Differentiation Syndrome: What AML Patients on Gilteritinib Need to Watch For

Targeted therapy is different from chemotherapy. Instead of killing cells instantly, Gilteritinib forces leukemia cells to “mature” (differentiate) into normal cells. Sometimes, this process releases a flood of immune substances (cytokines) into the body, leading to a condition called Differentiation Syndrome (DS).

Managing Mild Side Effects at Home

Many common side effects of Gilteritinib are mild and can often be managed with self-care measures at home. Always consult your healthcare team (oncologist, nurse, or pharmacist) before starting any new medication or supplement, even over-the-counter (OTC) products.

Side Effect	Home Management Advice	When to Contact Your Healthcare Team
Fatigue	Pace yourself: Plan activities for when you have the most energy. Take short, frequent naps (no more than 30 minutes). Gentle exercise: Short walks or light movement can sometimes help boost energy.	If fatigue is sudden, severe, or prevents you from performing necessary daily activities.
Nausea (Feeling sick)	Dietary changes: Eat small, frequent meals instead of 2-3 large ones. Avoid spicy, fatty, or strongly scented foods. Take anti-nausea medication as prescribed by your doctor, even if you feel mildly ill (prevention is often easier than treatment).	If nausea lasts more than 48 hours, or if you are vomiting more than once a day.
Diarrhea	Hydration: Drink plenty of clear fluids (at least 6-8 glasses a day, unless advised otherwise) to replace lost fluids. Dietary changes: Avoid artificial sweeteners, caffeine, alcohol, and high-fiber/fatty foods until diarrhea improves. Take anti-diarrhea medication only as prescribed by your healthcare team.
Constipation	Hydration and Fiber: Drink lots of fluids. Increase gentle fiber intake (e.g., fruit, vegetables, wholemeal bread) unless advised otherwise. Gentle exercise (like walking) can help.	If you have not passed stool for over 2 days, or if you have severe abdominal pain.
Muscle/Joint Pain	OTC Pain Relief: You may use Acetaminophen (e.g., Tylenol®) for mild pain, following your healthcare team’s dose limits. Rest/Warmth: Warm baths or gentle stretching may help.	If pain is severe, persistent, or interferes with your daily activities.
Mild Rash/Itching	Use a simple, non-perfumed moisturizer. Avoid irritating clothing or harsh soaps.	If the rash is widespread, blistered, oozing, or if you develop severe itching.
Sore Mouth (Mucositis)	Oral Hygiene: Gently brush your teeth after eating with a soft toothbrush. Rinse your mouth several times a day with a solution of $\frac{1}{4}$ teaspoon baking soda and $\frac{1}{4}$ teaspoon salt in 1 cup of warm water. Avoid hot, spicy, acidic, or crunchy foods.	If you have mouth sores that make it painful to eat, drink, or swallow, or if you suspect an infection.

Recognizing and Responding to Severe Side Effects

Gilteritinib can cause serious, though less common, side effects that require immediate medical attention. It is vital to know the warning signs for these conditions.

IMMEDIATE EMERGENCY: Call Emergency Services or Go to the Nearest Emergency Room

Call your doctor or seek emergency medical help right away if you experience any of the following symptoms, as they may indicate a severe or life-threatening condition:

A high fever with chills or shivering.

Signs of Differentiation Syndrome (DS): (Often occurs in the first 3 months of treatment)

• Fever ($38^\circ\text{C}$ or $100.4^\circ\text{F}$ or higher) or a temperature below $36^\circ\text{C}$ ($96.8^\circ\text{F}$)
• Difficulty breathing or cough (especially new or worsening).
• Rapid weight gain (more than 2 kg in a week) or significant swelling of your arms, legs, or face (edema).
• Dizziness or lightheadedness (hypotension).
• Fluid buildup around the lungs or heart (chest pain/tightness).

Signs of Heart Rhythm Problems (QT Prolongation):

• Fast, pounding, or irregular heartbeat (palpitations).
• Severe dizziness or fainting (syncope).
• Chest pain or tightness.
• Signs of Posterior Reversible Encephalopathy Syndrome (PRES):
• Seizures.
• Sudden, severe headache.
• Confusion or change in mental status.
• Vision problems (e.g., blurred vision, reduced eyesight).
• Unusual drowsiness or weakness.
• Signs of Pancreatitis (Inflammation of the Pancreas):
• Severe stomach pain (abdomen) that does not go away, possibly spreading to the back.
• Nausea and vomiting that is severe.
• Signs of Serious Bleeding/Infection:
• Unexpected bruising, bloody urine, black or tarry stools, or bleeding that won’t stop.

Essential Contact Advice

DO NOT STOP TAKING GILTERITINIB without first speaking to your prescribing physician. Stopping treatment abruptly can be dangerous. Your doctor may need to temporarily pause (interrupt) your dose or reduce the dosage to manage severe side effects.

Always keep the 24-hour contact number for your Oncology/Haematology team readily available. They are your primary resource for managing treatment-related side effects.

“Read more about how Gilteritinib fits into your treatment plan in our FLT3-Mutated AML Guide.

Reference: Mayo Clinic