ACUTE LYMPHOBLASTIC LEUKAEMIA

ACUTE LYMPHOBLASTIC LEUKAEMIA  is a malignant tumour of haemopoietic precursor cells of the lymphoid lineage probably arising from the marrow in most cases.

Incidence

Commonest malignancy in childhood with the majority of cases in the 2-10 age groups (median 3.5 years).  Rare leukaemia in adults, - 1 in 70,000 annually i.e. – 7 times less common than AML.  In adults, there is further slight peak in old age.

Aetiology

Unclear.  Known predisposing factors are high dose radiation e.g. in Chernobyl survivors, chronic benzene exposure and hereditary predisposition in Down’s and Fanconi’s syndromes.  Chemicals, pollution, viruses, urban-rural population movements, father’s radiation exposure, random levels and proximity to power lines have all been postulated.

Classification – morphological (French-American-British, FAB)

            L1        Commonest, small homogeneous blasts, single nucleolus

            L2        blasts larger, more pleomorphic and multinucleolate

L3        blasts larger, strongly basophilic and have cytoplasmic vacuoles – associated with B cell phenotype

·         Immunophenotyping – lymphocyte maturation markers distinguishes early or null cell ALL from pre-B or common ALL – the most frequent group.  <10% are T-cell lineage and <5% B cell lineage showing T and B lymphocyte markers respectively.

·         Karyotypic analysis – identifies some risk groups of which the presence of the Philadelphia chromosome is poor risk and occurs in 10—20% of cases.

Clinical features – acute, seriously ill presentation is common

·       Malaise, sweats, weight loss, anorexia, anaemic symptoms, infectious particularly upper and lower respiratory tracts, skin lesions, purpura, nosebleeds, gum bleeding on tooth brushing.

·       Signs include widespread lymphadenopathy, mild to moderate splenomegaly, hepatomegaly and orchidomegaly.

·       Leucostatic signs (eg. diffuse pulmonary shadowing, hypoxia and retinal haemorrhage).

·       SVC obstruction may occur with mediastinal nodes.

·       CNS signs include altered consciousness, cranial nerve palsies especially of facial VII nerve, sensory disturbances and meningism. 

Investigations and diagnosis

·       FBC and blood film, bone marrow aspirate and biopsy.

·       Total WBC usually high with blasts cells on film but may be low (previously known as aleukaemic leukaemia).

·       Hb. and platelets often low and clotting may be deranged.

·       BM heavily infiltrated with blasts – immunophenotyping and karyotyping on blood and marrow allows classification as above.

·       CXR and CT scan needed if B or T cell phenotype for abdominal or mediastinal LNs respectively.

·       LP mandatory (note- fundoscopy, CT head scan and platelet transfusion usually required)

Treatment emergency

·       Seek expert help immediately.

·       Cardiovascular and respiratory resuscitation may be needed if septic shock or massive haemorrhage.

·       Leucapheresis may be needed if peripheral blast count high or signs of leucostasis (retinal haemorrhage, reduced conscious level, diffuse pulmonary shadowing on CXR or hypoxia).

·       LP is meningism (note precautions above).

Supportive treatment

·       Provide explanation and offer counselling – the disease label and duration of treatment are often distressing.

·       RBC and platelet transfusion support will continue through treatment.

·       Start neutropenic regimen as prophylaxis against infections.

·       Start hydration and allopurinol.

Specific

·       Enter patient into MRC or other high quality trial if possible.

Treatment plan

·       2 phase induction chemotherapy to induce remission, then

·       2 or 3 intensification blocks of further chemotherapy interspersed with intrathecal methotrexate x 6 ± 3 cycles of IV methotrexate or cranial irradiation as CNS prophylaxis.

·       Outpatient based chemotherapy (2 years), known as maintenance therapy.

·       Transplant options:

-          allogeniec and autologous transplantation largely reserved for children who relapse but considered in first CR adults <60 especially if Philadelphia chromosome positive disease.

-          Major complications are infective episodes which may be bacterial (Gram+ve and Gram–ve), viral (esp. HSV, HZV) and fungal (Candida and Aspergillus).

·         In the longer term, relapse is the main complication.

  Prognosis

Childhood ALL now has a cure rate of >70% overall and up to 90% in the best prognostic group i.e. girls aged 1-10 years with low presenting WBC, no CNS disease and absence of Philadelphia chromosome who achieve CR after first phase induction chemotherapy.  This is perhaps the finest example of the achievements of modern intensive, combination chemotherapy.  Unfortunately, the adult results are less good.  Young patients in the best prognostic group with allogeniec BMT after chemotherapy may have 40% cure rate but overall for adults <60, the cure rate is <20%.