Complications
An oncological emergency requiring immediate management.
TLS is characterised by hyperkalaemia, hyperphosphataemia, hyperuricaemia, hypocalcaemia, and/or elevated serum lactate dehydrogenase, which can occur following treatment (including chemotherapy and targeted agents e.g., venetoclax) or spontaneously (rare), particularly if white blood cell (WBC) count (tumour burden) is high.
TLS can lead to cardiac arrhythmias, seizures, acute renal failure, and death, if untreated.
Vigorous hydration (with intravenous fluids), phosphate-binding agents, and hypouricaemic agents (e.g., allopurinol or rasburicase) should be used to prevent or treat TLS.
TLS associated with venetoclax may occur as early as 6 to 8 hours following the first dose in patients with AML.[93] TLS risk assessment should be carried out before administering venetoclax, and guidance on TLS prophylaxis, laboratory monitoring, dose titration, and drug interactions should be strictly adhered to during treatment with venetoclax.[39][93]
A life-threatening complication that may occur if white blood cell (WBC) count is extremely elevated (>100 × 10⁹/L [>100,000/microlitre]).
Symptoms of leukostasis include respiratory distress and altered mental status, caused by leukaemia cells impairing microvascular perfusion in pulmonary and central nervous system tissue, respectively.
In AML patients with hyperleukocytosis, hydroxycarbamide is recommended for leukoreduction.[24][39] It is recommended that WBC count is lowered to <25 × 10⁹/L (<25,000/microlitre), particularly before initiating treatment with hypomethylating agents and venetoclax.[24][39]
In APL patients, hydroxycarbamide should be considered to manage high WBC count during treatment with all-trans-retinoic acid (ATRA; also known as tretinoin) and arsenic trioxide (particularly if differentiation syndrome occurs).[39][117]
Urgent leukapheresis may be considered in a symptomatic patient with AML and a very high WBC count; however, this is not recommended in patients with acute promyelocytic leukaemia (APL) because leukapheresis may worsen coagulopathy.[39]
Consequence of bone marrow infiltration by leukaemic cells and of adverse effects of treatment.
Platelets should be prophylactically transfused once the thrombocyte count is <10 × 10⁹/L (<10,000/microlitre). Platelet count needs to be maintained at >50 × 10⁹/L (>50,000/microlitre) in patients with APL or those with significant bleeding.[39][117]
Packed red bood cell transfusion is recommended to keep haematocrit >25%.
Most infections are caused by gram-negative bacteria, gram-positive bacteria (mostly staphylococci), and, less commonly, invasive fungal and viral infections.
During acute illness and chemotherapy, all patients should receive antibiotic prophylaxis (e.g., a fluoroquinolone) to reduce the risk of infection and febrile neutropenia.[127] Patients should also receive antifungal prophylaxis with a mold-active antifungal agent (e.g., posaconazole).[127]
Other measures to reduce the risk of febrile neutropenia such as body hygiene, germ-reduced food, and reverse isolation or high-efficiency particulate air filtration are indicated.
Patients presenting with febrile illness need to be investigated and treated appropriately and promptly with antibiotics or anti-infective agents.
DIC is frequently present at diagnosis or occurs soon after APL patients commence chemotherapy. It occurs less commonly with monocytic AML.
Requires emergency management. If left untreated, it results in high-risk of haemorrhagic death. The induction of tumour cell differentiation with all-trans-retinoic acid (ATRA; also known as tretinoin) and supportive therapy with appropriate blood products can lead to a rapid reversal of the coagulopathy.
AML rarely involves the CNS in adult patients, but may be more common in paediatric AML patients.
Incidence of CNS leukaemia has decreased since the incorporation of cytarabine.[153]
Patients at high-risk for CNS disease include those with elevated white blood cell (WBC) count (>40 × 10⁹/L [>40,000/microlitre]), monocytic lineage, mixed-phenotype acute leukaemia, extramedullary disease, FLT3 mutations, or high-risk acute promyelocytic leukemia (APL).[39]
Morphological and flow cytometric examination of the cerebrospinal fluid confirms the diagnosis.
Treated with intrathecal cytarabine or methotrexate.
Treatments for AML (e.g., ivosidenib, enasidenib, olutasidenib, gilteritinib) and acute promyelocytic leukaemia (APL; e.g., all-trans-retinoic acid [ATRA; also known as tretinoin], arsenic trioxide) can cause differentiation syndrome, which can be life-threatening if not treated promptly.[102][112][125][126]
Differentiation syndrome is characterised by fever, fluid retention, respiratory distress, pulmonary infiltrates, pulmonary or pericardial effusion, and an elevated white blood cell (WBC) count (>10 × 10⁹/L [>10,000/microlitre]).
Patients should be monitored for hypoxia, pulmonary infiltrates, and pleural effusion.
Patients with differentiation syndrome should be promptly treated with dexamethasone.[117]
In severe cases, the drug causing differentiation syndrome may be temporarily discontinued until symptoms resolve.[117]
Long-term complications of chemotherapy include myelodysplasia, secondary malignancies, endocrine dysfunction (mainly hypothyroidism), and cardiomyopathy. Investigations are instigated on suspicion.
Infertility may be an issue for younger patients treated for AML, and they should be referred to specialised fertility/assisted conception units.
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