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PubMed1986

Cefotaxime monotherapy in septicemic patients with hematological malignancies.

Cefotaxime at a dosage of 3 gm intravenously every eight hours was administered to 80 patients with hematological malignancies and suspected septicemia. Blood samples for culturing were taken before and during antibiotic therapy. Nineteen patients had verified bacteremia and ten of them responded completely to cefotaxime. Twelve of the 19 patients had granulocyte counts of less than 0.5 X 10(9)/L. Minimal inhibitory concentrations of cefotaxime, ceftazidime, moxalactam, cefsulodin, cefoxitin, cefuroxime, and cefamandole against the pathogens were measured: cefotaxime was the best cephalosporin against gram-negative isolates and was found acceptable against gram-positive bacteria. In 61 patients no bacteremia could be demonstrated, but specific pathogens were isolated in 11 patients: from the urine in five, from the sputum in five, and from a perianal abscess in one. Complete response was obtained with cefotaxime in seven of these 11 patients. Monotherapy with cefotaxime in septicemic patients with hematological malignancies appears to be a valuable alternative to other antibiotic regimens.

Aged↗

PubMed1996

Impact of preexisting CNS involvement on the outcome of bone marrow transplantation in adult hematologic malignancies.

PURPOSE: To determine the impact of prior or current CNS disease on the outcome of high-dose chemotherapy for patients with hematologic malignancies. PATIENTS AND METHODS: In a 54-month period, 373 patients with hematologic malignancies underwent allogeneic or autologous bone marrow transplantation (BMT) or blood stem-cell transplantation using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen. Four patients with active CNS disease at BMT and 20 patients with a history of prior CNS disease were identified. The outcomes of those with a history of CNS disease were compared with those of a matched control group. RESULTS: Of four patients with active CNS disease at the time of BMT, two had CNS recurrences and one recurred in the bone marrow. One patient died of treatment-related toxicity. Four of 20 patients with prior CNS involvement currently remain free of disease. At 2 years, the disease-free survival (DFS) rate was 23% +/- 19%, and the DFS rate for the control group 39% +/- 24% (P = .053). An increased rate of treatment-related toxicity and especially grades II to IV CNS toxicity accounted for the poorer outcome of patients who had a history of CNS disease. Recurrence rates were not significantly different between the two groups. Prior radiation to the CNS correlated with CNS complications posttransplant (p = .01). CONCLUSION: Consolidation with TBC and BMT can induce prolonged DFS in a proportion of patients with a history of CNS disease. Such patients are at increased risk for CNS complications that lead to an inferior overall outcome when compared with a control group.

Adolescent↗

PubMed1996

XYY male and hematologic malignancy.

Two cases of XYY male with refractory anemia with excess of blasts are reported, and previous reported XYY males with hematologic malignancy are reviewed. Altogether 26 cases were collected for analysis: acute myeloid leukemia (10), acute lymphocytic leukemia (seven), acute leukemia (two), chronic myelocytic leukemia (three), myelodysplastic syndrome (three), and essential thrombocythemia (one). The age at the time of diagnosis ranged in age from 7.5 to 81 years. In three of six XYY/XY mosaicism cases, XYY clone was associated with malignancy. However, in two cases XYY clone was not involved. The evidence presented here suggests that the event of an XYY male with hematologic malignancy is incidental rather than a genetic etiology.

Adolescent↗

PubMed1988

Immunoglobulin allotypes Gm and Km in hematologic malignancies.

Immunoglobulin allotypes of the Gm and Km systems have been compared in patients with various forms of hematologic malignancies and healthy controls of the same ethnographic background. These comparisons found an increased frequency of the haplotype Gm and a decreased frequency of Gm in patients with Hodgkin's disease; a decreased frequency of Gm in diffuse, large-cell lymphoma patients; a decreased frequency of Gm and an increased frequency of Gm in acute myeloid leukemia patients; a decreased frequency of Gm in chronic myeloid leukemia patients, and an increased frequency of the phenotype Km(1+) in chronic lymphocytic leukemia patients. These results support previous suggestions of the involvement of immunoglobulin allotypes in the susceptibility to some forms of human hematologic malignancy.

Gene Frequency↗

PubMed2003

Nonmyeloablative stem cell transplantation with fludarabine and cyclophosphamide for patients with hematologic malignancies.

We conducted a multi-center phase I/II trial of nonmyeloablative stem cell transplantation for patients with hematologic malignancies. The aim of this trial was to assess the safety and feasibility of this treatment modality for older or younger patients with significant organ dysfunction, who could not be treated with conventional high dose chemoradiotherapy. Twelve patients were treated with a conditioning regimen consisting of fludarabine and cyclophosphamide, followed by peripheral blood stem cell transplantation from human leukocyte antigen (HLA) identical siblings. Nonhematologic toxicities were mild. Median time to absolute neutrophils above 0.5 x 10(9)/l, 1.0 x 10(9)/l and platelets above 50 x 10(9)/l were 8, 10 and 12 days, respectively. Donor dominant hematopoiesis was achieved in all patients, with or without donor leukocyte infusion. The cumulative incidence of acute and chronic graft-versus-host disease (GVHD) was 75 and 56%, respectively. Only one patient experienced early death within 100 days, caused by acute GVHD complicated by fungal infection. All patients except one achieved complete remission. With a median follow-up of 330 days, expected progression-free survival is 75%. Overall survival is 76%. Our study confirms that nonmyeloablative stem cell transplantation with cyclophosphamide and fludarabine conditioning is a safe and promising treatment for elderly patients with hematologic malignancies. A further study in large-scale setting is warranted.

Age Factors↗

PubMed2003

[Topotecan-based combined chemotherapy for refractory or relapsed hematologic malignancies].

OBJECTIVE: To evaluate the efficacy and toxicity of topotecan-based combined chemotherapy for refractory or relapsed hematologic malignancies. METHODS: Twenty-one patients with refractory or relapsed acute leukemia (AL), non-Hodgkin's lymphoma (NHL) or high risk myelodysplastic syndrome (MDS) were treated by topotecan with cytarabine, amsacrine or cyclophosphamide. All patients received a single course as salvage therapy. RESULTS: The overall response rate of one course was 61.9% with 9/21 (42.9%) CR and 4/21 (19%) PR. Severe myelosuppression was observed in all patients. Agranulocytic time was 12.6 days in AL and 7.5 days in NHL. Sixteen of 21 patients received G-CSF 300 micro g/d All patients received supportive treatment of transfusion. Fever and documented infection developed in 15 patients. Non-hematologic toxicity was mild. CONCLUSION: Topotecan-based combined chemotherapy has significant antitumour activity and acceptable toxicity as salvage therapy for high risk hematologic malignancies.

Adolescent↗

PubMed2005

[Interregulation of VEGF/R endostatin and MMP in the angiogenesis of hematologic malignancies--review].

Some kinds of angiogenic correlation factors, e.g. VEGF/R, MMP, endo statin, are relative to the process of hematologic malignancies. The mechanisms of adjusting themselves and controlling mutually have been hot points of the academic research in last few years. Although the rapid progress has been made in studies of this field, it is still hard to come into a systematic theory now. This article introduces the last progress in the field of positive and negative regulatory factors of VEGF/R system in the angiogenesis of hematologic malignancies, the regulation of MMP and its relation with VEGF/R, the regulation of ES and its relation with VEGF/R and MMP.

Endostatins↗

PubMed1984

Gram-negative septicemia in patients with hematologic malignancies.

The clinical records of 66 consecutive episodes of Gram-negative bacteremia occurring in 60 patients with hematologic malignancies during a 66-month period were reviewed to assess the major prognostic factors. The bacteremia-related mortality was 53%. Overall, Pseudomonas aeruginosa (54%) and Escherichia coli (24%) were the predominant isolates (fatality rate 78 and 31% respectively). The majority of patients (58/66) were granulocytopenic (PMN less than 1000/microliters). Among the 18 patients whose circulating granulocytes increased by one log10 or to above 1000/mmc during therapy, the fatality rate was 39%, as opposed to 70% in the 40 patients without such an increase. Pneumonia-associated bacteremia (56%) had a high fatality rate (73%) compared to isolated bacteremias (27%). Septic shock and inappropriate antibiotic therapy accounted for the highest mortality. Our data suggest that Pseudomonas etiology, persistent neutropenia, associated pneumonia, septic shock and inappropriate antibiotic therapy account for a bad prognosis in Gram-negative bacteremia in hematologic malignancies.

Agranulocytosis↗

PubMed1995

Abnormal liver function in patients undergoing autologous bone marrow transplantation for hematological malignancies.

Autologous bone marrow transplantation (AuBMT) is an accepted treatment modality for patients with high-risk or relapsed hematological malignancies. Hepatotoxicity, in particular veno-occlusive disease (VOD), is a significant complication of this therapy. The purpose of this study was to determine the clinical relevance of abnormal liver function in the patients who received high-dose cytotoxic therapy and AuBMT for hematological malignancies at Memorial Sloan Kettering Cancer Center. Medical records of 180 consecutive patients between 1984 and 1991 treated with cytotoxic chemotherapy and AuBMT for acute myelogenous leukemia, non-Hodgkin's lymphoma, and Hodgkin's disease were reviewed. Forty-six patients (26%) developed jaundice with bilirubin > 4 mg/dl. These patients had a 43% toxic death rate compared to an 11% toxic death rate in patients with lower bilirubins (p < 0.001). The main etiology of hyperbilirubinemia was VOD of the liver noted in 22 of the 180 patients (12%). Other etiologies of jaundice included hepatitis, sepsis with multiorgan dysfunction, cholecystitis, and recurrent disease. Hyperbilirubinemia of various etiologies is a significant complication of AuBMT. Several new strategies are under investigation to decrease the toxicity of intensive therapy.

Adolescent↗

PubMed2007

Efficacy and safety of micafungin in febrile neutropenic patients treated for hematological malignancies.

OBJECTIVE: The purpose of this study was to prospectively evaluate the efficacy and safety of micafungin (MCFG) in empirical therapy for febrile neutropenic patients for whom antibiotic therapy was not effective for hematological malignancies. PATIENTS AND METHODS: Twenty-three hematological patients aged 27-82 years with febrile neutropenia for whom antibiotic therapy was not effective were enrolled in this study and responses to treatment were evaluated. RESULTS: Treatment success rate was 73.9%. Treatment success rates by primary diagnosis were 77.8% in patients with AML, 50.0% in patients with NHL and 87.5% in patients with other diseases. Moreover, MCFG at a dose of 100 mg or more have a tendency to be effective. One or more adverse events occurred in five (27.7%) of the patients during the study. All of these adverse events were below grade 2 toxicity. CONCLUSIONS: Although the number of patients studied was limited, MCFG as a monotherapy seems to be effective and safe as an empirical therapy in patients with febrile neutropenia. However, further investigation using large-scale studies is needed. This study demonstrated the clinical efficacy and safety of MCFG in patients with febrile neutropenia and with hematological malignancies.

Adult↗

PubMed2004

Genomic approaches to hematologic malignancies.

In the past several years, experiments using DNA microarrays have contributed to an increasingly refined molecular taxonomy of hematologic malignancies. In addition to the characterization of molecular profiles for known diagnostic classifications, studies have defined patterns of gene expression corresponding to specific molecular abnormalities, oncologic phenotypes, and clinical outcomes. Furthermore, novel subclasses with distinct molecular profiles and clinical behaviors have been identified. In some cases, specific cellular pathways have been highlighted that can be therapeutically targeted. The findings of microarray studies are beginning to enter clinical practice as novel diagnostic tests, and clinical trials are ongoing in which therapeutic agents are being used to target pathways that were identified by gene expression profiling. While the technology of DNA microarrays is becoming well established, genome-wide surveys of gene expression generate large data sets that can easily lead to spurious conclusions. Many challenges remain in the statistical interpretation of gene expression data and the biologic validation of findings. As data accumulate and analyses become more sophisticated, genomic technologies offer the potential to generate increasingly sophisticated insights into the complex molecular circuitry of hematologic malignancies. This review summarizes the current state of discovery and addresses key areas for future research.

Gene Expression Profiling↗

PubMed2005

A lack of DNA mismatch repair on an athymic murine background predisposes to hematologic malignancy.

Inheritance of a germline mutation in one of the DNA mismatch repair genes predisposes human individuals to hereditary nonpolyposis colorectal cancer, characterized by development of tumors predominantly in the colon, endometrium, and gastrointestinal tract. Mice heterozygous for a mismatch repair-null mutation generally do not have an increased risk of neoplasia. However, mice constitutively lacking mismatch repair are prone to tumor development from an early age, particularly thymic lymphomas. Mismatch repair-deficient mice crossed to Apc(+/-) mice develop an increased spontaneous intestinal tumor incidence, demonstrating that the tumor spectrum can be genetically influenced. Here, we bred Msh2- and Msh6-deficient mice to athymic nude mice, hypothesizing that a broader tumor spectrum may be observed if mice are able to survive longer without succumbing to thymic lymphomas. However, Msh2(-/-);Foxn1(nu/nu) and Msh6(-/-);Foxn1(nu/nu) mice developed primarily early-onset lymphoblastic lymphomas. Using B-cell-specific markers, we found these tumors to be predominately B-cell in origin. The development of hematologic malignancy in the mouse, even in the absence of a thymus, parallels the development of B- and T-cell lymphoma and leukemia in the few rare mismatch repair-null human patients that have been identified. The persistent development of hematologic malignancy both in the mouse and in human patients deficient in mismatch repair leads us to implicate mismatch repair as an important repair mechanism in normal B- and T-cell development. Thus, mismatch repair-deficient mice may prove to be a good model to study human hematologic malignancy.

Animals↗

PubMed1996

[Clinical usefulness of 123I-BMIPP (beta-methyl iodophenyl pentadecanoic (acid) myocardial SPECT in patients with hematological malignancies with adriamycin-induced cardiomyopathy].

In order to investigate myocardial lipid metabolism in patients receiving chemotherapy regimens containing adriamycin (ADR) for hematological malignancies, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial SPECT was performed. Thirty-two patients with hematological malignancies received a mean total ADR dose of 245 mg/m2 (range: 0-550 mg/m2). A polar map based on data from 8 normal individuals was used to calculate the extent score (representing the area of decreased uptake) and the severity score (representing the severity of defects) in the patients given ADR. 1) There was a significant association between the total ADR dose and the extent and severity scores. 2) The left ventricular ejection fraction was significantly associated with the extent and severity scores. 3) The two scores were also significantly associated with the washout rate of 123I-metaiodobenzylguanidine (MIBG). These results suggest that 123I-BMIPP myocardial scintigraphy reflects dysfunction of the myocardial mitochondria and serves as a guide for determining whether administration of ADR should be discontinued or the dose reduced.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Prospective study of strongyloidosis in patients with hematologic malignancies.

Immunocompromised individuals infected with Strongyloides stercoralis may develop severe hyperinfection or disseminated disease with high mortality. Patients with hematological malignancies are at risk because of immunodepression produced either by the disease or its treatment. A prospective study was undertaken at the Hospital de Clínicas de Porto Alegre, from July 1994 to July 1995. Seventy-two (HIV negative), had 3 stool samples collected at different days and had not received recent anthelmintic therapy. Larvae, isolated in a modified Baermann method, were found in 6 patients, with a resultant prevalence of 8.3%. No complicated strongyloidosis was documented. The positive result for S. stercoralis larvae was significantly associated (p < 0.001) with eosinophilia. Knowledge of prevalence figures and incidence of severe disease is important to adequate guidelines for empirical treatment besides the rigorous search for strongyloidosis in patients with hematological malignancies.

Adolescent↗

PubMed2004

Mechanisms of glucocorticoid-induced apoptosis in hematologic malignancies: updates.

PURPOSE OF REVIEW: Glucocorticoids remain a central component of the therapeutic armamentarium for a broad spectrum of hematologic malignancies. There is an extensive body of evidence suggesting that the efficacy of glucocorticoids stems from their ability to mediate apoptosis in leukemia, lymphoma, and myeloma cells. RECENT FINDINGS: Traditionally, glucocorticoid-induced apoptosis is divided into three stages: an initiation stage, which involves glucocorticoid receptor activation and glucocorticoid receptor-mediated gene regulation; a decision stage, which engages the prosurvival and proapoptotic factors at the mitochondrial level; and an execution stage, which implicates caspases and endonuclease activation. Recent discoveries have clarified many aspects of the apoptotic pathway, including activation of the caspases cascade and multicatalytic proteasome, suppression of prosurvival transcription factors such as AP-1, c-myc, nuclear factor-kappaB, as well as cross-talk between the T-cell receptor and cytokine signaling pathways. SUMMARY: This review focuses primarily on insights gained during recent years into the mechanism of the signaling pathways responsible for mediating glucocorticoid-induced apoptosis in hematologic malignancies. This information provides a scientific basis to explore synergistic approaches that may enhance glucocorticoid-induced apoptosis and may bypass mechanism of resistance.

Apoptosis↗

PubMed1994

Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program.

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Adolescent↗

PubMed1986

Treatment of infections during hematologic malignancies with aztreonam, a new antibiotic.

Nineteen patients with hematological malignancies (5 malignant lymphomas, 9 acute leukemia and 5 other hematological diseases) were treated with aztreonam alone or in combination for infection. Four out of five patients in the lymphoma group, 6/9 in the leukemia group and 4/5 in the last group were considered cured of their infection. No important clinical side effects or consistent deterioration of hematology and chemistry tests were observed.

Acute Disease↗

PubMed2003

[Unrelated cord blood transplantation for the treatment of hematological malignancies].

OBJECTIVES: To investigate the engraftment, survival and graft-versus host disease (GVHD) after transplantation of unrelated cord blood for the treatment of childhood and adult hematological malignancies. METHODS: Seventeen patients (13 children and 4 adults) with hematological malignancies were enrolled in this study. Twelve patients were transplanted with one unit and 5 with 2 units of cord blood. There were HLA-matched in 6 and HLA-mismatched at 1 approximately 2 loci in 11 patients. Ten patients were transplanted at stable status, 7 at advanced stage of leukemia. Conditioning regimens were BU/CY for 13 and CY/TBI for 3 patients. Most patients received additional ATG at a dose of 15 approximately 20 mg x kg(-1) x d(-1) for 3 days. CsA, mycophenolate mofetil (MMF) and methylprednisolone were used for GVHD prophylaxis. RESULTS: Fourteen patients survived more than 40 days after transplantation were evaluated for engraftment. At day 60 after UCBT, 86% and 71% of the patients showed neutrophil and platelet engraftment, respectively. The time for an absolute neutrophil count > or = 0.5 x 10(9)/L was (21.0 +/- 1.3) days and platelet > or = 20 x 10(9)/L was (39.0 +/- 10.3) days. Four patients developed grade II acute GVHD and 2 chronic GVHD. Of the 17 patients, 11 were still alive and 8 of them were in event-free status. For the 10 patients transplanted at stable status, 2 year overall survival is 90%, and event-free survival (EFS) 70%. However, for the 7 patients transplanted at advanced stage of leukemia, only 2 survived without relapse. Of the 4 adult patients, 2 had sustained engraftment and survived for 18 and 14 months, respectively. CONCLUSIONS: HLA-matched or 1 approximately 2 loci-mismatched UCBT is a feasible procedure to cure a significant proportion of children or adults with leukemia, especially if performed in a favourable phase of disease. Two units of CBT can be used for adult patients if the cell number of one unit is not enough.

Adolescent↗