(F4) Treatment of high risk myelodysplastic syndromes with sequential intermediate dose cytosine arabinoside and mitoxantrone (S-HAM) with or without GM-CSF: A prospective double blinded randomised study

Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study

“…In the present study the overall CR rate was 44%, median CR duration was 14 months, and disease‐free survival at 2 years was 38%. These results are similar to those previously reported in the literature in MDS treated with intensive chemotherapy ( Martiat et al , 1988 ; Gajewski et al , 1989 ; Hoyle et al , 1989 ; Michels et al , 1985 ; De Witte et al , 1990 , 1995; Fenaux et al , 1991 ; Bernstein et al , 1993 ; Aul et al , 1994 , 1995; Ruutu et al , 1994 ; Hiddeman et al , 1995 ; Estey et al , 1995 ; Gore & Burke, 1995; Wattel et al , 1997 ; Gardin et al , 1997 ), i.e. a relatively low CR rate and short median CR duration in comparison with results obtained in de novo AML.…”

“…Estimation of sample size was based on the method described by George & Desu (1974), with a type I error of α = 0.05, a type II error of β = 0.20 for a one‐sided test. The CR rate in MDS patients expressing PGP treated with intensive chemotherapy without reversing agents was found to be 15–20% in previous studies ( Martiat et al , 1988 ; Michels et al , 1985 ; Hoyle et al , 1989 ; Gajewski et al , 1989 ; De Witte et al , 1990 , 1995; Feneaux et al , 1991 ; Bernstein et al , 1993 ; Ruutu et al , 1994 ; Aul et al , 1994 , 1995; Hiddeman et al , 1995 ; Gore & Burke, 1995; Wattel et al , 1997 ; Gardin et al , 1997 ) and the expected benefit of quinine was to reach a CR rate of 45–50%, i.e. identical to the one observed in PGP‐negative cases ( Lepelley et al , 1994 ).…”

“…Low‐dose chemotherapy gives overall limited results in MDS ( Cheson et al , 1986 ; Miller et al , 1992 ; Hellström‐Lingberg et al , 1992 ). Intensive anthracycline AraC chemotherapy, in MDS and AML following MDS, gives lower complete remission (CR) rates and shorter CR duration than in de novo AML ( Martiat et al , 1988 ; Michels et al , 1985 ; Hoyle et al , 1990; Gajewski et al , 1989 ; De Witte et al , 1990 , 1995; Fenaux et al , 1991 ; Bernstein et al , 1993 ; Ruutu et al , 1994 ; Aul et al , 1994 , 1995; Hiddeman et al , 1995 ; Gore & Burke, 1995; Wattel et al , 1997 ; Gardin et al , 1997 ). Reasons for the lower response rates to chemotherapy in MDS are unknown but could include a higher incidence of expression of the multidrug resistance (mdr) gene in MDS than in de novo AML, as mdr gene expression is generally associated with poorer results of intensive chemotherapy in AML and MDS ( Lepelley et al , 1994 ).…”

Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): An Eastern Cooperative Oncology Group Study

“…A preliminary randomized trial of high-risk MDS patients utilizing this principle, but with Escherichia coliderived GM-CSF accrued 28 patients [16]. Of these patients 11 (37%) achieved a CR, and an additional 7 patients had a lower stage of MDS after recovery of counts.…”

“…This pilot study utilized the recombinant GM-CSF [Immunex Corporation (Sargramostim) NSC-6137950] and the identical chemotherapy utilized by the German AML Trial Group in adults with AML [17] and in MDS [16] with intermediate-dose cytarabine (ARA-C) followed by mitoxantrone.…”