High-dose chemotherapy in high-risk myelodysplastic syndrome

Abstract

BACKGROUND Antileukemic chemotherapy has been used for two decades to treat high‐risk myelodysplastic syndrome (refractory anemia with excess of blasts [RAEB] and RAEB in transformation into acute leukemia [RAEB‐t]) patients. Because the results of standard regimens have been disappointing, high‐dose chemotherapeutic regimens were investigated recently. In the absence of randomized trials, the relative merits of various treatment regimens are unknown. METHODS The authors analyzed the outcome for 394 newly diagnosed patients treated between 1991 and 1999 with five regimens consisting of intermediate‐ or high‐dose cytosine arabinoside (A) in combination with idarubicin (I), and introduced cyclophosphamide (C) and the new agents fludarabine (F) and topotecan (T) into new combinations with A. In addition to defining the role of high‐intensity chemotherapy in the overall outcome for patients with RAEB‐t and RAEB, the authors determined the relative merits of the five regimens (IA, FA, FAI, TA, and CAT), accounting for the nonrandom distribution of the prognostic covariates. RESULTS The overall complete response (CR) rate of 58% was significantly associated with karyotype, performance status (PS), treatment in the laminar air flow room, duration of antecedent hematologic disorder and age, but not French–American–British or International Prognostic Scoring System risk categories. Multivariate analysis did not identify statistically significant differences in CR rates obtained with each regimen. Induction death rates increased with age with all but the TA regimen; they were lowest with TA (5.4%) and highest with FAI (20.7%), and these differences were significant in patients older than 65 years. The trend for time to death was the same as for time to recurrence in all groups. Multivariate analysis of time to death identified treatment regimen (FA, FAI, and CAT), cytogenetic status (−5/−7), increasing age, and PS greater than 2 as significant independent unfavorable prognostic factors. After prognostic variables were accounted for, survival with IA treatment remained superior to that of FA and FAI but comparable to TA, and CR duration was only marginally shorter with FA. Landmark analysis showed the overall survival of responders to be superior to that of nonresponders, the difference remaining significant after adjustment for prognostic covariates. CONCLUSIONS Although the newer regimens did not improve outcome, TA and CAT produced results comparable to those of IA and may be considered treatment alternatives. The TA regimen was particularly effective in RAEB patients and could be delivered safely, with low induction mortality. Our results indicated that although CR seemed associated with survival advantage, innovative post‐remission managements represent a challenge because improvement in outcome is not likely to come from intensified therapy. Cancer 2001;92:1999–2015. © 2001 American Cancer Society.

Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB

“…The median RFS time of the patients who achieved CR was 27.7 months. This compares favorably with the outcomes of traditional intensive chemotherapies reported previously (26,27,29). The patient selection appears to be likely reason for this, since a high proportion of younger patients was included.…”

A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome

“…by guest www.bloodjournal.org From Treatment for higher-risk MDS includes, in the relatively rare younger patients with MDS, allogeneic stem cell transplantation or cytarabine/anthracycline-based chemotherapy. 18,19 Older patients, who constitute the large majority, generally receive supportive care only, low-dose chemotherapy, or investigational agents. The United States FDA recently approved 5-azacytidine (Pharmion, Boulder, CO) for the treatment of patients with MDS based on study results showing a significantly higher overall response (CR ϩ PR) rate than supportive care alone (15.7% versus 0.0%).…”

Establishment of baseline toxicity expectations with standard frontline chemotherapy in acute myelogenous leukemia

“…[1][2][3][4][5] Patients with acute promyelocytic leukemia were excluded. Informed consent was obtained according to institutional guidelines and in accordance with the Declaration of Helsinki, and Institutional Review Board approval was granted by the University of Texas M. D. Anderson Cancer Center (MDACC).…”