Myelodysplastic syndromes--an overview for the practitioner

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematological diseases deriving from a clonally expanded precursor bone marrow cell. MDS are characterized by ineffective hematopoiesis, peripheral cytopenias of various degrees and increased risk for transformation into acute myeloid leukemia. The incidence is highest in elderly people. Diagnosis is based on morphology, exclusion of reactive causes of dyshematopoiesis and cytogenetics/FISH. Allogeneic stem cell transplantation, the only curative therapy so far, is not feasible for most of the patients. Other therapeutic options include supportive therapy such as blood transfusions and antibiotics, hematopoietic growth factors (rHuEPO, G-CSF), immunomodulating agents and chemotherapy. It is important to install iron chelation therapy in cases with long term transfusion dependency.     

SI32Management of Anaemia in MDS

The myelodysplastic syndromes (MDS) are clonal disorders of haemopoeisis. They share characteristic morphological abnormalities of the blood and bone marrow and a risk of evolution to acute leukaemia which varies according to the subtype of MDS and the prognostic score (IPSS). Overall annual incidence rates based on European studies are between 3 and 4 per 100 000 but the rate dramatically increases with age, exceeding 30 per 100 000 for patients over 80 years. It is therefore mainly a disease seen in older patients, where curative treatments are not an option, and supportive care is the reality. The majority of patients are anaemic at diagnosis and red cell transfusions are the mainstay of supportive care in those symptomatic. The aim is to achieve a haemoglobin level to maximise the patient's quality of life (QOL), which should be tailored to the individual. Red cell transfusions do however have risks associated, including the development of red cell antibodies and iron overload in multi‐transfused patients. Iron chelation therapy, due to its mode of delivery, further impacts on QOL. Alternatives to transfusions include growth factors and disease modifying agents. The aim of using Erythropoietin (EPO), is to improve the overall QOL by avoiding fluctuations in the haemoglobin levels. It also has the benefit therefore of avoiding the risks of transfusion. Unfortunately, it has been shown that those who would benefit most, are least likely to respond. Overall response rates (100% reduction in transfusion requirements) are in the order of 16–24%. Other options to avoid multiple transfusions are by modifying the disease. There are a number of approaches available including stem cell transplantation, immunosuppression, demethylating agents (azacitidine, decitabine) and thalidomide analogues (Lenalidomide). These should be tailored to the individual patient and where possible patients should be treated within clinical research protocols.     

S134Anaemia and Heart Failure

The myelodysplastic syndromes (MDS) are clonal disorders of haemopoeisis. They share characteristic morphological abnormalities of the blood and bone marrow and a risk of evolution to acute leukaemia which varies according to the subtype of MDS and the prognostic score (IPSS). Overall annual incidence rates based on European studies are between 3 and 4 per 100 000 but the rate dramatically increases with age, exceeding 30 per 100 000 for patients over 80 years. It is therefore mainly a disease seen in older patients, where curative treatments are not an option, and supportive care is the reality. The majority of patients are anaemic at diagnosis and red cell transfusions are the mainstay of supportive care in those symptomatic. The aim is to achieve a haemoglobin level to maximise the patient's quality of life (QOL), which should be tailored to the individual. Red cell transfusions do however have risks associated, including the development of red cell antibodies and iron overload in multi-transfused patients. Iron chelation therapy, due to its mode of delivery, further impacts on QOL. Alternatives to transfusions include growth factors and disease modifying agents. The aim of using Erythropoietin (EPO), is to improve the overall QOL by avoiding fluctuations in the haemoglobin levels. It also has the benefit therefore of avoiding the risks of transfusion. Unfortunately, it has been shown that those who would benefit most, are least likely to respond. Overall response rates (100% reduction in transfusion requirements) are in the order of 16–24%. Other options to avoid multiple transfusions are by modifying the disease. There are a number of approaches available including stem cell transplantation, immunosuppression, demethylating agents (azacitidine, decitabine) and thalidomide analogues (Lenalidomide). These should be tailored to the individual patient and where possible patients should be treated within clinical research protocols.     

Strategies for achieving transfusion independence in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of complex diseases of the myeloid stem cell that result in chronic cytopenias. In some instances, these disorders may progress to acute myeloid leukemia. Patients with MDS frequently experience chronic, symptomatic anemia, and many become dependent on chronic transfusions of packed red blood cells. However, long-term transfusion dependence has clinical and economic consequences, including a potentially negative impact on patients' quality of life (QOL). Recently, studies have investigated various strategies to reduce or eliminate transfusion needs in MDS patients. Supportive measures with hematopoietic growth factors such as erythropoietin are often less effective in MDS-associated anemia than in anemia from other causes, but some patients may benefit from this approach. Treatment with other agents, such as antithymocyte globulin, azacitidine, decitabine, thalidomide, and lenalidomide, has resulted in transfusion independence in some subsets of MDS patients. Nurses who care for patients with MDS should be aware of the impact of transfusion dependence on the patient's QOL, as well as the benefits and risks of the various other treatment options available to these patients. Such knowledge will enable the nurse to provide accurate, relevant information, so that patients can make informed choices regarding treatment options for MDS.     

Myelodysplastic syndromes

A cure for MDS has yet to be found. The aim of therapy is to attempt to restore normal hematopoiesis and prevent evolution to acute leukemia. The major trend is supportive care. Blood counts and bone marrow aspirations are taken to evaluate the disease, and transfusions of blood products and antibiotics are given when necessary. A new encouraging modality of therapy is the use of hematopoietic growth factors to reverse cytopenias. As there is no curative treatment for MDS, the patient is likely to be offered investigational drugs either singly or in combination. Future trends in the treatment of MDS will be combinations of agents including biological agents with retinoic acid or vitamin D, low-dose Ara-C, the interferons, and colony-stimulating factors.     

Management of transfusion-related iron overload in patients with myelodysplastic syndromes

Anemia is a common symptom for patients with myelodysplastic syndromes (MDS), a spectrum of hematopoietic malignancies characterized by ineffective hematopoiesis; 90% of these patients will become transfusion dependent (TD). Because of the closed nature of iron metabolism, the repeated input of packed red blood cells during transfusions inevitably leads to iron overload. Iron overload can cause iron-related toxicity as well as end-organ damage from iron deposition in tissues. Studies have shown that patients with MDS who are TD have shorter overall survival, shorter leukemia-free survival, and higher healthcare costs compared with patients who are not TD, suggesting that iron overload has a significant clinical and economic impact. Iron chelation therapy can bind and eliminate free iron from the body. Although studies in genetic anemias have shown improved clinical outcomes, clinical trials with patients with MDS are ongoing. Because iron chelation therapy can be toxic, the risks, benefits, and therapy-related costs must be weighed for each patient.     

Treatment of transfusional iron overload in patients with myelodysplastic syndrome or severe anemia: data from multicenter clinical practices

BACKGROUND: Patients with myelodysplastic syndrome (MDS) or severe anemia requiring repeated red blood cell (RBC) transfusions risk developing transfusional iron overload, which can reduce survival. Iron chelation therapy (ICT) has been shown to improve survival and quality of life in patients; however, ICT utilization in clinical practices is not well understood.
STUDY DESIGN AND METHODS: Medical records of patients diagnosed with MDS or severe anemia at least 6 months before data extraction, aged at least 21 years at diagnosis, and who received at least one RBC transfusion were reviewed. ICT eligibility was defined as at least 20 units of RBCs transfused or at least two serum ferritin levels exceeding 1000 µg/L. Study endpoint was ICT treatment rate among ICT-eligible patients with lower-risk MDS (International Prognostic Scoring System [low or intermediate-1]; World Health Organization [refractory anemia {RA}, refractory anemia with ringed sideroblasts {RARS}, refractory cytopenia with multilineage dysplasia {RCMD}, refractory cytopenia with multilineage dysplasia and ringed sideroblasts, or 5q]; French-American-British [RA/RARS]).
RESULTS: Among 78 ICT-eligible patients with lower-risk MDS, 32 (41%) received ICT. At ICT initiation, treated patients received on average 13.3 transfusions (27.6 units) and mean first post-ICT initiation serum ferritin was twice the MDS Foundation recommendation at 1949 µg/L. Median overall survival for all ICT-eligible patients was significantly longer for those ICT-treated patients than untreated patients (8.7 years vs. 4.7 years, log-rank p = 0.02; multivariate hazard ratio 0.372, p = 0.03).
CONCLUSION: This study finds only 41% of ICT-eligible patients with lower-risk MDS received ICT in clinical practice, and treatment was initiated later than recommended. Receipt of ICT was associated with significantly longer survival.     

Survival among children and adults treated with granulocyte transfusions: Twenty years’ experience at a Brazilian blood center

BackgroundIt remains controversial whether granulocyte transfusions as a supportive treatment improve survival in patients with febrile neutropenia or granulocyte dysfunctions. We describe survival rates subsequent to granulocyte transfusions in pediatric and adults patients treated at a major blood center in Brazil.Material and methodsWe retrospectively reviewed the clinical charts of pediatric and adult patients treated with granulocyte transfusions at our institution from January 2000 to October 2019. We assessed demographic characteristics, clinical features, indications for transfusion, units transfused, dose of granulocytes administered and survival rates 30 and 100 days after the initial transfusion.ResultsWe identified 64 pediatric and 67 adult patients treated with 262 granulocyte transfusions. An optimal dose (> 0.6 × 10⁹ granulocytes per kilogram per transfused unit) was available for transfusion in 80.4 % of pediatric patients but in only 19.6 % of adults (p = 0.017). Thirty days after their first granulocyte transfusion, 38 (59.4 %) pediatric and 61 (91 %) adult patients had died. Patients receiving the optimal dose of granulocytes had better survival outcomes, but even among this sub-group, adults were more likely to die than were children either at 30 days (OR = 8.67, 95 %CI 2.69–34.9) or 100 days (OR = 6.27, 95 %CI 1.86–25.9) after their initial granulocyte transfusion.ConclusionSurvival rates following granulocyte transfusion varied by the dose transfused and were higher in children than in adults.     

Treatment of myelodysplastic syndromes in elderly patients

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal neoplasms with the median age at diagnosis being in the seventh decade. If left untreated, the disease progresses to acute myeloblastic leukemia (AML). There are many options for the management of MDS, but the only potentially curative treatment is allogenic hematopoietic stem cell transplantation (allo-HSCT), which is often not an option because of advanced age or comorbidities at diagnosis or lack of a human leukocyte antigen-identical donor. MDS in the elderly should be managed similar to that in young patients, but the fact that many advanced age patients cannot undergo allo-HSCT precludes any chance of cure. Despite the main objective of prolonging overall survival and the time to progression to AML, the key is to improve quality of life for the longest possible time. To achieve these objectives, supportive care is essential. Likewise, immunomodulatory drugs, such as lenalidomide, can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients with MDS with chromosome 5q deletion. Elderly patients with high-risk MDS can benefit from 5-azacitidine (5-AZA), with efficacy and safety profiles comparable with those found in patients under 75 years of age. In any patient, predictive drug response scores are required in order to ensure more rational use of these medications.     

Treatment of myelodysplastic syndromes in elderly patients

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal neoplasms with the median age at diagnosis being in the seventh decade. If left untreated, the disease progresses to acute myeloblastic leukemia (AML). There are many options for the management of MDS, but the only potentially curative treatment is allogenic hematopoietic stem cell transplantation (allo-HSCT), which is often not an option because of advanced age or comorbidities at diagnosis or lack of a human leukocyte antigen-identical donor. MDS in the elderly should be managed similar to that in young patients, but the fact that many advanced age patients cannot undergo allo-HSCT precludes any chance of cure. Despite the main objective of prolonging overall survival and the time to progression to AML, the key is to improve quality of life for the longest possible time. To achieve these objectives, supportive care is essential. Likewise, immunomodulatory drugs, such as lenalidomide, can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients with MDS with chromosome 5q deletion. Elderly patients with high-risk MDS can benefit from 5-azacitidine (5-AZA), with efficacy and safety profiles comparable with those found in patients under 75 years of age. In any patient, predictive drug response scores are required in order to ensure more rational use of these medications.     

The use of erythropoiesis-stimulating agents in the intensive care unit

Anemia is common in critically ill patients, but treatment with red blood cell transfusions can have unwanted effects. Limiting the occurrence and severity of anemia by using erythropoietic agents (iron and/or recombinant erythropoietin), therefore, remains an attractive option during the intensive care unit stay but also after hospital discharge. Moreover, these agents may have additional beneficial properties. In this article the authors review the rationale for the administration of iron and/or erythropoietin in critically ill patients.     

Chemotherapy for prostate cancer: finally an advance!

Patients with metastatic prostate cancer can be treated with androgen deprivation strategies; however, most patients will eventually develop androgen-independent prostate cancer (AIPC). Until recently, chemotherapy has been shown to palliate symptoms of disease but not improve survival. Now 2 large phase 3 trials have demonstrated an overall survival advantage for docetaxel-based regimens compared with the best standard of care. This firmly cements docetaxel-based therapies as the standard of care for patients with metastatic androgen-independent disease. In addition, this foundation provides a platform for the translation of novel agents into new combination cancer therapies. In this paper, we not only review standard treatment options available for AIPC including the recently completed docetaxel trials, but also present some of the promising new drug combinations of currently available drugs.     

The use of granulocyte transfusion in neonatal sepsis

Many questions are raised in this review about the role of adult donor granulocyte transfusions in the setting of overwhelming bacterial neonatal sepsis. There clearly exists a number of variables, which influence the survival and morbidity associated with bacterial sepsis. The important differences in these studies highlight the need for prospective large multicenter studies to definitely clarify these issues. Important criteria, which are yet to be established and which impact significantly, include the time of administration of adjuvant granulocytes, the number of granulocytes that need to be harvested, which group of neonates require early granulocyte transfusions, the best method for optimal and easy granulocyte collection, the frequency and intervals of granulocyte transfusions, and improved methods for the early identification of neonatal candidates who would benefit from the granulocyte transfusions. The benefits of granulocyte transfusions (ie, the improvement in morbidity and mortality) in septic neutropenic neonates must be weighed against the possible and reported side effects associated with such transfusions. Adverse reactions including graft-versus-host disease, CMV, HIV and hepatitis infection, fluid retention and pulmonary edema, blood group sensitization, and pulmonary insufficiency may all result from the use of granulocyte transfusions in a host who has evidence of developmental immaturity. All future studies must continue to evaluate these potential complications to balance and analyze the true benefits of survival with reported treatment results. Recently, a number of investigators including ourselves, have begun to examine the role of alternate adjuvant immunotherapy in enhancing neonatal host defense in the clinical setting of overwhelming bacterial sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Managing Myelodysplastic Syndrome and the Nurse Practitioner’s Role

Patients with myelodysplastic syndrome (MDS) require expert, consistent monitoring and management of their blood counts, disease status, and treatment regimens. Understanding how MDS presents and progresses as well as understanding treatment options and how to implement them on an individualized patient basis is essential for patients to receive optimal care. Nurse practitioners play a central role in the care of MDS patients. They have an opportunity to develop trusting relationships with their patients and are crucial parts of the health care team in helping to coordinate care, facilitate treatment, improve quality of life, and avoid life-threatening complications of the disease.     

Hematologic toxicity of zidovudine in HIV-infected patients.

Zidovudine is now used extensively in an effort to control infection with the human immunodeficiency virus (HIV). The drug is associated with major hematologic toxicity, especially anemia and granulocytopenia. Conservative management of hematologic toxicity includes dosage reduction or cessation of therapy, diagnosis and treatment of chronic debilitating diseases, and supportive care, such as blood transfusions. New investigational agents, including hematopoietic growth factors, are being studied to combat the toxicities associated with zidovudine. The efficacy of these agents has yet to be established. Recent advances in drug efficacy at reduced dosage and in combination therapy promise to permit use of zidovudine with markedly reduced toxicity.     

Late-onset sepsis in preterm infants: update on strategies for therapy and prevention

Late-onset sepsis occurs in 15–25% of very low birth weight neonates. Early diagnosis and therapy optimize patient outcomes. Despite these efforts, mortality remains high (18–36%) and survivors suffer significant neurological and pulmonary morbidity. Although rapid diagnostics are improving, more are needed. Current therapy remains antibiotics and supportive care. Adjunctive therapies have either limited data (e.g., pentoxifylline) or have been found ineffective (e.g., granulocyte transfusions, granulocyte macrophage colony-stimulating factor/granulocyte colony-stimulating factor, and intravenous immunoglobulin). Preventive strategies that have proven beneficial include infection control measures (e.g., hand hygiene and universal precautions), early enteral feeds with human milk, early removal of central lines, catheter infection prevention bundles, antibiotic stewardship and focused quality improvement measures. Promising strategies to prevent late-onset sepsis include oral lactoferrin, and pathogen-specific monoclonal antibodies but more evidence is required to make practice recommendations.     

Combined pre-immunization and granulocyte transfusion therapy for treatment of pseudomonas septicemia in neutropenic dogs.

An experimental model was designed to evaluate a combined protocol of active immunization and granulocyte transfusions for treatment of Pseudomonas aeruginosa sepsis in the neutropenic host. One member of a pair of dogs was immunized with P. aeruginosa vaccine. Both dogs were then rendered transiently neutropenic with a single intravenous dose of cyclophosphamide (40 mg. per kilogram) and challenged with an intravenous inoculum of P. aeruginosa. Twenty-four and 48 hours after pseudomonas challenge each animal received granulocyte transfusions. Effectiveness of therapy was evaluated by observation of survival time, febrile response, and quantitative blood cultures. Results showed a significant increase in the survival period (P is less than 0.05), a lower febrile response (P is less than 0.025), negative blood cultures, and a greater recovery rate in the immune group. Immune dogs that died had negative blood cultures or less than or equal to 10 pseudomonas per milliliter of blood despite the presence of P. aeruginosa in tissues. In contrast, control dogs had septic deaths within 67 hours of pseudomonas challenge, marked febrile responses with 24 hours of infection, and positive blood cultures with 4,000 to 25,800 pseudomonas per milliliter of blood. These data show that combined therapy with immunization and granulocyte transfusions is effective in reducing the severity of P. aeruginosa infection and in preventing bacteremia during periods of leukopenia.     

Chelation therapy for iron overload: nursing practice implications

Many diseases of the blood are treated with blood transfusion therapy. Chronic transfusions can cause iron overload, and, if untreated, can cause end-organ damage. Chelation therapy provides a way of treating iron overload and minimizing its adverse effects. Nurses need to understand that iron overload is a consequence of chronic blood transfusion, and they need to know what effects it has on end organs and what treatment options are available.     

The myelodysplastic syndromes: diagnosis and treatment

The myelodysplastic syndromes (MDSs) are common, acquired, clinically challenging hematologic conditions that are characterized by bone marrow failure and a risk of progression to acute leukemia. These disorders can arise de novo, especially in elderly patients or, less often, as a consequence of prior chemotherapy or radiotherapy for an unrelated disease. The MDS classification systems were revised recently and updated. These refined classification and prognostic schemes help stratify patients by their risk of leukemia progression and death; this knowledge can help clinicians select appropriate therapy. Although many treatments for MDS have been proposed and evaluated, at present, only hematopoietic stem cell transplantation offers any real hope for cure, and no available therapy beyond general supportive care offers benefit to more than a minority of patients. However, recent clinical trials enrolling patients with MDS have reported encouraging results with use of newer drugs, including lenalidomide, decitabine, and darbepoetin alfa. Other exciting treatment regimens are being tested. Here, we present a contemporary, practical clinical approach to the diagnosis and risk-stratified treatment of MDS. We review when to suspect MDS, detail how to evaluate patients who may have a form of the condition, explain key features of treatments that are currently available in the United States, and summarize a general, common-sense therapeutic approach to patients with MDS.