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PubMed2004

Role of farnesyltransferase inhibitors in hematologic malignancies.

The treatment of hematologic malignancies has progressed in the last few years. Identification of new pathways and target molecules in leukemia has ushered in a promising new era of therapy. Ras mutations have recently been implicated in the pathogenesis of acute leukemia, and inhibition of Ras signaling through the use of farnesyltransferase inhibitors (FTIs) has shown promise in early trials in acute myeloid leukemia (AML). Responses have not correlated with the presence of Ras mutations, suggesting that novel pathways are involved. In several early trials, FTIs have shown activity as single agents in poor-risk AML, suggesting a potential role in combination with standard chemotherapy. FTIs are now being tested in other clinical settings, such as myelodysplasia, chronic myelogenous leukemia and multiple myeloma, with encouraging preliminary activity.

Enzyme Inhibitors↗

PubMed1998

Bacteremia in patients with hematologic malignancies.

The decision regarding the appropriate empirical antibiotic therapy for bacteremia in patients with hematologic malignancies must be individualized in each institution, by taking into account variations in the patterns of microbial isolates and their resistance profiles. Microbial isolates and antibiotic resistance patterns must be taken into account at each hospital. A shift from bacteremia due to infections caused by predominantly gram-negative organisms to predominantly gram-positive organisms in patients with hematologic malignancies has been noted in reports from other countries. We investigated bacterial isolates and their antibiotic sensitivities in patients with hematologic malignancies in the Veterans General Hospital-Taipei. A total of 185 episodes of bacteremia in 140 patients with hematologic malignancies were recorded during the period from 1995 to 1996. Unlike foreign reports, our investigation shows that gram-negative organisms still predominate, accounting for 72.7% of isolates, followed by gram-positive organisms, accounting for 26.3% of isolates, and anaerobes, accounting for 1% of isolates. Escherichia coli was the most commonly isolated organism, accounting for 23.9% of isolates, followed by Klebsiella pneumoniae (18.5%), Pseudomonas aeruginosa (12.2%), Enterobacter cloacae (7.3%), and methicillin-resistant Staphylococcus aureus (7.3%). A high mortality rate was observed in gram-negative bacteremia: 31% for E. coli, 26% for K. pneumoniae, 24% for P. aeruginosa, and 33% for E. cloacae. If methicillin-resistant S. aureus bacteremia occurred, mortality was high (47%). The antibiotic sensitivity profiles of the four most common gram-negative isolates (E. coli, K. pneumoniae, P. aeruginosa, and E. cloacae) indicated that, in our hospital, amikacin with either cefoperazone, ceftazidime, ciprofloxacin, or imipenem, would be an ideal combination for empirical therapy for bacteremia in patients with hematologic malignancies.

Adolescent↗

PubMed1999

Laparoscopic splenectomy for hematologic malignancies.

BACKGROUND: Patients with hematologic malignancy (HM) tend to have large spleens. The purpose of this study was to compare the outcomes of laparoscopic splenectomy for patients with HM to those with benign disease (BD). METHODS: A review was conducted of a prospectively accumulated database of 64 consecutive, unselected laparoscopic splenectomies performed by two surgeons between March 1992 and August 1997. RESULTS: Of 14 patients with HM (7 lymphoma, 6 leukemia, 1 myeloid metaplasia), three required conversion to open splenectomy (21%). In the remaining 11 patients, two had postoperation complications (18%), including one death from sepsis (9%). Of 50 patients with BD (36 idiopathic thrombocytopenic purpura [ITP], 5 spherocytosis, 4 hemolytic anemia, and 5 others), three were converted to open surgery (6%). Complications developed in 5 (11%) of the remaining 47 patients. No deaths occurred. All patients who had spleens larger than 27 cm in diameter required conversion. Patients undergoing laparoscopic splenectomy for HM were older (54 +/- 16 years vs. 36 +/- 18 years; p = 0.002), had larger spleens (median 17.0 cm vs. 11.0 cm; p < 0.001), and had lower preoperation hemoglobin levels (113 +/- 30 g/L vs. 132 +/- 23 g/L; p = 0.03) than patients with BD. The HM group required longer operation time (239 +/- 73 min vs. 180 +/- 61 min; p < 0.01), but showed no differences with respect to operation blood loss (median, 100 vs. 165 mL), requirement for transfusion (median, 0.0 vs. 0.0 units), and length of hospital stay (median 3.0 vs. 3.0 days). CONCLUSIONS: Although patients with HM had larger spleens and required longer operation time for laparoscopic splenectomy, surgical outcomes were equivalent. The laparoscopic approach should be preferred, even for patients with HM. The only limitation appears to be splenic size greater than 27 cm.

Adult↗

PubMed1987

High dose busulfan/etoposide as a preparatory regimen for second bone marrow transplants in hematologic malignancies.

Five patients with hematologic malignancies who had relapsed between seven months and eight years after their primary bone marrow transplants were prepared with high dose busulfan/etoposide for second marrow transplantations from the same donors who had provided the marrow for the primary transplants. The preparatory regimen was well tolerated. All patients engrafted and entered complete remission. Two patients are alive and in continued remission two and ten months after second transplant. One patient died with acute respiratory failure after two months and two patients relapsed again eight and 17 months after second marrow transplantation. The combination busulfan/etoposide may prove to be a suitable preparatory regimen for second bone marrow transplant attempts in selected patients.

Adolescent↗

PubMed1991

High efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2-ASP) in two patients with hematological malignancies.

Two patients with hematological malignancies were successfully treated with monomethoxypolyethylene glycol-conjugated Escherichia coli L-asparaginase (PEG2-ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to L-asparaginase (L-ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100-200 IU/day dose of PEG2-ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG2-ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG2-ASP. Thus, PEG2-ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of L-ASP.

Adult↗

PubMedDate not supplied

Computed tomography in hematologic malignancies of paranasal sinuses.

Hematologic malignancies of the paranasal sinuses are uncommon. Four young patients with ophthalmologic abnormalities as a chief complaint are presented. Lymphoma or leukemia should be considered in the differential diagnosis of destructive lesions in the paranasal sinuses, particularly in children and young adults.

Adult↗

PubMed1988

Alterations in bone marrow and blood mononuclear cell polyamine and methylglyoxal bis(guanylhydrazone) levels: phase I evaluation of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) treatment of human hematological malignancies.

Nine patients with hematological malignancies were treated with difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The number of circulating blast cells decreased in all of the patients treated with DFMO and MGBG for longer than 1 wk. Morphological evidence of myeloid maturation was evident in four patients with leukemia and the circulating M Protein decreased in one patient with multiple myeloma. The polyamine content of the mononuclear cells in both the peripheral blood and bone marrow was transiently increased after the initial MGBG dose. During administration of DFMO decreases were achieved in the peripheral blood mononuclear cell putrescine levels in 7 patients, spermidine levels in 5 patients, and spermine levels in 4 patients. Alterations in bone marrow mononuclear cell polyamine levels were similar to those which occurred in the peripheral cells. An average of 9 days of DFMO treatment was required to lower mononuclear cell polyamine levels. Three of the 4 evaluable patients receiving multiple MGBG doses had an increased mononuclear cell content of MGBG after DFMO pretreatment. Enhancement of cellular MGBG levels was not directly correlated to the degree of cellular polyamine depletion.

Adult↗

PubMed1987

[Single-agent trial with epirubicin in hematological malignancies].

Twelve patients with hematological malignancies were treated with epirubicin and ten patients were evaluable. One out of our four patients with ALL, who had a previous therapy of anthracycline, achieved a partial remission (PR: 25%). In two patients with AML, remission was not obtained. Of four patients with NHL, one with B-cell lymphoma achieved complete remission (CR) and one with ATLL partial remission (CR + PR: 50%). Stomatitis was observed as a major side effect in three patients with acute leukemia and in one with NHL. In conclusion, our trial seems to show the efficacy of epirubicin in lymphoid malignancies.

Acute Disease↗

PubMed2000

The utility of open lung biopsy in patients with hematologic malignancies.

The yield and impact of open lung biopsies in patients with hematologic malignancies and unexplained pulmonary processes were assessed and analyzed to determine factors that affected the yield. Records of 63 patients with hematologic malignancy, who underwent 67 open lung biopsies for diagnosis of an unknown pulmonary process from 1996 to 1998 at Memorial Sloan-Kettering Cancer Center, were retrospectively reviewed. A specific diagnosis was found in 41 (62%) of the biopsies. Changes in therapy were made in 37 (57%) of patients after biopsy results, but in 69% of those with a specific diagnosis. Survival at 30 and 90 d was increased in those with specific rather than a nonspecific pulmonary diagnosis. The factor most predictive of finding a specific diagnosis was the presence of a focal rather than a diffuse radiographic abnormality (79% versus 36%, p = 0.003). Neutropenic patients or those on mechanical ventilation had a low chance of finding a specific diagnosis. Having received pulmonary toxic chemotherapy in the 6 mo before the biopsy was associated with finding a nonspecific lung injury. Specific pulmonary diagnoses found were inflammatory diseases in 23% of cases, infections in 21%, and malignancy in 18%. Bronchiolitis obliterans with organizing pneumonia (BOOP) was the most common inflammatory disorder and fungi and bacteria were the most frequent infectious pathogens. Complications occurred in 13% of the biopsies, including five patients who required mechanical ventilation post-procedure; one death was associated with the biopsy. The risk was increased in those with less than 50,000 platelets. Complications were similar with video-assisted thoracoscopy (VATS) compared with thoracotomy. We conclude that open lung biopsy in patients with hematologic malignancy has a significant yield and impact on management of patients with hematologic malignancy.

Adolescent↗

PubMed2005

Risk factors for and attributable mortality from tuberculosis in patients with hematologic malignances.

BACKGROUND AND OBJECTIVES: Patients with hematologic malignancies are at increased risk of developing tuberculosis because of the T-cell immunodeficiency associated with the disease and/or its treatment. The objective of this study was to evaluate risk factors, clinical findings and the attributable mortality associated with tuberculosis in patients with hhematologic malignancies. DESIGN AND METHODS: We performed a retrospective review of the clinical records of 917 patients observed between 1990 and 2000. A risk classification for tuberculosis (low vs. high risk) was developed based on the underlying disease and previous exposure to agents that deplete T-cell mediated immunity. Patients with and without tuberculosis were compared by univariate and multivariate analyses with regard to demographic and clinical characteristics, underlying diseases and their treatment. The attributable mortality was assessed by matching cases and controls using the independent variables identified as risk factors as the matching parameters, and was estimated by subtracting the crude mortality of the controls from the crude mortality of the cases. RESULTS: We found 24 cases of tuberculosis (2.6%). Risk factors by multivariate analysis were malnutrition (OR 55.66, 95% CI 2.47--1254.82), use of fludarabine (OR 6.08, 95% CI 1.22--30.25), use of corticosteroids (OR 5.32, 95% CI 1.15--24.39) and belonging to the high-risk group (OR 3.73, 95% CI 1.09--12.76). The crude mortality of patients with tuberculosis was 75%, and the attributable mortality was 62.5% (risk ratio 6.0, 95% CI 2.03--17.70). INTERPRETATION AND CONCLUSIONS: The mortality attributable to tuberculosis is high in patients with hematologic malignancies. The identification of risk factors may be useful for evaluating strategies to be applied in high-risk patients.

Adolescent↗

PubMed2005

[Expression of stromal cell derived factor-1(SDF-1) and its receptor CXCR4 in hematologic malignancies].

The aim was to analyze the expression level of stromal cell derived factor-1 (SDF-1) and its functional chemokine receptor CXCR4 in the patients with hematologic malignant tumor and their clinic significance. 28 patients with hematologic malignant tumor and 12 normal controls were chosen to be experimental objects. CXCR4 expressed on the cell membrane in bone marrow was enumerated by flow cytometry and serum level of SDF-1 was determined by ELISA assay. The result showed that the expression of SDF-1 and CXCR4 in hematologic malignant tumor were higher than that in normal controls, and the expression levels of two molecules were correlated. What is more, the different hematologic malignant tumor had different CXCR4 expression. In conclusion, the high expression of SDF-1 and CXCR4 in serum and bone marrow cells can be used as detective factors to hematologic malignant tumor. A correlation exists between the high expression of CXCR4 and the infiltration of hematologic malignant cells.

Adolescent↗

PubMed1995

Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospective study.

PURPOSE: To evaluate the relationship between use of methotrexate in rheumatoid arthritis patients and development of hematologic malignancies. PATIENTS AND METHODS: We retrospectively analyzed all patients registered at the Mayo Clinic from 1976 through 1992 with rheumatoid arthritis (n = 16,263) cross-indexed with patients registered during the same period with a hematologic malignancy (n = 21,270). Adult patients were selected who had rheumatoid arthritis, were treated with a disease-modifying antirheumatic drug, and subsequently developed a hematologic malignancy. RESULTS: Thirty-nine patients met the selection criteria. Twelve of them had been given methotrexate. The characteristics of those who received methotrexate, including the type of hematologic malignancy, did not differ from those of patients who received other disease-modifying antirheumatic drugs. CONCLUSIONS: Hematologic malignancies are uncommon in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, including methotrexate. There does not appear to be a relationship between the peak or cumulative dose or the duration of methotrexate therapy and the subsequent development of hematologic malignancy. The histologic types of hematologic malignancy seen in the methotrexate-treated patients did not differ from those of patients treated with other disease-modifying antirheumatic drugs.

Adult↗

PubMed2026

Proteomic analysis identifies pathways related to immune dysregulation in patients with hematologic malignancies after COVID-19 infection.

Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.

Humans↗

PubMed2005

Immunological evaluation of vaccination of peptides derived from epithelial cancer-related antigens in two patients with hematological malignancy.

Recent advances in tumor immunology have resulted in identification of many epithelial cancer-related antigens and peptides applicable to specific immunotherapy. We and others have reported that several epithelial cancer-related antigens are also expressed in hematological malignancies. Two patients with hematological malignancy (multiple myeloma and chronic lymphocytic leukemia) were vaccinated with peptides derived from epithelial cancer-related antigens to evaluate the immune responses to peptides under a personalized peptide vaccination regimen. There was no adverse event except for local skin reaction at the injection site. The peptide vaccination augmented both peptide-specific CTLs cytotoxic to hematological malignant cells in post-vaccination peripheral blood mononuclear cells and peptide-specific IgG in post-vaccination sera. A transient but obvious decrease of malignant cells was observed at the early phase of the vaccination in both cases. Vaccines consisting of peptides derived from epithelial cancer antigens safely increased anti-tumor cell activity in patients with hematological malignancies. These results may provide a scientific rationale in use of epithelial cancer-related antigens for specific immunotherapy to patients with hematological malignancies.

Aged↗

PubMed2003

A workshop on the marrow microenvironment and hematological malignancy.

The Division of Cancer Biology of the National Cancer Institute hosted a workshop on hematological malignancies and the marrow microenvironment in Rockville, Maryland in the fall of 2002. There were 22 invited participants from the United States, Canada, and Europe, and the workshop was organized into disease-specific sessions. The sessions were designed to explore the basic science and therapeutic applications related to the stromal and nonstromal components of the marrow in malignant hematological diseases.

Animals↗

PubMed2002

Angiogenic and lymphangiogenic molecules in hematological malignancies.

In this review, the role of angiogenic and lymphangiogenic growth factors in hematological malignancies is summarized, alongside with possible therapeutic applications. Recent data demonstrate the importance of angiogenesis in hematologic malignancies including leukemia, lymphoma, and multiple myeloma. Expression of angiogenic polypeptides vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) associate with clinical characteristics in human leukemia and lymphoma, and their serum concentrations serve as predictors of poor prognosis. VEGF and VEGF-C also act as survival factors on leukemia. Furthermore, certain hematological malignancies both produce angiogenic or lymphangiogenic growth factors including VEGF and VEGF-C, and also express their receptors, resulting in the generation of autocrine loops that may support cancer cell survival and proliferation. Inhibition of the action of key regulators of endothelial cell growth, alone or in combination with other antiangiogenic drugs and/or established chemo- or immunotherapy regimens, is a potential target for therapeutic intervention in hematological malignancies.

Animals↗

PubMed2002

[An analysis of double autologous hemopoietic stem cell transplantation for hematological malignancies].

OBJECTIVE: To analyse the clinical efficacy of the double autologous hemopoietic stem cell transplantation (DAHSCT) for hematological malignancies. METHODS: 19 hematological malignant disease patients received the first AHSCT within 12 months after diagnosis. The first conditioning regimen was VP-16 or Ara-C, CTX +, TBI, nine of them received BCNU additionally. All patients received the second AHSCT in 4 to 10 months after the first AHSCT. The second conditioning regimen was VP-16 (or Ara-C), CTX +, Mel. RESULTS: All patients had rapidly hemopoietic reconstitution, the first hemopoietic reconstitution is faster than the second. There was no AHSCT related death. The median follow up duration was 1078 days. 12 of the 19 patients were still alive during the analysis. The 3-year disease-free suvival (DFS) was 63% +/- 10%. Those patients who had more blasts in bone marrow at the second AHSCT than the first AHSCT had greater probability to relapse. CONCLUSION: DAHSCT can be safety performed as an important treatment method in hematological malignancies.

Adolescent↗

PubMed1997

[Optimal antibacterial chemotherapy for infectious diseases associated with hematological malignancies].

The status quo of infectious diseases associated with hematological malignancies was examined for clinical consideration. In addition, in vitro antibacterial activities and combination effects were also examined by means of various isolated strains derived from sepsis. In clinical practice, 76% of the fevers in patients with hematological malignancies was attributed to infectious diseases mainly involving "fever with granulocytopenia", sepsis, and pneumonia. The detection rate of causal pathogen remained at a low level and more than half of the causes of death were infectious diseases. In the in vitro examination, a favorable antibacterial effect was noted with vancomycin (VCM) for methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus spp., imipenem (IPM) for methicillin sensitive S. aureus (MSSA), and ciprofloxacin, amikacin (AMK), and IPM for Pseudomonas aeruginosa and intestinal flora. But its clinical effect is not enough. Synergic and/or additive effect can be expected by combining IPM with VCM for MRSA and Enterococcus spp., and IPM with AMK for P. aeruginosa. These combination therapies were considered to be optimal as antibacterial chemotherapy for infectious diseases associated with hematological malignancies.

Adult↗