Haematologica 2003 - Supplements

Diagnosis requires a single area of bone destruction or an
extramedullary mass of clonal plasma cells, with a normal BM
aspirate and trephine, normal skeletal survey, no anaemia,
hypercalcaemia or renal impairment, and absent or low serum or
urinary paraprotein. In addition, diagnosis of SBP requires an
MRI of the spine showing no additional lesions. Over 50% of
patients with apparent SPB progress to multiple myeloma (MM)
and patients with an abnormal marrow appearance on MRI of the
spine have a higher rate of progression to overt MM. Such
patients should be considered to have MM at presentation.
Further investigations which may distinguish between SBP and
MM include immunophenotyping of bone marrow to look for an
excess of kappa or lambda staining plasma cells, MRI
examination of other areas to look for other plasmacytomas or
abnormal BM appearances, and FDG-PET scanning to look for
other foci of disease. In contrast to SBP, SEP rarely progresses to
myeloma and there is no data on the use of MRI of uninvolved
areas; the working group therefore considered that MRI of the
spine is not required for the investigation and diagnosis of SEP.
Management: SBP should be treated with radical radiotherapy
with a dose of 40 Gy in 20 fractions. A higher dose is
recommended for tumours >5cm. Surgery is reserved for patients
with vertebral instability or neurological compromise; such
patients should also receive radiotherapy. The timing of
radiotherapy in relation to surgery should be determined for
individual patients; while it may be preferable to carry out
surgery before radiotherapy, the placing of metal supports can
compromise the efficacy of radiotherapy. Reconstructive
orthopaedic surgery may be required in patients with anterior
column damage. Patients should be followed up carefully with
regular paraprotein measurements, as over 50% will progress to
myeloma. There is as yet no data on the use of the free light chain
assay in monitoring patients with SBP.
SEP of the head and neck is also best treated with radiotherapy
and radical surgery in this area should be avoided. A radiation
dose of 45 Gy in 25 fractions is recommended. For SEP in other
areas surgery should be considered as an alternative to
radiotherapy. If surgical margins are involved then adjuvant
radiotherapy should be given.
There are few data on adjuvant chemotherapy for either SBP or
SEP, but it may be considered in patients with bulky tumours or
histologically high-grade SEP.
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Guidelines for the Diagnosis and Management of AL
Amyloidosis
JM Bird, H Lachmann, J Cavenagh, A Mehta, PN Hawkins
and Diana Samson
For the UK Myeloma Forum
Systemic AL amyloidosis is a protein conformation disorder in
which monoclonal immunoglobulin light chains are deposited as
AL amyloid fibrils, which progressively disrupt normal organ
structure and function. It is often fatal within 2 years. AL
amyloidosis poses special problems for patient care; diagnosis
can be difficult and requires specialist expertise, while the
optimum management remains unclear. The UK Myeloma Forum
has been working with the UK National Amyloidosis Centre to
formulate evidence-based guidelines for diagnosis and
management. Some of the main recommendations are as follows:
Diagnosis requires histological confirmation of amyloidosis
followed by immunohistochemical staining to characterize the
fibril protein, although this technique is often not definitive in AL
type. Evidence should be sought of an underlying B-cell disorder
and serum and urine immunofixation should be performed in all
cases even if routine electrophoresis is negative. DNA analysis
may be required to exclude hereditary amyloidosis, since a
monoclonal gammopathy may incidentally co-exist.
Assessment of organ function requires assessment of renal,
hepatic and cardiac function in all cases and neurological
investigations in some patients. SAP scintigraphy allows
determination of the extent and distribution of visceral amyloid
deposits.
Monitoring Disease status should be monitored in terms of both
amyloid deposition and the underlying B-cell disorder, including
frequent monitoring of serum free light chains, serial SAP
scintigraphy and assessment of associated organ dysfunction.
Regression of amyloid and clinical improvement following
chemotherapy in AL amyloidosis is always delayed for many
months following adequate suppression of the underlying clonal
disease, and treatment strategies in individual patients are
presently best guided by their early effect on quantitative
measurements of serum free light chains.
Treatment Chemotherapy regimens in AL amyloidosis are
derived from those used in myeloma, but there have been few
randomised, controlled trials in AL amyloidosis. Colchicine is
ineffective. MP has been shown in phase III trials to be superior
to colchicine in terms of response and survival, although response
is slow and median survival still only 18-24 months. Alkylator
based combination chemotherapy regimens have not been shown
to be superior to MP. -Interferon has not been shown to be of
benefit. An important objective is rapid suppression of
amyloidogenic light chains, which infusional (VAD-type),
monthly iv melphalan 25 mg/m2 ± dexamethasone and high dose
regimens are able to achieve with broadly similar effect.
However, high dose therapy with PBSCT has a TRM of 15-40%
in AL amyloid. Its use should be restricted to selected patients
(those with no cardiac involvement, 1-2 organs involved and
GFR >50 ml/min), and particularly those who have not responded
to less intensive regimens. In patients who are sufficiently fit,
VAD is rational initial therapy, whereas monthly iv melphalan ±
dexamethasone is an alternative when VAD is contra-indicated or
ineffective. Other treatment options include oral MP,
dexamethasone, thalidomide, novel therapies and palliative care.
Supportive care is vital in all patients.
4.2 Characteristics of MGUS
079
MONOCLONAL GAMMOPATHY OF UNDETERMINED
SIGNIFICANCE (MGUS): CLINICAL PREDICTORS OF
MALIGNANT TRANSFORMATION IN 434 PATIENTS
FROM A SINGLE INSTITUTION WITH A LONG FOLLOW-
UP
J. Bladé, M. Rozman*, L. Rosiñol, B. Nadal, E. Giné, M.
Aymerich*, J. Esteve, F. Cervantes, A. López-Guillermo, F.
Bosch, B. Nomdedeu, E. Montserrat.
Institute of Hematology and Oncology, Department of Hematology
and Hematopathology Unit*, IDIBAPS, Hospital Clínic, Barcelona,
Spain.
Background: MGUS is a frequent disorder characterized by the
presence of a small serum M-protein in individuals with no
evidence of multiple myeloma (MM), Waldenström´s
macroglobulinemia (WM) or primary amyloidosis (AL).
Although about one fourth of these individuals will evolve into a
malignant disease, there are not well-established predictors of
outcome.
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