedDate not supplied

Imipenem-cilastatin monotherapy in severe infections accompanying hematological malignancies.

Imipenem-cilastatin (imipenem 1 to 4 g/day) was administered to patients with severe infections accompanying granulocytopenia in hematological malignancies. Monotherapy with imipenem-cilastatin was effective in 62.1% of the patients, and also effective even they were severely neutropenic. When imipenem-cilastatin was administered as the first-choice therapy, the efficacy was much better, at 73.3%. Both Gram-positive and Gram-negative infections were curable by the monotherapy with imipenem-cilastatin.

Agranulocytosis↗

PubMed1985

Levels of C-reactive protein in patients with hematologic malignancies.

The levels of C-reactive protein (CRP) were assayed in 282 serial sera of 70 patients with hematologic malignancies who were under antineoplastic medication, and surveyed with frequent blood cultures. The mean peak value of CRP in febrile patients with bacteriologically verified sepsis was 162 mg/l and differed significantly (p less than 0.001) from that (23 mg/l) of afebrile patients with negative blood cultures, but not from that (115 mg/l) of febrile patients without confirmed bacteremia. All the values in afebrile patients with negative blood cultures were less than 100 mg/l; 71% of their peak values were less than 40 mg/l. Thus the malignancy itself or its treatment did not considerably mount CRP response.

Adolescent↗

PubMed2004

[Clinical characteristics in 18 cases of sever pneumonia after allogeneic hematopoietic stem cell transplantation for malignant hematological disease].

To investigate the clinical features and outcome of severe pneumonia after allogeneic hematopoietic stem cell transplantation for malignant hematological disease, the clinical features of severe pneumonia, including symptoms, signs, blood-gas analysis and thoracic X-ray change were observed, the clinical therapeutical outcome is also evaluated. The results showed that after treatment with antibiotics or antibiotics + antiviral drugs or antibiotics + antiviral drugs + glucocorticosteroids, as well as mechanical ventilation, pulmonary changes in 17 patients with sever pneumonia completely disappeared, 1 case died. In conclusion, early diagnosis and proper treatment for complicated pneumonia after allogeneic hematopoietic stem cell transplantation can decrease the mortality.

Adolescent↗

PubMed1997

[Study on serum soluble interleukin-6 receptor levels in patients with malignant hematological diseases].

OBJECTIVE: To explore the clinical implication of soluble interleukin-6 receptor(sIL-6R) in patients with malignant hematological diseases. METHODS: Serum levels of sIL-6R in 26 multiple myeloma (MM), 34 acute leukemia (AL) and 17 non-Hodgkin's lymphoma (NHL) patients before and after chemotherapy and 20 normal controls were measured by immunoenzymetic assay. RESULTS: Serum levels of sIL-6R in MM and B-ALL patients at diagnosis were significantly higher than that in normal controls (P < 0.001, and P < 0.01, respectively), while the levels in ANLL, T-ALL and NHL patients were normal. Serum beta2 microglobulin and creatinine levels in MM patients with elevated serum sIL-6R were higher than that in patients with normal sIL-6R levels(P < 0.001, and P < 0.05, respectively). Serum sIL-6R levels did not relate to clinical stages. Serum lactic-dehydrogenase (LDH) levels in B-ALL patients with elevated sIL-6R were higher than that in patients with normal sIL-6R levels (P < 0.05). Serial measurement of serum sIL-6R in MM patients showed a good correlation with serum M-protein and plasma cell percentage in bone marrow. CONCLUSION: Serum sIL-6R levels were significantly increased in MM and B-ALL patients, and it is a predictive factor for responsiveness to chemotherapy and an indicator of disease activity.

Adult↗

PubMed1990

[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies].

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.

Acute Disease↗

PubMed1989

Lymphokine-activated killer function following autologous bone marrow transplantation for refractory hematological malignancies.

Disease recurrence remains the major factor which limits the success of autologous bone marrow transplantation (ABMT) for refractory hematological malignancies. The administration of interleukin 2 (IL2) with or without ex vivo generated lymphokine-activated killer (LAK) cells represents a potential approach to eradicating residual disease after ABMT. However, since LAK precursor activity is radiosensitive, high dose chemoradiotherapy may abrogate LAK function and preclude clinical responsiveness to IL2 after ABMT. Furthermore, since lymphocyte subsets which mediate LAK activity may recover at different rates after ABMT, LAK cells may be phenotypically and/or functionally altered after ABMT. To determine whether IL2 responsive LAK precursor cells are present in the circulation after ABMT, peripheral blood mononuclear cells (PBMC) from 21 patients with acute leukemia or lymphoma were tested for IL2-inducible LAK activity 17-83 days after ABMT. Cells were cultured with IL2 (1000-2000 units/ml) for 4 or 5 days and then tested for cytolytic activity and/or cell phenotype. LAK activity against the Daudi cell line was detected in every PBMC sample from every patient at every time point tested. The Raji cell line and a fresh allogeneic ovarian carcinoma were also lysed by LAK cells generated after ABMT. In the subgroup of patients transplanted for non-Hodgkin's lymphoma, LAK precursor activity appeared comparable to that of healthy controls. Culture with IL2 resulted in increased mean IL2 receptor expression in lymphocytes from patients after ABMT (3.1-9.9%) and from healthy controls (3.1-12.0%). After culture with IL2, the percentage of cells bearing the natural killer cell-associated Leu-19 determinant was significantly higher in patient PBMC than in normal control PBMC (28.3 versus 8.7%). Positive and negative cell selection by fluorescence sorting after culture with IL2 revealed that most of the LAK activity after ABMT was mediated by the Leu-19+ cells. Although CD5+ T-cells were devoid of LAK activity, a subset LAK effectors was CD8+. Thus, LAK activity is rapidly reconstituted after ABMT and is mediated by cells phenotypically similar to those in normal controls. These results support the feasibility of IL2 +/- LAK as consolidative immunotherapy after ABMT.

Antigens, CD↗