S48 Treatment (II): Chemotherapy

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THE EVALUATION OF LOW-DOSE CYTAR.mINE IN THE TREATMENT OF MYELODYSPLASTIC SYNDROMES. M Vasilica, D. Coriu, M Gociu. D Colita. Dept of Haematology, Fundeni Hospital, Bucarest, Romania.

The purpose of the study was to evaluate the low-dose cytarabine (LDAC) therapy’s efficiency in myelodysplastic syndromes (MDS). Between 1987 and 1996, 32 patients (pts) with MDS were treated at Fundeni Hospital with LDAC; mean age 51.4 years (range 21-77 years); sex: 19 male, 13 female. AI1 pts were classified according to FAB proposals: refractory anemia (RA) in 8 cases (25%); refractory anemia with ring sideroblasts (RAS) in 3 cases (9.3%); refiactoly anemia with excess of blasts (RAEB) in 12 (37.5%) cases; refractory anemia with excess of blasts in transformation (RAEB-t) in 9 (28.2%) cases. All pts. received cytarabine at a dose of 10 mg/m , subcutaneously, twice daily for 21 consecutive days. Pts. were monitored with blood counts and bone marrow aspirates and biopsies There were 4 complete remission (CR): 2 RAEB, I RA, 1 RAS, with a mean duration of 15.5 mo (range 4-24 mo). Partial remission (PR) was obsetied in 11 pts: 4 RAF$3 RAEB-t, 3 RA, 1 RAS, with a mean duration of 13.2 mo (S-36 mo). 17 pts presented a progressive evolution to a more advanced form of MDS or to an acute leuke.mia.For this group the mean survival was of 26 4 mo (range 7- 88 mo). The two years survival probability was 46ilO%. In the studied group of pts treated with LDAC there was obtained a favourable response (CR/PR) at 1 S pts. The responses were present at all subtypes of MDS but especially at pts with RAEB and MB-t. The cytopenia and infections were the most common complications of the treatment.The pts that benelitted from a single cycle of LDAC had a durable response.

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CLADRlBlNE (2-CD,\) IS ACTIVE IN ,.HIGH-RISK”-CHRONIC ~lYELOMONOCYTIC LEUKEMIA AND SECONDARY OR RELAPSED ACUTE JIYELO(AIONO)CITIC LEUKEAIIA. O.Kriecer. H.Knspnru. MGirrchiknfsk~, F.Lang. P.Oppita B D.Lutx 1st Inl. Depsrtmcnt. Elisnbcthincn Hwpitsl, Linx & KH Barmh.Schacstcrn. Lina md KH Bsrmh.Schacrtcrn, Wcls, AUSTRIA.

..Hixh rirli”-CMhlL and rrlal~.wd or .wcnndaq AML hwc s poor prngnnris snd adequnre conwntionnl chemothcr:~l~~- is n&in:. 2- Chlnn~dco~~rdcnosinc (2-CDA), a purine nnnloguc, u hich has hccn dcmonstrnted to he w1ivc nn I:mphuqte wnd monnc?tc pnpulrtions in yitrn, can rchicvc responses in chronic and rcu~e m~ek~(monn)c)~ic Icukemiar. Thcrcforc se intmduccd I-CDA into the therap! nf 26 paticnls (a!.~: 27- 76 vrrrs, mcdiun:61) ailh ,,high-risk”-CMML (acmrding Bnumcmouth ID6wcldnrf Score) and sccondrry or rclqwcd AM(M)L. 2-CDA wss rdminirtercd alone or in cumhinrtion with VP 16 md/nr ARA-C. The monnthcrspy of Clrdrihinc (0.2 mg/kdd fur 5 da?s, 2 huurr infusion) in 7 Patients silh CMML nhowcd s rapid dwrcwc of pcriphcrrl munnc!-tosis in all psticnts, hut onl~ in 117 a complctc remission (CR) conld hc achic\cd. For cldcrl? prtirntr wilh CMML in tranrformstion I combination of 2-CDA (O.Offi mlL/kJd) with ctoposidc (LO mg/m”2/d) fur 7 dnys usr &cn. So far. 517 patients rcrpnndcd sith tv n CR, lasting fur 2+ wnd 7 months with maintcnsnce thersp!. For rclnpwd AM(#)L-psticntr under the age nf 6S- !ears ac investigated P aalvap lwutucol (CLAEG-scheme) containing 2-CDA (a.2 mJkr/d) with ARA-C (1.5 g/mA2/d) and VP 16 (60 mdm”2/d) for 5 dr!r, folknvcd hy G-CSF (300 mcg/d) until PAIN rcrchcd 1l.S G/l. 12 .wconds~ or rclapscd AM(M)L-paticntx (2 rcl. rftcr wutoBMT) sith m n~c nf 3(I years (rnnp: 2X-62) wcehcd this ,,CLAEC”-proR~ul. n/l2 (66%) schicved a CR. InstinE fur I+ to IO months. Toxicity snd infcctiuur complications (mucnsitis. fulliculitir, FUO) acre mndcratc in 7/12 pat. with Ihrcc mrnagnhle m!cotic infcctinnr. Nn rcnrl d\sfunctinn nr ncurolngicrl complication ,,a$ ICE”: no curl? dcsth uccurcd. According to these first nhscwnlinna Clsdrihinc (I-CDA) ir rcti\c in CMML and comhinrtion thcmp! of 2-CDA with ARA-C nnd/ur VP 16 conk1 bc suitshlc for remission-induction of .,hiEh-risk”-CMML tir scr~~ntl;~r~/rclsl~sctl AM(M)L. rlthnngh furlhcr studies we v srrnntrd.

182 183

FLUDARABINE. CYTARABINE AND G-CSF (FLAG) FOR THE RESWTS OF TREATXENT IX PATIENTS WITH ACllTE NYELOID TREATMENT OF REFRACTORY ANEMIA WITH EXCESS OF BLASTS I.EUiiE?(IA PRECEEDED BY PRIMARY XYELJDYSPLASTIC SYNDROEIE IN TRANSFORMATION (RAEB-t) F. Farrara’, S. Mirto’. F. Leoni’,G. Mele’. L. Sebastlo’. A. Tedesch? and M. Mont6lo’. ‘Diiislone di Ematolcgia, Ospedale Cardarelli. Napoli: 2Divislone di Ematologia, Ospedale Cervdlo, Palenno; 3Cattedra di Ematolcgia, Univenita di Fimnze; ‘Divisiona di Ematdlogia. Oapedale Niiuarda Gil Granda. Milano. ltalia

H.Urbadska-RyJ,E.Krykowskl,A.Fronctak,A.Wrzesle~-Ku~, H.Blaslrlska-Morawiec.T.Robak. Clinic of Hematoloav.

Leukemic myelodysplastic syndromes ara charactetized by poor reapmsetocomferdiondchemdherapyandadversediiladasne,in paItlaJlar ti unfavou&la fealures are pmsad at diagno& PrelkninatyrewllshaveshwedVlatinthiscategaydpa6ef&shighCl? rates with acceptable toxii can be achieved by the FLAG regimen. With tbll regimen we treated 11 patients with RAE&t. Them were 6 males and 5 females, median age was 46 (27-58). Karyotyplc analysis re8ulla(evahmblaln10p&l&a)showedbisnmy8intwopaUe&.6p+ in1,moriosany7in1,canpiexabarr&onsin4andnormal~in 2.Allpa6erdsshwxdascoraof4accwdkgtotheBwmemadh prngncstlc ayslem. Tha treatment schedule included fludarabine 30 mg/m* (days l-5), ARA-C 2 gr/m* (days 1 to 5). and G-CSF 350 pg from dayOtoCRyihievamemLPoftmmiithempy2comistsdda ambinstiondIdau~(lRngm,)andARAC~)dsysl-2.Nine pa&rdsareevacl&defor respameatthathnedusilingandW6(lW%) achieved CR. The madian time to achieve a sustained neubonhil taunt hig~Man0.5x100/1andapl~~telstcounthigher~20xl~~wasof 22 (18-34) and 19 (16-35) days. respedively. Patle& received a median d 9 na&ed red cd&t 13-15) and 6 datelde m&i R%ltil WHO > 2 exb&m~toxi&&mlklc&&gd &&t&(3p&ienta), increasedsenmGOT(1~anddi&mea(1p&ie&).Tlmrawere no documented infections, tille 6 patients experienced FW. Median time of hospitaliiation was of 28 days (17-36). After a median follw-up d IO months, median DFS and OS have not yet been reachad; there wretwueadytelapsesdter2and4monlhafmmCRahievement, while 7 pa6e& are in omtinww CR (21+. Ia+. II+, 6*. 3+. ‘2+. I+ mcmthd. Two aatlents received albBMT. 2 wra autdransolanted with PBSC &oes&ully mobIllIed following &nsolidation and-3 are in a waiting list for transplantation procedure. We conclude that the FLAG is remarkably effeotive in RAEB-t with hiih CR rate and low toxicity Our results warrants fulther studies on larger series d patients.

L6dP. Poland .,,

We evaluated the treatment results of 35 patients with acute myelold leukemia (AML) preceeded by primary myelodysplastlc syndrome (MDS) observed in 1981-91. There were 16 females and 17 males in median age of 45.5 years (range 16-65). During MDS phase of disease there were: RA in 4 patients, RAEB in 9. CHHL in 3, RAEB-t in 17 and in 2 cases the subtype was not precl- sed. The combined chemotherapy was not applied to patients in the stage of MDS.and 10 patients received low doses of cytarablne (LD Ara-Cl with some reduction of the number of blasts,but without complete remission in any case. The following subtypes of AML with preceeding flDS were diagnosed: HO in 1 patlent,Ml-3, !42-10,M3-6,M4-10,M5-1,M6-4. As induction treatment of Af4L 16 patients (45.7%) with median age 46,6 years received polychemotherapy consisting of doxo- or daunorubicine and cytarablne. Seventeen patients -,40.5% (median age-641 received LD Ara-C. Two were treated with B-•ercaptopurlne. Complete remission (CR) was achieved in 22.6% of whole group including 43.7% of those.who received polychemotherapy and 5.9% treated with LD Ara-C. The median duration time of CR was 14.6 months lnclu- ding 16.4 in patients recelvlng polychemotherapy and 9 in LD Ara-C group. The median survival time in CR patients was 20;6 months (22.7 and 13 respectively). CR was more often obtained in patients with RAEB and RAEB-t preceeding AtiL,than with other subtypes of MDS. Polychemotherapy appeared to be a more effective method of treatment in patients with AMI. following MDS.