Acute lymphoblastic leukaemia

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Acute lymphoblastic leukaemia at a glance

Acute lymphoblastic leukaemia, or ALL, is a rapidly developing cancer of immature cells that would normally develop into lymphocytes, a type of white blood cell. These cells build up in the bone marrow, the soft tissue inside bones where blood cells are made, and crowd out healthy blood production. ALL can also affect lymph nodes, the spleen and other sites. It needs prompt specialist care, with treatment chosen according to cell type, genetic findings, age, fitness and early response.

The two main groups are B-cell ALL and T-cell ALL. B-cell ALL is further divided by important genetic features, including whether there is a Philadelphia chromosome change that joins two genes, BCR and ABL1. This joined gene is written BCR::ABL1. These distinctions matter because some medicines work only when a particular target is present. A treatment described as effective for B-cell ALL may not treat T-cell ALL.

ALL occurs in children and adults, but the treatment programmes are not identical. This guide explains the main principles, with an adult and adolescent focus. Children need a paediatric haematology-oncology pathway. Targeted medicines and treatments using modified immune cells also have age-specific eligibility rules.

Symptoms and urgent care

Tiredness, pallor, breathlessness, fever, recurrent infection, bruising, bleeding or bone pain may lead to investigation. Enlarged lymph nodes or a swollen abdomen can occur. Some people with T-cell disease have a mass in the chest that can cause cough, breathlessness or swelling of the face and neck.

Severe breathing difficulty, collapse, major bleeding, confusion, a new seizure or severe headache needs emergency assessment. A large chest mass can make sedation or lying flat unsafe, so tell the team about breathlessness before a procedure. Do not start steroids independently: they can alter the diagnostic picture and trigger rapid cell breakdown, although doctors may use them urgently when clinically necessary.

The first days after diagnosis

The team checks for infection, bleeding and tumour lysis syndrome, in which rapid breakdown of leukaemia cells can upset blood chemistry and damage the kidneys. Red-cell or platelet transfusions may be needed. Some treatment decisions can be made quickly; others depend on tests of cell proteins, called flow cytometry, and genetic results. Ask which results are needed before the full programme starts and who will explain them. ALL treatment often has several phases, so a written calendar and a reliable contact person can make the plan easier to follow.

Making this information useful to you

A cancer diagnosis can arrive before you have had time to understand the tests. You do not need to learn every treatment name at once. Begin with the exact diagnosis, where the cancer is, and what the team recommends next. A relative or friend can join the appointment if you would find that helpful. Ask for an interpreter when language makes a discussion harder; important decisions should not depend on guessing unfamiliar words.

This guide explains possibilities, not a prescription for your situation. Your blood and tissue test results, scan findings, general health, previous treatment and priorities determine which possibilities apply. Two people with the same cancer name may appropriately receive different treatment. If a recommendation differs from something you have read, ask the team to explain the reason and the evidence behind it.

Keep a list of medicines, allergies and other health conditions, including non-prescription products, vitamins and herbal remedies. Tell the team about previous cancer treatment, pregnancy or breastfeeding, and anything that could affect attending appointments. Do not stop an established medicine without advice. Bring your questions in the order that matters most to you, so that the most important concern is discussed first.

Understand

B-cell, T-cell and lymphoblastic lymphoma

B cells and T cells are different types of lymphocyte. In ALL, cells that would normally develop into these lymphocytes become cancerous before they mature. A laboratory test called flow cytometry identifies the cell type by looking at proteins on the cells. Some of these proteins, such as CD19 or CD22 in B-cell disease, can be targets for treatment.

Lymphoblastic lymphoma is closely related to ALL but presents mainly as a tissue or lymph-node mass with less marrow involvement. It is commonly treated with an ALL-style programme rather than the shorter regimens used for many mature-cell lymphomas. The distinction should be made by the specialist pathology team.

Philadelphia-positive and Philadelphia-negative disease

Philadelphia-positive, or Ph-positive, ALL has the BCR::ABL1 fusion, which produces an abnormal growth signal. A tyrosine kinase inhibitor, or TKI, blocks that growth signal and is an important part of treatment. Ph-negative ALL lacks that fusion but includes several biological groups with different risks and treatment considerations.

A report may mention Ph-like ALL. This means that the disease has a pattern resembling Ph-positive ALL, but it does not automatically have BCR::ABL1 or qualify for the same treatment. Further gene testing may identify a change that a particular medicine can target. The exact finding matters more than the resemblance implied by the name.

Other changes, including rearrangements of the KMT2A gene, chromosome-number abnormalities and particular fusion genes, can influence risk. Most changes in the leukaemia cells are acquired. An inherited predisposition is considered when the history or results suggest one, particularly before a related donor is selected.

The brain and spinal-fluid compartment

ALL cells can enter the fluid around the brain and spinal cord. The brain and spinal cord form the central nervous system (CNS). Finding ALL cells in the surrounding fluid is one form of CNS involvement. Treatment to protect this compartment is part of ALL care even when no leukaemia is found there, because ordinary bloodstream treatment may not provide adequate protection on its own.

Intrathecal treatment places chemotherapy into this fluid, usually through a lumbar puncture: a needle placed in the lower back. Some medicines given into a vein or by mouth also reach the CNS. Radiotherapy is reserved for selected circumstances rather than used automatically for everyone. CNS prevention remains important even when a targeted drug or immunotherapy is producing an excellent marrow response.

Tests and diagnosis

Establishing the diagnosis

A full blood count and examination of blood under a microscope may show too few healthy cells and immature cells called blasts. A bone marrow aspirate removes liquid marrow, and a biopsy takes a small core, usually from the back of the pelvic bone. These samples allow the laboratory to examine cell appearance, proteins and genes. Sometimes tissue biopsy is needed for a mass. Samples should be obtained before treatment where safely possible, because steroids and chemotherapy can change the findings.

Chromosome studies and molecular tests look for changes such as BCR::ABL1. One test, fluorescence in situ hybridisation (FISH), uses fluorescent probes to find particular chromosome changes. Where possible, the team also identifies a marker to track measurable residual disease (MRD): very small amounts of leukaemia remaining during or after treatment. Ask whether the sample has been reviewed by a pathologist experienced in acute leukaemia and whether additional tests are pending.

Checking sites of disease

Examination looks for enlarged lymph nodes, liver or spleen, and symptoms guide imaging. A chest image may be particularly important in T-cell ALL because of a mass between the lungs. Symptoms affecting the brain or nerves, such as headache or weakness, and testicular symptoms should be reported. Some sites require specific investigation and treatment planning.

A lumbar puncture collects cerebrospinal fluid, the fluid around the brain and spinal cord, and may be combined with the first intrathecal treatment. Timing depends on the patient's condition, platelet count and treatment protocol, meaning the planned programme. The team manages bleeding risk and procedural safety; it is not always appropriate to do the test immediately on arrival.

Baseline health and infection tests

Kidney, liver and heart function affect treatment selection. Tests for hepatitis and other infections help plan prevention and avoid reactivation. Pregnancy testing, contraception advice and fertility-preservation discussion should be offered when relevant. Urgent treatment may limit the time available, but the concern should still be acknowledged.

A central line is a thin tube placed in a large vein for repeated infusions, blood tests and transfusions. Learn how it is cared for and what to do if the dressing loosens, the line leaks or fever develops. Tell all clinicians that you are receiving leukaemia treatment before a procedure or a new prescription.

Response testing through the programme

Marrow and MRD assessments occur at defined points, often after the first phase of treatment, called induction, and during later treatment. In Ph-positive ALL, BCR::ABL1 measurements can help track response, sometimes alongside other MRD methods. Results are interpreted together, particularly if different tests do not agree.

Treatment can suppress blood production even when leukaemia is controlled. A marrow assessment may therefore be needed to explain prolonged low counts. Do not assume that a low count proves relapse or that a normal count proves complete clearance of the disease.

Preparing for your appointment

If scans have been performed, bring a CD containing your scan images in Digital Imaging and Communications in Medicine (DICOM) format, the standard used for medical images, together with the software needed to view them, along with the written scan reports. Bring your biopsy report and ask whether the pathology slides or tissue blocks are needed for specialist review or additional tests. Keep originals safe and agree how borrowed material will be returned. Having the actual images allows the team to compare changes and plan treatment accurately.

A repeat test is sometimes needed because an earlier sample was too small, a scan did not cover the necessary area, or a new result will change treatment. Ask what question the test will answer, how it may affect the plan, and when you should expect the result. A result described as uncertain does not automatically mean the cancer is worse. Sometimes discussion between the scan specialist (radiologist), tissue specialist (pathologist) and treating team resolves the uncertainty without another procedure.

Before a scan or procedure, mention kidney problems, previous contrast reactions, implanted devices, diabetes medicines, blood-thinning medicines and the possibility of pregnancy. Follow the testing centre's instructions about food, drink and medicines. If you have not received those instructions, contact the centre rather than making changes yourself.

Planning your treatment

Matching the programme to age and fitness

Adolescents and young adults may benefit from a paediatric-inspired regimen when they can tolerate it. Older adults or people with significant medical problems may need reduced-intensity chemotherapy combined with targeted treatment or immunotherapy. Fitness, organ function and the exact subtype guide this choice.

ALL treatment usually has several phases:

• Induction is the first phase, aiming for remission: no leukaemia detectable on routine assessment, with recovery judged by defined blood and marrow tests. More sensitive MRD tests may still find small amounts.
• Consolidation or intensification treats remaining leukaemia cells and reduces the chance of relapse.
• Maintenance uses continuing treatment to help keep the disease in remission when the programme calls for it.

CNS-directed treatment runs through the programme. The full course can be lengthy, especially when maintenance is included. Ask about time in hospital, outpatient visits, work or study and support at home rather than focusing only on the first cycle.

When transplant is considered

A donor stem-cell transplant replaces blood-forming cells and supplies a new immune system that can attack leukaemia. It may reduce the chance of the disease returning in selected high-risk disease, persistent MRD or relapsed ALL. It is not necessary for every person who achieves remission. Modern targeted and immune treatments have changed how this decision is made in some groups.

Assessment considers genetics, depth of response, age, health, donor options and treatment-related risks. If transplant might be needed, tissue typing, which checks immune-system markers to help match a donor, and donor searching can start early. The team should explain whether the recommendation is based on the disease at diagnosis, its response to treatment or both.

Setting expectations and making decisions

Ask whether the aim is cure and what the realistic alternatives are if the first treatment does not achieve the desired response. Decisions may change after genetic or MRD results. Supportive care, including symptom control, psychological support and fertility counselling, belongs within the treatment plan from the start.

A treatment's convenience should be weighed alongside its safety. An oral targeted medicine may still need frequent tests. A continuous infusion may be managed at home only with appropriate training and support. The team will explain which parts of care require hospital observation.

Questions to ask your care team

• What is the exact blood cancer type and risk category, and are any important results still pending?
• Is the aim to cure the cancer, reduce the chance of recurrence, control it, or relieve a particular symptom?
• What benefit do you expect from this option, and what are the reasonable alternatives for me?
• How will treatment affect everyday activities, fertility, sexual health and the things I most value?
• How will we know whether it is working, and when will we review the plan?
• Who should I contact between visits, including at night or over a weekend?

Clinical trials and newer treatments

A clinical trial can be worth considering at diagnosis or when treatment needs to change. Trials ask a defined question; some compare established treatments and others study a newer approach. Eligibility depends on the cancer, previous treatment, test results and health. Taking part is voluntary, and choosing not to participate does not remove your right to standard care. Ask about extra visits, possible randomisation (allocation to a treatment group by chance), travel, side effects and what happens when the study ends.

Newer treatments are considered using the clinical evidence, recognised guidelines and the exact cancer type, biomarkers (features found by laboratory tests) and previous treatment. Some options have less mature evidence than established treatments. Ask what is known, what remains uncertain and whether a clinical trial would be appropriate.

Your priorities and supportive care

Tell the team what you are hoping treatment will make possible: returning to work, caring for family, keeping independence, reducing pain or attending an important event. These priorities can influence a choice between reasonable options. If the likely benefit is small and the burden is substantial, discussing a less intensive approach is appropriate. Decisions can be revisited when your health or circumstances change.

Supportive and palliative care help with symptoms, sleep, mood, family concerns and planning. They can be provided alongside treatment intended to cure or control cancer. A referral does not mean that active treatment is ending. If the cancer cannot be cured, ask what treatments may help you live longer or more comfortably and how their burdens compare with their likely benefits.

Treatment options

Philadelphia-negative B-cell ALL

Combination chemotherapy commonly includes drugs such as a steroid, vincristine, an anthracycline such as doxorubicin, asparaginase, methotrexate and cytarabine at different phases. The exact programme varies by age and risk. These drugs are not all given together at every visit, and their doses and timing should not be inferred from a list of names.

Blinatumomab brings immune T cells close to leukaemia cells carrying the CD19 protein so they can attack them. It has an established role in appropriate B-cell ALL, including consolidation within a multiphase programme for CD19-positive Ph-negative disease. It is also used in defined MRD-positive or relapsed settings. Relapsed means the leukaemia has returned after remission; refractory means it has not responded adequately to treatment. Its use is no longer limited to people whose disease has visibly returned, but it does not replace all components of treatment or CNS protection.

Some programmes include rituximab when B-cell ALL carries the CD20 protein that this antibody targets. Older or less fit patients may receive regimens that reduce conventional chemotherapy and use blinatumomab or inotuzumab in carefully selected settings. The haematology team must judge the evidence and safety of the complete programme rather than simply adding an immune medicine to an existing schedule.

Philadelphia-positive B-cell ALL

A BCR::ABL1 TKI is combined with other treatment. Imatinib, dasatinib and ponatinib have different strengths, risks and eligible settings. Ponatinib with chemotherapy is an option for newly diagnosed adults with Ph-positive ALL. Cardiovascular disease, blood pressure, clotting history and mutation findings influence whether it is suitable.

Some specialist programmes combine a TKI with blinatumomab and reduce conventional chemotherapy. Their use depends on the patient's disease, MRD response and the chosen protocol. CNS-directed therapy is still required. Do not stop the TKI when symptoms improve or when the first molecular result becomes negative.

If the disease stops responding, testing for BCR::ABL1 resistance mutations can help select another TKI. A T315I mutation is relevant to drug choice, but the patient's other risks still matter. Transplant is discussed according to the whole response and risk picture, rather than assumed to be mandatory or unnecessary for every Ph-positive patient.

T-cell ALL

T-cell ALL generally needs an intensive, age-appropriate multiagent programme with CNS protection. Nelarabine may be incorporated in selected protocols or used for relapsed or refractory T-cell disease. Nelarabine can affect the brain and nerves, so new weakness, numbness, confusion or difficulty walking needs urgent advice.

CD19- and CD22-directed treatments used for B-cell ALL do not generally treat T-cell ALL because the targets differ. Persistent MRD or relapse may lead to a donor-transplant discussion and specialist salvage treatment. This guide does not present experimental treatments using genetically modified T cells as established routine care.

Maintenance and CNS-directed treatment

Maintenance commonly uses oral medicines such as mercaptopurine and methotrexate within a defined protocol, sometimes with other scheduled treatment. It may continue for years in some programmes. Adherence is important, but low counts, liver changes or infections can require supervised pauses or dose adjustments.

Methotrexate schedules require particular care. In many maintenance plans it is taken weekly, not daily. Follow your own written schedule and check immediately if the instructions are unclear. Never take additional doses to make up for a missed tablet without advice. Tell the team about antibiotics and other new medicines because interactions can be serious.

Intrathecal and CNS-penetrating systemic treatment prevent or treat disease in the spinal-fluid compartment. A normal spinal-fluid result does not mean that later planned preventive doses should be skipped. If CNS disease is present, the treatment intensity and monitoring may change.

If B-cell ALL returns or does not respond

Treatment depends on previous therapy, current CD19 or CD22 expression, genetics, site of relapse and fitness. Blinatumomab may be used for appropriate CD19-positive disease. Inotuzumab ozogamicin targets CD22 and can produce a response that allows a further treatment such as transplant. It can cause hepatic sinusoidal obstruction syndrome, a serious blockage of small blood vessels in the liver, particularly around transplantation. Liver assessment and the timing of any transplant are therefore important.

Chimeric antigen receptor (CAR) T-cell therapy modifies your own immune T cells in a laboratory, adding a receptor that helps them recognise and attack leukaemia cells. Options include tisagenlecleucel for defined younger-patient relapsed or refractory B-cell ALL, and brexucabtagene autoleucel or obecabtagene autoleucel for appropriate adult disease. Product-specific age and previous-treatment criteria differ. A specialist centre assesses whether collection, manufacturing and any bridging treatment to control the leukaemia while the cells are being prepared are feasible.

Revumenib is an option for relapsed or refractory acute leukaemia with a qualifying KMT2A translocation in patients aged one year and older. It is selected by the molecular finding, not simply because ALL has relapsed. Revumenib can cause differentiation syndrome, a serious inflammatory reaction as leukaemia cells mature. Fever, breathing difficulty, swelling or rapid weight gain needs urgent assessment. Heart-rhythm changes and medicine interactions also require close supervision.

A response to salvage treatment may be followed by donor transplant in selected patients. Some patients receive a different strategy after CAR T-cell treatment. There is no single sequence that suits every relapse; the duration of the previous remission and the disease's current biology matter.

Managing side effects

Infection, tumour lysis and low counts

Rapid leukaemia-cell breakdown can disturb blood salts and kidney function. Fluids, preventive medicines and frequent tests reduce this tumour-lysis risk. The team adjusts fluid advice for heart or kidney problems. Low neutrophils, the white cells that fight infection, damage to the lining of the mouth or gut, and steroids can increase infection risk throughout treatment, including during periods at home.

Report fever promptly and follow the emergency plan. Steroids can sometimes blunt the usual fever response, so severe illness without a high temperature also matters. Preventive antibiotics or antivirals do not rule out infection. Transfusions may be needed when red cells or platelets are low.

Asparaginase, steroids and nerve effects

Asparaginase can cause allergy, pancreatitis (inflammation of the pancreas), liver problems, high blood sugar and clotting or bleeding complications. Severe abdominal pain, jaundice, persistent vomiting or symptoms of a clot need urgent advice. A suspected allergy may require specialist testing or a change of preparation rather than simply abandoning the whole protocol.

Steroids can affect sleep, appetite, mood, blood sugar and bone health. Vincristine and some other medicines can cause nerve symptoms or constipation. Report new weakness, tingling, severe constipation or abdominal pain early. Medicines for nerve symptoms, bowel care and diabetes should be coordinated with the leukaemia team.

Immune-therapy monitoring

Blinatumomab and CAR T-cell treatment can cause cytokine release syndrome, an excessive inflammatory response from immune cells, and effects on the brain and nerves. Fever, low blood pressure, breathlessness, confusion, altered speech, tremor or seizures require urgent assessment. Follow the team's instructions about hospital monitoring, driving and staying near the centre.

If blinatumomab is delivered by a continuous pump, you and your caregiver need clear training. Do not restart a stopped infusion or adjust the pump independently; interruptions may require supervised restarting. Call the service specified in your treatment instructions.

Transplant and longer-term toxicity

A donor transplant adds risks of graft-versus-host disease, in which donor immune cells attack healthy tissues, infection and effects on organs and fertility. Prior inotuzumab exposure must be discussed when planning conditioning, the treatment given before a transplant, because of liver risk. Following any intensive programme, heart, hormone, bone and reproductive health may require long-term review.

Keeping treatment manageable

Keep the team's contact details available and know where to go outside clinic hours. Report side effects early rather than waiting until the next appointment. A short record of symptoms, temperature, fluid intake and medicines can help the team decide what is needed. Do not change cancer medicine doses, restart a stopped treatment, or use leftover antibiotics without instructions. A planned delay or dose adjustment can be an important part of safe treatment.

If you receive treatment that can lower white blood cells, a temperature of 38°C (100.4°F) or higher needs urgent advice. Follow any lower threshold or additional instructions your team gives you. Chills, sudden weakness, confusion or feeling very unwell also need urgent assessment, even without a fever. Do not wait for a blood test appointment or try to hide the fever with medicine before speaking to the team.

Severe breathlessness, chest pain, a new seizure, sudden weakness, heavy bleeding or collapse require emergency care. New severe back pain with leg weakness, numbness around the bottom, or loss of bladder or bowel control also needs immediate assessment. Contact the nearest emergency service when necessary; a website contact form or routine messaging service is not an emergency pathway.

Eating, drinking and energy

Treatment may change appetite, taste, bowel habits and energy. Small, frequent meals and foods containing protein can be easier than large meals. Ask for dietitian support if weight is falling, swallowing is difficult, or you are avoiding many foods. There is no single diet that treats cancer, and severe restriction or prolonged fasting can make it harder to tolerate treatment. Check supplements with your team because some interact with medicines.

Take anti-sickness medicine as prescribed and report vomiting that prevents you keeping down fluids or essential medicines. Seek advice for persistent diarrhoea, dizziness, very little urine or increasing weakness. Fluid recommendations may need adjustment if you have heart or kidney disease. Mouth ulcers, pain or infection that interferes with eating should be treated promptly rather than accepted as unavoidable.

Gentle movement, short walks and planned rest may help fatigue, but activity should match your condition and any surgical or bone-safety restrictions. Fatigue can also reflect anaemia, infection, hormone changes, pain, poor sleep or low mood. Let the team assess a marked or persistent change. Accepting help with shopping, transport or meals can conserve energy for the activities that matter to you.

Live well

Follow-up after treatment

Blood counts, examination and molecular or marrow testing are scheduled according to the subtype and protocol. A new lump, unexplained bruising, persistent fever, bone pain, neurological symptom or testicular change should be reported. These symptoms can have other causes, but they should not wait for a distant routine visit.

Keep a record of your treatment programme, the medicines and doses received over time, CNS therapy and any transplant or CAR T-cell product. This helps future clinicians plan vaccinations, fertility care and screening for late effects. Childhood and adolescent survivors need an age-appropriate survivorship plan as they move into adult care.

Living during maintenance and recovery

Maintenance can allow more normal routines, but it remains active cancer treatment. Ask about school, work, travel, alcohol, vaccination and infection exposure for your actual medicines and blood counts. Recovery after an intensive phase may be slower than you expect, and pacing activity can help rebuild stamina.

It is common to feel anxious before marrow or MRD results. Ask when results will arrive and who will explain them. A supportive routine, psychological help and clear communication can make uncertainty more manageable. Caregivers should also have a way to ask questions and obtain help when responsibilities become difficult.

Emotional and practical support

Feeling frightened, angry, sad or uncertain is understandable. You do not have to appear positive all the time. Ask about counselling, psycho-oncology (support for the emotional effects of cancer), support groups or a social worker if worry is affecting sleep, relationships or daily life. Persistent depression, panic or thoughts of self-harm need prompt professional help. Caregivers may need their own support and breaks; one person should not have to manage every appointment and household task alone.

It can help to agree who will update relatives and how much information you want shared. Children usually benefit from honest, age-appropriate explanations and reassurance about who will care for them. Ask permission before discussing private medical information with others. If concentration or memory is difficult, use reminders, a calendar and a trusted companion at important consultations.

Relationships, fertility and sexual health

Cancer and treatment can affect desire, comfort, fertility, body image and confidence. These are valid medical concerns. Raise fertility questions before treatment when possible, because some protective options need to be arranged early. The right approach depends on age, the treatment and how urgently it must start. Do not assume that absent periods or reduced fertility means pregnancy is impossible. Ask about contraception and the safe timing of pregnancy for your specific medicines.

Explain any pain, dryness, erection difficulties or changes in intimacy to the team. Appropriate treatments, rehabilitation and counselling can help. You can choose how much to involve a partner. Advice about hormone-containing treatments needs to take the cancer type and treatment into account; do not start them without discussing suitability.

Planning ahead while living well

Ask for a clear follow-up plan and know which symptoms should be reported between visits. Continue care for other conditions and discuss vaccinations with your oncology team; the timing and suitability of live vaccines can change during treatment. Avoid tobacco and ask for practical cessation support if needed. Activity, food and sleep plans should be realistic for your health rather than another source of pressure.

If treatment is long term, arrange periodic discussions about what is helping, what is difficult and what you want next. Planning for future care can protect your preferences and reduce uncertainty for family. You can discuss who should help with decisions if you become too unwell to speak for yourself, while continuing treatment and everyday life now.

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