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American Journal of Hematology Feb 2014Cancer-related anemia (CRA) is due to multiple etiologies, including chemotherapy-induced myelosuppression, blood loss, functional iron deficiency, erythropoietin... (Review)
Review
Cancer-related anemia (CRA) is due to multiple etiologies, including chemotherapy-induced myelosuppression, blood loss, functional iron deficiency, erythropoietin deficiency due to renal disease, marrow involvement with tumor as well as other factors. The most common treatment options for CRA include iron therapy, erythropoietic-stimulating agents (ESAs), and red cell transfusion. Safety concerns as well as restrictions and reimbursement issues surrounding ESA therapy for CRA have resulted in suboptimal treatment. Similarly, many clinicians are not familiar or comfortable using intravenous iron products to treat functional iron deficiency associated with CRA. This article summarizes our approach to treating CRA and discusses commonly encountered clinical scenarios for which current clinical guidelines do not apply.
Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Malnutrition; Neoplasms; Prevalence; Treatment Outcome
PubMed: 24532336
DOI: 10.1002/ajh.23628 -
Journal of Pediatric Hematology/oncology Oct 2014The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of... (Review)
Review
The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients' ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens to improve therapy for the individual patient.
Topics: Antimetabolites, Antineoplastic; Child; Drug Therapy, Combination; Humans; Maintenance Chemotherapy; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 24936744
DOI: 10.1097/MPH.0000000000000206 -
Oncology (Williston Park, N.Y.) Nov 2002Thrombocytopenia remains a significant clinical problem for patients with cancer. Management approaches include watchful waiting, platelet transfusions, and the use of... (Review)
Review
Thrombocytopenia remains a significant clinical problem for patients with cancer. Management approaches include watchful waiting, platelet transfusions, and the use of pharmacologic agents. Although platelet transfusion remains the gold standard for prophylaxis and treatment of thrombocytopenia, this approach is associated with transfusion-transmitted disease, infection, and platelet refractoriness. Because of these complications and the expense of platelet therapy, recent studies have examined the clinical evidence supporting the widely used platelet transfusion trigger of 20,000 cells/microL and found that values of 5,000 to 10,000 cells/microL are safe for selected patients. Several investigational agents offer promise for treatment of thrombocytopenia in patients undergoing myelosuppressive and myeloablative therapy. These agents include recombinant human interleukin-11, recombinant human thrombopoietin, and c-Mpl ligand mimetics.
Topics: Cross Infection; Humans; Interleukin-11; Neoplasms; Platelet Transfusion; Recombinant Proteins; Thrombocytopenia; Thrombopoietin
PubMed: 12469931
DOI: No ID Found -
Current Treatment Options in Oncology Jun 2004Waldenström macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by the presence of an immunoglobulin M monoclonal protein in the blood and... (Review)
Review
Waldenström macroglobulinemia (WM) is a low-grade lymphoproliferative disorder characterized by the presence of an immunoglobulin M monoclonal protein in the blood and monoclonal small lymphocytes and lymphoplasmacytoid cells in the marrow. The disease is uncommon and there is a lack of clear diagnostic criteria. WM is treatable but not curable and long-term survival is possible. Therefore, the treating physician needs to carefully balance the risks and benefits of treatment. Treatments are aimed at relieving symptoms resulting from marrow infiltration and the hyperviscosity syndrome. Therapies available for initiation of treatment include alkylating agents, purine nucleoside analogs, and rituximab. Chlorambucil has been the mainstay of treatment for many years and remains useful, especially in older patients. Rituximab has become an important new therapy for this disease because of its positive treatment responses, acceptable toxicity, and lack of therapy-associated myelosuppression and myelodysplasia. Currently, rituximab is being combined with chemotherapy. Other options of treatment include interferon and corticosteroids. Emerging therapies include stem cell transplantation (autologous and allogeneic) for younger patients. Currently, there are few comparative data on which to state an absolute opinion concerning the best available treatment for patients with WM.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Combined Modality Therapy; Decision Trees; Humans; Rituximab; Stem Cell Transplantation; Waldenstrom Macroglobulinemia
PubMed: 15115652
DOI: 10.1007/s11864-004-0015-5 -
Blood Dec 2014Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their... (Review)
Review
Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression( pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.
Topics: Antineoplastic Combined Chemotherapy Protocols; Benzamides; Bridged-Ring Compounds; Clinical Trials, Phase III as Topic; Drug Delivery Systems; Hematologic Neoplasms; Humans; Janus Kinase 2; Myeloproliferative Disorders; Neoplasm Proteins; Nitriles; Pyrazoles; Pyrimidines; Quality of Life
PubMed: 25472969
DOI: 10.1182/blood-2014-05-577635 -
WMJ : Official Publication of the State... Oct 2021The electronic health record and electronic prescribing have transformed the practice of medicine. Both have led to improved efficacy and safety in medication...
INTRODUCTION
The electronic health record and electronic prescribing have transformed the practice of medicine. Both have led to improved efficacy and safety in medication management. However, dangers may arise when electronic prescription requests are filled by default and when electronic health record medication lists are presumed accurate. In this case, our patient underwent 2 days of inpatient evaluation before a thorough medication reconciliation revealed that his symptoms had likely resulted from a medication that had been refilled reflexively.
CASE PRESENTATION
A 69-year-old man presented with worsening weakness, weight loss, decreased appetite, and nonbloody diarrhea. Imaging revealed a large right pleural effusion and a nonspecific colitis. Lab workup revealed significant bicytopenia, hypogammaglobulinemia, and hypolipidemia. Initial evaluation and diagnoses were focused toward causes of malnutrition and malabsorption. However, on hospital day 2, a pharmacist discovered that the patient had been taking long-term oral linezolid for unclear reasons. With cessation of linezolid, the patient's myriad symptoms resolved and all lab values progressively normalized.
DISCUSSION
The side effects of linezolid have been well documented and include reversible myelosuppression and gastrointestinal symptoms. However, medication reconciliation was imperative in diagnosing and treating our patient. Further, reflexive refilling of this patient's medication likely explains why he was taking linezolid for such a long period of time, as other forms of automation bias are known to introduce errors in electronic prescribing.
CONCLUSION
This case calls attention to the importance of medication reconciliation, the danger of overreliance on electronic health record medication lists, and the pitfalls in not maintaining vigilance with electronic prescribing. It also highlights the necessity of patient and caregiver education regarding their medications.
Topics: Aged; Drug-Related Side Effects and Adverse Reactions; Electronic Health Records; Humans; Male; Medication Errors; Medication Reconciliation; Pharmacists
PubMed: 34710309
DOI: No ID Found -
Clinical and Experimental Medicine Nov 2022Hyperthermia is a generic term for different techniques using heat in cancer therapies. Temperatures of about 42° Celsius in combination with chemo- or radiotherapy may... (Review)
Review
Hyperthermia is a generic term for different techniques using heat in cancer therapies. Temperatures of about 42° Celsius in combination with chemo- or radiotherapy may improve the effectiveness of those treatments. Clinical benefit is shown in "standard hyperthermia" with tumour temperatures assessed during treatment. This systematic review thoroughly assesses the state of evidence concerning the benefits and side effects of electro hyperthermia or whole-body hyperthermia ("alternative hyperthermia") in oncology. From 26 April 2021 to 09 May 2021, a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsycINFO, CINAHL and Medline) to find studies concerning the use, effectiveness and potential harm of alternative medical hyperthermia therapy on cancer patients. From all 47,388 search results, 53 publications concerning 53 studies with 2006 patients were included in this systematic review. The patients were diagnosed with different types of cancer. The hyperthermic methods included whole-body hyperthermia (WBH) with different methods and electro hyperthermia (EH). The majority of the included studies were single-arm studies, counting in total 32 studies. Six studies were randomized controlled trials (RCT). In addition, one systematic review (SR) was found. The most critical endpoints were tumour response, survival data, pain relief, myelosuppression and toxicities. Outcome was heterogeneous, and considering the methodological limitations, clinical evidence for the benefit of alternative hyperthermia in cancer patients is lacking. Neither for whole-body hyperthermia nor for electro hyperthermia there is any evidence with respect to improvement of survival or quality of life in cancer patients.
Topics: Humans; Neoplasms; Hyperthermia, Induced; Quality of Life
PubMed: 35767077
DOI: 10.1007/s10238-022-00846-9 -
Journal of Acupuncture and Meridian... Jun 2015The aim of this study is to review current studies on the effect of acupuncture therapy on bone marrow suppression after chemotherapy. The authors of the present paper... (Review)
Review
The aim of this study is to review current studies on the effect of acupuncture therapy on bone marrow suppression after chemotherapy. The authors of the present paper have searched related literature over the past 10 years at home and abroad, analyzing the features and the effects of acupuncture therapy (including acupuncture, moxibustion, point injection, point application, etc.) for treating myelosuppression after tumor chemotherapy. We also discuss the year of publication, document type, acupuncture therapy, acupoint selection, and adverse effects with figures. We analyzed 159 articles related to acupuncture therapy from 2004 to 2013, and the analysis revealed that point injection was the most frequently used therapy for clinical applications, and that Zusanli (ST36) was the most frequently used acupoint. The results showed that some problems regarding the design method, acupoint selection, and acupuncture intervention measure existed in those research studies. We hope to provide readers with an overall and objective understanding of acupuncture and moxibustion therapy for treating myelosuppression after tumor chemotherapy.
Topics: Acupuncture Therapy; Antineoplastic Agents; Humans; Immunocompromised Host; Immunosuppressive Agents; Neoplasms
PubMed: 26100065
DOI: 10.1016/j.jams.2014.09.003 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal... (Review)
Review
INTRODUCTION
Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.
MATERIALS AND METHODS
Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.
RESULTS
From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.
CONCLUSIONS
This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.
Topics: Adult; Humans; Kidney Transplantation; Living Donors; Immune Tolerance; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Transplantation Tolerance
PubMed: 37709652
DOI: 10.1016/j.trre.2023.100792 -
Clinical and Applied... 2022Thrombotic and hemorrhagic complications are related to a significant rate of morbidity and mortality in patients with myeloproliferative neoplasms (MPNs), they are...
Thrombotic and hemorrhagic complications are related to a significant rate of morbidity and mortality in patients with myeloproliferative neoplasms (MPNs), they are therefore called "thrombohemorrhagic" syndromes. Several clinical factors, such as age and presence of cardiovascular comorbidities are responsible for thrombotic complications. High blood counts, platelet alterations, presence of JAK2 mutation and possibly of other CHIP mutations such as TET2, DNMT3A, and ASXL1, procoagulant microparticles, NETs formation, endothelial activation and neo-angiogenesis are some of the parameters accounting for hypercoagulability in patients with myeloproliferative neoplasms. Bleeding complications emerge as a result of platelet exhaustion. They can be also linked to a functional deficiency of von Willebrand factor, when platelet counts rise above 1000G/L. The mainstay of management consists on preventing hemostatic complications, by antiplatelet and/or anticoagulant treatment and myelosuppressive agents in high-risk patients.Circumstances related to a high thrombohemorrhagic risk, such as pregnancy and the perioperative period, prompt for specific management with regards to anticoagulation and myelosuppression treatment type. In order to apply a patient-specific treatment strategy, there is a need for a risk score assessment tool encompassing clinical parameters and hemostasis biomarkers.
Topics: Blood Platelets; Female; Hemorrhage; Humans; Myeloproliferative Disorders; Neoplasms; Pregnancy; Thrombosis
PubMed: 35733370
DOI: 10.1177/10760296221097969