ISPO

Autologous stem cell transplantation after intensive chemotherapy in myelodysplastic syndromes updated results of a prospective study

EW Wattel, MD,PhD

Service d'Hématologie, Hôpital Edouard Herriot, France Centre léon Bérard, Lyon, Rhone France

AIM: Intensive chemotherapy (IC) in myelodysplastic syndromes (MDS) and AML following MDS gives shorter CR duration than in de novo AML, and a very low proportion of long survivors (10% at 4 years in our experience) is observed. IC followed by autologous stem cell transplantation (ASCT) provides an alternative therapy for MDS patients who lack a histocompatible donor. Retrospective studies revealed an ASCT-related mortality ranging between 10% and 28% and a 3 year disease free survival (DFS) of 33% (Br J Haematol 2000;110: 620-30). Little remains know about the prognostic factors of ASCT. In the EBMT experience, patients younger than 40 years had a significantly better DFS than older patients (Blood 1997;90: 3853-7). In a recent prospective study, we reported that ASCT could be performed in more than 60% of patients who achieve CR with IC and that peripheral blood stem cells (PBSC) collection yielded higher numbers of stem cells than marrow collection (Leukemia 1999;13 :524-9). With a median follow-up of 9 months, gender was the only prognostic factor of the outcome of autograft. METHODS: An updated analysis of this prospective study was performed at the reference date of January15, 2001. RESULTS: Between January 1993 and April 2000, 43 patients with high risk MDS in first CR after IC received autologous bone marrow transplantation (ABMT, 16 patients) or autologous peripheral blood stem cell transplantation (APSCT) (27 patients). The median age was 52 years (range: 18-66). There were 26 MDS-AML, 10 RAEB-T, and 7 RAEB. Bone marrow and PSC harvest were performed 0.5 to 5 months (median 2.3 months) and ASCT 1 to 7 months (median 3.7), after achievement of CR, respectively. The conditioning regimen combined cyclophosphamide and busulfan in 29 patients and cyclophosphamide, busulfan and etoposide in 14 patients. Four patients (9%) died from the procedure. Hematological reconstitution occurred in all of the remaining 39 patients without significant differences between the 2 conditioning regimens. As previously described, reconstitution was faster after APSCT than after ABMT. Twenty-four patients (56%) relapsed after 1 to 36 months and 15 (35%) were still in CR after 2 to 92 months. The Kaplan-Meier (KM) estimate of overall survival was 86 ±5% at 6 months, 74 ± 7% at 12 months, 44 ± 8% at 24 months and 35 ± 8% at 36 months. The KM estimate of DFS was 72 ± 7% at 6 months, 53 ± 8% at 12 months, 40 ± 8% at 24 months and 31 ± 8% at 36 months. Median KM DFS and survival were 16 and 22 months after autograft, respectively. In the 34 successfully karyotyped patients, the estimated 2-year survival rates were 50%, 42%, and 33% for patients in good- (n=15), intermediate- (n=13), and poor risk (n=6) IPSS cytogenetic subgroups, though the difference was not significant (p=0.273). In Cox univariate analysis, gender was the only prognostic factor of the outcome of autograft: males had both shorter DFS (median not reached in females versus 9 months in males, p=0.0290) and shorter overall survival (median 42 months in females versus 15 months in males, p=0.0096) after the autograft. Other factors such as age, FAB classification, time between diagnosis and treatment, interval between CR and ASCT, WBC count, hemoglobin level, platelet count, absolute number of circulating blasts, percentage of bone marrow blasts, and cytogenetic abnormalities (normal versus abnormal) at the time of induction chemotherapy did not significantly influence the overall outcome. Of the 23 patients autografted before 1997, with sufficient follow-up, 7 (30%) have survived more than 4 years after the autograft. Six of these were alive in first CR after 60+ to 92+ months, and probably cured, 1 relapsed 28 months after ASCT and achieved a second prolonged CR (23+ months) after IC. All the 6 long-term survivors were female (versus 4 of the 17 patients who survived less than 4 years, p=0.0012) and were characterized by a higher incidence of normal karyotype (p=0.036). CONCLUSION: The present results confirm that gender is a strong prognostic factor in autografted MDS patients and suggest that ASCT could increase CR duration in some patients, by comparison with consolidation chemotherapy.

KEY WORDS: intensive chemotherapy, transplantation.

For more information, contact wattel@lille.inserm.fr

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Stem Cell Biology.

http://www.cancerprev.org/Journal/Issues/26/101/1293/4254