Chapter 92 Haematological malignancies

The treatment of haematological malignancy has been an evolving success story. In recent years, the prognosis for patients with acute leukaemia has changed from death within 1–3 months without effective therapy to long-term survival and cure in many cases.^1,² In some diseases the potential for regular cure of patients has been realised, including Hodgkin’s disease, childhood acute lymphoblastic leukaemia, some high-grade lymphomas and some adult leukaemias.³ These advances have predominantly resulted from the introduction of a wide range of cytotoxic chemotherapeutic regimens which permit obliteration of the disease in conjunction with comprehensive supportive therapy. In some cases, ‘supralethal’ therapy is necessary, with bone marrow transplantation (autologous or allogeneic) being used as marrow ‘rescue’ therapy. The development of ‘engineered’ highly specific and targeted drugs is offering further promise (e.g. monoclonal antibodies, tyrosine kinase inhibitors for chronic myeloid leukaemia).¹

It is important that clinicians not regularly involved in the care of these patients do not take a nihilistic approach to management of patients with haematological malignancy. If patients can be adequately supported and complications treated during the severe neutropenic stage of chemotherapy, clinical improvement may occur rapidly following marrow recovery. However, in patients requiring prolonged ventilatory support and/or dialysis, the prognosis is poor and intensive supportive therapy can usually only be justified if marrow recovery is imminent and there is a reasonable anticipated life expectancy if the crisis can be survived.

CLASSIFICATION AND PATHOPHYSIOLOGY

The heterogeneous nature of the haemopoietic and lymphoid cells, their individual kinetic characteristics and the disseminated nature of haemopoietic and lymphoid tissue explains the complexity of haematological malignancy. The numerous confusing classification systems advocated to ‘clarify’ understanding have in many cases increased the confusion for the non-expert. In broad terms, the haematological malignancies with origins in the marrow are classified as leukaemia or multiple myeloma, and those arising in the peripheral lymphoid tissues as Hodgkin’s and non-Hodgkin’s lymphomas (nodal and extranodal).

The leukaemias are divided into acute and chronic, generally according to the time span of their clinical course. In general, a leukaemia that is blastic in appearance behaves in an acute and malignant manner with a rapidly fatal outcome without therapy. This is in contrast to the chronic leukaemias in which the cells are more differentiated (‘benign’), with the disease following a more indolent course. Leukaemias are classified on the basis of their cell of origin with broad division into those of myeloid origin (i.e. of haemopoietic marrow origin) and those of lymphoid origin (i.e. arising from the cells of the immune system).

Most patients with acute myeloid leukaemia present with features of bone marrow failure. Acute promyelocytic leukaemia is a unique subtype of acute myeloid leukaemia which may typically present with disseminated intravascular coagulation (DIC) requiring expert haematological management.⁴ Acute lymphoblastic leukaemia is the commonest encountered in children. The lymphomas are a complex and heterogeneous group of malignancies ranging from highly malignant disorders through to low-grade indolent disease not requiring therapy.

The myelodysplastic syndromes are a group of disorders in which the main feature is bone marrow dysplasia. They are a heterogeneous group of potentially malignant haematological disorders which may be the harbingers of more classic leukaemic states or may behave as slowly evolving marrow failure syndromes. They usually occur in the elderly, have an insidious onset and may have a variety of clinical manifestations.

Dysplasia may affect any of the haemopoietic elements, with the patient presenting with a range of peripheral blood abnormalities, most commonly including anaemia, thrombocytopenia and neutropenia. Diagnosis, classification, understanding of pathophysiology and therapy have undergone enormous changes in recent years and the non-specialist can be excused for feeling confused.^5,⁶ There is a rising prevalence and incidence of the myelodysplastic syndromes. Epidemiological data indicate that they are more common than initially thought and probably on the increase, especially due to the ageing population and their occurrence as a late complication of cytotoxic chemotherapy.

Awareness of these relatively common disorders is important as undiagnosed patients with relatively normal blood counts may present de novo with life-threatening infection or haemorrhage in a postoperative or trauma setting.

COMPLICATIONS OF HAEMATOLOGICAL MALIGNANCY AND ITS THERAPY

METABOLIC DISTURBANCES

At presentation, haematological malignancy may be associated with a range of metabolic derangements.⁷ Hyperuricaemia and hypercalcaemia are well-recognised complications which may be associated with renal failure.⁸ The tumour lysis syndrome is a rarer complication which may occur spontaneously or shortly after the initiation of therapy.^9,¹⁰ There is sudden liberation of intracellular contents in quantities that overwhelm the excretory capacity of the kidneys, resulting in hyperkalaemia, hyperphosphataemia, hypocalcaemia and occasionally lactic acidosis. Pre-empting the development of this syndrome usually allows control of the metabolic effects, especially with the maintenance of high intravenous fluid intake, alkalinising the urine and administration of allopurinol. More recently, intravenous rasburicase – a recombinant uricolytic agent which, in contrast to allopurinol, acts on existing uric acid concentrations – is being used for the management of anticancer therapy-induced hyperuricaemia.¹¹ Rasburicase is contraindicated in patients with methaemoglobinaemia and glucose-6-phosphate dehydrogenase deficiency.

Multiple myeloma may be complicated by renal insufficiency, hypercalcaemia, hyperviscosity and hyperuricaemia. Most of these can be managed conventionally; however, with large amounts of monoclonal protein, fluid management can be difficult due to the hypervolaemia with or without hyperviscosity and plasma exchange may be indicated (see Chapter 90).

Figure 92.1 illustrates the numerous interacting factors to be considered when managing patients with neutropenia in association with haematological malignancy and its therapy. Table 92.1 lists the organisms which may be associated with various defects in the host defence system.