High Dose Cytarabine, Mitoxantrone and L-Asparaginase (HAMA) Salvage For Relapsed Or Refractory Acute Myeloid Leukemia (AML) In The Elderly

AML is a disease of older adults with the median age at diagnosis of 68. Elderly AML, generally defined as patients ≥60 years of age, is a clinically distinct disease highlighted by worse overall survival (OS), lower complete remission (CR) rates, and higher treatment related toxicity. Most elderly AML patients who achieve a CR will eventually relapse and require further chemotherapy. Despite the central role of relapsed disease in elderly patients few studies have reported on outcomes using salvage chemotherapy in patients over 60 years of age and no standard regimen has been established.

We retrospectively examined data for 108 consecutive relapsed or refractory AML patients treated with the HAMA regimen at Wake Forest between May, 1999 and December, 2010. This regimen consists of high dose cytarabine (3gm/m² in patients <60, 1 to 3gm/m² in patients ≥60) given Q12 hours for 5 doses, mitoxantrone at 6mg/m² once daily for 3 days immediately following the cytarabine and a single dose of L-asparaginase at 6000 units/m² following the last dose of mitoxantrone. We collected data on age, gender, race, comorbidities, baseline lab values, cytogenetics at relapse, length of first remission (CR1), attainment of second complete remission (CR2), further therapy received and survival. Statistical analysis was performed using Kaplan-Meier estimates and Cox proportional hazards models.

Of the 108 patients analyzed, 75 were ≥60 years old and 33 were younger than 60 at the time of HAMA treatment. The median age for the younger cohort was 51 (range 20-59) and for the elderly cohort was 68 (range 60-84). Older patients were more likely to have refractory disease (25% vs 6%), one or more comorbidities (47% vs 12%) and poor risk cytogenetics (23% vs 16%). Early all cause mortality (30 and 60 day) was 13% and 22% respectively for all patients and 17% and 28% for those ≥60. The percentage of patients that died during hospitalization or were discharged to hospice was 25% for all patients (12% <60, 31% ≥60). CR2 was achieved in 41% of patients (49% <60, 37% ≥60). Median OS was 7 (2.1-14.3), 13.6 (4.9-68) and 5.8 (1.3-11.9) months for all patients, <60 and ≥60 cohorts respectively. For those patients ≥60 who achieved a CR median OS was 11.9 months. At 12 months 56% of patients <60 were alive compared with 24% for patients ≥60. By 24 months these numbers fell to 40% and 3% respectively. In the <60 cohort 27% (9/33) went on to allogeneic hematopoietic stem cell transplant (HCT) compared to 12% (9/75) in the ≥60 cohort. The only significant predictors for OS were cytogenetic risk score (p=0.0050) and length of first CR >1 year (p=0.0005). Of the 16 patients in the cytogenetic poor risk group only 12% (2/16) achieved CR2 and none were alive more than 14 months from relapse. Median survival for patients with CR1 >1 year was 13.6 (5.9-19.7) months compared to 5.8 (3.3-7.2) months for patients with CR1 <1 year.

In conclusion, the HAMA salvage regimen when given to older patients results in a 37% complete remission rate with a median survival of almost one year in this subgroup, however only 12% went on to allogeneic HCT and only 3% were alive 24 months after relapse. Patients with poor risk cytogenetics regardless of age were not effectively salvaged with this regimen and should be offered experimental therapy when possible.