Treatment of acute leukemia arising from myelodysplastic syndromes with oral idarubicin, etoposide, and 6-thioguanine

Third International

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Symposium on Myelodysplastic Syndromes

Trcatnwnt of acute leukemia arising from myelodyspiastic syndromes with oral idarubicin, ctoposidc, cad 6-d1io8uanine Montillo M., Tcdcschi A, Olivieri A, Ccnhaioni R, l Pclliccia G, Marohc8iani Go, Leoni P Dtpattmcnt of Hacmatology Torrcttc University Hospital - Ancona, l Dcpartmcnt of Internal Medicine- S. Elpidio, ODcpcrtmcnt of Internal Medicine - Tolcntb~o, Italy. Transformation to acute non-lymphoid kokcmia (ANLL) is a very frcqacnt cvcnt in myclodysplartic syndromes (MDS). This group of patients, mainly elderly, is chanctcrized by unfavorable pm8nostic facmrs wbii make tbc cute a vay remote possiiility. Totally oml induction trcatmcnt of kukcmia is now fu&k with the avail&@ of an oral aafJuacyclme, Idambicin. Tbis cpprocch could prcscwc the quality of life rcduoiog mC need for iatmvcaous infusion and might p&c&ally shorten the hospitalization. In or& to study tbc efficacy of an oral induction mgimcn composed of ctoposidc 100 mg!mq and 6-thioguanlnc 100 mg/m’ twice a day on days I-S, and Idarubicin IS mK/m* on days 1,3,5, we trcatcd 10 patients with ANLL arisiig atlcr a variabk phase of myclodysplapia llxc rc+nsc was chcckcd afkr each one of 2 cycles, given as iadwtioa, and whco c complctc remission wcs obscwcd they received hvo more cycles of this Wcatmcnt as wwolidation. Since a partial remission was in tbc same way, two more demonstrated after the t&t two courses the patitnts wived, cycks as consolidation. Si patients wae maks and fcur fcmaks, their median age was 69.5 (range 56-76). Nine paths wtm axcptabk for malysis cigbt of them m&cd apla!di with WBC < lOOO/jJ and PM?4 <500/j& Scverc thmmbofytclpcnia was obsttvcd only in patients with low values bcfon tmatmcnt. 8cvcn pi&n@ cxhlbitcd lcacopcnia bcforc trcalmcnt. Two patients showed lcuwcytosis 47,000/~1 and 137.000&l, rcspcctivtly. Tmatmcnt was normally well tolcratcd cad only one patient had scvcrc nausea cnd vomiting cpi.xnjcs. Four patients manifested fcbrik cpisodcs, in one cast dut to Aspergil/zufumigahu and in Uuw cases they remained FUO. These episodes of fcvcr appca& at?cr the tirst trcatmcnt of induction, the consolidation phase was normally hater tolcmtcd. In all casts the trcatmcnt was given cs oatpaticnt and tvcry cast had to rcccivt supptivt beatmeat with pa&cd red cell tmostii and platckt units. The patknts totally received 17 comxcs of cbcmotbcrapy and only six of them had to be butcd as iapaticots. Ihe mqoadcm were 5 patients (55%), with 3 complctc rcmisskms (33%), aad 2 partial rcmis.Gons. llucc paticats mwakd a progression(33%)andinonccascthcdiscasemmaincdstabkattcrtwocourses(ll%). ‘Iht median survival was 6 months (ran8c 3-9) and the three patients in complctc remission did not show any pro8rcssion after 9 months. These results dcmonsmttc the reliability and the effcacy of a total oral trcatmcnt of secondary leukemia a&r my&dysplasia.

Treatment With Alpha-Lymphoblastoid Interferon (Wellferon) in High Risk Myelodysplastic Syndromes (HR-MDS) Petti MC, Latagliata R, Aloe Spiriti MA, Avvisati G, DeGregoris C. Pontis P, Spadea A, Mandelli F. Cattedra di Ematologia, Dipartimento di Biopathologia Usana, Universitk degii Studi di Roma “La Sapienza”. To evaluate the efficacy of Wellfcron, a phase I-11 trial in HR-MDS (bone marrow blasts >lO%) with cytopcnias (HB <8 g/dL and/or PLTS count <3O,OOO/~L and/or PMN count GO0 rL) was conducted at our institution. From l/92, I I patients (pts) (9 males and 2 females, median age 63 yrs, range 41-69 yn) were enrolled into the study. Median time from the diagnosis to treatment was 7 months (range l-36 months). A transfusional requirement was present in 811 I pts, 411 I had a PLTS count <30,00O/~L and 2/l I a PMN count 8 g/dL after 3 months; after an additional 3-month period Hb levels rose up to >I4 g/dL and marrow blasts decreased ~5%. He stopped IFN after IO months of treatment and is still in complete response I4 months after the discontinuation of the treatment. The 2nd responder showed only a marrow blasts reduction >50% (from 25% to 10%) after 3 months: however. as in the lint responder, he Increased Hb levels from 8.1 g/dL to 12.8 g/dL and reduced marrow blasts ~5% during the subsequent 3-month period of treatment; 3 months later he relapsed as RAEBt. The 3rd responder became transfusion-free without Hb levels normalization and reduced marrow blasts from 22% to 12% after 3 months; after an additional 3-months period of treatment she showed a rise in Hb levels from 8.4 ddL to 10.7 g/dL but relapsed 7 months later. The last responder, still on treatment, reduced marrow blasts from 20% to 8% during the first 3month period. No toxicity related to IFN treatment was observed. and no reduction of dosage was needed. In conclusion; I) Wellferon Seems to be effective in some patients with HR-MDS: 2) the best treatment duration seems to be at least 6 months. However, these preliminary results need to be coniirmed in a larger population after a longer follow-up.

Therapeutic trial of combiiion therapy and low dose cytosine RAEB and RAEB-t

of rGM-CSF, androgen arabinoaide (An-C) in

A.P. GUERCI, S. RAUH, 0. CUERCI Service de M&k&w A. CHU Brabois. 54511 Vandoeuvre-lb-Nancy Cedex. FRANCE. Supported by Scheting-Plough Research Department. Infection is a major cause of death in MDS. Differentiation induction therapy as low dose Ara-C may increase cytopenias and the risk of severe infections. Therefore, we designed a pilot study of low dose Ara-C and androgen therapy combined with rGM-CSF (Leucomax). Combination treatment was administered for 12 months. The regimen schedule was: androgens (1 mg/kg/d continuously), low dose Ara-C: 3 mg/m2/12h 14 days per month and rGM-CSF: 3 mg/kg/d subcutaneously for the following 14 consecutive days. The response was defined as an increase in Hb level more than 1 g/dl, a decrease in the need of red blood cells transfusion by SO%, an increase in ANC by 0.5109/l and/or an increase of platelet count of at least 25.109/l. 19 patients (pts) were included. 6 pts were removed from the study for progression to acute myeloid leukemia. In 7 pts, treatment was dicontinued due to grade 3 toxicity: skin reaction (n= l), arthralgia and musculoskeletal pain (n= l), fluid retention (n= 3), fhromboembolism (n= 1) and central hyperthermia (n=l). 6 patients were evaluable for response to 12 months. A significant decrease in red blood cells transfusions requirement was observed in one patient with a significant increase of HB level (8.8 and 13.9 g/dl). ANC increased significantly in 4 pts. Platelet count increased in 1 patient (108 and 172. 10y/l). No severe infections requiring hospitalization were observed in any patient. These data suggested that the feasability of this combination regimen including rGM-CSF was difficult with regard to high toxicities. Moreover this combination therapy as administered in this study had limited effectiveness in improving hematopoiesis in pts with MDS. The maintenance of hematological improvement needs to lx confirmed.