Disappearance of cytogenetic abnormalities and clinical remission during therapy with 13-cis-retinoic acid in a patient with myelodysplastic syndrome: inhibition of growth of the patient's malignant monocytoid clone

Abstract

Median survival is as little as 6 months for patients with refractory anemia with excess blasts who demonstrate an abnormal karyotype in the majority of marrow cells. We treated a patient who presented with 29% marrow blasts and 90% abnormal metaphases with 13-cis-retinoic acid. He achieved a complete clinical and cytogenetic remission during therapy. To determine the mechanism of the response, serial studies were done of the effects of 13-cis-retinoic acid and dexamethasone on in vitro growth of his marrow cells. During clinical remission, when the drug was not administered, marrow growth remained significantly depressed. During relapse, the remission growth pattern was replaced by overgrowth of the karyotypically abnormal monocytoid clone. Clonal growth occurred in cultures containing colony-stimulating activity or dexamethasone but was absent in cultures containing concentrations of 13-cis-retinoic acid achieved in vivo. After the drug was reinstituted, a second clinical stabilization developed. Since 13-cis-retinoic acid inhibits normal monocyte colony growth, we postulate that the patient's unusual clinical responses to the drug were due to in vivo growth inhibition of the malignant monocytoid clone.

Vitamin A and its Derivatives- Retinoic Acid and Retinoid Pharmacology

“…He obtained a complete clinical and cytogenetic remission therapy [44][45][46][47][48][49]. This clinical response to 13-cis RA drug was due to in vivo growth inhibition of malignant monocytoid clone [50]. Continued follow-up of this study in this field will be of interest [51][52][53][54] (Table 1).…”

The Myelodysplastic Syndromes

“…A variety of drugs capable of differentiating AML and MDS cells in vitro can be safely given to patients and have been evaluated in clinical studies in MDS. Other than lowdose cytarabine, as mentioned above, retinoids have been most widely used, with response rates from 0% to approximately 20% with 13-cis-retinoic acid or isoretinoin in MDS [49,[110][111][112][113][114][115][116][117], and two randomized trials failed to demonstrate any activity or a survival advantage associated with 13-cis-retinoic acid therapy [118][119][120]. Although all-trans retinoic acid exhibits major activity in patients with acute promyelocytic leukemia [121][122][123], its activity in MDS has been minimal [124][125][126].…”

Διερεύνηση Του Μηχανισμού Της Αιμοποίησης Στα Μυελοδυσπλαστικά Σύνδρομα Με Μακράς Διάρκειας Καλλιέργειες Μυελού Των Οστών

“…Ακόμη μεγαλύτερο ενδιαφέρον παρουσίαζε η χρήση του φαρμάκου σε πάσχοντες από ΜΔΣ, κυρίως RAEB και RAEB-t, ποίηση κυτταρικών σειρών, όπως της HL-60 και κυττάρων ασθενών με ΜΔΣ (Tohyama K et al, 1989). Είχε επίσης χορηγηθεί και σε μερικούς ασθενείς, με ποικίλα αποτελέσματα (Abrahm J et al, 1986). Η ετερογένεια των συνδρόμων και η ποικιλία των σχημάτων χορήγησης, εξηγούν εύκολα την ποικιλομορφία της έκβασης αυτών των προσπαθειών.…”