To the Editor:
The recent article by Fenaux et al in Blood continues the interesting and exciting work being conducted in the treatment of acute promyelocytic leukemia.1 Given the 2 randomization points (induction regimen and maintenance regimen) designed in the APL93 trial, data presented on the results of the various maintenance treatments can be dense to dissect. Specifically, it would be helpful to review the results (relapse rates, event-free survival, and overall survival) of the 4 individual maintenance regimens administered divided according to the initial induction regimen used (all-trans-retinoic-acid [ATRA]→chemotherapy [CT], ATRA + CT for white blood cell [WBC] ≤5,000/μL, or ATRA + CT for WBC >5,000/μL). For the elder group of patients, the authors state that the “numbers of patients were too small in the elderly group for adequate comparisons” to be analyzed. Tables 3 and 4, Fig 3, and the Discussion section of the article all provide some of this data, but not the complete data, for all subgroups needed for a full comparison.
Response
In our previous paper,1-1 we reported the results of a random- ized clinical trial that was designed to assess the effects of all trans-retinoic acid (ATRA) followed by chemotherapy (CT) compared to that of ATRA plus CT, and the role of maintenance therapy. As mentioned in the report, we adjusted maintenance comparisons for baseline prognostic covariates as well as for the results of the induction assignment. Nevertheless, it would be helpful to review the results of the 4 maintenance groups according to the initial induction randomized group. This is depicted in Table 1-1.
Role of Maintenance According to the Induction Regimen Administered
| Outcomes . | Maintenance Randomized Group . | ||||
|---|---|---|---|---|---|
| Induction Group . | ATRA Alone . | No Maintenance . | ATRA and Chemotherapy . | Chemotherapy Alone . | P Value . |
| ATRA → CT | n = 18 | n = 23 | n = 19 | n = 21 | |
| Relapse at 2 yr | 12% | 22% | 12% | 7% | .06 |
| EFS at 2 yr | 88% | 71% | 88% | 88% | .03 |
| Survival at 2 yr | 100% | 79% | 92% | 95% | .16 |
| ATRA + CT | n = 20 | n = 17 | n = 20 | n = 16 | |
| Relapse at 2 yr | 7% | 29% | 0 | 8% | .056 |
| EFS at 2 yr | 87% | 71% | 100% | 92% | .096 |
| Survival at 2 yr | 86% | 92% | 100% | 100% | .23 |
| High WBC group | n = 30 | n = 28 | n = 29 | n = 30 | |
| Relapse at 2 yr | 35% | 47% | 8% | 26% | .002 |
| EFS at 2 yr | 75% | 53% | 92% | 74% | .005 |
| Survival at 2 yr | 88% | 67% | 95% | 92% | .018 |
| Elderly group | n = 4 | n = 6 | n = 6 | n = 4 | |
| Relapse at 2 yr | 0 | 17% | 17% | 0 | .76 |
| EFS at 2 yr | 100% | 83% | 67% | 100% | .52 |
| Survival at 2 yr | 100% | 100% | 67% | 100% | .13 |
| Outcomes . | Maintenance Randomized Group . | ||||
|---|---|---|---|---|---|
| Induction Group . | ATRA Alone . | No Maintenance . | ATRA and Chemotherapy . | Chemotherapy Alone . | P Value . |
| ATRA → CT | n = 18 | n = 23 | n = 19 | n = 21 | |
| Relapse at 2 yr | 12% | 22% | 12% | 7% | .06 |
| EFS at 2 yr | 88% | 71% | 88% | 88% | .03 |
| Survival at 2 yr | 100% | 79% | 92% | 95% | .16 |
| ATRA + CT | n = 20 | n = 17 | n = 20 | n = 16 | |
| Relapse at 2 yr | 7% | 29% | 0 | 8% | .056 |
| EFS at 2 yr | 87% | 71% | 100% | 92% | .096 |
| Survival at 2 yr | 86% | 92% | 100% | 100% | .23 |
| High WBC group | n = 30 | n = 28 | n = 29 | n = 30 | |
| Relapse at 2 yr | 35% | 47% | 8% | 26% | .002 |
| EFS at 2 yr | 75% | 53% | 92% | 74% | .005 |
| Survival at 2 yr | 88% | 67% | 95% | 92% | .018 |
| Elderly group | n = 4 | n = 6 | n = 6 | n = 4 | |
| Relapse at 2 yr | 0 | 17% | 17% | 0 | .76 |
| EFS at 2 yr | 100% | 83% | 67% | 100% | .52 |
| Survival at 2 yr | 100% | 100% | 67% | 100% | .13 |
ATRA → CT, ATRA followed by chemotherapy; ATRA + CT, chemotherapy started on day 3 of ATRA treatment; high WBC group, patients with presenting WBC count above 5,000/μL; elderly group: patients older than 65.
Abbreviation: EFS, event-free survival.
These detailed results clearly show that the effects of maintenance, especially when using ATRA and chemotherapy, were particularly beneficial to patients with initial white blood cell (WBC) count above 5,000 μL. However, these effects were also found in patients with lower initial WBC counts. The effect of maintenance was more difficult to assess in the elderly group due to the small sample size.
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