In:
Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2934-2934
Abstract:
In adult AML, effective postremission consolidation is obtained with HD-ARA-C and either autologous or allogeneic stem cell transplantation (SCT). HD-ARA-C is highly myelotoxic, causing remissional deaths and nonlethal toxicity that often precludes the administration of repetitive courses especially in older patients. We are evaluating a risk-oriented strategy that specifically considers the use of multiple, stem cell-supported HD-ARA-C courses. After double induction (ICE/IC or ICE/sequential HD-ARA-C-I when primary resistance is documented), ARA-C 1 g/m2/bd is given on dd 1–4, followed by G-CSF to collect autologous CD34+ blood stem cells. Then, patients with high risk cytogenetics, i.e. -5/del(5q), -7, t(11q23), t(9;22), abn 3q, 9q, 11q, 20q, 21q, 17p, iso(17q), t(3;5), t(6;9), or & gt;3 unrelated clonal anomalies, and those with intermediate risk cytogenetics (normal or not known, non-high, non-favourable) plus any additional risk feature (WBC & gt;50, MDS/secondary, late CR, FLT-3 mutation, hepatosplenomegaly, FAB M0,6,7) are grouped together in the high-risk (HR) category and are preferentially submitted to an allogeneic SCT. In the remaining cases, i.e. the standard-risk (SR) group, three HD-ARA-C-based cycles (2 g/m2/bd on dd 1–5, plus idarubicin) are planned, each one followed by the reinfusion of 1–2x106/kg CD34+ cells on day 6, and by G-CSF; HR patients unable to undergo SCT are transferred to HD-ARA-C, and those with an insufficient CD34+ cell yield are given one-two courses with intermediate-dose ARA-C. Ninety-one unselected patients (males 46) aged 17–68 years (median 50 years, 38 & gt;55 years) with either de novo or secondary/MDS-related (23%) non-M3 AML (cytogenetics: favourable 10, intermediate 13, normal 45, unfavourable 15, unknown 8) are thus far evaluable: 67 HR and 24 SR. CR rate was 76% (96% in SR, 69% in HR). Stem cell harvest was successful in 43/58 (74%). So far, SCT was performed in 16 HR cases, while 89 HD-ARA-C courses were administered to 34 other patients (16 SR and 18 HR), with a median intercycle time of 39 days (only 17% & gt;45 days), a median duration of neutropenia & lt;0.5 and thrombocytopenia & lt;20 of 9 and 6 days, respectively, and no toxic death while pancytopenic/in-hospital (vs. 8% in historical, unsupported HD-ARA-C-treated cohort). By treatment intention, median overall survival is 21 mos. (37% at 4 years, 57% in SR and 30% in HR), and median DFS is 25 mos. (43% at 4 years, 56% in SR and 36% in HR). DFS is 57% and 19% in HR patients with (n=21) and without (n=25) HLA/DR identical family-related/unrelated donor, respectively (P=0.01). In conclusion low-dose autologous CD34+ cell rescue (plus G-CSF) may sensibly limit HD-ARAC-related toxicity in unselected adults with AML, up to an age of 68 years in this study, allowing an effective increase in dose intensity. This translated into a DFS rate & gt;50% at 4 years in the SR group (mainly cases with normal/intermediate risk cytogenetics without additional risk factors), whereas an allo-SCT was more beneficial to the HR group. These results document the role of blood stem cell-supported, repetitive HD-ARA-C courses, particularly in intermediate-risk patients and/or those aged & gt;55 years or with contraindications to allogeneic SCT.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V106.11.2934.2934
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2005
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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