Recurrence of ALL occurs most frequently in the bone marrow and is associated with a worse prognosis if it occurs during maintenance therapy. CNS recurrence, detected by the presence of leukaemic blast cells in the cerebrospinal fluid, is now less frequent since the regular use of CNS prophylaxis. Treatment comprises intrathecal drugs plus radiotherapy to the meninges surrounding the brain and spinal cord, followed by reinduction chemotherapy if the recurrence is limited to the CNS. Unfortunately, it often occurs in association with bone marrow recurrence, when induction of a second CR followed by myeloablative therapy with allogeneic or autologous BMT is the only potentially curative option.
Testicular recurrence is usually manifest by painless enlargement of one or both testicles. It can occur in isolation, shortly before, or concurrent with bone marrow recurrence. Treatment involves radiotherapy to the testes, followed by reinduction chemotherapy (for isolated testicular recurrence) or, if the marrow is also involved, the latter followed by myeloablative therapy with allogeneic or autologous BMT, provided a second remission can be achieved.
Chronic myeloid leukaemia
The majority of patients die within 5 years of diagnosis. The illness has a progressive clinical course which starts with a chronic phase of 3-4 years’ duration. This evolves into an accelerated phase which may be manifest by fever, weight loss, increasing splenomegaly, anaemia, thrombocythaemia and refractory leukocytosis with increasing numbers of blast cells. The duration of the accelerated phase is variable though blastic transformation usually supervenes within a few months. Unlike de novo acute leukaemia, the blastic phase of CML is characterized by the development of acute leukaemia which may be myeloid (60%), lymphoid (30%) or erythroid (10%) in origin. The blastic phase is generally refractory to treatment, the median survival being less than 6 months. Less frequently, CML transforms into myelofibrosis, death ensuing from bone marrow failure.
CLINICAL FEATURES
ymptoms
These are usually of insidious onset:
• Anaemia
• Sweating at night, fever, weight loss
• Abdominal discomfort due to splenic enlargement
Signs
• Anaemia
• plenomegaly
INVESTIGATION
BLOOD COUNT:
Hb low or normal.
WCC raised with characteristically the whole spectrum of myeloid precursors, including a few blast cells.
Platelet count low, normal or raised.
BONE MARROW ASPIRATE shows a hypercellular marrow with an increase in myeloid precursors. On cytogenetic analysis, the Ph chromosome t(9;22) is present in most patients.
TREATMENT
CONVENTIONAL TREATMENT – the aim is to relieve symptoms, keep the WCC under control and reduce the size of the spleen. Most patients are currently treated with hydroxyurea (or busulphan) given orally with allopurinol to prevent hyperuricaemia.
MYELOABLATIVE THERAPY SUPPORTED BY ALLOGENEIC BMT can be curative but the approach is limited by donor availability, the age of the patient, and the morbidity and mortality of the transplant procedure .
EXPERIMENTAL TREATMENT – trials involving IFN are currently in progress to determine whether this drug is any ‘better’ than the conventional treatment.
Chronic lymphocytic leukaemia
CLL is an incurable disease of older people, characterized by an uncontrolled proliferation and accumulation of mature B lymphocytes (although T-cell CLL does occur). The symptoms are a consequence of bone marrow failure, i.e. anaemia, infection and bleeding. A proportion of patients remain asymptomatic and never need any treatment, dying of an unrelated cause; in the remainder, the disease can usually be kept under control for 9-10 years, infection being the predominant cause of death.
leukaemia.
CLINICAL FEATURES
As mentioned above, some patients may be asymptomatic, the diagnosis being a chance finding on the basis of a blood count done for a quite different reason.
Symptoms
• Symptoms of anaemia ma develop rapidly in the context of haemolysis, which is usually precipitated by infection.
• Recurrent infections are due to neutropenia with or without reduced immunoglobulin levels.
• Painless lymph node enlargement.
Signs
Any combination of:
• Signs of anaemia
• Lymph node enlargement
• Enlarged liver and/or spleen
INVESTIGATIONS
BLOOD COUNT:
Hb low or normal WCC >15 x 109/litre of which at least 40% are lymphocytes.
Platelets low or normal
SERUM IMMUNOGLOBULINS low or normal COOMBS’ TEST positive if haemolysis is occurring Two different staging classifications are in use. They are useful because they correlate closely with prognosis. The median survival of patients with stage 0 (or stage A) CLL is 8 years as compared with 2 years for patients presenting with stages III or IV (or stage C) disease
TREATMENT
The disease may remain stable for several years. There is no advantage to starting treatment before there is a clinical indication, e.g. anaemia, recurrent infections, bleeding, ‘bulky’ lymphadenopathy or increasing splenomegaly. Chlorambucil is most often used. The purine analogues, fludarabine and 2-cWoroadenosine acetate, are being evaluated, interest lying in the fact that CR can be achieved although such remissions are rarely durable.
Hairy cell leukaemia (HCL)
A rare disease of late middle age, HCL represents again a clonal proliferation of abnormal B (or very rarely, T) cells which, as in CLL, accumulate in the bone marrow and spleen. The bizarre name relates to the appearance of the cells on a blood film where they have an irregular outline due to the presence of filament-like cytoplasmic projections.
CLINICAL FEATURES
Symptoms
• Symptoms of anaemia
• Recurrent infections
• Abdominal discomfort due to splenic enlargement
Signs
• Signs of anaemia
• Palpable spleen
INVESTIGATIONS
BLOOD COUNT:
Hb usually low
WCC usually low (or raised with circulating ‘hairy cells’)
Platelets usually low
BONE MARROW shows increased cellularity with characteristic infiltration by ‘hairy’ cells
TREATMENT
The use of IFN has revolutionized the management of patients with this illness. Although CR is rarely achieved, in the majority of cases the blood count reverts to normal obviating the need for regular blood transfusions and admissions to hospital with life-threatening infections. Such remissions are temporary but treatment can be given repeatedly. Two new drugs, deoxycoformycin and 2-chloroadenosine acetate (2- CDA), are of interest because CR is achieved much more frequently than with IFN.
Prolymphocytic leukaemia
Another rare B-cell disorder, often mistaken for CLL, prolymphocytic leukaemia, is characterized by bone marrow failure (anaemia, neutropenia and thrombocytopenia) and, as in HCL, splenomegaly. Treatment is generally with chlorambucil as for CLL, though splenectomy may be indicated and, again, fludarabine is being evaluated.
