Page 292 - Essential Haematology

278 / Chapter 21 Multiple myeloma and related disorders

phatase is normal (except following pathologi- markedly reduced, peripheral blood stem cells are
cal fractures). usually collected after mobilization using a combi-

9 The serum creatinine is raised in 20% of cases. nation of chemotherapy and granulocyte colony -
Proteinaceous deposits from heavy light chain stimulating factor (G - CSF). High - dose melphalan,
proteinuria, hypercalcaemia, uric acid, amyloid with or without radiotherapy, is the typical condi-
and pyelonephritis may all contribute to renal tioning regimen for autologous SCT. Two consecu-
failure (Fig. 21.7 ). tive SCT procedures are used in some centres.
10 A low serum albumin occurs with advanced Maintenance treatment after autologous SCT with
disease. thalidomide, lenalidomide, bortezomib and other
11 Serum β 2 - microglobulin is often raised and is a drugs is under trial as are protocols that omit SCT
useful indicator of prognosis. Levels less than altogether.
3.5 mg/L imply a relatively good prognosis, Although allogeneic transplantation may cure
above 5.5 mg/L bad. the disease it carries a high procedure - related mor-
12 Cytogenetic analysis shows that approximately tality and patients frequently relapse after the
half the tumours have an increased number of procedure.
chromosomes ( hyperdiploid ) whereas non - Non - intensive therapy In elderly patients
hyperdiploid cases have a high incidence of courses of the oral alkylating agent melphalan
translocations involving the immunoglobulin usually in combination with prednisolone, thali-
heavy - chain gene ( IGH ). The D - cyclin genes, domide or bortezomib are eff ective in reducing

D 1 , D 2 or D 3 , are often involved in the translo- the tumour burden. Typically, paraprotein levels
cations. Monoallelic loss of 13q is frequent in gradually fall, bone lesions show improvement and
both categories and all these genetic abnormali- blood counts may improve. Cyclophosphamide is
ties may also be seen in MGUS (see p. 282 ) . also effective and simple to use as a single agent.

However, after a variable number of courses a
‘ plateau phase ’ is reached in which the paraprotein
Treatment
level stops falling. At this point treatment is stopped

This may be divided into specific and supportive and the patient is seen at regular intervals in the

(Fig. 21.8 ). outpatient clinic. After a variable period of time,
‘
often around 18 months, the disease escapes ’ from
plateau with rising paraprotein and worsening
Specifi c
symptoms. Further chemotherapy may be given
At the current time the disease remains incurable although the disease becomes increasingly diffi cult
except for those very few, mostly younger, patients to control.
who may be cured by allogeneic stem cell transplan-
tation (SCT). For all other patients the major treat- Notes on s pecifi c d rugs u sed in m yeloma

ment decision is between the use of intensive Th alidomide is useful in first - line therapy and also
therapy (mostly for patients aged less than 65 – 70 in the management of relapsed disease. Its precise
years) and non - intensive therapy for older patients. mechanism of action is unknown and it has a

Intensive therapy involves the combination of number of side - effects such as sedation, constipa-
4 – 6 courses of chemotherapy to reduce the tumour tion, neuropathy and thrombosis (Table 21.3 ). Th e
burden usually followed by stem cell collection and addition of dexamethasone increases the response
autologous SCT after high - dose chemotherapy. rate but venous thrombosis becomes a major
Repeated intravenous or oral chemotherapy cycles concern. Prophylactic anticoagulation with heparin,
use drugs such as cyclophosphamide, dexametha- warfarin or aspirin is needed when thalidomide is
sone and thalidomide (CDT), lenalidomide, used in induction regimens.
dexamethasone, Adriamycin or the proteasome Lenalidomide is an analogue of thalidomide
inhibitor, bortezomib. After several courses of treat- and is highly active in the management of myeloma.
ment, when the number of tumour cells has been It is widely used for relapsed disease and is being