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Treatment and the treatment process

Alkylating agents

Alkylating agents are one of the oldest groups of chemotherapy. In leukemia they are used in ALL protocols, in CLL and before stem cell transplants.

Last updated: ~2 min read
On a dark navy background, the two strands of a DNA helix held together by small golden clasps.
Figure 1.An alkylating agent binds DNA’s two strands together.

01Short answer

Alkylating agents attach small chemical groups (alkyl groups) to DNA and "stitch" its two strands together. Such DNA cannot unwind or be copied, so the cell cannot divide and dies. They work in any phase of the cell cycle. The ones most used in leukemia are cyclophosphamide (ALL protocols, transplant preparation, some post-transplant regimens), bendamustine and chlorambucil (formerly widely used in CLL, now less so), busulfan and melphalan (conditioning before transplant), ifosfamide (some relapse regimens) and thiotepa (transplant). The main side effects are low blood counts, nausea, hair loss, effects on fertility and a slightly higher risk of a second blood cancer many years later.

02Simple explanation

Stitching. The drug links DNA’s two strands together.

The result. The cell cannot unwind its DNA and divide.

Where? In ALL, CLL and before transplant.

Protection. Plenty of fluids and sometimes a bladder-protecting drug are given.

03Scientific explanation

Mechanism: electrophilic alkyl groups bind the N7 atom of guanine, creating inter-strand and intra-strand cross-links; the action is not cycle-specific (NCI, ACS).

Specific toxicities: acrolein, a breakdown product of cyclophosphamide and ifosfamide, can irritate the bladder (haemorrhagic cystitis) — prevented with plenty of fluids and mesna; ifosfamide can cause encephalopathy, and busulfan seizures (prevention is given) and veno-occlusive disease of the liver.

Long-term risks: reduced fertility (depending on dose and age), therapy-related myelodysplasia and AML (usually after 5–10 years) and lung fibrosis (busulfan). This is part of follow-up after treatment.

04What happens in the body?

How does it work?

Picture DNA as a two-sided zip. An alkylating agent fastens the zip’s teeth together so it can no longer open. A cell that wants to divide cannot get past this block.

Before a transplant

High doses of busulfan, melphalan, cyclophosphamide or thiotepa "clear" the marrow for new stem cells and weaken the immune system so the donor cells can take. This is called conditioning.

Under a dark navy sky, a field of light is cleared and new golden seeds of light are planted.
Figure 2.Conditioning makes room in the marrow for new cells.

Protecting the bladder

With high-dose cyclophosphamide and with ifosfamide, plenty of fluids and a drug called mesna are given. You are advised to pass urine often and not hold it in.

A translucent bladder shape with a steady clear teal stream of light flowing through it.
Figure 3.Plenty of fluids protects the bladder.

05Treatment with an alkylating agent

A simplified outline.

Preparation — Fertility talk, tests.1PreparationFertility talk, tests.
Fluids — Plenty; sometimes mesna.2FluidsPlenty; sometimes mesna.
Giving — Drip or tablets.3GivingDrip or tablets.
Follow-up — Blood, urine, long term.4Follow-upBlood, urine, long term.
Strong effectNot phase-dependent.
ProtectionBladder and organs.
The futureFertility and follow-up.

06Alkylating agents in leukemia

DrugWhereWatch for
CyclophosphamideALL, transplantBladder, fluids
BendamustineCLL (selected cases)Rash, infections
ChlorambucilCLL (now rare)By mouth
BusulfanBefore transplantSeizure prevention, liver
MelphalanBefore transplantMucositis
Ifosfamide, thiotepaRelapse, transplantNervous system and bladder monitoring

* Your doctor sets the drug and amount according to the protocol.

07Key terms

Alkylating agent
A drug that attaches an alkyl group to DNA.
Cross-link
DNA strands bound together.
Conditioning
High-dose treatment before a transplant.
Haemorrhagic cystitis
Bleeding inflammation of the bladder.
Mesna
A drug that protects the bladder.
Second cancer
A new cancer arising years after treatment.

08Key points

  • Alkylating agents "stitch" DNA.
  • They work in any phase of the cycle.
  • They are widely used before transplant.
  • Plenty of fluids protects the bladder.
  • Discuss fertility beforehand.
  • Long-term follow-up matters.

09Frequently asked questions

Why drink so much?

Fluids flush the drug’s harmful products out of the bladder faster.

Will I be able to have children?

It depends on the drug, the amount and your age; ask about fertility preservation before treatment.

Is the risk of a second cancer high?

The risk is low but real; the benefit of treatment is usually far greater.

Will my hair fall out?

For many people, yes, especially at high doses; usually temporarily.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Why drink so much?

  2. Will I be able to have children?

  3. Is the risk of a second cancer high?

  4. Will my hair fall out?

My questions

12Sources

  1. National Cancer Institute (NCI). Chemotherapy to Treat Cancer
  2. American Cancer Society. How Chemotherapy Drugs Work
  3. Cancer Research UK. Chemotherapy
  4. MedlinePlus. Cancer Chemotherapy
  5. MedlinePlus. Cyclophosphamide
  6. MedlinePlus. Bendamustine injection
  7. MedlinePlus. Acute lymphocytic leukemia (ALL)
  8. Cancer Research UK. Treatment for chronic myeloid leukaemia (CML)
  9. Leukemia & Lymphoma Society. CML treatment
  10. American Cancer Society. Treating Chronic Lymphocytic Leukemia
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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