Course Of Hematological Malignancies Research Articles

Are the GLIM Criteria Guiding in the Course of Hematological Malignancies?

Different degrees of malnutrition are seen in patients with hematological malignancies. None of the approaches used to determine malnutrition risk have general acceptance. The use of the GLIM criteria developed by the Global Leadership Initiative on Malnutrition has promising results. A total of 67 patients with leukemia, lymphoma, and multiple myeloma were included in the study. NRS-2002 (Nutritional Risk Screening-2002) was used to screen the nutritional status of the patients, and malnutrition was diagnosed and graded using the GLIM criteria in patients who were found to be at risk of malnutrition in this test. The parameters followed in the groups with and without malnutrition were compared. The Kolmogorov-Smirnov, Mann-Whitney U, and Chi-square test were used for statistical analysis. Patients were analyzed by dividing them into two groups as those with and without malnutrition. The presence of infection, duration of fever, antibiotic, and antifungal use were significantly higher in malnourished than in nonmalnourished patients. Platelet counts and sodium levels were significantly lower in the malnourished arm. Early nutritional support can increase the immunological status of patients with malignant disorders as well as their tolerability to treatment. Minimizing the risk of malnutrition and providing timely calorie and vitamin support are factors that may directly affect febrile neutropenia, duration of fever, and antifungal use, which will consequently lead to a decrease in the length of hospitalization.

A pilot randomized study for optimal red cell transfusion in acute myeloid leukemia patients with intensive chemotherapy.

Although blood transfusion is fundamental throughout the course of hematologic malignancies, acute myeloid leukemia (AML) patients requiring intensive chemotherapy are left at the edges of patient blood management programs because current guidelines do not have established recommendations for red blood cell (RBC) transfusion threshold in patients treated for hematological disorders with anemia and accompanied severe thrombocytopenia. To provide answers for the trigger and doses of ideal RBC transfusion in such situation, we conducted this prospective randomized trial. Newly diagnosed non-acute promyelocytic AML patients undergoing chemotherapy were considered eligible for enrollment. Patients were randomized into 4 groups using a 2 by 2 factorial design, according to the RBC transfusion trigger (hemoglobin [Hb], 7 vs 8 g/dL) and the number of units per transfusion episode (quantity, single vs double-unit). Initially 91 patients were randomized into 4 groups, but the protocol adherence rate was 90.1%. Hb trigger did not affect the amount of RBC transfusion required during treatment. Patients receiving RBC transfusion at Hb <7 g/dL used a median of 4 units of RBC (range 0-12), and those receiving transfusion at Hb <8 g/dL also used a median of 4 units of RBC (range 0-24) (p=0.305). The number of RBC units per transfusion did not affect the total amount of RBC transfusion required during treatment. AML treatment outcomes and bleeding events did not differ across the 4 groups. This study demonstrated the feasibility for restrictive RBC transfusion (Hb <7 g/dL, RBC 1 unit) in AML patients undergoing chemotherapy, regardless of chemotherapy intensity.

Dermatological manifestations of hematologic neoplasms. Part II: nonspecific skin lesions/paraneoplastic diseases

Cutaneous manifestations occur in the course of hematologic malignancies and precede, accompany or occur late in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, immunosuppression resulting from the hematologic disease itself or its treatment. The dermatologist must be aware of these conditions that may be helpful both in the diagnosis of the underlying disease and in reducing patient morbidity. This review (part II) addresses the paraneoplastic dermatological changes associated with systemic hematologic malignancies.

Dermatological manifestations of hematologic neoplasms. Part I: secondary specific skin lesions

Cutaneous manifestations occur during the course of hematologic malignancies and precede, follow, or are late events in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, and immunosuppression resulting from the hematologic neoplasia itself or its treatment. The dermatologist must be aware of these conditions, which can help both in the diagnosis of the underlying disease and in the reduction of patient morbidity. This review (part I) addresses skin lesions associated with direct infiltration by systemic hematologic malignancies.

Perceptions and Misperceptions of Early Palliative Care Interventions for Patients With Hematologic Malignancies Undergoing Bone Marrow Transplantation

Hematopoietic stem cell or bone marrow transplantation (BMT) is one of the most promising and potentially curative therapeutic options available for eligible patients with hematologic malignancies (HMs) or leukemias. However, the nature and clinical course of HMs, specifically for patients undergoing BMT, are associated with significant morbidity, symptomatology, healthcare service utilization, psychosocial and end of life issues, and overall decreased quality of life. Early palliative care (PC) consultations and utilization for patients with HMs have been shown to improve patient outcomes, satisfaction, and autonomy as well as caregiver burden, shared-decision making, and holistic care management. Despite the complexity of care and complications for patients with HM undergoing BMT, early PC interventions are systematically underutilized and understudied in this population compared to patients with solid tumors or non-HMs. Herein, the authors reviewed the current literature and knowledge to assess and report the perceptions and barriers to early PC utilization in the care of patients with HMs undergoing BMT. Clinical and cultural aspects of PC perceptions as well as current PC care models and potential directions for PC implementation were reviewed to inform future research studies and clinical practice guidelines necessary for the improvement of care and quality of life for HM patients undergoing BMT.

Bone marrow niche-derived extracellular matrix-degrading enzymes influence the progression of B-cell acute lymphoblastic leukemia

Specific and reciprocal interactions with the bone marrow microenvironment (BMM) govern the course of hematological malignancies. Matrix metalloproteinase-9 (MMP-9), secreted by leukemia cells, facilitates tumor progression via remodeling of the extracellular matrix (ECM) of the BMM. Hypothesizing that leukemias may instruct the BMM to degrade the ECM, we show, that MMP-9-deficiency in the BMM prolongs survival of mice with BCR-ABL1-induced B-cell acute lymphoblastic leukemia (B-ALL) compared with controls and reduces leukemia-initiating cells. MMP-9-deficiency in the BMM leads to reduced degradation of proteins of the ECM and reduced invasion of B-ALL. Using various in vivo and in vitro assays, as well as recipient mice deficient for the receptor for tumor necrosis factor (TNF) α (TNFR1) we demonstrate that B-ALL cells induce MMP-9-expression in mesenchymal stem cells (MSC) and possibly other cells of the BMM via a release of TNFα. MMP-9-expression in MSC is mediated by activation of nuclear factor kappa B (NF-κB) downstream of TNFR1. Consistently, knockdown of TNF-α in B-ALL-initiating cells or pharmacological inhibition of MMP-9 led to significant prolongation of survival in mice with B-ALL. In summary, leukemia cell-derived Tnfα induced MMP-9-expression by the BMM promoting B-ALL progression. Inhibition of MMP-9 may act as an adjunct to existing therapies.

Tumor Lysis Syndrome in the Course of Burkitt Lymphoma Revealed by Medullar Compression

Background: Tumor lysis syndrome is unknown to many neurosurgical teams. A dreaded complication, especially in the course of hematological malignancies, like it was the case in two of our patients operated for spinal cord compression by Burkitt’s lymphoma. Objectives: To describe the clinical and biological presentation of this potentially fatal complication, which can be improved by early preventive or curative treatments. Case Reports: Patient 1: A 49-year-old woman was admitted for vertebral and intercostal pain and paraparesis. Myelography revealed epidural medullary compression at the 7th thoracic vertebrae (Th7) level. Patient 2: A 67-year-old woman was admitted for cervico-thoracic pain and paraparesis. MRI showed posterior epidural medullary compression between the 1st thoracic vertebrae (Th1) and 5th thoracic vertebrae (Th5). In both cases, an urgent decompressive laminectomy was performed. They had also received postoperative corticosteroid therapy. The multi-visceral failure occurred on the 1st day (D1) and 3rd day (D3) postoperatively, respectively. In the absence of adequate management, the outcome was fatal for the two patients respectively at D3 and D5 postoperatively. This syndrome was retained in the presence of glucocorticoid (triggering factor) and the histological result in favor of Burkitt lymphoma (target disease). Conclusion: Malignant hemopathies is a common cause of spinal cord compressions. From these two cases, the importance of biological and clinical surveillance emerges, with patients requiring urgent management for radiculo-medullar tumor compression.

Abnormal microRNA expression in the course of hematological malignancies.

Research on the carcinogenesis process is currently focused primarily on understanding its genetic basis and molecular abnormalities that may be predictive factors and therapeutic targets. It was clearly confirmed recently that microRNAs are involved in the mechanisms of leukocyte development, differentiation, and apoptosis, as well as in the pathogenesis of proliferative diseases of the hematopoietic system. Currently, research strategies allow determination of the deregulation of microRNA profiles in relation to other cytogenetic aberrations, as well as prognostic factors and primary end points. The problem of the possibility of their use as therapeutic targets is also increasingly discussed. In this article, we analyze literature data on abnormalities in microRNA expression in proliferative diseases of the hematopoietic system in the context of classic cytogenetic and molecular aberrations.

Incidence of venous thromboembolism and use of anticoagulation in hematological malignancies: Critical review of the literature.

Venous Thromboembolism (VTE) frequently complicates the course of hematologic malignancies (HM) and its incidence is similar to that observed in high-risk solid tumors. Despite that, pharmacologic prophylaxis and treatment of VTE in patients with HM is challenging, mainly because a severe thrombocytopenia frequently complicates the course of treatments or may be present since diagnosis, thus increasing the risk of bleeding. Therefore, in this setting, safe and effective methods of VTE prophylaxis and treatment have not been well defined and hematologists generally refer to guidelines produced for cancer patients that give indications on anticoagulation in patients with thrombocytopenia. In this review, besides to summarize the incidence and the available data on prophylaxis and treatment of VTE in HM, we give some advices on how to use antithrombotic drugs in patients with HM according to platelets count.

Characteristics and predictors of mortality of patients with hematologic malignancies requiring invasive mechanical ventilation.

RATIONALE:Acute respiratory failure (ARF) may complicate the course of hematologic malignancies (HMs). Our objective was to study the characteristics, outcomes and predictors of mortality of patients with HMs who required intubation for ARF.METHODS:This retrospective cohort study evaluated all patients with HMs who were admitted to the Intensive Care Unit (ICU) of King Abdul-Aziz Medical City-Riyadh between 2008 and 2013 and required invasive mechanical ventilation. We noted their baseline characteristics, treatments and different outcomes. Multivariable logistic regression analysis was performed to evaluate predictors of hospital mortality.RESULTS:During the 6-year period, 190 patients with HMs were admitted to the ICU and 122 (64.2%) required intubation for ARF. These patients had mean age of 57.2 ± 19.3 years and Acute Physiology and Chronic Health Evaluation II score of 28.0 ± 7.8 and were predominantly males (63.4%). Lymphoma (44.3%) and acute leukemia (38.5%) were the most common hematologic malignancy. Noninvasive ventilation (NIV) was tried in 22 patients (18.0%) but failed. The code status was changed to “Do-Not-Resuscitate” for 39 patients (32.0%) during ICU stay. Hospital mortality was 70.5% and most deaths (81.4%) occurred in the ICU. The mortality of patients with “Do-Not-Resuscitate” status was 97.4%. On multivariable logistic regression analysis, male gender (odds ratio (OR), 6.74; 95% confidence interval (CI), 2.24–20.30), septic shock (OR, 6.61; 95% CI, 1.93–22.66) were independent mortality predictors. Remission status, non-NIV failure and chemotherapy during ICU stay were not associated with mortality.CONCLUSIONS:Patients with HMs requiring intubation had high mortality (70.5%). Male gender and presence of septic shock were independent predictors of mortality.

Application of Hematopoietic Progenitor Cell Count: To Optimize Peripheral Blood Stem Cell Harvest

background.High dose therapy and autogenic or allogeneic stem cell transplantation plays an important role in the treatment course of hematological malignancies. In some countries, major method of unrelated stem cell donation programs had shifted from bone marrow harvest (BM) to peripheral blood stem cell harvest (PBSCH). PBSCH is a heavy duty not only for donor or patient, also for medical staffs. In some cases, poor mobilization may cause poor collection of stem cells. Hemogram needs time for May-Giemsa stain, and CD34 count needs complicated technique and running cost. New simple tool to predict the count of mobilized stem cell is needed to optimize PBSCH.methods.Since 2009, we started measuring peripheral blood hematopoietic progenitor cell (HPC) with Sysmex XE-5000(R) blood cell counter. With IMI channel method, we could rapidly know the count of circulating stem cells. Daily HPC count and yielded CD 34 positive cell count were analyzed.results.189 samples were collected from 122 donors/patients. Diagnosis of patients: malignant lymphoma (n=29), leukemia (3), multiple myeloma (74), amyloidosis (5), cryoglobulinemia (1). 10 healthy donors were also included. Age: 18-66, Sex: male 82/female 40. Mobilization regimen: G-CSF 57, chemo+G-CSF 74, G-CSF+plerixafor 1HPC count (cells/ul) and collected CD34 positive cells (106cells/kg) had positive correlation. When HPC count was above 25/ul, collected CD34 positive cells were above 1x106/kg (positive predictive value: 80.9%). Number of PBSCH operation was 1.59 in average. We also show three cases in which HPC count was useful to make clinical decision of initiating PBSCH.discussion.HPC and CD34 had positive correlation, and HPC >25/ul seems to be appropriate cut-off to start PBSCH. With our former threshold of PBSCH (G-CSF day>4, WBC >3000/ul), 241 operations were to be planned. Including HPC count, we could reduce PBSCH operation to 204.Hematopoietic progenitor cell count is rapid and inexpensive method. Within 5 minutes, mobilized stem cells can be measured, and it may be also useful in outpatient-based harvest settings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Should we try antiviral therapy for hepatitis C virus infection with pyoderma gangrenosum‐like lesions?

Should we try antiviral therapy for hepatitis <scp>C</scp> virus infection with pyoderma gangrenosum‐like lesions?

Rare germline variants in regions of loss of heterozygosity may influence clinical course of hematological malignancies

Rare germline variants in regions of loss of heterozygosity may influence clinical course of hematological malignancies

CXCR4 antagonists in hematologic malignancies: more than just mobilizers?

Stromal cell-derived factor-1 (SDF-1) is a chemokine constitutively expressed and produced in bone marrow (BM) stromal cells. It plays a central role in the migration and homing of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) through signaling via its receptor CXCR4. AMD3100 is a small bicyclam molecule, which was originally developed as a CXCR4 antagonist that could block the entry of the HIV into T cells. It inhibits the binding of SDF-1 to CXCR4 and induces peripheral mobilization of HSCs and HPCs [1]. AMD3100 safely and rapidly mobilizes stem cells in healthy donors and in patients with lymphoma and myeloma, and it does so in synergy with the granulocyte-colony stimulating factor (G-CSF) [2]. A recent phase III clinical study on autologous stem cell transplantation showed that a combination of AMD3100 and G-CSF allowed for the collection of a large number of stem cells in fewer apheresis sessions and can help the patients in whom mobilization with G-CSF alone was ineffective [3]. On the basis of these findings, the FDA has recently approved the use of AMD3100 in combination with G-CSF for stem cell mobilization in patients with non-Hodgkin's lymphoma and multiple myeloma. Leukemia and myeloma cells also express different levels of CXCR4 and respond to SDF-1, resulting in the migration and stable localization of these cells in the BM [4]. AMD3100 induces the segregation of leukemia and myeloma cells in the BM microenvironment, thereby mobilizing these cells to the peripheral blood and sensitizing them to chemotherapy [5]. Studies are underway for testing the use of AMD3100 as an adjunct to chemotherapy in patients with refractory acute myeloid leukemia (AML) and other hematologic malignancies; if successful, this strategy may be used to sensitize leukemic cells to chemotherapy and improve clinical outcomes. SDF-1 alone has a minimal or negligible effects on the survival and growth of normal and malignant hematopoietic cells in vitro, but the SDF-1/CXCR4 axis is involved in the progression and dissemination of a variety of hematologic malignancies and solid tumors [6]. Patients with multiple myeloma and extramedullary plasmacytoma, which is a manifestation of an advanced stage of multiple myeloma, show elevated levels of serum SDF-1 and CXCR4 expression, respectively. Moreover, BM endothelial cells in multiple myeloma patients secrete CXC chemokines, including SDF-1, that mediate interactions with the myeloma cells. Similar findings have been reported in leukemia patients. For example, AML patients with high levels of CXCR4 in CD34+ cells had a significantly lower survival rate and higher probability of relapse than those with low levels of CXCR4. A polymorphism in the SDF-1 gene correlated with the risk of distant tissue being infiltrated by AML cells. Compared to the Philadelphia chromosome (Ph)-negative CD34+CXCR4+ cells, the Ph-positive CD34+CXCR4+ cells from chronic myelogenous leukemia patients showed limited migration. In addition, SDF-1 has been shown to play a role in tumor neoangiogenesis. On the basis of these observations, the modulation of the SDF-1/CXCR4 axis has been suggested to influence the biological characteristics and disease course of hematologic malignancies. Contradictory to early studies, CXCR4 antagonists have been shown to inhibit the survival and proliferation of leukemia and myeloma cells in vitro. AMD3100 and TC140012, another CXCR4 antagonist, significantly inhibited stroma-dependent proliferation of leukemia cells in a population of patients with acute lymphoblastic leukemia. In addition, AMD3100 and TC140012 were shown to enhance the cytotoxic and antiproliferative effects of the cytotoxic agents vincristine and dexamethasone [7]. AMD3100 arrested proliferation in AML cell lines and triggered changes that mimicked differentiation, including morphological changes and the expression of myeloid differentiation antigens [8]. A recent study has shown that another CXCR4 antagonist, BKT140 4F-benzoyl-TN14003 (BKT140), exhibited CXCR4-dependent preferential cytotoxicity toward malignant cells of hematopoietic origin. BKT140 significantly and preferentially stimulated apoptotic cell death in multiple myeloma cells. BKT140 treatment induced morphological changes and phosphatidylserine externalization; it also decreased mitochondrial membrane potential, caspase-3 activation, sub-G1 arrest, and DNA double-stranded breaks. In vivo, subcutaneous injection of BKT140 significantly reduced the growth of human AML and multiple myeloma xenografts in a dose-dependent manner. Compared to the tumor samples obtained from animals not treated with BKT140, those obtained from the animals treated with BKT140 were smaller in size and lower in weight and had larger necrotic areas and high apoptotic scores [9]. In this issue of the Korean Journal of Hematology, Kim et al. report that higher concentrations of AMD3100 enhanced the proliferation of AML cells during the early course of in vitro incubation. Conversely, after 5-7 days of culture, AMD3100 decreased the number of AML cells and induced cell apoptosis more rapidly than the control did [10]. In summary, recent studies have suggested that CXCR4 antagonists may potentially be used in the treatment of hematologic malignancies not only as stem cell mobilizers for transplantation and sensitizers to chemotherapy but also as direct cytotoxic agents.

Clinical signs and symptoms at diagnosis and its differential diagnosis

Anorexia, or loss of appetite, during the course of hematological malignancies can be due to gastrointestinal (GI) factors, treatment, neurological damage, psychiatric conditions, uncontrolled pain or cachexia. Cachexia is caused by cytokines produced by the tumor cells or the tumor microenvironment acting directly on the brain to cause a centrally induced anorexia or the cytokines can interfere with metabolic pathways. Different metabolic changes accompany increase in basal body expenditure, such as increased gluconeogenesis, increased consumption and decreased synthesis as well as increased catabolism of fats and proteins. Tumor necrosis factor, one of the main cytokines involved in cachexia, suppresses the function of lipoprotein lipase which is necessary for the storage of fat in tissues. Interleukin-1 (IL-1) may influence cachexia by increasing the levels of tryptophan, a precursor to serotonin in the brain. Serotonin and IL-1 have anorectic effects on the hypothalamus. The proinflammatory cytokine IL-6 is also involved in cachexia. A number of circumstances other than the hematologic malignancy may cause weight loss: chemotherapeutic agents and oral antibiotics, neurological impairment of swallowing or chewing, psychiatric disorders, oral abnormalities, hyperthyroidism, other severe chronic diseases, etc.

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.