High-dose cytarabine induction is well tolerated and active in patients with de novo acute myeloid leukemia older than 60 years

BACKGROUND:

High‐dose cytarabine (HiDAC) is safe and very effective in younger patients with acute myeloid leukemia (AML), but it generally is not well tolerated in the elderly.

METHODS:

The authors explored the safety and tolerability of a modified HiDAC induction regimen consisting of 6 daily doses of cytarabine at 2 g/m² in combination with 3 daily doses of daunorubicin at 45 mg/m² in 59 consecutive patients aged >60 years who had de novo AML diagnosed between July 1996 and February 2005.

RESULTS:

The median patient age was 68 years (range, 60‐86 years). The regimen was well tolerated. Infections were common and occurred in 39% of patients, but cerebellar toxicities occurred in only 7% of patients and were reversible. The day‐30 induction‐related mortality rate was 10%. Overall, 69% of patients achieved complete remissions (CR), and 80% received up to 3 consolidations with HiDAC. The median follow‐up for surviving patients was 53 months (range, 17‐114 months). The median overall survival was 15.3 months (range, 1‐114 months), and the relapse‐free survival was 13.8 months (range, 1‐113 months). Survival for patients who achieved CR was 27 months (range, 2‐114 months).

CONCLUSIONS:

The modified HiDAC regimen was well tolerated in patients aged >60 years with AML and was associated with low induction mortality and high rates of CR. Nevertheless, these high remissions still were associated with poor overall outcomes. Cancer 2011;. © 2011 American Cancer Society.     

FA方案用于急性髓系白血病不同治疗阶段疗效分析

Objective  To evaluate the therapeutic effect of the fludarabine and cytarabine (FA) regimen on acute myeloid leukemia (AML) at different phases during treatment. Methods  A total of 185 patients with AML were divided into 4 groups based on the outcome of previous treatments. Patients in Group 1 had no remission after the first course of induction chemotherapy (n = 55). Patients in Group 2 had no remission after no less than two courses of induction chemotherapy (n = 41). Patients in Group 3 had early relapse (n = 40). Patients in Group 4 had late relapse (n = 49). Patients in groups 2, 3 and 4 had refractory AML or AML with relapse. We assessed the efficacy and toxicity of FA combination chemotherapy in each of these 4 groups. Results  The complete remission (CR) rates of Groups 1, 2, 3 and 4 were 74.5% (41/55), 45.9% (19/41), 17.5% (7/40) and 38.8% (19/49), respectively. The CR rate was higher in Group 1 than in the other 3 groups (34.6%, 45/130) (P = 0.000). A significant correlation was found between CR rate and the number of chemotherapeutic courses (P = 0.023). The main adverse reactions included bone marrow suppression and secondary infection. Conclusion  FA regimen is a good choice for patients with AML, especially those who have failed to achieve CR after the first course of induction chemotherapy. Supported by a grant from the Planned Science and Technology Project of Guangzhou (No. 2006Z3-E0401).     

Improved outcome of patients with low- and intermediate-risk cytogenetics acute myeloid leukemia (AML) in first relapse with gemtuzumab and cytarabine versus cytarabine: results of a retrospective comparative study

BACKGROUND:

Acute myeloid leukemia (AML) in first relapse is associated with a poor outcome even when treated with intermediate‐ to high‐dose cytarabine (IHDAraC). Gemtuzumab ozogamycin (GO) used as a single agent has clinical activity in relapsed and refractory AML. Various combination regimens of GO have been developed, but few data are available regarding their efficacy compared with IHDAraC‐based regimens.

METHODS:

The authors performed a retrospective analysis of response and survival in 90 AML patients in first relapse treated with either IHDAraC (n = 56) or IHDAraC + GO (n = 34). Patient characteristics of the two groups were comparable.

RESULTS:

Median follow‐up was 37 months. Compared with IHDAraC, IHDAraC + GO induction was associated with a better response rate (68% vs 45%, P = .04), a better overall survival (median, 35 months vs 6 months, P = .001), and a better event‐free survival (24 months vs 6 months, P = .002). This effect was limited to patients with low‐risk and intermediate‐risk cytogenetics. In multivariate analysis, age, cytogenetic risk, first complete remission duration, and the use of IHDAraC + GO were independently associated with better results.

CONCLUSIONS:

This study showed that the addition of GO to IHDAraC is associated with a better efficacy for patients in first relapse of AML with low‐ or intermediate‐risk cytogenetics. Prospective controlled studies of GO in this population are warranted. Patients with high‐risk cytogenetics should be offered investigational new drugs. Cancer 2011. © 2010 American Cancer Society.     

Post-remission therapy of adult acute myeloid leukaemia: One cycle of high-dose versus standard-dose cytarabine

Background: Intensification of post-remission therapy improves thecure rate of acute myeloid leukemia (AML) but is often accompanied byunacceptable toxicity. From 1985 to 1992 the Swiss Group for Clinical CancerResearch (SAKK) performed a randomized phase III trial to evaluate theeffectiveness of one single postremission course of high-dose cytarabine(HDAC) in terms of leukaemia-free and overall survival in adults with de novoAML.Patients and methods: Adult (15–65 years) AML patients inremission after two induction courses were randomly assigned to oneconsolidation course either with standard (SDAC: 100 mg/sqm 24 hours infusionover seven days) or with high-dose cytarabine (HDAC: 3000 mg/sqm every 12hours as one-hour-infusion for six days). In addition, both arms includeddaunorubicin (45 mg/sqm daily on days 1 to 3). Thereafter, patients wereobserved without maintenance until relapse.Results: After two induction courses 208/276 eligible patientsachieved remission (CR: 169, 61%, PR: 39, 14%), 41 wereresistant (15%) and 20 died early (7%). Seventy-one patients inremission were not randomized. One hundred thirty-seven were randomized inCR/PR (67 SDAC, 70 HDAC). 4/70 patients randomized to HDAC did not receive it.Treatment-related mortality in HDAC was 1.4% (1/66). WHO grade3–4 toxicities occurred in 14/67 SDAC and in 38/66 HDAC patients (P <0.0001). The median event free survival was 10.8 (SDAC) vs. 12.2months (HDAC; P = 0.18). The median overall survival was 24.6 (SDAC) vs.32.6 months (HDAC; P = 0.07). Although statistically uncertain, HDACreduced the hazard of progression (hazard ratio: 0.69, P = 0.08) and ofdeath (hazard ratio: 0.70, P = 0.13). For 112 patients stratified as CRthe estimated four-year disease-free survival was 25%(±6%) withSDAC and 37% (±6%) with HDAC (P = 0.09). Theoverallsurvival rates at four years were 38% (+7%) and 48%(+7%), respectively (P = 0.10). In multivariate analysis HDACsignificantly reduced the hazard of relapse by 39% compared to SDAC(hazard ratio = 0.61, 95% CI: 0.37–0.99; P = 0.049).Conclusions: We conclude that early consolidation of adult AML in CRwith a single course of HDAC is superior in terms of outcome to one cycle ofSDAC. The results of our intensive, single course HDAC group comparefavourably with less intensive, repetitive HDAC cycles, suggesting that Ara-Cdose intensity may be more important than total dosage. In addition, ourtreatment strategy is much less toxic and less expensive.     

Reduced-intensity conditioning therapy with fludarabine,idarubicin, busulfan and cytarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndrome

We retrospectively analyzed allogenic stem cell transplantation (allo-SCT) outcomes in 82 patients with AML or MDS were conditioned with fludarabine, idarubicin, intravenous-busulfan and cytarabine (FIBA) or busulfan and cyclophosphamide (BuCy). Compared to BuCy regimen, reduced intensity conditioning (RIC) with FIBA was associated with a lower incidence of severe acute GVHD, lower NRM and a similar relapse rate. There was no significant difference in the 3 year overall survival (OS), but this is possibly due to the limited number of patients. The FIBA regimen is promising to replace BuCy regimen because of better security and similar relapse rate.     

Hematological features and treatment outcome in acute myeloid leukemia with t(8;21)

We analyzed the hematological features and treatment outcome in 18 patients with t(8;21) acute myeloid leukemia (AML) diagnosed in Queen Mary Hospital, Hong Kong. They comprised 15 cases of M2, two cases of M4 and one case of M1 according to FAB criteria. Auer rods (17 cases) and dysgranulopoietic features (15 cases) were very frequently observed. Two cases showed marrow eosinophilia while blast cells in one patient demonstrated erythrophagocytic activity. Chromosome changes in addition to t(8;21) were seen in 14 patients, the most common of which was loss of a sex chromosome (10 cases). Of the 14 patients treated with intensive chemotherapy, 13 (93 per cent) entered complete remission with a median event-free survival (EFS) and overall survival (OS) of 11 and 24 months respectively. The probability of EFS and OS at 3 years were 33±14·3 per cent and 55·1±15·6 per cent respectively with a median duration of follow-up of 22 months. When compared with AML having no t(8;21) treated similarly in the same period, we could not demonstrate a better clinical outcome for t(8;21) AML. © 1997 John Wiley & Sons, Ltd.