Understanding Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is an aggressive and rapidly progressing cancer of the blood and bone marrow, characterized by the uncontrolled proliferation of immature myeloid cells called blasts. The manifestation of AML is quite dramatic, in contrast to Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), which follow a more gradual course. The abnormal cells in AML crowd out healthy blood cells, leading to life-threatening complications including infections, anemia, and bleeding. AML primarily affects older adults, with a median age at diagnosis of around 68 years, though it can occur at any age. 1
The treatment landscape for AML has evolved significantly in recent years, with the introduction of targeted therapies like VENCLEXTA (venetoclax). This BCL-2 inhibitor has revolutionized the management of AML, particularly for elderly patients and those with specific genetic mutations who are ineligible for intensive chemotherapy. 2
Diagnosis of Acute Myeloid Leukemia3
The diagnosis of AML requires a systematic approach involving clinical evaluation, laboratory tests, and advanced molecular studies. The following steps are critical in confirming AML:
1. Clinical Presentation and Initial Evaluation
Patients with AML often present with nonspecific symptoms such as fatigue, fever, unexplained weight loss, and frequent infections due to neutropenia. Bruising or prolonged bleeding may occur due to thrombocytopenia. A thorough medical history and physical examination help identify potential risk factors and guide further testing.
2. Complete Blood Count (CBC) and Peripheral Blood Smear
A CBC typically reveals abnormalities such as:
- Leukocytosis or leukopenia (high or low white blood cell count)
- Anemia: A low red blood cell count .
- Thrombocytopenia: A low platelet count.
- Neutropenia: A low White Blood Cells count.
A peripheral blood smear may show circulating blast cells, which are immature leukemic cells not normally present in the blood.
The presence of ≥20% blasts in the bone marrow is diagnostic for AML.
3. Bone Marrow Aspiration and Biopsy
A bone marrow biopsy is the gold standard for AML diagnosis. It involves extracting a small sample of bone marrow (usually from the hip bone) to assess:
- Blast percentage (≥20% confirms AML), the cellularity of bone marrow (hypercellular marrow is common in AML) and any changes in cell maturation
4. Immunophenotyping and Flow Cytometry
Flow cytometry helps classify AML based on cell surface markers (CD markers). This test distinguishes AML from other leukemias (e.g., acute lymphoblastic leukemia, ALL) and identifies specific subtypes.
5. Cytogenetic and Molecular Testing
Genetic profiling is crucial for risk stratification and treatment selection. Common mutations tested include:
- FLT3-ITD : Associated with poor prognosis
- NPM1: Favorable prognosis if FLT3-negative
- IDH1/IDH2: Targetable with specific inhibitors
- TP53: Indicates high-risk disease
Acute Myeloid Leukemia (AML) in India: Underdiagnosis and Key Challenges
Is AML Underdiagnosed in India? 4, 5
Yes, Acute Myeloid Leukemia (AML) is significantly underdiagnosed in India due to several systemic and socioeconomic factors:
- Many AML symptoms (fatigue, fever, bruising) mimic common infections or nutritional deficiencies, leading to delayed or incorrect diagnoses.
- Primary care physicians, especially in rural areas, may not suspect leukemia, resulting in late referrals to hematologists.
- Bone marrow biopsies, flow cytometry, and genetic testing—essential for AML diagnosis—are often unavailable easily, especially in small towns and rural hospitals.
- Patients must travel to major cities for confirmatory tests, causing delays.
- Many AML patients die undiagnosed or are recorded under nonspecific terms like "blood disorder."
Key Challenges Faced by AML Patients in India 4 ,5
1. Delayed Diagnosis and Advanced Disease at Presentation
- Most patients seek medical help only after severe symptoms (e.g., bleeding, infections), when AML is already aggressive.
- Without early detection, treatment outcomes worsen significantly.
2. Limited Availability of Specialized Care
- Hematologists and oncologists are concentrated in metros; tier-2/3 cities lack specialists.
- Few centers offer stem cell transplants or clinical trials for AML.
3. Shortage of Essential Drugs and Blood Products
- Chemotherapy shortages and platelet/blood transfusions are often delayed due to high demand and donor scarcity.
4. Lack of Genetic Testing and Personalized Medicine
- Many hospitals cannot perform FLT3, IDH, or TP53 mutation testing, leading to suboptimal treatment selection. Without mutation profiling, patients miss out on targeted therapies.
5. Poor Follow-Up and Relapse Management
- Most hospitals providing adequate care are located in the city- patients not living in tier1 cities struggle with long-term follow-up visits, increasing relapse risks.
- Supportive care (antibiotics, antifungals) for immunocompromised patients is often inadequate.
Risk Factors for AML 4,5
Understanding the risk factors for AML is essential for early detection and prevention. Major risk factors include:
1. Age and Genetic Predisposition: Advanced age and inherited syndromes (e.g., Down syndrome, Fanconi anemia)
2. Prior Cancer Treatments: Chemotherapy (alkylating agents, topoisomerase II inhibitors) and Radiation therapy (increases AML risk years after exposure)
3. Hematologic Disorders: Myelodysplastic syndrome (MDS), Myeloproliferative neoplasms (MPN)
4. Environmental and Lifestyle Factors: Benzene exposure (industrial chemicals, cigarette smoke), tobacco use.
First-Line Treatment and Life Expectancy 6
The treatment approach for AML depends on the patient’s age, overall health, and genetic profile.
1. Intensive Chemotherapy: The standard induction regimen is chemotherapy with Cytarabine (Ara-C) for 7 days & Anthracycline (daunorubicin/idarubicin) for 3 days
Patients who achieve remission may undergo consolidation therapy (high-dose cytarabine) or allogeneic stem cell transplant (SCT)for high-risk cases.
2. Non-Intensive Therapies: For patients who cannot tolerate intensive chemotherapy, options include: Hypomethylating agents (azacitidine, decitabine), Low-dose cytarabine (LDAC), and Targeted therapies (e.g., VENCLEXTA + azacitidine)
3. Life Expectancy and Prognosis
Survival rates vary significantly based on risk stratification:
- Favorable-risk AML (e.g., NPM1-mutated, CBF-AML): 5-year survival ~50-60%
- Intermediate-risk AML: 5-year survival ~30-40%
- Poor-risk AML (e.g., TP53-mutated, FLT3-ITD): Median survival
Older patients (>65 years) generally have worse outcomes due to comorbidities and higher-risk mutations.
How Does VENCLEXTA Help in AML? 2, 7
VENCLEXTA is a BCL-2 inhibitor that disrupts cancer cell survival by promoting apoptosis. It is particularly effective in:
- Older/unfit AML patients
- Patients with IDH1/2 mutations
- Relapsed/refractory AML
Venclexta’s Top-notch Mechanism of Action: BCL-2 is an anti-apoptotic protein overexpressed in AML cells. VENCLEXTA binds to BCL-2, releasing pro-apoptotic proteins (BAX, BAK) that trigger cancer cell death. It addresses the problem at its origin and has shown outstanding clinical efficacy and better prognosis.
Is VENCLEXTA a Monotherapy? 2, 7
In Chronic Lymphocytic Leukemia, Venclexta can be used as monotherapy to induce deep cancer remissions.
However, it is not used alone in AML due to limited efficacy as a single agent.
It is combined with:
- Azacitidine or decitabine (preferred for older/unfit patients)
- Low-dose cytarabine (LDAC)
Family Considerations Before Opting for VENCLEXTA 8, 9
Families must evaluate several factors before starting VENCLEXTA:
Side Effects and Monitoring :
- Tumor lysis syndrome (TLS): Venclexta requires hospitalization for initial dosing to monitor for TLS- any signs of TLS are managed with dose adjusting and consistent hydration.
- Cytopenias (low blood cell counts): increased infection/bleeding risk as well as anemia risk.
- Gastrointestinal issues like nausea and diarrhea as well as fatigue and increased risk of infections.
Caregiver Support: Frequent hospital visits for monitoring of AML patients, knowing they may not have much time left, are mentally and physically taxing. Families may benefit from considering emotional and psychological support.
Realistic Expectations: VENCLEXTA improves survival but is not curative for most AML patients. Difficult conversations about palliative care and end-of-life planning may be necessary.
AML Prevalence and Prognosis in India 8, 9, 10
AML accounts for 80-90% of acute leukemias in adults, in India. Incidence is rising due to better diagnostics and an aging population. Challenges remain, as the lack of awareness and limited access to specialized centers lead to delayed diagnoses.
Survival Outcomes in India are lower compared to Western countries, with a 5-year survival rate of ~20-30%. This difference can now be compensated for as targeted therapies like Venclexta make their way into India through Rx4u’s Named Patients Purchase program.
Conclusion and Accessing Venclexta in India
VENCLEXTA has transformed AML treatment, offering hope for older and high-risk patients who previously had limited options. While its combination with other chemotherapies has improved survival, challenges for AML patients in India remain management of side effects, early diagnosis, expanded access to genetic testing, as well as access to Venclexta.
Venclexta is a life-altering drug for AML patients, and can be imported from authorized distributors for Indian patients who can benefit from it, even if the authorized distributors or the pharmaceutical companies are across the globe- Rx4u’s global supply chain network and legal team ensures timely delivery and authentic medications so that you and your loved ones have a better chance at life and health.
Visit https://rx4u.in/ for more information.
Note:
The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment.
References:
2. https://www.venclexta.com/aml
8. https://www.onuregpro.com/assets/commercial/us/onureghcp/en/pdf/aml-caregiver-brochure-Onureg.pdf
