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Critical Reviews in Oncology/hematology Jun 2014Neutropenia with fever (febrile neutropenia [FN]) is a serious consequence of myelosuppressive chemotherapy that usually results in hospitalization and the need for... (Review)
Review
Neutropenia with fever (febrile neutropenia [FN]) is a serious consequence of myelosuppressive chemotherapy that usually results in hospitalization and the need for intravenous antibiotics. FN may result in dose reductions, delays, or even discontinuation of chemotherapy, which, in turn, may compromise patient outcomes. It is important to identify which patients are at high risk for developing FN so that patients can receive optimal chemotherapy while their risk for FN is appropriately managed. A systematic review of the literature was performed to gain a comprehensive and updated understanding of FN risk factors. Older age, poor performance status, advanced disease, certain comorbidities, low baseline blood cell counts, low body surface area/body mass index, treatment with myelosuppressive chemotherapies, and specific genetic polymorphisms correlated with the risk of developing FN. Albeit many studies have analyzed FN risk factors, there are several limitations, including the retrospective nature and small sample sizes of most studies.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Febrile Neutropenia; Humans; Neoplasms; Risk Factors
PubMed: 24434034
DOI: 10.1016/j.critrevonc.2013.12.006 -
Blood Jan 2024Most patients with acute myeloid leukemia (AML) develop refractory/relapsed (R/R) disease even in the presence of novel and targeted therapies. Given the biological...
Most patients with acute myeloid leukemia (AML) develop refractory/relapsed (R/R) disease even in the presence of novel and targeted therapies. Given the biological complexity of the disease and differences in frontline treatments, there are therapies approved for only subgroups of R/R AML, and enrollment in clinical trials should be first priority. Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative strategy for most patients. Therapeutic approaches, including allogeneic HCT, triggered by the presence of measurable residual disease (MRD), have recently evolved to prevent overt hematologic relapse. Salvage therapy with chemotherapy or targeted therapy is frequently administered before HCT to reduce the leukemic burden. Gilteritinib is approved by the Food and Drug Administration and European Medicines Agency for patients with relapsed FLT3 mutated AML, whereas targeted therapy for relapsed IDH1/2 mutated AML has only FDA approval. Patients who are R/R after azacitidine and venetoclax (AZA/VEN) have a dismal outcome. In this setting, even available targeted therapies show unsatisfactory results. Examples of ongoing developments include menin inhibitors, a targeted therapy for patients with mutated NPM1 or KMT2A rearrangements, antibodies targeting the macrophage immune checkpoint CD47, and triple combinations involving AZA/VEN. The latter cause significant myelosuppressive effects, which make it challenging to find the right schedule and dose.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Azacitidine; Antineoplastic Combined Chemotherapy Protocols; Leukemia, Myeloid, Acute; Salvage Therapy
PubMed: 37944143
DOI: 10.1182/blood.2023022481 -
Oral Surgery, Oral Medicine, Oral... Sep 1999Because the etiology of mucositis is multifactorial , approaches to prevention and management have also been multifactorial. Effective prevention and management of... (Review)
Review
Because the etiology of mucositis is multifactorial , approaches to prevention and management have also been multifactorial. Effective prevention and management of mucositis will reduce the pain and suffering experienced during cancer treatment. Oropharyngeal pain in cancer patients frequently requires systemic analgesics, adjunctive medications, physical therapy, and psychologic therapy in addition to oral care and topical treatments. Good oral hygiene reduces the severity of oral mucositis and does not increase the risk of bacteremia. Current approaches to management include frequent oral rinsing with saline or bicarbonate rinses, maintaining excellent oral hygiene, and using topical anesthetics and analgesics. Cryotherapy is a potential adjunctive approach in some cases. There are a number of approaches that appear to represent viable candidates for further study. Biologic response modifiers offer the potential for prevention and for acceleration of healing. Various cytokines will enter clinical trials in the near future; these offer the potential for reduction of epithelial cell sensitivity to the toxic effects of cancer therapy or for stimulation of repair of the damaged tissue. Other approaches include the use of medications to reduce exposure of the oral mucosa to chemotherapeutic drugs that are secreted in saliva. Antimicrobial approaches have met with conflicting results, little effect being seen with chlorhexidine and systemic antimicrobials in the prevention of mucositis in radiation patients. In patients with BMT and patients with leukemia, chlorhexidine may not be effective in preventing mucositis, although there may be reduction in oral colonization by Candida. Initial studies of topical antimicrobials that affect the gram-negative oral flora have shown reductions in ulcerative mucositis during radiation therapy but have not been assessed in leukemia/BMT. Among other approaches that require further study are low-energy lasers and anti-inflammatory medications. These approaches to management have undergone initial study, but additional investigation is needed to determine their effectiveness with respect to the prevention of mucositis and symptom management and to determine appropriate doses and frequencies of intervention. Current studies and our increasing understanding of the pathogenesis of oral mucositis will lead to new approaches to management and improved quality of life for these patients.
Topics: Antineoplastic Agents; Bone Marrow Transplantation; Cranial Irradiation; Humans; Immunosuppression Therapy; Mouth Mucosa; Neoplasms; Stomatitis; Transplantation Conditioning
PubMed: 10503852
DOI: 10.1016/s1079-2104(99)70026-0 -
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 -
Hematology/oncology Clinics of North... Apr 1996Myelosuppression is the most common toxicity associated with the administration of dose-intensive cytotoxic chemotherapy. The basic understanding of neutrophil biology... (Review)
Review
Myelosuppression is the most common toxicity associated with the administration of dose-intensive cytotoxic chemotherapy. The basic understanding of neutrophil biology and the physiology of chemotherapy-induced neutropenia has advanced tremendously in the past 2 decades. Concordantly, the ability to reduce the morbidity associated with neutropenia has improved. Adjunctive cytokine and progenitor cell support of hematologic recovery after myelosuppressive therapy have proved to be models of translational research and have led to novel therapeutic initiatives for patients with cancer and hematologic malignancies. In this article, fundamental aspects of neutrophil production are discussed, and the clinical development of hematopoietic cytokines active on cells of the leukocyte lineages is presented.
Topics: Antineoplastic Agents; Bone Marrow; Cell Division; Drug Administration Schedule; Growth Substances; Humans; Neutropenia; Neutrophils; Reference Values
PubMed: 8707761
DOI: 10.1016/s0889-8588(05)70344-0 -
Drugs Sep 2017Myelofibrosis (MF) is a myeloproliferative neoplasm that is pathologically characterized by bone marrow myeloproliferation, reticulin and collagen fibrosis, and... (Review)
Review
Myelofibrosis (MF) is a myeloproliferative neoplasm that is pathologically characterized by bone marrow myeloproliferation, reticulin and collagen fibrosis, and extramedullary hematopoiesis. Constitutive activation of the Janus associated kinase (JAK)-signal transducers and activators of transcription signaling pathway with resultant elevation in pro-inflammatory cytokine levels is the pathogenic hallmark of MF. JAK inhibitors, namely ruxolitinib, have been successful in alleviating symptoms and reducing splenomegaly, but therapy-related myelosuppression has led to the further development of highly selective JAK2 inhibitors. Additionally, ruxolitinib does not appear to affect the malignant hematopoietic clone substantially, evidenced by lack of molecular remissions, bone marrow histopathologic responses, and a proportion of treated patients developing progressive disease and leukemic transformation while receiving therapy. A number of other pharmacotherapeutic strategies are currently being explored in the clinic. Non-JAK inhibitor strategies being evaluated in MF include non-JAK signaling pathway inhibitors, epigenetic-directed therapies, immune-modulating agents, anti-fibrotic agents, and telomerase inhibitors. This review highlights the current landscape of MF pharmacotherapy and explores therapeutic advances underway.
Topics: Drug Approval; Drug Therapy, Combination; Epigenesis, Genetic; Histone Deacetylases; Humans; Immunotherapy; Janus Kinases; Nitriles; Primary Myelofibrosis; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Telomerase; United States; United States Food and Drug Administration
PubMed: 28791654
DOI: 10.1007/s40265-017-0797-y -
International Journal of Hematology Jul 2022Cases of pediatric acute myeloid leukemia (AML) with complex karyotypes including chromosome 5 abnormalities are rare and have a very poor prognosis. Management of AML...
Decitabine combined with minimally myelosuppressive therapy for induction of remission in pediatric high-risk acute myeloid leukemia with chromosome 5q deletion: a report of three cases.
Cases of pediatric acute myeloid leukemia (AML) with complex karyotypes including chromosome 5 abnormalities are rare and have a very poor prognosis. Management of AML with monosomy 5/del(5q) has been inconsistent. We treated three adolescents with this AML subtype using combined low-dose cytarabine and mitoxantrone, concurrently with decitabine and G-CSF, for remission induction. Decitabine was also included in the conditioning regimen before hematopoietic cell transplantation (HCT). All three patients achieved complete remission after treatment with this combination therapy. The treatment was well tolerated, and the patients are alive and free of disease at 3.6, 3.2, and 3.0 years after HCT, respectively.
Topics: Abnormal Karyotype; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Chromosome Aberrations; Chromosome Deletion; Cytarabine; Decitabine; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Remission Induction
PubMed: 35181851
DOI: 10.1007/s12185-022-03309-9 -
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 -
Journal of Oncology Pharmacy Practice :... Dec 2017Myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm characterized by abnormal hematopoiesis. Alterations to the Janus kinase-signal transducer and activator... (Review)
Review
Myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm characterized by abnormal hematopoiesis. Alterations to the Janus kinase-signal transducer and activator of transcription pathway result in dysregulation of gene transcription and cell proliferation. Patients with symptomatic myelofibrosis present with a variety of signs and symptoms including, but not limited to myelosuppression, marked splenomegaly, abdominal discomfort, fatigue, and blood transfusion-dependence. Traditional myelosuppressive therapies including hydroxyurea, azacitidine, and cladribine aim to reduce constitutional symptoms and control the burden of disease. Immunomodulators can potentially reverse anemia associated with myelofibrosis, but are poorly tolerated by most patients. The novel Janus kinase 2 (JAK2) inhibitor, ruxolitinib, has demonstrated marked improvements to constitutional symptoms and splenomegaly. While survival benefit has not yet been demonstrated, continued research into pharmacologic management of myelofibrosis offers the promise of altering the course of disease progression.
Topics: Anemia; Disease Management; Humans; Janus Kinase 2; Nitriles; Primary Myelofibrosis; Pyrazoles; Pyrimidines; Splenomegaly
PubMed: 27672139
DOI: 10.1177/1078155216670229 -
Transplantation May 2024Donor-specific tolerance remains a goal in transplantation because it could improve graft survival and reduce morbidity. Cotransplantation of donor hematopoietic cells... (Review)
Review
Donor-specific tolerance remains a goal in transplantation because it could improve graft survival and reduce morbidity. Cotransplantation of donor hematopoietic cells to achieve chimerism is a promising approach for tolerance induction, which was successfully tested in clinical trials. However, current protocols are associated with side effects related to the myelosuppressive recipient conditioning, which makes it difficult to introduce them as standard therapy. More recently, adoptive cell therapy with polyclonal or donor-specific regulatory T cells (Treg) proved safe and feasible in several transplant trials, but it is unclear whether it can induce tolerance on its own. The combination of both approaches-Treg therapy and hematopoietic cell transplantation-leads to chimerism and tolerance without myelosuppressive treatment in murine models. Treg therapy promotes engraftment of allogeneic hematopoietic cells, reducing conditioning requirements and enhancing regulatory mechanisms maintaining tolerance. This review discusses possible modes of action of transferred Treg in experimental chimerism models and describes translational efforts investigating the potent synergy of Treg and chimerism.
Topics: T-Lymphocytes, Regulatory; Animals; Humans; Bone Marrow Transplantation; Transplantation Tolerance; Transplantation Chimera; Graft Survival; Adoptive Transfer; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Treatment Outcome
PubMed: 37789519
DOI: 10.1097/TP.0000000000004814