Principal Side-Effects of the Treatment of Leukemias, Lymphomas, and Myelomas
Tariq I Mughal, John M Goldman, Sabena T Mughal in Understanding Leukemias, Lymphomas, and Myelomas, 2017
The first such drug to receive Food and Drug Administration (FDA) approval in November 1997 was interleukin-11 or oprelvekin (Neumega). It was approved for adult patients with non-myeloid cancers for chemotherapy-related thrombocytopenia based on studies confirming the drug’s efficacy in patients who had experienced severe thrombocytopenia following chemotherapy. In general the drug is indeed quite safe but in early 2009 there has been some concern about changes in visual acuity and visual field defects, possibly related to optic neuropathy, in addition to ventricular arrhythmias. Further tests are now in progress. The other two platelet-stimulating drugs are the subcutaneously administered romiplostim (AMG-531) and the orally administered eltrombopag (Promacta). Both drugs received regulatory approval by the FDA in 2008 for use in chronic immune thrombocytopenia and chemotherapy-induced thrombocytopenia.
Principal Treatment-Related Side Effects
Tariq I. Mughal in Precision Haematological Cancer Medicine, 2018
Myelosuppression is probably the most frequently observed haematological toxicity of cancer therapies in general. Cytotoxic, chemotherapy-associated myelosuppression can often be more serious than that caused by targeted therapies, since febrile neutropenia requiring urgent intervention is not an uncommon event. For most of the drugs, the nadir is at 7 to 10 days, when patients will be at risk of acquiring a bacterial or fungal infection as a result of neutropenia. Early administration of broad-spectrum antibiotics, and in some cases use of G-CSF to promote recovery of the neutrophils, may be indicated. Chemotherapy-associated anaemia is common and usually mild and may not require red cell transfusions. Thrombocytopenia can also occur and, if severe, may require the administration of platelet transfusions, and occasionally a TPO receptor agonists, such as romiplostin or eltrombopag. TKIs, in particular dasatinib, typically lead to a dose-dependent transient neutropenia, but can also result in anaemia and thrombocytopenia. Other manifestations of haematological toxicities include thrombotic-thrombocytopenic purpura/haemolytic-uraemic syndrome with VEGFR inhibitors, such as sunitinib, and bone/bone marrow necrosis, which can be seen in patients receiving steroids, particularly in high doses for long periods, as is often the case in particular in patients with acute lymphoblastic leukaemia. This is irreversible and requires most patients to discontinue the treatment; surgical correction may be indicated. There has been much concern about osteonecrosis of the jaw (ONJ), particularly in patients receiving bisphosphonates (Figure 13.5). B-cell aplasia has also been reported in rare patients receiving immunotherapies.
Case 37
Atul B. Mehta, Keith Gomez in Clinical Haematology, 2017
Chronic myelomonocytic leukemia is a slowly progressive condition which is usually treated with oral chemotherapy (e.g. hydroxyurea or etoposide). Splenectomy is helpful if patients become transfusion-dependent or if there are symptoms due to an enlarged organ. Transformation to acute leukemia occurs with a median interval of 18–24 months, but intensive chemotherapy is rarely successful. Younger patients should be considered for intensive therapy, possibly followed by bone marrow transplantation; however, this particular patient did not have a suitable donor 5 azacitidine is often helpful. Recent publications have indicated a role for eltrombopag as an orally active agent.
The efficacy and safety of eltrombopag in treating TKI-induced thrombocytopenia in patients with chronic myeloid leukemia
Published in Hematology, 2023
Li Liu, Yilin Chen, Yan Liang, Li Meng, Jingming Guo, Chuancai Liu, Zhe Zhao, Jing Zou, Wenjuan He, Jiangzhao Zhang, Zhenya Hong, Caixia Liang, Xianjie Fu, Hui Wu, Youshan Zhang, Yanli Zhang, Weiming Li
Domestic and international guidelines recommend granulocyte colony-stimulating factor(G-CSF) as a clinical treatment for TKI-induced neutropenia. In addition, human erythropoietin injection is used clinically for TKI-induced anemia. However, there are fewer therapeutic drugs for TKI-induced thrombocytopenia. Eltrombopag is an oral, synthetic, non-peptide, small-molecule human thrombopoietin agonist used for the treatment of immune thrombocytopenia, aplastic anemia, and hepatitis C-associated thrombocytopenia [8–10]. Recently, a non-rando-mized, phase II, single-arm study in America has established that eltrombopag can relieve TKI-induced thrombocytopenia in CML patients, thereby improving the efficacy of TKI [11]. However, there is a lack of studies in China and the Asia-Pacific region. Therefore, we retrospectively analyzed the clinical data of 21 CML patients treated with eltrombopag for TKI-induced thrombocytopenia to provide a reference for its efficacy and safety in CML patients.
Development and validation of a nomogram for steroid-resistance prediction in immune thrombocytopenia patients
Published in Hematology, 2021
Jieni Yu, Zhiqiang Xu, Yuanyuan Zhuo, Huahua Wei, Yinhai Ye, Qinhong Xu, Youli Li, Lihong Yu, Weiying Feng, Pan Hong, Kejie Zhang
Although most ITP patients are primary, hepatitis viruses can cause ITP [28–31], including hepatitis A, hepatitis B, hepatitis C, hepatitis E, which can cause immune dysfunction and affects the function of megakaryocyte [32–37]. Series of studies indicated that the sensitivity of HCV-ITP patients to corticosteroids was significantly lower than the one without HCV and was correlated with HCV level [38–40]. Different from foreign countries, the most common form of viral hepatitis in China is hepatitis B. Our study found that ITP patients with positive expression of HBsAg appear poor responses to corticosteroid. There are occult hepatitis B infection(OBI) cases that occur the reactivation of hepatitis B virus and lead to hepatic dysfunction when using rituximab, corticosteroid and other immunity inhibitors [28,41,42]. The treatment of ITP patients with hepatitis B should be specific but there is no consensus so far. Studies pointed out that eltrombopag can increase the counts of platelets and had been approved for the treatment of hepatitis C virus-associated immune thrombocytopenia(HCV-ITP) [43–45]. However, there are few studies about the therapy in HBV infected ITP patients, and require further discussion.
Cytokine control of megakaryopoiesis
Published in Growth Factors, 2018
Kira Behrens, Warren S. Alexander
High-throughput screening for non-peptide Mpl agonists resulted in the identification of Eltrombopag. Stimulation of human CD34+ cells with this agent increased megakaryocytic proliferation and differentiation and, upon administration in vivo, stimulated increased platelet counts (Erickson-Miller et al., 2005; Jenkins et al., 2007). Unlike Romiplostim, this small molecule does not compete with Tpo for Mpl-receptor binding sites, but instead interacts with the transmembrane domain of the receptor activating downstream JAK/STAT signalling, via STAT5, MAPK and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (Erickson-Miller et al., 2005; Kim et al., 2007). Interestingly, unlike Romiplostim and Tpo itself, Eltrombopag does not stimulate STAT3 and AKT signalling, suggesting that Eltrombopag and Tpo may potentially act additively to increase platelet production. Eltrombopag proved effective in clinical trials in ITP (Stasi et al., 2010) and was approved as a second-line treatment for ITP as well as for hepatitis-C-related thrombocytopenia in patients undergoing antiviral treatment. Clinical trials have further proved Eltrombopag capable of restoring tri-lineage haematopoiesis in aplastic anaemia (Desmond et al., 2014; Townsley et al., 2017).
Related Knowledge Centers
- Cirrhosis
- Megakaryocyte
- Splenectomy
- Platelet
- Corticosteroid
- Thrombocytopenia
- Oral Administration
- Immune Thrombocytopenic Purpura
- Immunoglobulin Therapy
- Jak-Stat Signaling Pathway