Abstract 132

Late relapse in acute myeloid leukemia (AML) has been infrequently studied and variably defined in the literature. Two series have shown that late relapse of AML ≥5 years after first complete remission (CR1) is uncommon, with rates of 1.19–3% (Medeiros et al, Leuk Lymphoma 2007; Verma et al, Leuk Lymphoma 2010). We searched the long-term data available on 784 adults (<60 years-old) who were treated on 1 of 4 ECOG clinical trials (E3483, PC486, E3489, or E1900) and achieved CR1 for reports of late relapse (defined as recurrence of AML ≥3 years after CR1). Median follow-up for the 553 patients last known alive was 11.1 years. The longest median follow-up was 17.2 years on trial PC486.

Outcomes

We found that 11 patients (1.4%) relapsed late; of these, 2 were treated on E3483, 1 on PC486, 5 on E3489, and 3 on E1900. Seven patients with late relapse died from their disease and 4 were living at last known follow-up. Only 1 patient (0.13%) had recurrence of AML ≥5 years after achieving CR1. It is possible that more late relapses will occur on E1900 (a more recent study with ongoing follow-up).

Table 1
Characteristics and outcome of patients under the age of 60 with late relapse of AML ≥3 years after achieving CR1: The ECOG experience
E3483PC486E3489E1900Total
No. of patients (<60 years-old and CR1) 90 51 245 398 784 
No. of patients receiving autoHCT 0 35 63 141 239 (30%) 
No. of patients receiving alloHCT 45 17 92 36 190 (24%) 
Follow-up (years)*      
    Median 14.7 17.2 12.6 6.4 11.1 
    Range 0.81-17.6 10.8-19.6 0.6-16.3 0.07-8.6 0.07-19.6 
No. of early relapses (<3 years) 58 37 158 181 434 (55%) 
No. of late relapses (≥3 years) 2 1 5 3 11 (1.4%) 
No. of late relapses deceased 2 0 4 1 7 (64%) 
No. of late relapses after autoHCT/alloHCT 0/0 0/0 0/0 2/0 2/0 
Time to relapse (years)**      
    Median 4.7 4.5 3.8 3.3 – 
    Range 3.3-5.99 n/a 3.3-4.7 3.29-4.9 – 
Age at initial presentation (years)**      
    Median 26 30 40 50 – 
    Range 19-33 n/a 32-51 33-54 – 
Characteristics and outcome of patients under the age of 60 with late relapse of AML ≥3 years after achieving CR1: The ECOG experience
E3483PC486E3489E1900Total
No. of patients (<60 years-old and CR1) 90 51 245 398 784 
No. of patients receiving autoHCT 0 35 63 141 239 (30%) 
No. of patients receiving alloHCT 45 17 92 36 190 (24%) 
Follow-up (years)*      
    Median 14.7 17.2 12.6 6.4 11.1 
    Range 0.81-17.6 10.8-19.6 0.6-16.3 0.07-8.6 0.07-19.6 
No. of early relapses (<3 years) 58 37 158 181 434 (55%) 
No. of late relapses (≥3 years) 2 1 5 3 11 (1.4%) 
No. of late relapses deceased 2 0 4 1 7 (64%) 
No. of late relapses after autoHCT/alloHCT 0/0 0/0 0/0 2/0 2/0 
Time to relapse (years)**      
    Median 4.7 4.5 3.8 3.3 – 
    Range 3.3-5.99 n/a 3.3-4.7 3.29-4.9 – 
Age at initial presentation (years)**      
    Median 26 30 40 50 – 
    Range 19-33 n/a 32-51 33-54 – 
*

For patients last known alive (14 patients last known alive were excluded because of missing overall survival time).

**

Data apply to late relapsed patients only.

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All of these trials except E3483 treated some patients with autologous hematopoietic cell transplantation (autoHCT) as part of post remission therapy. On PC486, no post remission consolidation chemotherapy was administered before autoHCT. Ninety-eight total patients on E3489 and PC486 received autoHCT, and there were no late relapses; on E1900, 2 of the 141 patients treated with autoHCT developed late relapse. No patients who underwent allogeneic (allo) HCT in CR1 experienced late relapse on any of the 4 clinical trials. Nine of the 11 patients with late relapse did not undergo HCT; of these, 5 were consolidated with high-dose cytarabine, 2 received maintenance with low-dose cytarabine and 6-thioguanine, and 2 received unknown post remission therapy. Of the 3 patients with late relapse on E1900, 2 received standard-dose and 1 high-dose daunorubicin with induction.

Conclusions

Across all 4 trials, only 2 of the 239 patients (0.8%) treated with post remission autoHCT experienced late relapse of AML (≥3 years after CR1), which reinforces previously published data that late relapse after autoHCT is uncommon (Cassileth et al, J Clin Oncol 1993). Furthermore, of the 35 patients treated with autoHCT on PC486, 11 relapsed early and no patients relapsed late, suggesting that post remission chemotherapy may not be necessary before autoHCT.

Based on this large AML cohort of nearly 800 patients with long-term follow-up, patients who remain in CCR for at least 3 years have a very low risk of relapse and can be considered cured of their disease. Moreover, given that recurrent AML was extremely rare after 5 years or more of CCR (<0.2%), the risk of therapy-related AML from contemporary induction and post remission strategies including HCT appears to be minimal.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
complete remission, eastern cooperative oncology group, electrocorticogram, leukemia, myelocytic, acute, disease remission, follow-up, chemotherapy regimen, cytarabine, lymphoma, allopurinol

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Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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