ABSTRACT
The variability in myelosuppression after chemotherapy for acute myeloid leukaemia (AML) can affect its prognosis; however, the underlying mechanism remains controversial. In the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study, we showed that prolonged neutropenia was associated with high overall survival (P = 0·011) and low frequency of relapse (P = 0·042) in patients without granulocyte-colony stimulating factor (G-CSF) who completed the indicated treatment protocol. Our data indicate that predisposition to prolonged neutropenia after chemotherapy is correlated with a better outcome of AML treatment. Our results promote the usage of individualised drug dosing strategies to improve the therapeutic outcome in AML patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Granulocyte Colony-Stimulating Factor/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/immunology , Neutropenia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Failure Disorders/chemically induced , Child , Disease Susceptibility , Female , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Japan/epidemiology , Leukemia, Myeloid, Acute/mortality , Male , Neutropenia/epidemiology , Prognosis , Survival AnalysisABSTRACT
COVID-19 has now spread globally, and 10-20% of the cases are thought to proceed to a severe condition. However, information on COVID-19 in immunodeficient patients remains limited. We treated a 56-year-old man who developed COVID-19 after chemotherapy for mantle cell lymphoma. After 1 month of prolonged fever, the patient's respiratory condition deteriorated rapidly, and he died. COVID-19 in immunocompromised patients after chemotherapy, even with mild symptoms, can cause rapid immune reconstitution and respiratory deterioration. Therefore, caution is advised until negative PCR test results for SARS-CoV-2 are confirmed.
Subject(s)
Bone Marrow Failure Disorders/chemically induced , COVID-19/etiology , Cross Infection/chemically induced , Lymphoma, Mantle-Cell/drug therapy , SARS-CoV-2/isolation & purification , Bone Marrow Failure Disorders/complications , COVID-19/diagnostic imaging , Cross Infection/complications , Cross Infection/etiology , Humans , Immunocompromised Host , Lymphoma, Mantle-Cell/complications , Lymphoma, Mantle-Cell/immunology , Male , Middle Aged , Pharynx/virology , Polymerase Chain Reaction , Radiography, Thoracic , SARS-CoV-2/genetics , Tomography, X-Ray Computed , COVID-19 Drug TreatmentSubject(s)
Aldehyde Oxidase/deficiency , Arthritis, Juvenile/drug therapy , Azathioprine , Bone Marrow Failure Disorders , IgA Deficiency/diagnosis , Purine-Pyrimidine Metabolism, Inborn Errors , Uric Acid , Xanthine Dehydrogenase/deficiency , Aldehyde Oxidase/genetics , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Antirheumatic Agents/pharmacokinetics , Arthritis, Juvenile/immunology , Azathioprine/administration & dosage , Azathioprine/adverse effects , Azathioprine/pharmacokinetics , Bone Marrow Failure Disorders/blood , Bone Marrow Failure Disorders/chemically induced , Bone Marrow Failure Disorders/therapy , Erythrocyte Transfusion/methods , Humans , Immune Tolerance/genetics , Immunologic Tests/methods , Male , Pharmacogenomic Testing/methods , Purine-Pyrimidine Metabolism, Inborn Errors/diagnosis , Purine-Pyrimidine Metabolism, Inborn Errors/genetics , Purine-Pyrimidine Metabolism, Inborn Errors/physiopathology , Sulfurtransferases/genetics , Uric Acid/blood , Uric Acid/urine , Xanthine , Xanthine Dehydrogenase/genetics , Young AdultABSTRACT
Chronic benzene (BZ) exposure is associated with multiple adverse health effects and leads to progressive bone marrow failure (BMF). BZ-induced BMF is an acquired aplastic anemia characterized by severe anemia, neutropenia and thrombocytopenia, which is likely caused by immunotoxicity and oxidative stress. Previous studies showed that Epimedium polysaccharides (EPS), a natural and major herbal compound derived from Epimedium, has immunomodulatory and antioxidant potential. The purpose of this study was to evaluate the potential efficacy of EPS against BZ-induced BMF. BMF mouse model was established by subcutaneous injection of 2 ml/kg BZ in CD1 mice. Mice received daily oral treatment with 100 mg/kg high-dose EPS and 20 mg/kg low-dose EPS for four weeks. Our data showed that EPS treatment alleviated BZ-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in bone marrow. Furthermore, EPS treatment decreased apoptotic rate and reactive oxygen species production, S-phase arrest in bone marrow cells. Finally, EPS treatment improved T cell-mediated immune suppression by increasing CD3+, CD4 + T-cell counts, and CD4+/CD8+ ratio. and modulated hematopoietic cytokines including EPO, IL-11, and IL-2 in peripheral blood. Our study suggests that EPS is a potential therapeutic target to attenuate hematotoxicity induced by BZ.
Subject(s)
Benzene/toxicity , Bone Marrow Failure Disorders/drug therapy , Drugs, Chinese Herbal/therapeutic use , Epimedium , Oxidative Stress/drug effects , Polysaccharides/therapeutic use , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Bone Marrow Failure Disorders/chemically induced , Bone Marrow Failure Disorders/immunology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/pharmacology , Immunity, Cellular/drug effects , Immunity, Cellular/immunology , Male , Mice , Oxidative Stress/immunology , Polysaccharides/pharmacology , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/immunologySubject(s)
Biological Therapy/methods , Clinical Decision-Making/ethics , Lymphoma/chemically induced , Neoplasms/therapy , Biological Therapy/adverse effects , Bone Marrow Failure Disorders/chemically induced , Bone Marrow Failure Disorders/epidemiology , Denmark/epidemiology , Humans , Infections/chemically induced , Infections/epidemiology , Lymphoma/epidemiology , Neoplasms/psychology , Quality of Life , Recurrence , Registries , Risk , Tumor Necrosis Factor Inhibitors/adverse effectsABSTRACT
A 20-year-old college student presented with high grade, intermittent fever for 10 days associated with blood stained loose stools after taking tablet levamisole for 17 days for vitiligo vulgaris. He was febrile, had a toxic appearance and appeared pale. Investigations showed neutropaenia with thrombocytopaenia. Blood cultures were sterile and stool cultures did not grow any enteric pathogens. His bone marrow examination was suggestive of an aplastic anaemia. He was administered empirical antibiotics, granulocyte colony stimulating factor and platelet transfusions. However, his fever and blood stained stools persisted. A repeat bone marrow examination after 2 weeks still revealed a hypoplastic marrow. Hence, a diagnosis of a levamisole induced bone marrow failure was made. While being worked up for an allogeneic stem cell transplantation, he developed neutropaenic enterocolitis and refractory septic shock with carbapenem resistant Klebsiella pneumoniae and succumbed to his illness.
