Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders

Abstract

We analyzed outcomes after hematopoietic cell transplantation (HCT) in 257 patients, 3 to 72.7 years old (median, 43 y), with secondary myelodysplastic syndrome (MDS) including those with transformation to acute myeloid leukemia (tAML). Conditioning regimens included high-dose total-body irradiation (TBI)/chemotherapy (n = 83); busulfan (BU)/cyclophosphamide (CY) (BUCY, n = 122; with BU targeting [tBUCY], n = 93); fludarabine (Flu) with tBU (FLUtBU; n = 12); Flu plus 200 cGy TBI (n = 26); and miscellaneous regimens (n = 14). Donors were HLA-identical or partially mismatched family members in 135 and unrelated individuals in 122 patients. Five-year relapse-free survival was highest (43%) and nonrelapse mortality lowest (28%) among tBUCY-conditioned patients. Outcomes were compared with results in 339 patients who received transplants for de novo MDS/tAML, and a multivariate analysis failed to show significant differences in outcome between the 2 cohorts. Relapse probability and relapse-free survival correlated significantly with disease stage (P < .001) and karyotype (P < .001). Relapse incidence was lower (P = .003) and relapse-free survival superior (P = .02) with unrelated donor transplants. The data suggest that overall inferior outcome in patients with secondary MDS/tAML was related to the frequency of high-risk cytogenetics. For both cohorts, transplantation outcomes improved over the time interval studied.

Figure 1

Probability of overall survival and relapse-free survival in patients who received transplants for secondary MDS/tAML. Censored indicates censored observations at the date of last contact.

Figure 2

Probability of relapse-free survival by disease stage at the time of transplantation in patients with secondary MDS/tAML. Censored indicates censored observations at the date of last contact; RA/RARS, refractory anemia/refractory anemia with ringed sideroblasts; RAEB, refractory anemia with excess blasts; tAML, transformation to AML; and tAML Rx, patients with tAML who received chemotherapy before HCT and were categorized as RA or RAEB at the time of HCT.

Figure 3

Cumulative incidence of nonrelapse mortality by preparative regimen in patients with secondary MDS/tAML. High-dose TBI indicates high-dose TBI-containing regimens; BU/CY, busulfan and cyclophosphamide; tBU/CY, busulfan targeted to plasma levels of 600 to 900 ng/mL and cyclophosphamide; FLU/BU, busulfan targeted to plasma levels of 600 to 900 ng/mL and fludarabine; and FLU/TBI, fludarabine and TBI (200 cGy).

Figure 4

Probability of relapse-free survival in patients with secondary and de novo MDS/tAML (unadjusted P = .03). Censored indicates censored data of patients alive and in remission at date of last contact.

Figure 5

Impact of cytogenetic risk category on outcome in patients with secondary and with de novo MDS/tAML. (A) Probability of relapse. Low secondary indicates low risk in secondary group; low de novo, low risk in de novo group; int secondary, intermediate risk in secondary group; int de novo, intermediate risk in de novo group; high secondary, high risk in secondary group; and high de novo, high risk in de novo group. (B) Probability of relapse-free survival by cytogenetic risk for patients with secondary and de novo MDS/tAML. Cytogenetic risk groups according to IPSS criteria.