A Case of Acute Myeloid Leukemia
Mohana1, Subadhra Devi2, Mahalakshmi3
1Oncology Nurse, Kauvery Hospital, Cantonment
2Nurse Educator Kauvery Hospital, Cantonment
3Nursing Superintendent, Kauvery hospital, Cantonment
Abstract
Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European Leukemia Net expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion–based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all-trans retinoic acid– and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.
Introduction
After the initial therapeutic success reported in 1973 using an anthracycline (daunorubicin), the management and outcome of acute promyelocytic leukemia (APL) has been revolutionized by the introduction of all-trans retinoic acid (ATRA; tretinoin) and arsenic trioxide (ATO) in 1988 and 1996, respectively. Multicenter studies over the past 3 decades have demonstrated the efficacy of ATRA plus chemotherapy and, subsequently, of ATRA plus ATO, with or without chemotherapy. However, the optimal management of APL also requires early diagnosis, institution of aggressive supportive measures, appropriate management of treatment-related complications, and monitoring of measurable residual disease (MRD).
In 2009, a detailed list of recommendations for the management of APL was reported by an expert panel on behalf of the European Leukemia Net (ELN). Since then, several studies have provided important insights about frontline therapy. In particular, 2 large randomized trials exploring the role of ATO have established a new standard of care in this setting. Based on the results of these studies, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recently approved ATO for the treatment of newly diagnosed patients with low-to-intermediate risk APL (defined as white blood cell [WBC] count ≤10 × 109/L). This review will address this and other recent advances.
Case Presentation
A 44-year-old female, was admitted with complaints of breathlessness on exertion and headache for 2 days, along with a history of menorrhagia, on initial examination, the patient was conscious and oriented. Cardiovascular examination revealed normal heart sounds (S1 and S2), and respiratory examination showed bilateral air entry. Abdominal examination revealed a soft, non-tender abdomen with no organomegaly. Pallor was noted, but there was no evidence of lymphadenopathy.
Laboratory investigations revealed pancytopenia with a normocytic blood picture. The differential count was lymphocyte predominant. Liver and renal function tests were within normal limits, and LDH levels were normal. Peripheral smear revealed the presence of blasts. Further evaluation with peripheral blood immunophenotyping was consistent with acute myeloid leukemia (AML), which was later confirmed through bone marrow aspiration and cytogenetic analysis.
Following the diagnosis, the patient and her family were thoroughly counseled about the nature of the disease, its progression, and the need for immediate treatment. Detailed discussions were held regarding the treatment plan, which included chemotherapy and supportive care measures such as transfusions and infection prophylaxis. The potential complications of therapy—including febrile neutropenia, bleeding, and treatment-related toxicities—were explained clearly. The family was also informed about the estimated costs of treatment, the need for long-term follow-up, and the overall prognosis.
Informed consent was obtained after ensuring that the patient and her family had a comprehensive understanding of the disease, treatment options, associated risks, and financial considerations. The case was managed with a multidisciplinary approach involving hematology, infectious disease specialists, and critical care support.
Treatment Course:
Patient was initiated on the 7+3 induction regimen on 14/08/2023:
Daunorubicin 100 mg IV OD for 3 days (14/08/2023 to 16/08/2023)
Cytarabine 400 mg/day as a continuous 24-hour infusion for 7 days (14/08/2023 to 20/08/2023)
On Day 5 of induction, FISH test revealed (15;17) translocation, hence the 7+3 regimen was discontinued
Patient was started on:
Arsenic trioxide 10 mg/day from 18/08/2023
ATRA (All-trans retinoic acid) 40 mg BD from 28/08/2023
Complications During Hospital Stay:
Developed hematuria, managed with intensive platelet and packed cell transfusions
Had subconjunctival hemorrhage in the left eye
Complained of headache; CT brain revealed left parieto-occipital intracerebral hemorrhage, managed conservatively with platelet support
No deterioration in sensorium or focal neurological deficit observed
RT-PCR for PML-RARA showed BCR1 transcript
Cytogenetics confirmed t (15;17) translocation and trisomy 8
Developed febrile neutropenia, managed with broad-spectrum IV antibiotics
Developed left cheek and neck swelling during neutropenic phase
Fungal infection was suspected and managed with antifungals and antimicrobials
Serum galactomannan was negative; antifungal therapy was stopped
Blood cultures remained sterile
ATRA was held for 6 days due to neutropenia, but restarted after platelet recovery
Patient received a total of 76 units of platelets and 13 units of packed red cells
Coordination of Care
AML is a common hematological malignancy in adults. Despite many advances, the malignancy still carries a poor prognosis. Hence, it is best managed by a multidisciplinary team that includes a hematologist, oncologist. internist, pathologist, and an intensivist. The oncology nurse is vital for treatment administration and monitoring for potential complications. The pharmacist should educate the patient on potential adverse effects of the potent drugs used to treat this malignancy. The primary care physician should educate the patient on personal hygiene, hand washing, and immunization. Overall, the life expectancy has increased slightly but most patients have a markedly shortened lifespan.
Social History
Nil
Past Medical History:
She reported a history of menorrhagia. Her past medical history was significant for hypertension and type 2 diabetes mellitus, both diagnosed three years ago.
Physical Examination:
Patient was conscious and oriented
SpO₂: 98%
Pulse: 90/min
BP: 130/80 mmHg
Heart sounds: S1 and S2 present
Breath sounds: Bilateral air entry present
Abdomen: Soft, no organomegaly
Pallor noted, but no lymphadenopathy or organomegaly
Investigations:
Laboratory evaluation showed pancytopenia with a normocytic blood picture, lymphocyte-predominant differential count, and normal hepatorenal function
LDH was within normal limits
Peripheral smear showed blasts
Bone marrow aspiration confirmed acute myeloid leukemia (AML)
Peripheral blood immunotyping also confirmed AML
The family was counseled regarding the diagnosis, treatment cost, and possible complications
Diagnostic workup and supportive care
| Recommendation | Level of evidence–grade of recommendation | Compared with the 2009 recommendations |
|---|---|---|
| 1.1. Once a diagnosis of APL is suspected, the disease should be managed as a medical emergency | IV–C | Unchanged |
| 1.2. Patients should be managed by an experienced and multidisciplinary team in centers with rapid access to genetic diagnosis, blood products, and specific drugs, such as ATRA, ATO, and chemotherapy | IV–C | Unchanged |
| 1.3. Diagnosis should be confirmed by molecular detection of PML-RARA fusion (or rare molecular variants) | IIa–B | Unchanged |
| 1.4. In addition to FISH, RT-PCR, RQ-PCR, RT-QLAMP, and immunostaining with anti-PML antibody can be used for rapid diagnosis of APL | IIa–B | Updated |
| Management of coagulopathy | ||
| 1.5. Treatment with ATRA should be started immediately when a diagnosis of APL is suspected | Ib–A | Unchanged |
| 1.6. Transfusions of fibrinogen and/or cryoprecipitate, platelets, and fresh-frozen plasma should be given immediately upon suspicion of the diagnosis, and then daily or more than once a day if needed, to maintain the fibrinogen concentration above 100-150 mg/dL, the platelet count above 30 × 10⁹/L to 50 × 10⁹/L, and the INR below 1.5 | IIb–B | Slightly modified |
| 1.7. Platelet counts and routine coagulation parameters, prothrombin time, activated partial thromboplastin time, and thrombin time, as well as levels of fibrinogen and fibrinogen-fibrin degradation products, should be monitored at least daily and more frequently if required, until disappearance of all clinical and laboratory signs of the coagulopathy | IIb–B | New recommendation |
| 1.8. The benefit of heparin, tranexamic acid, or other anticoagulant or antifibrinolytic therapy remains questionable and should not be used routinely outside of the context of clinical trials | IV–C | Unchanged |
| 1.9. Central venous catheterization, lumbar puncture, and other invasive procedures (e.g., bronchoscopy) should be avoided before and during remission induction therapy due to high risk of hemorrhagic complications | IV–C | Unchanged |
| Management of hyperleukocytosis (WBC count >10 × 109/L) at presentation | ||
| 1.10. Cytoreductive chemotherapy should be started without delay, even if the molecular results are still pending: • For patients to be treated with ATRA + chemotherapy, idarubicin or daunorubicin alone or combined with cytarabine should be given • For patients to be treated with ATRA + ATO, cytoreduction can be done with idarubicin (12 mg/m²) or GO (6-9 mg/m²) | IV–C | Updated |
| 1.11. Leukapheresis should be avoided due to risk of precipitating fatal hemorrhage | III–B | Unchanged |
| 1.12. Prophylactic corticosteroids can be given, which may reduce the risk of APL differentiation syndrome | IV–C | Unchanged |
| Management of APL differentiation syndrome | ||
| 1.13. Corticosteroids (10 mg of dexamethasone IV twice daily) should be started immediately at the earliest clinical suspicion of incipient APL differentiation syndrome; once the syndrome has resolved, steroids can be discontinued and ATO/ATRA recommenced | IIa–B | Unchanged |
| 1.14. Temporary discontinuation of differentiation therapy (ATRA or ATO) is indicated only in case of severe APL differentiation syndrome | IIa–B | Unchanged |
| Management of treatment with ATO | ||
| 1.15. An increase of WBC levels above 10 × 10⁹/L after treatment initiation with ATRA and/or ATO should be interpreted as a sign of ATRA/ATO-induced differentiation and should not lead to reclassification of the patient as having high-risk disease | IV–C | New recommendation |
| 1.16. For patients who develop a significant increase of WBC counts after treatment initiation with ATRA and/or ATO, the addition of hydroxyurea (2 g/day) or, in case of extreme hyperleukocytosis, idarubicin (12 mg/m²) or GO (6-9 mg/m²) can be considered | IV–C | New recommendation |
| 1.17. Treatment with ATO should be restricted to cases confirmed to be PML/RARA+ | IIb–B | Unchanged |
| 1.18. Treatment with ATO requires careful monitoring to maintain electrolytes in the normal range, keeping the serum potassium above 4.0 mEq/L and serum magnesium above 1.8 mg/dL | IV–C | Unchanged |
| 1.19. Treatment with ATO requires monitoring of the QT/QTc interval at least twice weekly: • For routine ECG surveillance of QT interval prolongation, alternative rate adjustment formulas other than the classical Bazett correction (e.g., Fridericia, Hodges, or Sagie/Framingham) should be used • Patients with episodes of significant QT prolongation or torsades de pointes, with clinical symptoms, such as dizziness and syncope, or with other risk factors should be closely monitored; telemetered ECG monitoring can be strongly considered in some patients at very high risk • If the QT (or QTc for patients with heart rate >60 beats per minute) interval is prolonged longer than 500 ms, ATO should be withheld, the electrolytes repleted (potassium and magnesium), and other medications that may cause prolonged QTc interval sought and possibly discontinued • Once the QT/QTc returns to ∼460 ms, and the electrolytes are repleted, ATO may be resumed | IV–C | New recommendation |
Table:2 Management during induction, consolidation therapy, and beyond
| Recommendation | Level of evidence–grade of recommendation | Changes compared with the 2009 recommendations |
|---|---|---|
| 2.1. Eligible patients should be offered entry into a clinical trial | IV–C | Unchanged |
| Induction therapy | ||
| 2.2. For patients with a WBC count ≤10 × 10⁹/L, induction therapy should consist of ATRA and ATO without chemotherapy; ATRA and anthracycline–based chemotherapy is a second option when ATO is contraindicated or unaffordable | Ib–A | New recommendation |
| 2.3. For patients with a WBC count >10 × 10⁹/L, there are 2 valid options, either ATRA + ATO with a certain amount of chemotherapy or conventional ATRA + anthracycline–based chemotherapy | Ib–A | New recommendation |
| 2.4. Induction therapy should not be modified based on the presence of leukemia cell characteristics that have variably been considered to predict a poorer prognosis (e.g., secondary chromosomal abnormalities, FLT3 mutations, CD56 expression, and BCR3 PML-RARA isoform) | IIa–B | Unchanged |
| 2.5. Treatment with ATRA should be continued until terminal differentiation of blasts and achievement of CR, which occurs in virtually all patients following conventional ATRA + anthracycline or ATRA + ATO induction treatment | IIa–B | Updated |
| 2.6. Clinicians should refrain from making therapeutic modifications on the basis of incomplete blast maturation (differentiation) detected up to 50 days or more after the start of treatment by morphology or cytogenetic or molecular assessment | IV–C | Unchanged |
| Consolidation therapy | ||
| 2.7. For patients treated with chemotherapy-free approaches, 4 consolidation courses of ATO (0.15 mg/kg/d 5 days/week, 4 weeks on 4 weeks off) and 7 courses of ATRA (45 mg/m²/day for adults; 25 mg/m²/day for children, 2 weeks on 2 weeks off) are recommended | Ib–A | New recommendation |
| 2.8. For patients treated with the conventional ATRA + chemotherapy approach: • 2–3 courses of anthracycline-based chemotherapy should be given for consolidation therapy • The addition of ATRA to chemotherapy in consolidation seems to provide a clinical benefit • Consolidation for high-risk patients younger than 60 years of age with WBC counts >10 × 10⁹/L should include at least 1 cycle of intermediate- or high-dose cytarabine | Ib–A, IIb–B, IIb–B | Slightly modified |
| 2.9. Molecular remission in the bone marrow should be assessed at completion of consolidation by RT-PCR or RQ-PCR assay affording a sensitivity of at least 1 in 10⁴ | IIa–B | Slightly modified |
| Management after consolidation | ||
| 2.10. For patients treated with chemotherapy-free approaches (WBC count ≤10 × 10⁹/L), no maintenance is needed | Ib–A | New recommendation |
| 2.11. For patients treated with conventional ATRA + chemotherapy approaches: maintenance therapy should be used for patients who have received an induction and consolidation treatment regimen wherein maintenance has shown a clinical benefit | Ib–A | Unchanged |
| 2.12. Because early treatment intervention in patients with evidence of MRD affords a better outcome than treatment in hematologic relapse, MRD monitoring of BM every 3 months should be offered to high-risk patients (WBC count >10 × 10⁹/L) for up to 3 years after completion of consolidation therapy; given the very low probability of relapse for non–high-risk patients (WBC count ≤10 × 10⁹/L), prolonged MRD monitoring could be avoided in this setting or carried out using PB | IIb–B | Slightly modified |
| 2.13. Bone marrow generally affords greater sensitivity for detection of MRD than blood and therefore is the sample type of choice for MRD monitoring to guide therapy | IIa–B | Unchanged |
| 2.14. For patients testing PCR+ at any stage following completion of consolidation, it is recommended that a BM is repeated for MRD assessment within 2 weeks and that samples are sent to the local laboratory, as well as to a reference laboratory for independent confirmation | IV–C | Unchanged |
| 2.15. CNS prophylaxis can be considered only for patients with hyperleukocytosis | IV–C | Unchanged |
Nursing Management
- Check labs for coagulation parameters
- Check vitals
- Provide skin protection
- Monitor for infection and sepsis
- Promote normothermia
- Educate the patient and family
- Monitor input and output
- Check if nutrition is sufficient
- Promote hand washing
- Encourage self-care
When To Seek Help
- Fever
- Hypotension
- Bleeding
- LOC
- Altered mental status
- Severe bruising
- Pain
Outcome Identification
- Normal appetite
- Vitals stable
- No signs of infection
- Afebrile
- No pain
Monitoring
- Vitals
- Input and output
- Body weight
- Neurovitals
- Dehydration
- Nutrition
- Signs of infection
Health Teaching and Health Promotion
- Hand washing
- Rinse all fruits and vegetables
- Avoid crowd
- Maintain good personal hygiene
- Follow up with a clinician
- Take medications as prescribed
Discharge Planning
- Hand washing
- Rinse all fruits and vegetables
- Avoid crowd
- Maintain good personal hygiene
- Follow up with clinician
- Take medications as prescribed
- Patient symptomatically better
- Platelet counts are improving
- She is being discharged in stable condition and advised to follow up on an outpatient basis
Conclusion:
She transitioned to ATRA and arsenic trioxide-based therapy. Her hospital course was complicated by intracerebral hemorrhage, hematuria, subconjunctival hemorrhage, febrile neutropenia, and suspected fungal infection, all of which were managed effectively with supportive care including platelet and packed cell transfusions, antimicrobials, and antifungals. She has shown symptomatic improvement, with a rising trend in platelet counts, and no neurological deficits. She is now clinically stable and discharged with instructions for regular outpatient follow-up and continued monitoring.
References
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