Autologous bone marrow abmtj or peripheral blood stem cell (absct) transplantation after intensive chemotherapy in myelodysplastic syndromes (mds)

Intensive chemotherapy (1C), m MDS, gives lower complete remission (CR) rates and shorter CR duration than in de novo AML in spite of consolidation chemotherapy (CT). Few cases of ABMT have been reported in MDS who reached CR with 1C, and reports were retrospective. We designed a trial of 1C in pts aged <65 years with " high risk " MDS (i. e. RAEB, RAEB-T, CMML) or MDS having progressed to AML (MDSAML). Pts received Mitoxantrone 12mg/m ²/d 02-5 + AraC Ig/m ²/12h di_5, with on without (randomized) quinine 30mg/kg/day, an agent capable of reverting the multidrug resistance phenomenon in vitro. CR criteria were stringent: bone marrow blasts <5%, normalization of cytopenias and of karyotype, disappearance of MD9 features, Pts <55 years with no HLA identical sibling and achieving CR were scheduled to receive ABMT preceded by a consolidation CT course. As bone marrow harvest was insufficient in some pts, peripheral blood stem cell (PBSC) harvest was subsequently proposed after mobilization by consolidation CT followed by G-CSF The conditioning regimen was: Cy 50mg/Kg/d and Bu 4mg/Kg/d during 4d. From Oct 1992 to May 1996, 165 pts were included (162 available for response). 66 pts (41%) achieved CR. Median age of the 96 pts aged < 55 was 485 years (range: 18-55) ; 50 pts had MDS-AML, 14 RAEB, 30 RAEBt and 2 CMML. 11 pts had therapy related MDS Cytogenetic analysis (64 pts) was abnormal in 41 pts: del 5q: 4 pts; -7: 8 pts; other single abn: 14; complex abn: 15 pts. 45 pts (47%) achieved CR. 5 of them were alloerafted in CR and 23 of the remaining 40 pts (57%) received ABMT {17 pts) on ABSCT (6 pts). Reasons for not performing ABMT or ABSCT were: early relapse (6 pts), poor clinical condition (6 pts), poor marrow stem cell harvest (3 pts), patien refusal (2 pts). ABMT and ABSCT were performed 1 to 7 months (median: 4) after CR achievement. 2 pts were found to be in relapse at the time of autograft. Hematologicaî reconstitution occurred in all pts. In the 17 pts who received ABMT, median duration of leukopenia, neutropenia and thrombocytopenia were 19 (range 11 to 30), 20 (range 11 to 36) and 44 days (range 11 to 99), respectively. In the 6 pts who received ABSCT median duration of leukopenia, neutropenia and thrombocytopenia were 14 (range 11 to 18), 15 (range 11 to 20) and 53 days (range 17 to 76), respectively. Median follow up was 16 months after autograft. 3 pts died from the procedure, 10 relapsed after 2 to 18 months and 10 (44%) were still in CR after 9 to 45 months. Median Kaplan-Meien (KM) DPS was 13 months from the autograft and 17 months from CR achievement. In the 23 autografted pts, the KM estimate of survival from the autograft was 68±10% at 12 months and 55+11% at 24 months. Median KM survival of the 96 pts aged < 55 who received 1C was 13 months from the onset of 1C. Median KM DPS and survival from the onset of treatment of pts who achieved CR and were not autografted (excluding allografted cases) were 11 and 17 months, respectively. In conclusion 1) Thia prospective study shows that ABMT or ABSCT can be performed in about 60% o( MDS who achieve CR with 1C. 2) PBSC collection may yield higher numbers of stem cells than marrow collection in some cases, and could improve the percentage of MD9 pts autografted in CR. However, it does not seem to shorten the duration of aplasia. 3) With a median follow up of sixteen months from transplantation, median DPS is 13 months with 68 % of patients alive at 12 months. This suggests that autologous transplantation may proJonged,survival in patients with-MDS.