When we just start to take Imatinib, we often encounter the situation that white blood cells, platelets and red blood cells are substantially lower than normal, as well as some non-hematological toxic reactions, which make us don’t know how to cope with them, and NCCN gives us this information.
I. Hematologic toxicity Wu Hongbo, Department of Internal Medicine, Henan Cancer Hospital
When taking Imatinib for about a month, most people will experience hematologic toxicity, and low neutrophils are the most common (we used to focus on white blood cell levels), followed by low platelets.
1. 3 to 4 degrees of neutropenia (absolute neutrophil count ANC <1000/mm3, with neutrophils indicated by NEUT on some routine blood reports. (If the absolute neutrophil count is not available on the report, it can be calculated by multiplying the white blood cell count by the relative neutrophil count).
Solution: Suspend medication until ANC ≥ 1500/mm3. If recovery occurs within 2 weeks, treatment can be restarted at the original dose; if ANC <1000/cubic mm for more than 2 weeks, the dose needs to be reduced by 25%~33% to restart treatment, but the dose cannot be less than 300mg/d.
2.3~4 degree of thrombocytopenia (platelet count <50,000/mm3).
Solution: Suspend medication until platelet count ≥ 75,000/mm3. If recovered within 2 weeks, you can restart treatment with the original dose; if platelet count <50,000/cubic mm for more than 2 weeks, the dose needs to be reduced by 25%~33% to restart treatment, but the dose should not be less than 300mg.
3. In the accelerated and acute phase, disease induced erythrocytopenia may occur. If the hematocrit is unrelated to disease and the hematocrit persists for 2 weeks, reduce the imatinib dose to 400 mg or 300 mg. If the hematocrit persists for 4 weeks, suspend imatinib until ANC ≥ 1000/mm3 and platelet count ≥ 20,000/mm3, then restart therapy with 300 mg.
4, For patients with recalcitrant neutropenia and platelets, growth factors may be applied in combination with imatinib therapy.
5. In 3rd to 4th degree anemia, despite the effectiveness of erythropoietin, recent CMS (Centers for Medicare and Medicaid Services) and FDA (U.S. Food and Drug Administration) guidelines do not support the use of erythropoietin (ESAs) in myeloid malignancies.
Hematologic Toxicity Remark.
1. The above information is from the FDA (U.S. Food and Drug Administration).
2. Many of the toxicities are self-limiting and transient and may be considered for re-dose increment after a period of time.
3. If there is still no response to erythrogenic or myeloablative support therapy, consider bone marrow infusion support.
4, CML patients taking Imatinib therapy during the chronic phase, when leukocyte and neutrophil toxicity of degree 3 to 4 occurs, granulocyte growth hormone drugs should not be used, except in critical times of acute change.
Second, specific measures
1, diarrhea: supportive treatment. Imatinib diarrhea is not very common.
2, edema: diuretics, supportive therapy under the guidance of a doctor. Edema is the most common toxic reaction to imatinib, mainly in the face. Mild edema does not need to be treated.
3. Fluid retention (pleural effusion, pericardial effusion, edema and ascites): take diuretics, supportive therapy, medication reduction, and interruption of medication under the direction of a physician. Consider echocardiography to detect LVEF (left ventricular ejection fraction).
4. Gastrointestinal reactions: take the drug with a meal and deliver it with a large glass of water. After taking the drug, when the appetite is difficult, you can eat some snacks and drink some cola to help relieve.
5. Muscle cramps: calcium supplementation, sports drinks. This is the more common toxic side effects.
6. Skin rash: local or systemic application of steroid hormones, drug reduction, interruption or discontinuation of medication.
Third, non-hematological toxicity
1. Degree 3: Apply the specific interventions mentioned above. If symptomatic treatment is ineffective, treat according to degree 4 toxicity.
2. Degree 4: Suspend medication until symptoms return to degree 1 or better, then consider restarting treatment with a dose reduction of 25% to 33% (no less than 300 mg). Switch to dasatinib or bosutinib.
IV. Non-hematologic toxicity —- liver
At ≥2 degrees, suspend dosing until symptoms return to ≤1 degree. Reduce dose by 25% to 33% (no less than 300 mg) to restart therapy. Evaluate other drugs with possible hepatotoxicity, including acetaminophen. Consider switching to dasatinib or bosutinib.