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aldenström

’

macroglobulinemia

–

review

ssoc

ras

2014; 60(5):490-499

497

are necessary to reduce the concentration of IgM from 30

to 60%. The sessions should be repeated daily until symp-

toms subside or until normalization of serum viscosity.

Subsequent treatment should be started quickly, as the

concentration of IgM will return to its initial level after 4

to 5 weeks.

These patients should be treated with the de-

xamethasone, rituximab and cyclophosphamide (DRC)

combination regimen. The main reasons for choosing this

regimen in these patients are the good treatment toleran-

ce, reduced myelosuppression and the lack of toxicity for

stem cells.

3,65

In patients with relapses or who are refractory to the-

rapy, the choice of treatment depends on the first-line

treatment already utilized, the quality/duration of the

response and other variables, such as age, tolerance to ini-

tial treatment, and also the possibility of the patient be-

ing a candidate for stem cell transplantation.

The reuse of the first-line treatment is recommended

if the response to initial treatment was maintained wi-

thout maintenance for at least 12 months. Otherwise,

another first-line agent or combination therapy should

be used.

In patients with short-term remission or resistance

to initial treatment, therapy with a drug of different phar-

macological class as monotherapy or combined is recom-

mended. In association therapy, a regime using rituximab,

fludarabine and cyclophosphamide is highlighted; howe-

ver, the latter should be avoided in younger patients and

candidates for autologous stem cell transplantation.

The use of bortezomib (proteasome inhibitor) has pro-

ven promising, as well as alemtuzumab (anti-CD52 mono-

clonal antibody) datalidomida, enzastaurin (protein kina-

se C inhibitor), everolimus (inhibitor of mammalian target

of rapamycin - mTOR) and perifosine (Akt inhibitor).

62,64,72

Histone deacetylase inhibitors treatment agents, such as

panobinostat (LBH589), new proteasome inhibitors, such

as carfilzomib, human anti-CD20 monoclonal antibody,

such as ofatumumab, and alkylating agents, such as ben-

damustine, also seem to be promising agents.

Transplantation of hematopoietic stem cells is indi-

cated in younger patients with multiple recurrences or who

have been refractory to previous treatments.

Autologous

transplantation is associated with improved survival and

long periods without disease progression, and should be

considered in all candidate patients presenting relapse.

The concentration of monoclonal IgM is one of the

parameters most commonly used among the criteria for

assessing response to treatment. However, this biomar-

ker is not always reliable, since its concentration can be

affected by the treatment itself.

Taking into account the criteria for treatment res-

ponse, complete response is observed when IgM serum

levels normalize with complete disappearance of IgMmo-

noclonal protein (by immunofixation), histological eva-

luation of the bone marrow shows no evidence of disea-

se, and all symptoms, lymphadenopathy and/or

organomegaly are resolved. Partial response is conside-

red in a scenario of ≥ 50% decrease in the monoclonal IgM

serum concentration, decreased lymphadenopathy/orga-

nomegaly and absence of new symptoms and/or signs of

active disease on electrophoresis of serum proteins com-

pared to the baseline values. A minimal response is ob-

served when the reduction in electrophoresis of mono-

clonal IgM is

50 but ≥ 25%, and no new symptoms and/

or signs of active disease are observed. The stable disease

corresponds to cases in which the value of monoclonal

IgM relative to baseline undergoes a reduction of

25%

and increases

25%, with no progression of lymphadeno-

pathy/organomegaly and cytopenias, and no significant

clinical signs or symptoms. The disease is considered pro-

gressive when there is an increase in the detectable amount

of protein electrophoresis and monoclonal IgM serum

levels ≥ 25% (confirmed by a second assessment) or pro-

gression of complications resulting from the disease or

symptoms attributed to WM.

The concentration of sCD27 and assessment of the

amount of monoclonal free light chains have been pre-

sented as potential biomarkers for laboratory monito-

ring of therapy.

74,75

The investigation of alternative bio-

markers is essential for a more reliable and less invasive

clinical evaluation.

esumo

Macroglobulinemia de Waldenström – uma revisão.

A macroglobulinemia de Waldenström (MW) é uma doen-

ça linfoproliferativa dos linfócitos B, caracterizada por um

linfoma linfoplasmocítico na medula óssea e por hiperga-

maglobulinemia monoclonal de tipo IgM. Foi descrita pela

primeira vez em 1944, por Jan Gösta Waldenström, que

descreveu dois doentes com hemorragia oronasal, adeno-

patias, anemia, trombocitopenia, velocidade de sedimen-

tação eritrocitária e viscosidade sérica elevadas, radiogra-

fia óssea normal e medula óssea infiltrada por células

linfoides.

AMW é uma doença rara comumpercurso clínico normal-

mente indolente, atingindo principalmente os indivíduos

com idades entre 63 e 68 anos. A maioria dos doentes apre-

senta sintomas e manifestações clínicas relacionadas com a