Introduction

Published on 03/04/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

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Introduction

The leukaemias are a heterogeneous group of malignant blood disorders. In this introductory section, general characteristics such as definitions, aetiology and classification are discussed. Each of the more common types of leukaemia is subsequently described in more detail.

Definition

Leukaemia is a type of cancer caused by the unregulated proliferation of a clone of immature blood cells derived from mutant haematopoietic stem cells. The disease is the result of multiple acquired genetic and epigenetic events which can vary widely between patients. Leukaemic transformation is assumed to occur at or near the level of the leukaemic stem cell prior to definite lineage commitment. The leukaemic cells do not differentiate normally. They may avoid standard mechanisms of cell death (apoptosis) and they may also retain the stem cell signature of self-renewal. This relentless proliferating clone of aberrant cells eventually squeezes out normal cells from the bone marrow causing marrow failure and death.

Leukaemia is not a common disorder but it is a significant cause of death from cancer (Fig 19.1). There is a male preponderance in most types of leukaemia. Geographic variations exist; for instance, chronic lymphocytic leukaemia is the predominant form of leukaemia in the Western world but is much less frequent in Japan, South America and Africa.

Fig 19.1 Annual causes of death from malignancy in the year 2011
(estimated data from United States).

Aetiology

As for other malignancies, the evolution of leukaemia is likely to be a multistep process. Thus, accumulated genetic mutations corrupt normal cellular pathways controlling proliferation and differentiation and lead to the production of an autonomous proliferating stem cell clone (‘clonal evolution’). It is easiest to think about the aetiology in terms of these acquired genetic abnormalities and other more general predisposing factors.

Table 19.1

Factors predisposing to leukaemia

Radiation exposure

Previous chemotherapy (particularly alkylating agents)

Occupational chemical exposure (e.g. benzene)

Some genetically determined disorders (e.g. Down syndrome)

Viral infection (only HTLV-1 proven as a causative factor)

Myelodysplastic and myeloproliferative disorders

Other possible (e.g. cigarette smoking)

The incidence of acute leukaemia and chronic myeloid leukaemia increases with radiation dose exposure in all age groups. Classic studies have included people exposed to the atomic bombs in Japan and patients receiving radiotherapy for ankylosing spondylitis in the middle years of the 20th century. Results from studies of diagnostic radiation and adult leukaemia are inconsistent and in appropriate radiological procedures the benefit is likely to outweigh what appears to be at most a very small risk. Paternal preconception exposure to ionising radiation has been associated with an increased incidence of acute leukaemia in offspring.

Cytotoxic chemotherapy, particularly with alkylating agents, leads to an increased risk of leukaemia (Fig 19.3). The risk appears to be greatest in older patients also treated with radiotherapy. The best established occupational leukaemogenic exposure is undoubtedly to benzene. A number of genetically determined diseases also predispose to leukaemia. Here the liability to leukaemia is probably caused by factors such as increased chromosomal breakage (e.g. Fanconi’s anaemia) and immunosuppression (e.g. ataxia telangiectasia).

Fig 19.3 Peripheral blood film in a young woman with acute myeloid leukaemia.
She had received chemotherapy for choriocarcinoma several years previously.

Viruses are known to be the main cause of leukaemia in many animals but in humans the only well-proven association is of the HTLV-1 virus with the rare disorder T-cell leukaemia lymphoma (Fig 19.4). Myelodysplastic syndromes (pp. 50–51) and myeloproliferative disorders (pp. 64–67) may transform to acute myeloid leukaemia.

Fig 19.4 Bone marrow trephine appearance in human T-cell leukaemia lymphoma.
The only human leukaemia with a known viral causation.

Classification

In such a potentially complex group of disorders it is helpful to use a relatively simple classification. The leukaemias can most broadly be divided into acute and chronic types depending on their clinical course. The classification illustrated here (Table 19.2) further divides leukaemias into their cell of origin (i.e. myeloid or lymphoid) and refers to the microscopic appearance (morphology) of the leukaemic cells. The traditional classification of the acute leukaemias is that of the FAB group – the abbreviation being for the French, American and British nationalities of the terminologists – but this has been overtaken by the World Health Organization (WHO) system. Basic morphological techniques (e.g. microscopic inspection of a blood film and bone marrow sample) remain important in the initial diagnosis but cytogenetic and molecular genetic techniques are becoming increasingly important in classification as acquired genetic changes frequently have prognostic significance and can guide treatment.

Table 19.2

Classification of leukaemia ¹

Acute leukaemia	Acute myeloid leukaemia
	Acute lymphoblastic leukaemia
Chronic leukaemia	Chronic myeloid leukaemia
	Chronic lymphocytic leukaemia
Other types	Hairy cell leukaemia
	Prolymphocytic leukaemia
	T-cell leukaemia lymphoma