Acute lymphocytic leukemia (ALL) in adults.
Acute lymphoblastic leukaemia in adults, a cancer of B or T lymphoblasts that is the commonest cancer of childhood but harder to cure with every decade of age. This page covers what sets it apart from acute myeloid leukaemia, the Philadelphia chromosome, and how residual disease, antibodies and CAR-T cells have changed treatment.
- 14 min read
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- Checked 29 Oct 2026
Contents6 sections
At a glance
- Acute lymphoblastic leukaemia (ALL) is a cancer of B or T lymphoblasts. It is the commonest cancer of children, about 9 in 10 of whom are cured; in adults it is rarer and harder to cure, the more so with age.
- It presents like AML with marrow failure, but more often with bone pain, lymph nodes, an enlarged liver and spleen, CNS disease and, in T-ALL, a mediastinal mass. Its emergencies (neutropenic sepsis, tumour lysis, hyperleucocytosis) are those of every acute leukaemia.
- Flow cytometry sets the lineage, and BCR::ABL1 (the Philadelphia chromosome) must be known within days: it is present in about a quarter of adults and calls for a tyrosine kinase inhibitor from the start.
- Treatment lasts about 2 to 2.5 years (induction, consolidation and maintenance), with CNS-directed therapy throughout. Young adults do better on regimens built on paediatric protocols.
- Measurable residual disease (MRD) is the main guide: persisting MRD calls for blinatumomab and an allogeneic transplant, and blinatumomab now joins consolidation for MRD-negative patients too.
- Relapse is treated with antibodies (blinatumomab, inotuzumab ozogamicin), CAR-T cells and a transplant.
- Vincristine is fatal if given intrathecally. Asparaginase causes allergy, pancreatitis, thrombosis and liver damage, and mercaptopurine needs a TPMT and NUDT15 check.
Definition and overview
Acute lymphoblastic leukaemia (ALL) is a cancer of lymphoid precursors, lymphoblasts, of the B lineage (about three quarters of adult cases) or the T lineage. The blasts fill the marrow and cause marrow failure within weeks, and, being lymphoid, they also gather in lymph nodes, spleen, liver, the central nervous system and the testes. When the disease lies mainly in nodes or a mass, with few blasts in the marrow (by convention under 25 per cent), it is called lymphoblastic lymphoma: the same disease, treated the same way.
The presentation, first tests, emergencies and supportive care of acute leukaemia are set out under acute myeloid leukaemia. This page covers what is particular to ALL in adults.
| Feature | ALL | AML |
|---|---|---|
| Age | peak at 2 to 5 years, a second rise after 50 | median about 70 |
| Blasts | lymphoblasts, with scanty cytoplasm and no granules or Auer rods | myeloblasts, with granules and often Auer rods |
| Markers | B: CD19, CD22, CD79a, usually CD10; T: cytoplasmic CD3, CD7; TdT in most | CD13, CD33, CD117, myeloperoxidase |
| Where else it goes | lymph nodes, spleen, CNS, testes, mediastinum (T-ALL) | gums and skin; CNS rarely |
| The genetic lesion that matters most in adults | BCR::ABL1, the Philadelphia chromosome | NPM1 and FLT3 mutations |
| Treatment | many drugs over 2 to 2.5 years, with CNS therapy; antibodies and CAR-T cells | 7+3 and consolidation over months |
The WHO 2022 and ICC 2022 classifications name B-ALL by its genetics (BCR::ABL1, BCR::ABL1-like, KMT2A rearranged, ETV6::RUNX1, hyperdiploid, hypodiploid and others) and separate T-ALL, including early T-precursor ALL. Burkitt leukaemia, a mature B-cell cancer once called ALL L3, is not ALL: it is treated as Burkitt lymphoma.
- with ALL have the Philadelphia chromosome, more with age
- 1 in 4adults
- with ALL are cured
- 9 in 10children
- of treatment, from induction to the end of maintenance
- 2 to 2.5years
Etiology and pathophysiology
Causes
Most ALL has no known cause. The known risks are Down syndrome, inherited cancer syndromes (Li–Fraumeni syndrome, with germline TP53 mutations and low-hypodiploid ALL, and ataxia–telangiectasia, with T-cell leukaemias), common inherited variants of genes such as ARID5B and IKZF1 that raise the risk slightly, ionising radiation and earlier chemotherapy. In children the first lesion often arises before birth (a fusion such as ETV6::RUNX1 can be found in neonatal blood spots), and one hypothesis holds that an abnormal response to common infections, in a child with little early exposure to them, supplies the second hit.
How the leukaemia develops
As in AML, the leukaemia grows from a precursor that gathers two kinds of lesion. Some block maturation, often in genes that drive B-cell development (IKZF1, PAX5, EBF1); others drive growth, such as fusion kinases like BCR::ABL1 or the JAK–STAT signalling of Philadelphia-like ALL. In T-ALL, activating mutations of NOTCH1 are found in more than half. The blasts fill the marrow and home to lymph nodes, the meninges and the testes, sanctuary sites that most drugs reach poorly, which is why CNS-directed therapy is part of every protocol. The picture simplifies: most ALLs carry several lesions, and relapse often comes from a subclone present at diagnosis.
The genetic subgroups
| Lesion | How common | What it means |
|---|---|---|
| BCR::ABL1, t(9;22), the Philadelphia chromosome | about a quarter of adults and more than 40 per cent of older patients; about 3 per cent of children | once the worst group, now treated with tyrosine kinase inhibitors from the start; mostly the p190 form of the fusion |
| Philadelphia-like (BCR::ABL1-like) | more than 20 per cent of adults | a gene expression pattern like Ph-positive ALL without the fusion: CRLF2 rearrangements (about half), JAK–STAT changes or ABL-class fusions, some of which respond to tyrosine kinase inhibitors; poor outcome |
| KMT2A rearrangement, mostly t(4;11) KMT2A::AFF1 | most infant ALL, a minority of adults | pro-B (CD10-negative) blasts and a high count; poor outcome |
| Low hypodiploidy or near-triploidy | a minority, more with age | TP53 mutations; poor outcome |
| IKZF1 deletion | common in Ph-positive and Ph-like ALL | adverse, above all with other deletions (IKZF1plus) |
| High hyperdiploidy, ETV6::RUNX1 | together about half of childhood B-ALL; uncommon in adults | favourable |
| T-ALL | about a quarter of adult ALL | NOTCH1 activation; early T-precursor ALL is an immature subtype; outcome depends on MRD |
Clinical features
Anaemia, infection and bleeding from marrow failure are the same as in any acute leukaemia. What points to ALL is the lymphoid spread:
- Bone pain and joint pain from the expanding marrow, commoner in children (a limp, a misdiagnosis of arthritis).
- Lymphadenopathy and hepatosplenomegaly.
- A mediastinal mass in T-ALL, typically in young men: cough, stridor, breathlessness lying flat, superior vena cava obstruction, and pleural or pericardial effusions.
- CNS involvement in about 5 per cent of adults at diagnosis: headache, vomiting, cranial nerve palsies, or no symptoms at all.
- Painless testicular enlargement, mostly in boys.
- A high white count, frequent in T-ALL and KMT2A-rearranged ALL. Leucostasis is rarer than in AML, but the risk of tumour lysis syndrome is higher, above all in T-ALL with a large mass.
Severity means the risk of relapse. At diagnosis it is raised by older age, a high white count (traditionally above 30 × 10⁹/L in B-ALL and 100 × 10⁹/L in T-ALL), adverse genetics and CNS disease; during treatment, persisting MRD outweighs them all.
Diagnosis and management
Making the diagnosis
The tests are those of AML (blood count and film, marrow, flow cytometry, genetics, clotting and biochemistry), with these points particular to ALL:
| Test | What it adds |
|---|---|
| Flow cytometry | B or T lineage and maturation stage; the target antigens CD19, CD22 and CD20 for antibody treatment; a baseline for MRD |
| Genetics | BCR::ABL1 by PCR or FISH within days; karyotype; KMT2A; testing for Ph-like lesions; the patient's own immunoglobulin and T-cell receptor gene rearrangements as MRD markers |
| Lumbar puncture | blasts in the cerebrospinal fluid, in every patient, usually with the first intrathecal chemotherapy, by an experienced operator, ideally once circulating blasts have fallen and with platelet support, as a bloody tap can seed the CNS |
| Imaging | chest film or CT for a mediastinal mass; echocardiogram before anthracyclines |
| Before treatment | TPMT and NUDT15 status for mercaptopurine; HLA typing; viral serology; fibrinogen and liver tests before asparaginase; sperm or egg storage where time allows |
Measurable residual disease (MRD) is measured by flow cytometry or by quantitative PCR for the patient's immunoglobulin or T-cell receptor rearrangements (or for BCR::ABL1), after induction and during consolidation. MRD negativity means below 0.01 per cent, one leukaemic cell in 10,000. It is the strongest prognostic factor in ALL, and treatment is adapted to it.
Treatment of Philadelphia-negative ALL
- 1
Pre-phase
Five to seven days of steroid, sometimes with cyclophosphamide, to lower the leukaemia load gently, with fluids and allopurinol or rasburicase against tumour lysis.
- 2
Induction
Four to six weeks of vincristine, a glucocorticoid (dexamethasone or prednisolone), an anthracycline and pegaspargase, with intrathecal chemotherapy, and rituximab for CD20-positive B-ALL in many protocols (off-label). Complete remission in 80 to 90 per cent of younger adults.
- 3
Consolidation
Months of rotating blocks: high-dose methotrexate, cytarabine, cyclophosphamide, asparaginase and a reinduction, with blinatumomab cycles in B-ALL and an allogeneic transplant for high-risk disease.
- 4
Maintenance
Daily oral mercaptopurine and weekly oral methotrexate, with vincristine and steroid pulses in some protocols, to a total of 2 to 2.5 years of treatment.
CNS-directed therapy runs through every phase: intrathecal methotrexate (alone or with cytarabine and hydrocortisone) and high-dose systemic methotrexate and cytarabine. Cranial irradiation, once routine, is now kept for overt CNS disease in some protocols.
Adolescents and young adults do far better on paediatric protocols, which give more asparaginase, vincristine and steroid, less anthracycline and earlier CNS therapy, than on traditional adult regimens. In an American trial in patients aged 17 to 39 (median 24), a paediatric regimen gave 73 per cent survival at three years, less with obesity and Ph-like disease. European study groups use adapted versions up to about 55 to 60.
MRD, blinatumomab and transplantation
- Persisting MRD (0.01 per cent or more) after induction or consolidation predicts relapse in most patients. Blinatumomab, a bispecific antibody that binds CD19 on the blasts and CD3 on T cells, cleared MRD of 0.1 per cent or more (the level its EU licence for this use requires) after one cycle in 78 per cent of patients in a trial, and is followed by an allogeneic transplant.
- MRD-negative patients: in a randomised trial of 224 adults aged 30 to 70 with Ph-negative B-ALL, adding blinatumomab to consolidation raised three-year survival from 68 to 85 per cent, with more neurological side effects. Since 2025 the EU licence covers blinatumomab in consolidation for any adult with newly diagnosed Ph-negative, CD19-positive B-ALL, whatever the MRD.
- An allogeneic stem cell transplant in first remission is kept for high-risk disease, above all persisting MRD, and for some adverse genetic groups. After a relapse it is the aim once a second remission is reached.
Philadelphia-positive ALL
- A tyrosine kinase inhibitor (TKI) starts as soon as BCR::ABL1 is found, with steroids and usually less intensive chemotherapy. Imatinib is licensed in the EU for this with chemotherapy. Dasatinib is licensed in adults only after resistance or intolerance, though protocols use it first-line. Ponatinib, a third-generation TKI that also covers the T315I mutation, doubled the rate of MRD-negative remission at the end of induction against imatinib (34 against 17 per cent) in a randomised trial, both with reduced-intensity chemotherapy, and was licensed in the EU for that use in 2026.
- Chemotherapy-free treatment: in an Italian study of 63 adults (median age 54), dasatinib with steroids and then blinatumomab gave complete remission in 98 per cent and 95 per cent survival at 18 months. This is not an EU-licensed use of blinatumomab, which in Ph-positive ALL is licensed only after two TKIs have failed.
- BCR::ABL1 measured by quantitative PCR guides what follows: patients with an early, deep molecular response may be spared a transplant, while those without it go on to one, with a TKI after it. A rising level means a mutation test, and a T315I mutation means ponatinib.
Older and unfit patients
Beyond about 55 to 60, intensive chemotherapy kills more patients and cures fewer. Age-adapted, less intensive regimens are used, increasingly with inotuzumab ozogamicin or blinatumomab and little chemotherapy (mostly in trials), and for Ph-positive disease a TKI with steroids. Long-term survival is still only about 20 to 30 per cent on dedicated protocols, and lower in the unfit.
Relapsed and refractory ALL
| Treatment | What it is | Key facts |
|---|---|---|
| Blinatumomab | CD19 and CD3 bispecific antibody, a continuous infusion for 4 weeks | median survival 7.7 against 4.0 months with chemotherapy; cytokine release syndrome and neurotoxicity (tremor, confusion, speech disturbance, seizures) |
| Inotuzumab ozogamicin | CD22 antibody carrying the toxin calicheamicin | remission in 81 against 29 per cent; veno-occlusive disease of the liver in 13 per cent, more after a transplant, so two cycles are given before one |
| CAR-T cells | the patient's T cells engineered to attack CD19 | remission in about 70 to 80 per cent; in the EU, brexucabtagene autoleucel and (since 2025) obecabtagene autoleucel from age 26, tisagenlecleucel up to 25; cytokine release syndrome, neurotoxicity, B-cell aplasia |
| Nelarabine | a purine analogue toxic to T cells | T-ALL after two regimens; severe and sometimes irreversible neurotoxicity |
| Allogeneic transplant | the aim once a second remission is reached |
Toxicities to know
| Drug | Danger | What is done |
|---|---|---|
| Vincristine | fatal if given intrathecally; neuropathy, constipation and ileus, jaw pain; worse with azole antifungals | intravenous only, from a minibag, never alongside intrathecal syringes |
| Asparaginase | allergy or silent inactivation by antibodies; pancreatitis; liver damage; thrombosis, including cerebral venous sinus thrombosis, as antithrombin falls; bleeding; high glucose and lipids | activity levels; Erwinia asparaginase (crisantaspase) after allergy or inactivation; stopped for good after severe pancreatitis |
| Glucocorticoids | infection, high glucose, osteonecrosis (above all in adolescents), myopathy, mood change | glucose checks, bone pain taken seriously |
| High-dose methotrexate | mucositis, kidney injury, liver damage, leukoencephalopathy | hydration and an alkaline urine, levels, folinic acid rescue, glucarpidase for toxic levels; no co-trimoxazole, NSAIDs or proton pump inhibitors alongside |
| Anthracyclines | heart failure | cumulative dose limits, echocardiography |
| Mercaptopurine | myelosuppression with low TPMT or NUDT15 activity (NUDT15 variants are common in East Asian and Hispanic people); liver damage | dose by TPMT and NUDT15; a quarter of the dose with allopurinol |
Supportive care is as in AML, with co-trimoxazole against Pneumocystis throughout treatment (paused around high-dose methotrexate), antifungal prophylaxis chosen with vincristine in mind, G-CSF after intensive blocks in many protocols, and immunoglobulin replacement for low IgG with infections after CAR-T cells.
Epidemiology
ALL is uncommon in adults. In Europe about 1.3 new cases arise per 100,000 people a year, and in the USA 1.9, half of them under 20 (median age at diagnosis 18). The incidence peaks at 2 to 5 years, falls through adult life and rises again after about 50. It is slightly commoner in males, and T-ALL especially affects young men; in the USA it is commonest in Hispanic people. In adults ALL makes up about one in five acute leukaemias, and B-ALL about three quarters of adult ALL.
Prognosis
Children do best: about 9 in 10 are cured. In adults, outcome falls with age, and MRD, genetics and fitness decide the rest:
| Group | Outcome |
|---|---|
| All ages, England | 70 per cent alive at five years |
| Age 15 to 39 | about 65 per cent at five years (regional registry) |
| Age 40 and over | about 25 per cent at five years (regional registry) |
| Older and unfit adults | about 20 to 30 per cent long term on dedicated protocols, less if unfit |
| Ph-positive ALL | about 1 in 5 long term before TKIs; now more than half long term |
| Young adults on a paediatric regimen | 73 per cent alive at three years |
| MRD-negative after induction, with blinatumomab | 85 per cent alive at three years in the trial |
| Relapse treated with chemotherapy | median survival about 4 months |
Most relapses come within 2 to 3 years, in the marrow, the CNS or the testes. Follow-up is with blood counts and MRD for several years, and survivors are watched for late effects: osteonecrosis, anthracycline heart damage, infertility, neurocognitive effects after CNS therapy, second cancers and, after a transplant, chronic graft-versus-host disease. New cytopenias, blasts in the blood or new neurological symptoms mean relapse until shown otherwise.
Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.
1A 19-year-old man has two weeks of breathlessness when lying flat, a swollen face and a white count of 85 × 10⁹/L with blasts. His chest film shows a large anterior mediastinal mass. What is the safest way to make the diagnosis?
2A 48-year-old woman with newly diagnosed B-ALL has BCR::ABL1 detected by PCR on day 3 of her pre-phase. What changes in her treatment?
3A 35-year-old man with Philadelphia-negative B-ALL is in complete remission by microscopy after induction and consolidation, but flow cytometry finds 0.3 per cent leukaemic cells in his marrow. What is the usual next step?
4During induction with pegaspargase, a 24-year-old woman develops severe abdominal pain going through to her back. Lipase is 12 times normal and CT shows necrosis of the pancreas. What should happen to her asparaginase?
5A 27-year-old man starts maintenance with daily mercaptopurine at the standard dose and weekly methotrexate. Within three weeks his neutrophils are 0.2 × 10⁹/L and his platelets 15 × 10⁹/L. Which test should have guided the dose?
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