Specific toxicities
| Toxicity . | Etiology/risk factors . | Management . |
|---|---|---|
| At presentation | ||
| Fever | Usually disease related and resolves on initiation of ALL therapy | Infection screen |
| May be caused by infection (impossible to distinguish from disease related and may be present as a result of neutropenia and immune dysregulation) | Broad spectrum antibiotics until fever resolved and infection excluded | |
| Hypoxia in vital organs as a result of increased blood viscosity and microvasculature damage | Maintain euvolemia | |
| Leucostasis | More likely in infants, males, high white count, T-cell disease, and KMT2A or BCR-ABL rearrangements | Avoid red cell transfusions until white count reduced |
| Platelet transfusion to reduce risk of CNS bleeding | ||
| Early cytoreduction (steroids with or without vincristine) | ||
| Management of concomitant tumor lysis or sepsis | ||
| Leucopheresis no longer generally used | ||
| Beware: pseudohyperkalemia | ||
| Sudden tumor cell death with release of intracellular cytokines | Hyperhydration | |
| TLS | ||
| More likely in those with preexisting renal impairment or high tumor burden | Correction of metabolic abnormalities | |
| Management of seizures, arrhythmias, and renal insufficiency | ||
| Prevention: Allopurinol if white count <100 × 109/L, Raspuricase if white count >100 × 109/L (beware: check G6PD) | ||
| Nurse in semiupright position | ||
| Compression of superior vena cava and/or large airways | Mediastinal mass composed of blasts, primarily seen in T-cell ALL | Avoid imaging requiring the patient to lay flat, because this may result in cardiac arrest |
| Immediate administration of corticosteroids and early initiation of chemotherapy | ||
| Disseminated intravascular coagulation | Rapid release of procoagulants resulting in uncontrolled systemic activation of coagulation pathways; this may cause (1) microvascular thrombosis and multiorgan dysfunction and (2) hemorrhage because of consumption of clotting factors and platelets | Initiation of all chemotherapy |
| Replacement of coagulation factors (eg, fibrin concentrate, fresh frozen plasma) if there is bleeding and to cover procedures (eg, bone marrow biopsy, lumbar punctures) | ||
| Management of thrombosis is rarely required (eg, LMWH) | ||
| During chemotherapy | ||
| Infection | Down syndrome, age (infants and adolescents at higher risk than children ages 1-9 y), female sex, higher-intensity regimens, failure to achieve neutrophilia after dexamethasone pulses, and white race | Early recognition of sepsis, rapid access to expert care, and early institution of antimicrobials |
| Intravenous immunoglobulin may be considered for those with hypogammaglobulinemia or recurrent infections | ||
| Mechanism poorly understood? CNS folate homeostasis disruption | Supportive care with control of seizures, correction of electrolytes, maintenance of airway | |
| Methotrexate encephalopathy | More common with children >10 y, more intensive regimes, concomitant administration of cyclophosphamide and cytarabine | Exclude CNS thrombosis, hemorrhage, or infection |
| Folinica acid, aminophylline, or dextromethorphan may be effective in severe cases | ||
| Reexposure to methotrexate safe >80% but avoid concomitant administration with cyclophosphamide or cytarabine | ||
| LMWH | ||
| Caution around procedures | ||
| Thrombosis | Prothrombotic state because of a combination of the leukemia itself, host factors, and exposure to asparaginase; other risk factors include increasing age, presence of a central venous catheter, concomitant administration of anthracycline and prednisolone, and inherited thrombophilic syndromes | Reexposure to asparaginase is safe once thrombosis symptoms have resolved and the patient is fully anticoagulated |
| Insufficient evidence currently exists for thromboprophylaxis in newly diagnosed patients | ||
| Deferring insertion of a central venous catheter until the end of induction should be considered where possible | ||
| Pathophysiology is unknown | Fluid resuscitation, analgesia, and antibiotics for infected pancreatic necrosis ? Octreotide to reduce pancreatic inflammation | |
| Pancreatitis | Asparaginase is the primary etiology | |
| Higher cumulative dose or duration of asparaginase exposure, older age, concomitant steroid and anthracycline administration, severe hypertriglyceridemia, and genetic predisposition (RGS6, UKL2, ASNS, and CPA2 genes) | ||
| Pathophysiology unknown | Supportive care, including careful fluid balance (to prevent fluid overload but ensuring adequate intravascular volume to prevent renal injury), small volume ascetic taps, hemodialysis, intensive care unit support | |
| Veno-occlusive disease (VOD) of the liver (sinusoidal obstruction syndrome) | Risk factors include thiopurine exposure, thiopurine methyltransferase polymorphisms, hemopoietic stem cell transplantation | Defibrotide |
| Small hepatic vessel thrombi classically lead to acute VOD with painful hepatomegaly, ascites, hyperbilirubinemia, thrombocytopenia, multiorgan failure, and a high risk of mortality | ||
| The use of thiopurines may result in chronic veno-occlusive disease, which presents with disproportionate thrombocytopenia and evidence of chronic portal hypertension | ||
| Pathophysiology is unknown | Supportive care with intravenous fluids, parenteral nutrition, gut rest, correction of electrolyte imbalance, analgesia, and broad spectrum antibiotics | |
| Neutropenic enterocolitis (typhlitis) | Transmural inflammation primarily of the cecum; the ascending and transverse colon may also be involved | Omit chemotherapy and consider the use of granulocyte colony stimulating factor (GCSF) |
| The role of surgery is controversial and generally avoided unless typhlitis is complicated (eg, by perforation, bowel necrosis, uncontrolled bleeding, or abscess formation) |
| Toxicity . | Etiology/risk factors . | Management . |
|---|---|---|
| At presentation | ||
| Fever | Usually disease related and resolves on initiation of ALL therapy | Infection screen |
| May be caused by infection (impossible to distinguish from disease related and may be present as a result of neutropenia and immune dysregulation) | Broad spectrum antibiotics until fever resolved and infection excluded | |
| Hypoxia in vital organs as a result of increased blood viscosity and microvasculature damage | Maintain euvolemia | |
| Leucostasis | More likely in infants, males, high white count, T-cell disease, and KMT2A or BCR-ABL rearrangements | Avoid red cell transfusions until white count reduced |
| Platelet transfusion to reduce risk of CNS bleeding | ||
| Early cytoreduction (steroids with or without vincristine) | ||
| Management of concomitant tumor lysis or sepsis | ||
| Leucopheresis no longer generally used | ||
| Beware: pseudohyperkalemia | ||
| Sudden tumor cell death with release of intracellular cytokines | Hyperhydration | |
| TLS | ||
| More likely in those with preexisting renal impairment or high tumor burden | Correction of metabolic abnormalities | |
| Management of seizures, arrhythmias, and renal insufficiency | ||
| Prevention: Allopurinol if white count <100 × 109/L, Raspuricase if white count >100 × 109/L (beware: check G6PD) | ||
| Nurse in semiupright position | ||
| Compression of superior vena cava and/or large airways | Mediastinal mass composed of blasts, primarily seen in T-cell ALL | Avoid imaging requiring the patient to lay flat, because this may result in cardiac arrest |
| Immediate administration of corticosteroids and early initiation of chemotherapy | ||
| Disseminated intravascular coagulation | Rapid release of procoagulants resulting in uncontrolled systemic activation of coagulation pathways; this may cause (1) microvascular thrombosis and multiorgan dysfunction and (2) hemorrhage because of consumption of clotting factors and platelets | Initiation of all chemotherapy |
| Replacement of coagulation factors (eg, fibrin concentrate, fresh frozen plasma) if there is bleeding and to cover procedures (eg, bone marrow biopsy, lumbar punctures) | ||
| Management of thrombosis is rarely required (eg, LMWH) | ||
| During chemotherapy | ||
| Infection | Down syndrome, age (infants and adolescents at higher risk than children ages 1-9 y), female sex, higher-intensity regimens, failure to achieve neutrophilia after dexamethasone pulses, and white race | Early recognition of sepsis, rapid access to expert care, and early institution of antimicrobials |
| Intravenous immunoglobulin may be considered for those with hypogammaglobulinemia or recurrent infections | ||
| Mechanism poorly understood? CNS folate homeostasis disruption | Supportive care with control of seizures, correction of electrolytes, maintenance of airway | |
| Methotrexate encephalopathy | More common with children >10 y, more intensive regimes, concomitant administration of cyclophosphamide and cytarabine | Exclude CNS thrombosis, hemorrhage, or infection |
| Folinica acid, aminophylline, or dextromethorphan may be effective in severe cases | ||
| Reexposure to methotrexate safe >80% but avoid concomitant administration with cyclophosphamide or cytarabine | ||
| LMWH | ||
| Caution around procedures | ||
| Thrombosis | Prothrombotic state because of a combination of the leukemia itself, host factors, and exposure to asparaginase; other risk factors include increasing age, presence of a central venous catheter, concomitant administration of anthracycline and prednisolone, and inherited thrombophilic syndromes | Reexposure to asparaginase is safe once thrombosis symptoms have resolved and the patient is fully anticoagulated |
| Insufficient evidence currently exists for thromboprophylaxis in newly diagnosed patients | ||
| Deferring insertion of a central venous catheter until the end of induction should be considered where possible | ||
| Pathophysiology is unknown | Fluid resuscitation, analgesia, and antibiotics for infected pancreatic necrosis ? Octreotide to reduce pancreatic inflammation | |
| Pancreatitis | Asparaginase is the primary etiology | |
| Higher cumulative dose or duration of asparaginase exposure, older age, concomitant steroid and anthracycline administration, severe hypertriglyceridemia, and genetic predisposition (RGS6, UKL2, ASNS, and CPA2 genes) | ||
| Pathophysiology unknown | Supportive care, including careful fluid balance (to prevent fluid overload but ensuring adequate intravascular volume to prevent renal injury), small volume ascetic taps, hemodialysis, intensive care unit support | |
| Veno-occlusive disease (VOD) of the liver (sinusoidal obstruction syndrome) | Risk factors include thiopurine exposure, thiopurine methyltransferase polymorphisms, hemopoietic stem cell transplantation | Defibrotide |
| Small hepatic vessel thrombi classically lead to acute VOD with painful hepatomegaly, ascites, hyperbilirubinemia, thrombocytopenia, multiorgan failure, and a high risk of mortality | ||
| The use of thiopurines may result in chronic veno-occlusive disease, which presents with disproportionate thrombocytopenia and evidence of chronic portal hypertension | ||
| Pathophysiology is unknown | Supportive care with intravenous fluids, parenteral nutrition, gut rest, correction of electrolyte imbalance, analgesia, and broad spectrum antibiotics | |
| Neutropenic enterocolitis (typhlitis) | Transmural inflammation primarily of the cecum; the ascending and transverse colon may also be involved | Omit chemotherapy and consider the use of granulocyte colony stimulating factor (GCSF) |
| The role of surgery is controversial and generally avoided unless typhlitis is complicated (eg, by perforation, bowel necrosis, uncontrolled bleeding, or abscess formation) |