Acute lymphoblastic leukaemia – tumour lysis syndrome

Cite this article as:
Tessa Davis. Acute lymphoblastic leukaemia – tumour lysis syndrome, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.6185

Treating leukaemia produces its own complications. The most common time to have complications is during induction. For any new presentations of tumours, or for patients at the start of treatment, be aware of tumour lysis and how it can present.

View all our Acute Lymphoblastic Leukaemia Week posts

Tumour lysis syndrome is most commonly seen at the start of treatment as this is when there is the highest tumour load.

What is tumour lysis syndrome (TLS)?

TLS results from cell death and the subsequent release of chemicals from these cells.

It can be triggered by steroids, chemotherapy, fever, or dehydration.

What are the chemical abnormalities in TLS?

When cells die, they release their intracellular potassium and phosphate. Calcium then binds to the phosphate in the tissues. Urate is also deposited in the kidneys. The usual order of detected abnormalities is:

  1. High potassium
  2. High phosphate
  3. Low calcium – this can also be associated with kidney calcification
  4. High urea and creatinine  – this is due to renal failure and if this happens then the renal team need to be involved and the patient will likely require dialysis.

How do we treat TLS?

Treatment is through three main ways:

  • Hydration
  • Allopurinol – aiming to reduce the urate
  • Rasburicase – a medication that converts uric acid to allantoin which is water soluble and excreted in the urine.

Also, beware that if the patient has a high potassium, they are at risk of cardiac arrest so may also need standard hyperkalaemia management.

What are the other potential complications of ALL?

Anaemia – often the presenting complaint and result of treatment. Most patients require platelet & red cell transfusions.

Febrile neutropenia – most patients will have an episode of febrile neutropenia during induction. This can be due to life-threatening sepsis. Find your hospital guideline and if you suspect febrile neutropenia, talk to your consultant early.

Hyperviscosity syndrome – can be a presenting complaint, associated with WCC >100×109/L 

Acute lymphoblastic leukaemia – risk factors and prognosis

Cite this article as:
Henry Goldstein. Acute lymphoblastic leukaemia – risk factors and prognosis, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.6182

 We suspect that Hamish has ALL – how do we confirm this, and more importantly, what is his prognosis?

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What are the initial investigations?

  • Repeat FBC & send group & hold; coagulation profile; blood cultures if febrile; electrolytes, including PO4-, Mg+, Ca++ as high WCC at risk of tumor lysis syndrome; liver function tests; Hep B, C, HIV, EBV, CMV, herpes simplex, HHV6, syphilis & toxoplasma serology
  • Blood film must be reviewed & reported by a consultant haematologist
  • ECG – sinus tachycardia, normal axis
  • Chest radiograph – to check for mediastinal mass
  • Urinalysis
  • Official height & weight – for chemotherapy & body surface area calculations (standard scales/measure, sighted by two staff)
  • Pregnancy test in females of childbearing age

Once clinically stabilised (including meeting minimum platelet counts), they will have a GA lumbar puncture (usually with intrathecal chemotherapy) a bone marrow aspirate, and if there is no contraindications, insertion of a tunnelled central line.

What are the risk factors for ALL?

  • Family history
  • Immunosuppression
  • Alkylating agents (more commonly linked to AML rather than ALL)
  • Trisomy 21
  • Neurofibromatosis
  • Ataxia telangiectasia
  • Bloom syndrome

What are good prognostic factors for ALL?

1. Age  >1yo and <10yo at diagnosis

2. White cell count <50×109/L at presentation

3. No testicular involvement at presentation

4. Not a child with Down Syndrome

5. No prior steroid exposure – this is important, as steroids are themselves chemotherapeutic and can put a child into remission as a single agent. If there has been a history of URTI or wheeze, they may have been prescribed (or been given a sibling’s) steroids. There are reports of spontaneous tumour lysis syndrome in undiagnosed patients as a result of steroids. Steroid exposure will move the child to a high-risk protocol.

6. No CNS disease – established with first CSF examination

In recent years, cytogenetics & minimal residual disease (MRD) has added a further layer to prognosis and treatment. This analysis requires CSF & bone marrow samples.

What do remission, relapse, and cure mean?

For diagnosis – a patient has to have over 25% blasts in the peripheral blood film

For remission – a patient has to have <5% blasts in the peripheral blood film

For cure – a patient has to have no evidence of leukaemia over 5 years from diagnosis

Bone marrow is the most common site for relapses and 10% of relapses are central nervous system only. In boys, testes are a known site of relapse and present as a hard testicular lump – so make sure you examine the tests during follow-up appointments.

Using the most up to date study outcomes, the 5 year survival is 85%

Once the child gets further through the initial treatment and is given a standard risk, then the 5 year survival is 97%

Acute lymphoblastic leukaemia – presentation

Cite this article as:
Henry Goldstein. Acute lymphoblastic leukaemia – presentation, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.1248

Hamish, 5, has been tired and miserable for the last week of the school holidays. On the second day back at school, his Mum is asked to collect him after a bleeding nose that lasts about fifteen minutes. The teacher comments to Mum that Hamish is looking a bit “thin & pale”, and they’ve noticed a lot of bruising on his shins.

The GP agrees and orders a full blood count, which shows: Hb 50 g/L (100 – 150); Plt 2 x109/L (150 – 450); WCC 45.8 x109/L (80% lymphocytes, 30% blasts); “Blasts seen on film”.

View all our Acute Lymphoblastic Leukaemia Week posts

Bottom Line

ALL is the most common childhood haematological malignancy

Paediatric oncology is strongly consultant-driven

First presentation to the tertiary oncology centre is extremely stressful and a medically intense time

Aim is to achieve remission in induction

ALL may present in a broad variety of signs & symptoms<

The GP phones you, the Paeds Oncology registrar, with these results, and Hamish soon arrives into Emergency. You phone the consultant, who attends to meet family, take the history and examine Hamish.

Hamish looks pale but bright eyed. Vitals are 36.9oC, HR 130, RR 25, SaO2 97%, BP is normotensive with brisk capillary refill.

Further History

Has been grizzly and “not himself” for the last ten days: picking at food; complaining of sore legs for 2/7.  Not recently unwell/coryzal symptoms/diarrhoea. No wheeze. No steroid exposure. No blurry vision. Developmentally meeting milestones. No FHx of childhood malignancy.

(When taking the history, specifically ask about B symptoms: fever, night sweats, and weight loss).

Further examination

Pale boy with signs of weight loss. Bruising of the elbows, knees and legs. HS 2+ flow murmur. Lungs – no wheeze, good equal air entry. Abdomen soft, bowel sounds, liver 5cm below the costal margin, spleen 8cm below costal margin, not tender. Enlarged inguinal nodes bilaterally. Testicular examination – normal size for age. Aside from the bruising, you identify no areas of broken skin, boils, erythema or rashes. ENT examination is unremarkable. Fundoscopy unremarkable.

(Also, note any dysmorphism, Tanner stage, Lansky performance score).

What is ALL?

Acute lymphoblastic leukaemia is the most common childhood cancer. It is bimodal in incidence in childhood with peaks at around 2 years, and then at around 16 years of age.

ALL accounts for around 80% of childhood leukaemias, the remainder being acute myeloid leukaemia and rarer types. Approximately 85% of children with acute lymphoblastic leukaemia have B-cell ALL, with ~15% having T-Cell ALL. 2-3% will have Burkitt lymphoma, a mature B-cell leukaemia, treated differently from most leukaemias.

How does ALL usually present?

The most common presentations are with bone pain. Many children experience bone aches due to ‘growing pains’, so it’s important to know how to differentiate bone pain related to oncology issues, and growing pains.

  • bone pain tends to wake you up in the middle of the night, whereas growing pains are usually felt more when the child is falling asleep
  • children with growing pains should not have difficulty walking
  • growing pains tends to present as a pattern i.e. same type of pain at the same of day
  • children with growing pains will have completely normal blood counts
  • there should be no fever or weight loss associated with growing pains

As with this case, ALL can also present with bleeding. Other presentations include splenomegaly (10-20%), mediastinal mass, renal failure (due to hyperuricaemia), or leukostatic symptoms (respiratory distress, altered mental status) in patients with a high WCC .

Rarely patients who initially are thought to have ITP actually turn out to have ALL.

ALL can also include extramedullary sites e.g. CNS, testes, liver/spleen, kidneys, skin (rare). With this in mind, the list of presenting features include…

  • Typically weight loss (or failure to thrive), anaemia, fatigue will be present
  • Bone or joint pain
  • Bruising
  • Epistaxis or bleeding gums
  • Recurrent fever (low grade)
  • Persistent cough
  • Dizziness
  • Lymphadenopathy (including tonsillar hypertrophy)
  • Priapism
  • Wheeze (from a mediastinal mass) or
  • Blurry vision/diplopia
  • Testicular enlargement
  • Headaches (with papilloedema & retinal haemorrhages)
  • Respiratory distress (hyperviscosity)
  • Cranial nerve palsies

Practical points at diagnosis

For some paeds oncology departments, there is a policy that the most senior ED doctor should place the cannula for a patient’s first presentation. In a stressful time for the child and family, this is a drip that needs to go in first time with as little fuss as possible. It is important for the medical staff to build trust with child and family early.

Although most specialties would have the registrar or senior resident “do the admission”, oncologists will often meet the family as soon as they are referred. The family will be seeing a lot of their oncologist, and establishing trust and rapport very early in the piece is important.

In this kind of presentation – from the community in a stable child during daylight hours – the oncologist will often have spoken to the haematologist about the film prior to meeting the patient. This enables them to give the most likely diagnosis (based on the film and history/examination) & answer a few questions.

References

National Cancer Institute – Childhood Acute Lymphoblastic Leukaemia Treatment (PDQ) – Risk-based Treatment Assignment

Peppercorn J et al. Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review. Lancet 2004; 363: 263–70

QPHON Guide to the Care of Children with Cancer in Queensland Document No. 2.1 15062012 © 2012 State of Queensland Queensland Health. via Q-Health intranet.