Acute leukaemia NS MOM

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Efforts are made to ensure the accuracy and agreement of these guidelines. However, we cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties

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Macmillan 2WW guidance

Scope:

• assessment and management of acute leukaemias – acute myeloid leukaemia (AML and acute lymphoblastic leukaemia (ALL) in children and adults in primary, secondary, and specialist care

Out of scope:

• chronic leukaemias and lymphomas

Definition:

• AML – type of acute leukaemia in which the white blood cells (WBC) produced in excess are immature granulocytes or monocytes, ie WBC formed from myeloid stem cells [1], or immature erythroid or megakaryocytes, ie platelet forming cells [17]:
  • to be called acute leukaemia, the bone marrow should include more than or equal to 20% leukaemic blasts [10]
  • acute promyelocytic leukemia (APL) is a subtype of AML and requires different treatment [10]
• ALL – type of acute leukaemia in which the WBCs produced in excess are immature lymphocytes, ie WBCs formed from lymphoid stem cells [1]

Incidence:

• both types of acute leukaemia can occur at all ages [17]:
  • ALL is more common in children and is the most common form of childhood leukaemia [20]
  • AML is more common in adults – incidence is highest in the elderly [21]
• annual incidence of acute leukaemia is estimated to be approximately 2400 in adults in England and Wales [1]
• annual incidence in the UK in children is approximately 450 for ALL and 70 for AML [2]

Risk factors associated with AML:

• age [21]
• initial leukocyte count [21]
• co-morbidities [21]
• prolonged exposure to petrochemical, solvents, pesticides, or ionising radiation [10]
• previous cytotoxic cancer therapy or radiotherapy [10]
• inherited syndromes [7]: 
  • chromosomal imbalances, eg Down's syndrome
  • chromosomal instability syndromes
  • syndromes of growth and cell survival signalling pathway defects
• acquired syndromes, eg severe aplastic anemia
• myelodysplasia [25]
• myeloproliferative agents [25]

Risk factors associated with ALL include [7]:

• chromosomal disorders such as Down’s Syndrome
• prenatal exposure to X-rays
• postnatal exposure to high doses of radiation
• inherited genetic polymorphism

Prognosis:

• in children, ALL survival rates are better than AML survival rates [17]:
  • for children with ALL, the cure rate is approximately 80% [20]
  • for adults with ALL, the cure rate is approximately 30−40% [20]
• in adults, AML survival rates are better than ALL survival rates [17]
• 5-year survival:

  • National Cancer Institute (NCI) statistics are 58% for children under age 15 years, and approximately 40% for adolescents age 15-19 years [25]

  • adult patients with ALL who are under age 60 years and treated on clinical trials have a 5-year survival rate of 30−40% [3]

  • adult patients with AML who are under age 60 years and treated on clinical trials have a 5-year survival rate of 40−50% [3]
  • adult patients over age 60 years with AML or ALL have a 5-year survival rate of under 20% [17]

• prognosis is dependent on a number of factors, including:

  • age [8]
  • laboratory parameters, eg WBC count, immunophenotypic, and karyotype [8]
  • initial response to treatment [8]
  • molecular factors, eg the presence of BCR-ABL confirming Philadelphia chromosome-positive (Ph+) ALL (worsens prognosis), and FL-T3 mutation and gene abnormalities in AML are both high-risk molecular abnormalities [17]
  • central nervous system (CNS) involvement [7]
  • Down's syndrome [7]

References:

[1] National Institute for Clinical Excellence (NICE). Improving outcomes in haematological cancers - the manual. London: NICE; 2003

[2]  Practice-informed recommendation. London; 2009.

[7] National Cancer Institute (NCI). Childhood acute lymphoblastic leukemia: treatment (PD®). Bethesda, MD: NCI; 2012.

[8] National Cancer Institute (NCI). Childhood acute myeloid leukemia/other myeloid malignancies: treatment (PD®). Bethesda, MD: NCI; 2012.

[10] National Comprehensive Cancer Network (NCC). Acute Myeloid Leukemia: 2.01. Fort Washington, PA; 2013.

[17] Contributors representing the National Cancer Action Team (NCAA); 2012.

[20] National Comprehensive Cancer Network (NCC). Acute Lymphoblastic Leukemia: 1.2. Fort Washington, PA: NCC; 2013.

[21] Fey MF, Dreaming M, on behalf of the ECMO guidelines working group. Acute myeloblastic leukaemias and myelodysplastic syndromes in adult patients: ECMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Onoclea 2010; 21: Suppl. 5:v158-61.

[25] National Cancer Institute (NCI). Adult acute myeloid leukemia (PD®). Bethesda, MD: NCI; 2012.

 At time of referral please issue the patient information leaflet below:

BNSSG  2WW Patient Information Leaflet. - COVID-19 Edition

Link to leaflet on CCG website: https://bnssgccg.nhs.uk/library/understanding-two-week-wait-urgent-referrals-and-covid-19/

• Leukaemia (URL) from Macmillan Cancer Support at http://www.macmillan.org.uk
• Leukaemia (URL) from Cancer Research UK at http://www.cancerresearchuk.org/about-cancer

• 'Leukaemia - a general overview' (PDF) from Patient UK at http://www.patient.co.uk

• 'Acute lymphoblastic leukaemia' (URL) from Cancer Research UK at http://www.cancerresearchuk.org/about-cancer
• 'Acute myeloid leukaemia (AML) (URL) from Cancer Research UK at http://www.cancerresearchuk.org/about-cancer
• 'Acute lymphoblastic leukaemia' (URL) from Macmillan Cancer Support at http://www.macmillan.org.uk
• 'Acute myeloid leukaemia (AML)' (URL) from Macmillan Cancer Support at http://www.macmillan.org.uk

  NSCCG Sign off form Jan 2018

 Updated in line with NICE Guideline NG12: Suspected cancer: recognition and referral to coincide with updated  BNSSG 2WW Referral forms

 Acute Leukaemia NSCCG Sign Off Forms Sept 2016

Date of publication: 31-Oct-2013

This care map has been drafted using the Map of Medicine editorial methodology (URL) and represents best clinical practice according to the highest quality evidence available, including the following:

• [7] National Cancer Institute (NCI). Childhood acute lymphoblastic leukemia treatment (PDQ®). Bethesda, MD: NCI; 2012.
• [8] National Cancer Institute (NCI). Childhood acute myeloid leukemia/other myeloid malignancies treatment (PDQ®). Bethesda, MD: NCI; 2012.
• [10] National Comprehensive Cancer Network (NCCN). Acute Myeloid Leukemia: 2.2013. Fort Washington, PA; 2013.
• [13] Scottish Intercollegiate Guidelines Network (SIGN). Long term follow up of survivors of childhood cancer. SIGN Publication no.132. Edinburgh: SIGN; 2013. 
• [16] ASBMT Executive Committee. The role of cytotoxic therapy with haematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence based-review. Biol Blood Marrow Transplant 2012; 18: 16-7.
• [19] National Institute for Health and Clinical Excellence (NICE). Azacitidine for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia. Technology appraisal guidance 218.  London: NICE; 2011.
• [20] National Comprehensive Cancer Network (NCCN). Acute Lymphoblastic Leukemia: 1.2013. Fort Washington, PA: NCCN; 2013. 
• [21] Fey MF, Dreyling M, on behalf of the ESMO guidelines working group. Acute myeloblastic leukaemias and myelodysplastic syndromes in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21: Suppl 5:v158-61.
• [22] Pidala J, Djulbegovic B, Anasetti C et al. Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission. Cochrane Database Syst Rev 2011; CD008818.
• [23] Gurion R, Belnik-Plitman Y, Gafter-Gvili A et al. Colony-stimulating factors for prevention and treatment of infectious complications in patients with acute myelogenous leukemia. Cochrane Database Syst Rev 2012; CD008238.
• [24] National Cancer Institute (NCI). Adult acute lymphoblastic leukemia treatment (PDQ®). Bethesda, MD: NCI; 2012.
• [25] National Cancer Institute (NCI). Adult acute myeloid treatment (PDQ®). Bethesda, MD: NCI; 2012.
• [26] Kouroukis CT, Haynes AE. The prophylactic use of filgrastim in patients with hematological malignancies. Toronto (ON): Cancer Care Ontario (CCO); 2009. 
• [27] Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: recommendations. Toronto, ON: Cancer Care Ontario Program in Evidence-based Care; 2009.
• [28] Ram R, Gafter-Gvili A, Vidal L et al. Management of adult patients with acute lymphoblastic leukemia in first complete remission: systematic review and meta-analysis. Cancer 2010; 116: 3447-57.

 Acute leukaemia may present with the following:

• breathlessness [1]
• unexpected bruising/petechiae/bleeding [1]
• recurrent infections [1]
• pain in joints or extremities – may be the only presenting symptom in children [20]
• fatigue [1]
• headaches [17]
• visual disturbances [17]
• persistent bone pain [1]
• bone fractures [1]

Patients presenting as emergencies [1]:

• likely to have acute infections
• disease is usually diagnosed by a blood test at the time of admission 

References:

[1] National Institute for Clinical Excellence (NICE). Improving outcomes in haematological cancers - the manual. London: NICE; 2003.

[17] Contributors representing the National Cancer Action Team (NCAT); 2012.  

[20]  National Comprehensive Cancer Network (NCCN). Acute Lymphoblastic Leukemia: 1.2013. Fort Washington, PA: NCCN; 2013. 

 Ask the patient about [20]:

• fatigue
• unexplained fever
• night sweats
• dyspnoea
• dizziness
• infection
• unexplained bleeding/petechiae
• persistent or unexplained bone pain [1]
• pain in the joints or extremities

Conduct a physical examination, which may reveal the following:

• pallor [17]
• lymphadenopathy [20]
• hepatosplenomegaly [20]
• petechiae [1] or ecchymosis [9]
• abdominal or testicular masses [20]
• chin numbness from cranial nerve involvement [20]
• unexplained bruising [1]
• gum hypertrophy or bleeding  [9]
• skin infiltrations [9]

Central nervous system (CNS) involvement is rare at presentation in patients with AML [10].

For children with a persistent headache, undertake a neurological examination; if the GP is unable to perform an adequate examination, an urgent referral to a paediatrician should be made [2]. - see Childhood cancer suspected pathway 

References:

[1] National Institute for Clinical Excellence (NICE). Improving outcomes in haematological cancers - the manual. London: NICE; 2003.

[2] Practice-informed recommendation. London; 2009. 

[9] Raj K, Mehta P. Acute myelogenous leukaemia. Best Practice. London: BMJ Publishing Group Ltd; 2010.

[10] National Comprehensive Cancer Network (NCCN). Acute Myeloid Leukemia: 2.2013. Fort Washington, PA; 2013.

[17] Contributors representing the National Cancer Action Team (NCAT); 2012.  

[20]  National Comprehensive Cancer Network (NCCN). Acute Lymphoblastic Leukemia: 1.2013. Fort Washington, PA: NCCN; 2013. 

 Initial investigations [5,17]:

• full blood count (FBC) [20]:
  • in acute leukaemia this will typically show a raised white cell count with low haemoglobin and platelets [3]
• blood film [1]:

  • usually shows the presence of excess blasts [3]

  • however, in some cases clearly identifiable blasts may not be present, or the white blood cell (WBC) count may even be lower than normal – the only abnormal sign in these cases may be a few atypical cells in the blood film or the presence of leukoerythroblastic features [11]

Also consider the following:

• liver function tests (LFTs) [3]
• renal function tests [3]
• bone profile [3]
• uric acid [20]
• lactate dehydrogenase (LDH) [20] 
• immunoglobulins [3]
• thyroid function tests (TFTs) and blood glucose – particularly if investigating lethargy [5]
• coagulation profile, particularly if the patient presents with bruising/bleeding [5,20]:
• acute promyelocytic leukaemia (APL) is associated with disseminated intravascular coagulation (DIC), ie [17]:
  • prolonged coagulation times
  • reduced fibrinogen – can be very low in the presence of normal prothrombin time (PT)/activated partial thromboplastin time (APTT) [5]
  • raised fibrin and fibrinogen degradation products (FDPs)
• erythrocyte sedimentation rate (ESR) [1]
• screening for active infections [20]
• monospot, Epstein-Barr virus (EBV) IgM [2] or EBV polymerase chain reaction (PCR) [17]
• chest X-ray to rule out mediastinal lymphadenopathy [2]

References:

[1] National Institute for Clinical Excellence (NICE). Improving outcomes in haematological cancers - the manual. London: NICE; 2003.

[2] Practice-informed recommendation. London; 2009.

[3] Contributors representing the National Cancer Action Team (NCAT); 2011.

[5] Practice-informed recommendation. 2013.

[11] Mitchell C, Hall G, Clarke RT. Acute leukaemia in children: diagnosis and management. BMJ 2009; 338: 1491-95.

[17] Contributors representing the National Cancer Action Team (NCAT); 2012.  

[20]  National Comprehensive Cancer Network (NCCN). Acute Lymphoblastic Leukemia: 1.2013. Fort Washington, PA: NCCN; 2013. 

 Differential diagnoses include:

• chronic leukaemias
• leukemoid reaction to infection
• Epstein Barr virus (EBV)
• cytomegalovirus (CMV)
• thrombocytopenic purpura
• solid tumour, particularly neuroblastoma
• parvovirus B19
• severe aplastic anaemia
• myelodysplasia
• lymphoma
• toxoplasmosis
• auto-immune diseases
• depression [5]

References:

[1] National Institute for Clinical Excellence (NICE). Improving outcomes in haematological cancers - the manual. London: NICE; 2003.

[2] Practice-informed recommendation. London; 2009.

[3] Contributors representing the National Cancer Action Team (NCAT).  2011.

[4] Fauci AS, Braunwald E, Kasper DL et al. Harrison's Principles of Internal Medicine, 17th Edition. New York, NY: McGraw-Hill Medical; 2008.

 The usual route to diagnosis is either :

• emergency admission without a blood test; or
• GP carries out a blood test, and the laboratory contacts GP to advise same or next day emergency admission 

If a blood film suggests an acute leukaemia please arrange an immediate admission with a haematologist.

2WW Haematology Services are available at Weston (WAHT), Bristol Haematology & Oncology Centre (UHB) and Southmead (NBT)