6-MP (6-mercaptopurine) in the Treatment of Childhood Acute Leukemia

6-MP (6-mercaptopurine) is one of the basic components of standard chemotherapy protocols in the treatment of Childhood Acute Lymphoblastic Leukemia (ALL). It plays an important role especially in the maintenance treatment phase. The basic properties of the drug are as follows:

🔬 1. Mechanism of Action:

6-Mercaptopurine (6-MP) is a purine analog antimetabolite. It interferes with DNA and RNA synthesis, especially in rapidly dividing leukemic cells.

It is converted inside the cell into active metabolites such as:
6-thioguanine nucleotide (6-TGN) and methyl-mercaptopurine nucleotide (MeMPN)
These metabolites integrate into DNA and promote apoptosis.
It is particularly effective during the S phase of the cell cycle (DNA synthesis).

💊 2. Treatment Phase Involved:

6-MP is mainly used during the maintenance phase of treatment.
It is administered orally, daily, often in combination with methotrexate.
The maintenance phase usually lasts 2–3 years, aiming to prevent relapse.

🧬 3. Pharmacogenetics and Dose Adjustment:

TPMT (thiopurine S-methyltransferase) and NUDT15 gene polymorphisms influence toxicity risk.
Genetic testing is recommended before initiating therapy.
- Low TPMT activity → higher risk of myelosuppression.
- In such cases, dose reductions are necessary.

⚠️ 4. Side Effects:

Myelosuppression (most common – neutropenia, anemia, thrombocytopenia)
Hepatotoxicity (elevated liver enzymes, rarely jaundice)
Nausea, vomiting, appetite loss
Rare: pancreatitis, hypersensitivity reactions

🧪 5. Monitoring and Follow-up:

Regular CBC (Complete Blood Count) and Liver Function Tests (LFTs) are essential.
In some centers, active metabolite levels (e.g., 6-TGN) are also monitored.
Dose adjustments are made based on neutrophil count and liver function status.

📚 6. Place in Clinical Guidelines:

Included in international protocols such as ALL-BFM, COG, CCLG, UKALL, etc.
Standard combination: Methotrexate + 6-MP + Prednisone for long-term maintenance.