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PubMed2002

Multidimensional flow cytometry immunophenotyping of hematologic malignancy.

Immunophenotyping of hematologic malignancies represents one of the most relevant clinical applications of flow cytometry. Classically, leukemic/lymphomatous cells have been considered to reflect the immunophenotypic characteristics of different precursors and mature healthy cells blocked at certain differentiation stages. Recently, accumulating evidence has shown that neoplastic cells display several aberrant phenotypic patterns. These aberrant phenotypes are believed to reflect genetic abnormalities present in pathologic cells, and recent data have shown that at least in acute leukemias, myelodysplastic syndromes, chronic lymphoproliferative disorders, and plasma cell dyscrasias, they may be present in almost all patients. The aim of this work is to review recent advances in flow cytometry and the role of gating strategies more useful in the identification and characterization of neoplastic cells of different hematologic malignancies.

ADP-ribosyl Cyclase↗
PubMed2006

[Study on serum erythropoietin levels in patients with hematologic malignancies].

OBJECTIVE: To study whether hematologic malignancy patients with anemia have a lower erythropoietin (EPO) response. METHODS: Serum EPO levels were detected by ELISA in patients with hematologic malignancies and with iron deficiency anemia (IDA). Eighty patients with hematologic malignancies, including 13 multiple myeloma (MM), 7 chronic lymphocytic leukemia (CLL) and 60 non-Hodgkin's lymphoma (NHL) were studied. Thirty of them had anemia(21 NHL,6 MM and 3 CLL). Twenty patients with IDA were studied as the control. RESULTS: Hematologic malignancy patients with anemia had higher EPO levels [(97.8 +/- 183.9) IU/L] than those with normal Hb values [(27.8 +/- 85.4) IU/L; P <0.01]. In patients with IDA, serum EPO response was inversely correlated with Hb level (r= -0.5, P <0.05) , but no such inverse correlation was found in the hematologic malignancy patients with anemia (r = -0.14). After corrected for Hb level, the serum EPO levels were significantly lower in anemic patients with hematologic malignancies than in IDA patients (P = 0.032) , indicating a decreased EPO response in the former group. CONCLUSION: Anemia associated with hematologic malignancy might result from an inappropriately low EPO response. EPO treatment for these patients may be beneficial.

Adolescent↗
PubMed2005

Cutaneous vasculitis in the course of hematologic malignancies.

BACKGROUND: In patients with hematologic malignancies, cutaneous vasculitis is an important manifestation which may be secondary either to the malignancy itself or to many frequent events in these patients such as infections or drug intake. OBJECTIVE: To assess the underlying events responsible for cutaneous vasculitis in patients with hematologic malignancies. METHODS: Twenty-three patients with hematologic malignancies who had a skin biopsy in a single institution between January 1990 and June 1995 disclosing vasculitis were included in this study. Clinical, biological and immunological data, infectious enquiry and drug exposure were reviewed. RESULTS: The 23 patients represented 22% of 95 patients with hematologic malignancies in whom 105 skin biopsies were done. A lymphoproliferative disorder was found in 12/23 (52%) and a myeloproliferative disease in 11/23 (48%). The cutaneous vasculitis developed concomitantly with the malignancy in 39%, before in 26% and after the diagnosis of malignancy in 35%. The hematologic condition seemed to be the sole cause for vasculitis in 61% of the patients while the vasculitis could be attributed to another mechanism than the hematologic malignancy itself in 39%. These consisted in infections, medication and mixed cryoglobulinemia in 13% each. CONCLUSION: Cutaneous vasculitis constitutes a symptom developing in association with hematologic malignancy and may follow, accompany and also precede the condition. However, search for other triggering factors such as infection, drugs and cryoglobulinemia is required since they are the culprits of the vasculitis in 39% of cases.

Adult↗
PubMed1996

Outcome of mechanical ventilation for adults with hematologic malignancy.

BACKGROUND: Patients with hematologic malignancy who develop respiratory failure generally have a very poor prognosis. A few such patients, however, enjoy long-term survival. The objective of this study was to identify clinical characteristics of patients with hematologic malignancy and respiratory failure that are predictive of outcome. METHODS: We performed a retrospective chart review of all patients who required mechanical ventilation for acute respiratory failure while on the leukemia or bone marrow transplantation units at the Johns Hopkins Oncology Center between January 1985 and October 1991 (n = 157). RESULTS: Overall hospital mortality was 83%. Major organ system dysfunction, as measured by the acute physiology score (APS) of the APACHE III prognostic system, was significantly (P < 0.05) related to hospital mortality. Three disease-specific clinical characteristics were predictive of mortality: 1) stage beyond first complete remission, 2) duration of neutropenia greater than 30 days, and 3) treatment with bone marrow transplantation, especially if HLA-mismatched. None of the 15 (10%) patients with neutropenia greater than 30 days or the four patients who underwent HLA-mismatched transplantation survived to discharge. Age was also a significant predictor of hospital mortality. CONCLUSIONS: Overall outcome of patients with hematologic malignancy and acute respiratory failure is poor. A larger prospective study will be required to confirm the relative value of disease-specific variables identified in this study when combined with established predictive variables. In the future, it may be possible to develop a predictive instrument that is specifically tailored for patients with hematologic malignancy who develop respiratory failure.

APACHE↗
PubMed2003

Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy.

Farnesyltransferase inhibitors (FTIs) are small-molecule inhibitors that selectively inhibit farnesylation of a number of intracellular substrate proteins such as Ras. Preclinical work has revealed their ability to effectively inhibit tumor growth across a wide range of malignant phenotypes. Many hematologic malignancies appear to be reasonable disease targets, in that they express relevant biologic targets, such as Ras, mitogen-activated protein kinase (MAPK), AKT, and others that may depend on farnesyl protein transferase (FTase) activity to promote proliferation and survival. A host of phase 1 trials have been recently launched to assess the applicability of FTIs in hematologic malignancies, many of which demonstrate effective enzyme target inhibition, low toxicity, and some clinical responses. As a result, phase 2 trials have been initiated in a variety of hematologic malignancies and disease settings to further validate clinical activity and to identify downstream signal transduction targets that may be modified by these agents. It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents.

Alkyl and Aryl Transferases↗
PubMed2003

[Infection control for the treatment of hematological malignancies: a survey of the Kyushu Hematology Organization for Treatment Study Group (K-HOT)].

The Kyushu Hematology Organization for Treatment Study Group (K-HOT) consisted of 22 institutions specializing in hematology in Kyushu. This study is aimed at reviewing the daily practice of infection control for the treatment of hematological malignancies in our group. Nominal questionnaires were mailed to the hematology department in each institution from November 2001 to April 2002. For the first general surveys, 19 of 22 (86%) institutions responded. The second survey was mailed to the 19 respondents and 17 answered the detailed questionnaires with a response rate of 89%. Prophylactic use of trimethoprim-sulfamethoxazole (ST) against Pneumocystis carinii and anti-mycobacterial drugs in patients who had a history of tuberculosis was routine especially for patients with adult T-cell leukemia/lymphoma (ATL). Furthermore, the neutrophil counts to start a granulocyte-colony stimulating factor appeared to be high in ATL as compared with other hematological malignancies. In the setting of autologous stem cell transplantation (SCT), prophylactic use of acyclovir, immunoglobulin and ST was not routine and was reduced in duration, if used at all, as compared with allogeneic SCT. For allogeneic SCT, the cumulative dose of immunoglobulin significantly varied from institutions to institutions. The benefit of this study is the ability to recognize practical management patterns for infection control.

Hematologic Neoplasms↗
PubMed2004

Cardiac operations in patients with hematologic malignancies.

OBJECTIVES: Patients with hematologic malignancies are frequently in need of major cardiac operations. Previous reports suggest an increased risk for perioperative complications in these immunodeficient patients. METHODS: Patients diagnosed with any type of hematologic malignancy who underwent open-heart surgery at our institution between 7/1996 and 6/2002 were identified. Their hospital charts were reviewed; demographics, perioperative data and outcomes were recorded. RESULTS: There were 24 patients (20 men, 4 women); mean age was 68+/-13 years (range 31-84 years). Ten patients had chronic lymphocytic leukemia, seven non-Hodgkin lymphomas, three multiple myeloma and one Hodgkin's disease, chronic myelocytic leukemia, hairy cell leukemia and cutaneous T-cell lymphoma each. The mean pre-operative duration of the hematologic disease was 6.6 years. Twenty-two patients underwent coronary artery bypass grafting (with valve replacement in three patients) and two patients had isolated valve replacement. There was one in-hospital death (4.1%). Twelve patients (50%) had a minor or major complication. Seven reoperations were required-five during the same admission (one for mediastinal bleeding, one for an expanding femoral pseudoaneurysm, one for acute cholecystitis and two for IACD/pacer insertion) and two within 30 days (one for deep sternal wound infection and one for leg wound infection). Mean post-operative stay was 8.2+/-5.8 days and mean ICU stay was 1.6+/-1.1 days. There were three late deaths-two were due to progression of the hematologic disease. The 3-year actuarial survival was 83%. CONCLUSIONS: Cardiac operations can be performed with acceptable mortality but significant morbidity rates in patients with hematologic malignancies. Bleeding and infectious complications are most frequently seen and usually lead to reoperations. These findings warrant caution during patient selection.

Adult↗
PubMed2001

Intracellular cytokine profile of CD14 positive cells in patients with hematologic malignancies and solid tumors during hematologic recovery phase after intensive chemotherapy designed to mobilize peripheral blood stem cells.

We studied intracellular cytokines in monocytes by flow cytometry from 28 patients with hematologic malignancies and solid tumors to analyze the role of monokines in the hematologic recovery phase for peripheral blood stem cell harvest. The patients were divided into three groups: the first group, A, had a documented infection; the second group, B, had fever of unknown origin; and the third group, C, was afebrile. We found an increase in intracellular IL-1alpha, IL-6, IL-8 and TNF-alpha positive monocytes as CD14 positive gated cells cultured with lipopolysaccharide in all groups, but no increase was found with medium only when cultured for 4 h. We also found an increase in intracellular IL-1a, IL-6, IL-8 and TNF-alpha positive monocytes cultured with autologous serum for 4 h, but only in group A. The rate of intracellular cytokine positive cells was higher in monocytes cultured with only autologous serum from group A patients compared to those cells from the other groups; the data concerning IL-1a, IL-6 and TNF-alpha reached statistical significance (P < 0.05). However, increasing intracellular cytokine levels in the control group of patients exhibiting only infectious disease were observed. Thus, it appear that pro-inflammatory intracellular cytokine levels in monocytes are only related to microbial infections.

Adult↗
PubMed2001

[Angiogenesis in patients with hematologic malignancies].

Angiogenesis in Patients with Hematologic Malignancies The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. Emerging data suggest an involvement of angiogenesis in the pathophysiology of hematologic malignancies as well. Recently, we and others have reported increased angiogenesis in the bone marrow of patients with acute myeloid leukemia (AML) and normalization of bone marrow microvessel density when patients achieved a complete remission (CR) after induction chemotherapy. Tumor angiogenesis depends on the expression of specific mediators that initiate a cascade of events leading to the formation of new microvessels. Among these, VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor) and angiopoietins play a pivotal role in the induction of neovascularization in solid tumors. These cytokines stimulate migration and proliferation of endothelial cells and induce angiogenesis in vivo. Recent data suggest an important role for these mediators in hematologic malignancies as well. Isolated AML blasts overexpress VEGF and VEGF receptor 2. Thus, the VEGF/VEGFR-2 pathway can promote the growth of leukemic blasts in an autocrine and paracrine manner. Therefore, neovascularization and angiogenic mediators/receptors may be promising targets for anti-angiogenic and anti-leukemic treatment strategies. The immunomodulatory drug thalidomide inhibits angiogenesis in animal models. Moreover, it has significant activity in refractory multiple myeloma. In a current phase II study for patients with primary refractory or relapsed multiple myeloma using a combination of thalidomide with hyperfractionated cyclophosphamide and dexamethasone (Hyper-CDT), we observed a partial remission in 12 of 14 evaluable patients (86%). Thus, this combination seems to be very potent. Furthermore, we evaluated the safety and efficacy of thalidomide in patients with AML not qualifying for intensive cytotoxic chemotherapy. 20 patients aged 58-85 (median 69) years were recruited to this phase I/II study and were treated with a dose of 200-400 mg per os daily for a duration of 1-40 (median 6) weeks, dependent on the individual tolerability of the drug. In 4 patients we observed a partial response (PR - defined as more than 50% reduction in leukemic blast infiltration in the bone marrow). This was accompanied by an increase in platelet counts and hemoglobin values. One additional patient showed a significant improvement of peripheral blood counts without fulfilling the criteria of a PR. In parallel, we observed a significant decrease in microvessel density in these 5 patients during treatment with thalidomide. In conclusion, thalidomide seems to have anti-angiogenic as well as anti-leukemic activity in AML. The VEGF/VEGFR-2 pathway seems to play an important role in AML. Therefore, receptor tyrosine kinase inhibitors like SU5416 or SU6668 are currently evaluated in the context of phase II studies in AML. We could recently induce a stable remission in a patient with second relapse of her AML refractory towards chemotherapy by administration of SU5416 (compassionate use), a tyrosine kinase inhibitor of VEGFR-2 and ckit. Current and future studies will clarify the role of anti-angiogenic treatment strategies in AML and other hematologic malignancies.

Aged↗
PubMed2004

Pleural effusions in hematologic malignancies.

Nearly all hematologic malignancies can occasionally present with or develop pleural effusions during the clinical course of disease. Among the most common disorders are Hodgkin and non-Hodgkin lymphomas, with a frequency of 20 to 30%, especially if mediastinal involvement is present. Acute and chronic leukemias, myelodysplastic syndromes, are rarely accompanied by pleural involvement. Furthermore, 10 to 30% of patients receiving bone marrow transplantation develop pleural effusions. In cases of hematologic pleural effusions, drug toxicity, underlying infectious, secondary malignant or rarely autoimmune causes should be carefully sought. In most cases, the pleural fluid responds to treatment of the primary disease, whereas resistant or relapsing cases may necessitate pleurodesis.

Bone Marrow Transplantation↗
PubMed2026

Limited evidence for causal effects of circulating inflammatory cytokines on the risk of selected hematologic malignancies: a two-sample Mendelian randomization study.

BACKGROUND: Hematologic malignancies have been linked to inflammatory cytokine levels; however, whether a causal relationship exists between inflammatory cytokines and hematologic malignancies remains uncertain. This study aimed to explore the causal association between inflammatory cytokines and hematologic malignancies using Mendelian randomization (MR) analysis. METHODS: Summary statistics from genome-wide association studies of 41 inflammatory cytokines, C-reactive protein, and selected hematologic malignancies were obtained from the UK Biobank, YFS, FINRISK, and FinnGen consortia. The inverse-variance weighted (IVW) method with false discovery rate (FDR) adjustment was used as the primary MR method. The weighted median, MR-Egger regression, MR-Robust Adjusted Profile Score, and MR pleiotropy residual sum, and outlier methods were used as supplied analyses. MR-Egger intercept estimates and Cochran's Q test were used to assess pleiotropy and heterogeneity. Leave-one-out analysis and the MR Steiger test were used to assess sensitivity and the direction of causality. RESULTS: Although the primary IVW analysis indicated that some inflammatory cytokines were associated with risk of selected hematologic malignancies, no significant causal relationship between cytokines and selected hematologic malignancies was detected after FDR correction. CONCLUSION: Genetically predicted cytokine levels did not have a significant effect on the risk of the selected hematologic malignancies. Further research is warranted to confirm the potential association between cytokine levels and the risk of selected hematologic malignancies.

C-reactive protein↗
PubMed2005

Hematologic malignancies in pregnancy.

Hematologic malignancies complicating pregnancy are uncommon, but a delay in diagnosis or treatment can mean the difference between life and death. It is the responsibility of the obstetrician, nurse-midwife, or nurse practitioner to maintain a high index of suspicion when patients present with unexplained lymphadenopathy or protracted constitutional symptoms. Management of these patients requires a multifaceted team from the oncology, pediatrics, and obstetrics services. With most hematologic cancers now requiring multiagent chemotherapy for optimal survival, the patient, her family, and her physicians are often faced with what seems to be a Faustian dilemma. Most infants exposed in utero to multiagent chemotherapy, however, seem to suffer no long-term detrimental consequences.

Female↗
PubMed2025

Liquid Biopsy in Hematologic Malignancies: Advances, Challenges, and Future Directions.

Hematologic malignancies are cancers that affect the bone marrow, lymphatic system, and hematopoietic cells, resulting in various cancer subtypes and clinical manifestations. Currently, tissue biopsy in hematological malignancies is typically performed for genomic profiling and has limitations such as invasiveness, lengthy procedures, and high expense. On the other hand, liquid biopsy serves as an emerging tool used for examining the blood or other bodily fluids of patients, for the purpose of identifying genetic mutations, biomarkers, or cancer-related substances. Liquid biopsy biomarkers include circulating tumor DNA (ctDNA), microRNA (miRNA), and exosomes. In the context of hematological malignancies, these biomarkers offer valuable insights into disease etiology, enabling effective disease monitoring and guiding treatment decisions owing to their differential expression patterns. This review critically examines the recent advancements and effectiveness of liquid biopsy biomarkers in the areas of diagnosis, therapy, and monitoring. The challenges and future directions of liquid biopsy for hematological malignancies are also discussed.

Humans↗
PubMed2000

Glycemic crises in patients with hematologic malignancies.

Persons with hematologic malignancies such as leukemia, lymphoma, or myeloma often have coexisting medical conditions. Among these may be diabetes mellitus. The physiologic and psychologic stress of diagnosis and treatment may precipitate the life-threatening complications of DKA or HHNS in this group of patients. People with personal risk factors may develop diabetes mellitus secondary to diagnosis and treatment and present with either DKA or HHNS. It is essential that the health care team have a heightened awareness of potential complications. These are complex syndromes involving severe hyperglycemia, metabolic acidosis, fluid and electrolyte imbalances, and neurologic and cardiovascular collapse. Working collaboratively with the critical care team to provide optimal care, nurses play an essential role in the management of these challenging complications of diabetes mellitus.

Anti-Inflammatory Agents↗