title: Efficacy of a combination of human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3 to improve moderate to severe anaemia in low/intermediate risk myelodysplastic syndromes.
abstract: The efficacy of human recombinant erythropoietin (rEPO) in myelodysplastic syndromes (MDS) has generally been best in untransfused patients with 'refractory anaemia' according to the World Health Organization (WHO). We treated 63 MDS patients [excluding refractory anaemia with excess blasts, type 2 (RAEB2)] with a previously tested combination of 13-cis-retinoic acid and dihydroxylated vitamin D3 +/- 6-thioguanine in addition to rEPO. Most patients were categorized as refractory cytopenia with multilineage dysplasia and RAEB1, with intermediate 1 International Prognostic Scoring System (IPSS) score; all had Hb <95 g/l, and 70% required regular erythrocyte transfusions. Treatment was well tolerated, and erythroid response rate according to new International Working Group criteria was 60%: 50% in RAEB1 and 64% in non-RAEB patients (P = 0.383). Response rate was not affected by transfusion requirement (63%; 58% in untransfused), IPSS and WHO Prognostic Scoring System scores, and weekly rEPO dosage (30-50 000 U vs. 80 000 U). Median response duration was 16 months. Median survival reached 14 months for RAEB1 and 55 months for non-RAEB patients, with a significant difference in the latter between responders and non-responders (median 82 months vs. 44 months; P = 0.036). Our combined therapy, independent of rEPO dosage, achieved in patients with unfavourable response predictors, a rate of anaemia improvement comparable to the best obtained in lower risk patients by high-dose rEPO.
authors.affiliation: Divisione di Ematologia dell' Università di Torino, Azienda Ospedaliera S. Giovanni Battista di Torino, Torino, Italy. dario.ferrero@unito.it
authors.forename: Dario
authors.initials: D
authors.lastname: Ferrero
authors.forename: Antonella
authors.initials: A
authors.lastname: Darbesio
authors.forename: Valentina
authors.initials: V
authors.lastname: Giai
authors.forename: Mariella
authors.initials: M
authors.lastname: Genuardi
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Dellacasa
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorasio
authors.forename: Marilena
authors.initials: M
authors.lastname: Bertini
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D002117:Calcitriol / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011994:Recombinant Proteins; D012306:Risk; D015996:Survival Rate; D016896:Treatment Outcome; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D014815:Vitamins; D004921:Erythropoietin; D015474:Isotretinoin; D002117:Calcitriol