[Effect of treatment with 13-cis-retinoic acid and ara-C on the hematopoietic stem cells of patients with myelodysplastic syndromes].
OBJECTIVE
To assess the "in vivo" effect of 13-cis-retinoic acid and low dose Ara-C in MDS as well as to establish "in vitro" advantage of retinoid dose-related growth pattern on bone marrow cultures as defined by culture timing and CFU-GM proliferative response.


METHODS
We evaluated 28 patients diagnosed of MDS according to FAB classification, of whom 4 cases had RA, 8 cases SRA, 14 cases RAEB and 2 cases RAEB-T. Patients who had RA and SRA were treated with oral 13-cis-retinoic acid at doses of 20-40 mg daily for 4 months and those cases with RAEB and RAEB-T had subcutaneous Ara-C at doses of 3 mg/m2 twice a day for 21 days. The "in vivo" and "in vitro" effect of retinoic acid on the haemopoietic differentiation was evaluated by the growth CFU-GM in semisolid cell culture methods.


RESULTS
Increasing in vitro concentrations of 13-cis retinoic acid did not enhance the growth of myelodysplastic progenitors. Nevertheless, our study did not find any beneficial therapeutic effect of retinoic compounds in MDS patients. In this study, low-dose Ara-C (3 mg/m2) showed similar effects when compared with higher doses reported by others. Furthermore, in terms of CFU-GM proliferation the concentration of colonies before and after treatment were fairly similar in all but two patients.


CONCLUSIONS
The results drawn from our study demonstrated that there is no beneficial advantage of 13-cis-retinoic acid as a differentiation inducing agent on myelodysplastic patients. In contrast, lower doses of Ara-C showed similar effects on haemopoiesis of MDS patients than standard doses of 10-20 mg/m2 but with less side effects.
García Marco
J
J
Servicio de Hematología del Hospital General Universitari, Valencia.
Miguel Sosa
A
A
García Conde
J
J
Miguel García
A
A
Arbona
C
C
Escrig
V
V
Benet
I
I
Navarro
I
I
Ruiz
A
A
Carbonell
F
F
D001772:Blood Cell Count; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000494:pharmacology* / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012074:Remission Induction; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use
D003561:Cytarabine; D014212:Tretinoin
Efecto del tratamiento con ácido 13 cis-retinoico y Ara-C sobre las células precursoras hematopoyéticas en pacientes con síndromes mielodisplásicos.