Treatment of anemia in low-risk myelodysplastic syndromes with amifostine. In vitro testing of response.
Amifostine (AMF) promotes in vitro growth and survival of hematopoietic progenitors. In this study we evaluated the efficacy of AMF in the treatment of anemia in patients with low-risk myelodysplastic syndromes (MDS) and the possible predicting value for response to AMF therapy of two types of in vitro clonogenic assays. Two different doses of AMF, 300 mg/m2 (group A, 11 patients) or 400 mg/m2 (group B, 16 patients), were studied. AMF was given three times weekly for 3 weeks, i.v., followed by 2 weeks off therapy. Patients were evaluated after two cycles of treatment. Partially or nonresponding patients of group A received 400 mg/m2 AMF and were reevaluated. An increase of hemoglobin (Hb) values of more than 2 g/dl and a 100% decrease in transfusion requirements for at least 6 weeks were defined as a complete response (CR) while an increase of Hb values of 1-2 g/dl or a 50% decrease in transfusion requirements was considered as a partial response (PR). In group A, two out of 11 (18.1%) patients achieved a CR with the initial dose and one of the nine that received 400 mg/m2 AMF achieved a PR. In group B, three out of 16 (18.7%) patients achieved a PR; the overall response rate in both groups was 22.2%. In group A, bone marrow progenitor assay was performed pre- and post-amifostine treatment. Erythroid burst-forming units (BFU-E) were increased in six out of 11 (54.5%) patients, and this increase preceded the rise in Hb levels in three of them. In group B, a clonogenic assay was performed in 11 out of 16 patients before AMF treatment. In vitro results after pretreatment with 500 microM amifostine confirmed the response of two MDS patients that achieved a PR. No response in vitro was observed in all eight nonresponding patients and in one PR patient. The lack of response in the clonogenic assays predicted for nonresponse to treatment with a predictive power of 91.8%. We conclude that 300 mg/m2 is an adequate initial treatment for low-risk MDS patients and both clonogenic assays have a strong predicting value for response to treatment.
Viniou
N
N
1st Department of Internal Medicine, University of Athens School of Medicine, Laikon General Hospital, 24 Sofokleous Street, 17671, Greece, jbnv@otenet.gr
Terpos
E
E
Galanopoulos
A
A
Kritikou-Griva
E
E
Akel
S
S
Michalis
E
E
Apostolidou
E
E
Georgiadou
D
D
Kouraklis
A
A
Parharidou
A
A
Kokkini
G
G
Symeonidis
A
A
Anagnostopoulos
N I
NI
Christakis
J I
JI
Tasiopoulou
A
A
Loukopoulos
D
D
Yataganas
X
X
D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000008:administration & dosage*; D000753:Anemia, Refractory / Q000188:drug therapy* / Q000209:etiology; D001854:Bone Marrow Cells / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000188:drug therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors
D006454:Hemoglobins; D004999:Amifostine