Internal Medicine

0521779407-14 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:17

Myelodysplastic Syndrome 1031

Treatment Options

■5-Azacytidine(Vidaza, Pharmion, Inc.) interferes with DNA methy-

lation and prolongs median time of progression to AML, and median

survival. 5-Azacytidine is now FDA approved for treatment of MDS

and is indicated for MDS patients with symptomatic cytopenias.

Another methyltransferase inhibitor, decitabine (Dacogen, MGI-

Pharma), also has activity and is currently under review at the

FDA.

■Lenalidomide:Agents with putative anti-angiogenic activity have

been at the forefront of one of the most promising developments

in treatment of MDS, although their precise mechanism of action

in MDS is not fully understood. Lenaliodmide (CC-5013, Revlimid,

Celgene) is a 4-amino-glutaramide analog of thalidomide and has

remarkable activity in treatment of MDS. A landmark safety and effi-

cacy study with oral lenalidomide in erythropoietin-unresponsive

MDS patients resulted in a remarkable 58% overall response rate; the

majority of pts achieved transfusion independence. Response rate

was karyotype-dependent and highest in patients with chromoso-

mal deletions of 5q31.1 (83%) compared with 56% of MDS patients

with normal karyotype, and only 12% of patients with other kary-

otypic abnormalities. Based on these findings and results of addi-

tional phase II studies, lenalidomide has recently been approved

by the FDA for treatment of transfusion-dependent patients with

del5q.

■G-CSF(Neupogen) for treatment of selected cases of MDS with neu-

tropenia, in particular in setting of acute infection

■Erythropoietinas above for treatment of symptomatic anemia

■Allogeneic or Unrelated Donor Stem Cell Transplantation (SCT)

➣Only curative therapy. Disease-free survival (DFS) variable,

depends on age of recipient, stage of MDS, performance status,

donor match. 70–80% DFS in best prognostic groups (age <40,

good performance status, low risk MDS, HLA identical donor).

OR

■Enrollment in Clinical Trial

Side Effects and Complications of SCT

■May be severe and life-threatening; morbidity and/or mortality

from infection, failure of engraftment, pulmonary hemorrhage,

acute and/or graft vs. host disease, veno-occlusive disease, among

others.