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1760 Part XI: Malignant Lymphoid Diseases Chapter 107: Myeloma 1761

show hypointensity on T1-weighted images and hyperintensity on short catastrophes possibly linked to arrhythmias, caused by fluid overload
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tau inversion recovery (STIR)–weighted images, whereas amyloidoma- or cytokines. There is a prevailing misconception that high-dose
type lesions remain hypointense. dexamethasone pulsing, alone or with added thalidomide, even at low
Appropriate biopsy techniques should be applied to clarify the doses, is safer and better tolerated than appropriately dosed melpha-
presence and extent of accompanying amyloidosis or, similarly, LCDD lan with stem cell support. Owing to its hematopoietic stem cell–com-
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in these patients. The diagnosis of AL amyloid (Chap. 108) often can be promising properties, melphalan, even at 50 to 70 mg/m , is still best
made by fine-needle aspiration of subcutaneous fat or by biopsy of the administered in the context of autologous stem cell support.
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rectal mucosa, although biopsy of accessible clinically involved tissue
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is preferable. AL amyloid also may be detectable on marrow biopsy.
Staining the tissue with Congo red may reveal perivascular amyloid SMOLDERING MYELOMA
with its classical apple-green birefringence when viewed under polar- Patients with smoldering myeloma have historically been followed
ized light. Thioflavin T is also a useful stain, producing intense yellow without therapy. 629–631 At this time, there is no role for treating smolder-
619
green fluorescence in AL amyloidosis. LCDD require immunofluores- ing myeloma patients. Patients should be followed at close intervals of
cence analysis of unfixed tissue; formalin fixation should be avoided every 3 to 6 months and clinical trials should be offered where available.
whenever it is suspected. At a median followup of 40 months in a small, randomized, pro-
Even though the tumor load is very low, patients with AL amy- spective study of 125 patients with high-risk smoldering myeloma,
loidosis and immunoglobulin deposition disease suffer from the con- treated with either lenalidomide and dexamethasone or observation,
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sequences of myeloma secretory products, even at relatively modest TTP was not reached by the intervention arm compared to 21 months
amounts, resulting in damage to kidneys, heart, gastrointestinal tract, in the observation arm (p <0.001), and the 3-year OS was 94 percent
liver, spleen, and peripheral and autonomic nerves. All current treat- versus 30 percent (p = 0.03). Despite these favorable finding, the high-
ment targets the monoclonal plasma cell population and advances risk criteria employed by this study are not those commonly used in
have paralleled the advances in treatment of myeloma. Whereas stan- practice. High-risk in this study was defined as having at least 10 percent
dard melphalan-prednisone has been only marginally effective, high- marrow infiltration with plasma cells, a M-protein of 3 g/dL or greater,
dose dexamethasone pulsing plus interferon, effecting more rapid and or a urinary Bence Jones protein level of more than 1 g/24 hours. Based
profound responses in myeloma, has also shown encouraging results on these criteria, some patients with active myeloma were classified as
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in AL amyloidosis. Similarly, positive results have been obtained having high-risk smoldering myeloma, which may have contributed to
621
with dexamethasone plus melphalan. The Boston University group the differences in the outcomes between the two arms of the trial. The
has pioneered the use of high-dose melphalan with auto-HSCT (see IMWG has advised that those smoldering myeloma patients who have
622
Fig. 107–16), which is an effective regimen in carefully selected greater than 60 percent marrow plasma cells, κ:λ FLC ratios greater
633
patients. In a study of 312 patients, high-dose melphalan (100 to 200 than 100, and two lesions on MRI or PET-CT imaging may bene-
634
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mg/m ) with auto-HSCT resulted in a median survival of 4.6 years with fit from therapy. 635–637 Further investigation of treatment in high-risk
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a treatment-related mortality of 13 percent. There was also significant myeloma is warranted before changing the treatment paradigm in this
improvement in organ function. The role of allogeneic transplantation population.
in AL amyloidosis is unclear.
Incorporation of the newer agents, such as the IMiDs and pro-
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