Hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia in the context of acute kidney injury give concern for spontaneous TLS. Coagulation parameters including prothrombin time PT , partial thromboplastin time PTT and international normalized ratio INR should similarly be assessed to evaluate for signs of DIC, which may be present at the time of diagnosis. Liver function tests LFTs should be assessed primarily, as liver function may have implications for chemotherapeutic agents available for treatment.
Most patients with AML should have a chest radiograph in order to assess for signs of pneumonia. Given the functional neutropenia even in the absence of low absolute neutrophil count ANC , the diagnostic possibilities for infiltrates are broad and include fungal or other atypical pathogens. Symmetric, bilateral infiltrates, particularly in individuals with very high white counts and hypoxia, should prompt concerns for leukostasis syndrome in the lungs.
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Echocardiogram should be obtained soon after diagnosis as for patients eligible for aggressive treatment; anthracyclines are a preferred agent and echocardiographic assessment is key to proceeding with these agents. Prior to any chemotherapy or disease specific therapy, however, patients must undergo stabilization. In the context of hyperleukocytosis, cytoreduction may be pursued with hydroxyurea, but only under the supervision of a hematologist. Patients with severe leukocytosis and immediate neurologic or pulmonary compromise may need urgent cytoreduction with leukapheresis.
Aside from assessment of kidney and liver function, echocardiogram should be performed to assess ejection fraction, as this is necessary to treat with anthracycline crucial to the initiation of therapy in those eligible for aggressive management. Finally, most candidates for initial therapy should have central venous access obtained prior to chemotherapy and likely therapy induced neutropenia and thrombocytopenia.
The preferred type of central access is somewhat institution dependent and should ideally be chosen in consultation with the primary hematologist who will manage the patient in the long term. This is due to both more treatment resistant disease and poorer tolerance of aggressive therapy.
Acute Myeloid Leukemia (AML) in Children
Now there is broad if not uniform agreement that patients over age 65 with no comorbidities and generally good organ function may benefit from aggressive induction and that those previous mortality rates likely no longer hold true with better supportive care. For patients of greater ages or with comorbidities there have been considerable efforts to develop new agents or use alternative agents. This management would fall to hematologist consultation.
This typically includes empiric treatment with a broad-spectrum beta lactam with broad gram negative including anti-pseudomonal activity. Cefepime and ceftazidime are the most commonly used agents, though pipercillin-tazobactam or carbapenems are also reasonable with aztreonam typically used for patients with true, severe penicillin allergies. Gram positive activity with vancomycin should be provided for individuals with signs of redness or inflammation around indwelling lines, severe mucositis, pulmonary infiltrates, or any risk factors for gram positive infection, and for individuals who remain neutropenic and fail to defervesce after hours of broad gram negative coverage.
Finally, patients with new diagnoses of AML may present with fungal mold infections in the context of functional neutropenia.
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Aspergillus infection is associated with the highest mortality and is of particular concern with individuals with atypical pulmonary infiltrates and may prompt empiric treatment with voriconazole, posaconazole, or echinocandins depending on formulary and protocol issues. Diagnostic work-up should not postpone therapy but should include blood and urine cultures as well as chest radiograph to look for sources of infection. The use of growth factors to improve counts has been debated but is currently not recommended for individuals who will receive aggressive chemotherapy for their malignancy.
The Infectious Diseases Society of America IDSA guidelines recommend narrowing therapy if a presumptive source is identified and that in stable patients without a clear source of infection who have no gram-positive organisms in culture at 48 hours, vancomycin can be discontinued. Otherwise antibiotics should be continued until neutropenia resolves.
TLS is a metabolic syndrome associated with rapid tumor cell breakdown and release of intracellular electrolytes causing metabolic, renal, neurological, and cardiac toxicity. TLS consists of a combination of high potassium and phosphate with low calcium as well as high uric acid and increased creatinine.
Hyperkalemia should be managed as with primary hyperkalemia. Patients should be monitored on telemetry until the potassium has normalized. Hydration is the mainstay of TLS prophylaxis with the use of loop diuretics to maintain urine output should it be inadequate in a well hydrated patient. Aside from this and managing other elecrolyte abnormalities the primary concern is for urate nephropathy, which can cause acute renal failure and ultimately lead to end stage renal disease. Allopurinol was long the mainstay of uric acid lowering therapy and should be used unless there is a clear contraindication.
The addition of rasburicase, a highly effective but expensive recombinant urate oxidase, to the therapeutic armamentarium has made the aggressiveness with which to pursue prophylaxis a major issue. This has led to dedicated efforts to come up with a risk stratification system to help determine how aggressively patients should be pretreated and how often they need to be monitored.
High-risk patients require rasburicase prophylactically and monitoring every hours. Moderate risk patients should receive alopurinol and times daily checks of electrolytes and low risk patients can likely be treated with hydration alone. Patients are typically transfused in order to maintain safe platelet and red blood cell RBC counts. The bleeding patient or patient with symptomatic anemia should be transfused to correct their current symptomatology regardless of transfusion thresholds.
All patients should be transfused leukoreduced, irradiated products if available to reduce the risk of RBC sensitization and prevent transfusion associated GVHD respectively. This is thought to be due to the release of proteolytic enzymes as cells and granule lysis causing microvascular damage and activation of the clotting cascade. Fibrinogen of less than should trigger treatment with cryoprecipitate in order to reach a level of more than Platelets and fresh frozen plasma FFP should be transfused for bleeding patients with platelet counts less than 50 and INR greater than 2 respectively.
For patients with APML, bleeding diathesis continues to be a major cause of early death and previously led to high rates of mortality in induction or prior to induction. This danger is dramatically reduced with prompt treatment with differentiation therapy ATRA or more recently arsenic trioxide , which helps maturation of the neoplastic promyelocyte and reverses the coagulopathy.
Hyperleukocytosis also increases the odds of spontaneous TLS and the number of blasts contributing to the uric acid load.
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This does, however, require the placement of a large central catheter for pheresis posing risks of bleeding and infection and data regarding actual mortality benefit has not been shown. All patients with hyperleukocytosis should also receive hydration, allopurinol, and almost always rasburicase for tumor lysis prophylaxis.
Exam during initial management should be focused on assessing complications of therapy and disease.
Daily evaluation for signs of bleeding used with the platelet count will help target platelet goals to stop further bleeding. Careful monitoring for localized signs of infection and or sources of infection which may precipitate broadening of coverage i. Daily weights and exam to assess volume status, particularly in the acute setting, can be crucial.
Patients with hyperleukocytosis receiving hydroxyurea for cytoreductions should receive at least twice daily CBCs to assess response to therapy and assure the WBC count is declining as well as to monitor results of transfusions. TLS and renal failure similarly require at least times daily assessment of electrolytes to assure hyperkalemia and hyperuricemia are not worsening, contributing to possible further cardiotoxicity or nephrotoxicity respectively. Patients with APML treated with ATRA or arsenic trioxide may develop a differentiation syndrome associated with rapid transition from promyeloblasts to mature promeylocytes.
This syndrome is associated with respiratory distress, increasing WBC count, pulmonary infiltrates, fever, weight gain, and less commonly effusions, hypotension and renal failure.
Management is with discontinuation of ATRA and glucocorticoids. Mortality without these management steps is high. Generally, ATRA will only be given under subspecialty guidance and this is unlikely to be an issue for the lone hospitalist. Significant renal or hepatic dysfunction in particular will usually exclude an individual from consideration of stem cell transplant, which may be the only curative option for a particular leukemia. Renal insufficiency predisposes patients to more severe and less reversible kidney dysfunction than TLS.
This may lead to a more aggressive approach to alkalinization and earlier use of rasburicase.
Monitoring fluid status throughout chemotherapeutic treatment is crucial, and chemotherapeutic agents will need to be renally dosed. Liver disease and resulting coagulopathy may affect assessment of coagulopathy associated with malignancy. The most feared toxicity of anthracyclines is cardiotoxicity and reduction of the ejection fraction EF. This is related to lifetime dose and thus a diminished EF is not an absolute contraindication to treatment with anthracyclines but may raise concern due to decreased reserve.
All patients treated with anthracyclines undergo sequential echocardiograms to monitor EF. Many chemotherapeutic agents are given with large fluid volumes to minimize side effects and toxicity and this must be monitored closely in the context of systolic or diastolic dysfunction. Patients with active coronary artery disease CAD are often transfused to a higher threshold of hematocrit typically 25 given the concern for hypoperfusing at risk areas. Continued clopidogrel and aspirin in those with fresh coronary artery stents in the context of thrombocytopenia and bleeding risk is without clear guidelines.
Often higher platelet counts will be aimed for in order to prevent bleeding in patients whose antiplatelet agents cannot be stopped. Most chemotherapeutic regimens are given with glucocorticoids to minimize nausea. This will often cause increased blood glucose values. American Cancer Society Also in Spanish. Diagnosis and Tests. National Heart, Lung, and Blood Institute. Prevention and Risk Factors. Treatments and Therapies.enter site
Acute myeloid leukemia - Wikipedia
Statistics and Research. Clinical Trials. Article: Clinician-friendly reports of molecular measurable residual disease monitoring in acute promyelocytic Acute Myeloid Leukemia -- see more articles. Post-remission therapy aims to destroy any leukemic cells that may still linger. This involves high doses of chemotherapy. Chemotherapy is effective for most patients with AML, but prognosis depends on other factors, too, such as age and genetic traits.
AML normally only recurs while the patient is in treatment or shortly after the completion of chemotherapy. It is rare for the disease to recur after AML has been absent from the body for a long time. Diagnostic investigations should continue every few months for several years following treatment to rule out recurrence and identify any potential side effects from the chemotherapy.
Without treatment, the life expectancy after diagnosis stands at an average of around 8 months. If a policy covers cancer treatment, this should include leukemia treatment. Article last updated on Mon 10 April Visit our Leukemia category page for the latest news on this subject, or sign up to our newsletter to receive the latest updates on Leukemia. All references are available in the References tab.
Acute myeloid leukaemia. Acute myeloid leukemia AML. Adult acute myeloid leukemia treatment PDQ : Health professional version. Disease overview. El Rassi, F. Update on optimal management of acute myeloid leukemia. Clinical Medicine Insights 7 Gundestrup, M.