All-trans retinoic acid in adult chronic myelomonocytic leukemia: results of a pilot study.
Retinoids can inhibit the spontaneous in vitro growth of CFU-GM observed in juvenile chronic myeloid leukemia (JCML) and, when administered in vivo, have shown some clinical benefit in this disease. Because adult chronic myelomonocytic leukemia (CMML) has many features in common with JCML, we treated 10 cases of advanced adult CMML with ATRA (45 mg/m2/day). Five of them were also tested in vitro. After two patients had a rapid increase in WBC counts and clinical signs reminiscent of the 'ATRA syndrome' seen in acute promyelocytic leukemia, with fatal outcome in one of them, it was decided to add hydroxyurea (HY) to ATRA to patients with high WBC at inclusion or during ATRA treatment, and no more cases of ATRA syndrome were seen. Overall, six patients received ATRA + HY and four ATRA alone. Four patients had a minor but significant response with reduction of transfusion requirement (two cases) or increase in platelet counts (two cases). Apart from the ATRA syndrome, no other side-effect of ATRA was seen. Bone marrow mononuclear cells showed spontaneous growth of CFU-C in methylcellulose in the five patients tested in vitro, with a predominance of CFU-M. ATRA (10(-7) M) inhibited CFU-M growth in all cases, but increased CFU-G growth in one patient who developed the ATRA syndrome. No differentiation of bone marrow myeloid cells after short-term liquid culture with ATRA was observed. A decrease of CFU-C growth was observed in the four patients reevaluated during follow-up. In some cases of CMML, ATRA can improve anemia or thrombocytopenia but not other parameters. Furthermore, it can also induce hyperleukocytosis and ATRA syndrome in some patients, requiring the rapid addition of cytoreductive agents such as HY.
Cambier
N
N
Laboratorie de Biologie Cellulaire Hématologique, Hopital St Louis, Paris, France.
Wattel
E
E
Menot
M L
ML
Guerci
A
A
Chomienne
C
C
Fenaux
P
P
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003114:Colony-Forming Units Assay; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D015477:Leukemia, Myelomonocytic, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007964:Leukocytosis / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010976:Platelet Count / Q000187:drug effects; D013577:Syndrome; D014212:Tretinoin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D014212:Tretinoin; D006918:Hydroxyurea