Secondary acute myeloid leukemia (AML) refers to a condition in patients who have had prior myelodysplasia (MDS), myeloproliferative disorder, or aplastic anemia that converts to myeloid leukemia. It can occur with or without treatment for those conditions, or as a result of previous exposure to a chemotherapeutic agent.
Older age, adverse risk cytogenetics, and antecedent hematological disorder are well-established prognostic factors for poorer outcome in AML.
According to led by Andrew Kuykendall, MD, of Moffitt Cancer Center in Tampa, Florida, population-based studies suggest that secondary AML accounts for about 25% of all AML cases, with 18% to 20% evolving from previous myeloid disease, and 6% to 8% related to therapy.
"One of the important challenges with secondary AML is that a lot of these patients, if they've been treated for something like MDS, and then they progress to AML, tend to respond poorly to standard treatment," said Prajwal Boddu, MD, of Yale School of Medicine in New Haven, Connecticut.
"Secondary AML is also known to be resistant to standard treatment," Boddu told 番茄社区 Medical Today. For conditions such as MDS or myeloproliferative disorder, he said, this has typically consisted of "7+3" chemotherapy which involves 7 days of standard-dose cytarabine, and 3 days of daunorubicin.
According to , median survival among patients with secondary AML is estimated to be only 6 to 12 months, even with treatment with intensive standard chemotherapy.
Among patients who received intensive induction treatment in that study, complete response was seen in 72% of patients with de novo AML, compared to 39% in patients with antecedent hematological disease AML, and 54% in therapy-related AML.
The investigators found in a multivariable analysis that both antecedent hematological disease AML (HR 1.51, 95% CI 1.26–1.79) and therapy-related AML (HR 1.72, 95% CI 1.38–2.15) were independent risk factors for poor survival.
This study included 3,363 patients, 26.4% of whom had secondary AML. Mean age at diagnosis was 71 years, demonstrating "its true population‐based nature," the authors noted. "Strikingly, for younger patients with secondary AML, the median survival equaled that of elderly patients with secondary AML in clear contrast to de novo AML where younger patients fared much better compared to the older."
According to Boddu, AML arising from MDS or myeloproliferative disorder has been treated in a fashion similar to that used for de novo AML. This includes chemotherapy regimens, which, as demonstrated above, have repeatedly shown outcomes in secondary AML as inferior to those seen with de novo AML.
In their review, Kuykendall and colleagues noted that allogeneic hematopoietic cell transplant has also had inferior outcomes in patients with secondary AML compared to patients with de novo AML.
However, in Stockholm, researchers using two nationwide Swedish registries – the Swedish AML Registry and the Swedish Cancer Registry -- found that allogeneic hematopoietic cell transplantation was a more effective alternative than consolidation chemotherapy in patients with secondary AML.
The population-based study found that the proportion of patients with AML achieving complete remission who undergo allogeneic hematopoietic cell transplantation (HCT) was 23% in those with de novo AML, 28% in AML with an antecedent hematologic disorder, and 27% in therapy-related AML.
The researchers found that at 5 years after diagnosis, patients with secondary AML who did not undergo HCT had extremely poor outcomes. The survival rate was 0% in those with AML preceded by myeloproliferative neoplasm, 2% in patients with AML preceded by myelodysplastic syndrome, and 4% in patients with therapy-related AML (t-AML).
Patients who underwent HCT at any time point or disease stage, however, had survival rates that ranged from 18% to 32%.
These survival figures suggest that "HCT is the sole realistic curable treatment option for [secondary] AML," the researchers wrote.
For the future, however, Kuykendall and colleagues noted that increased understanding of the biologic features of secondary AML was leading to "development of novel therapeutic agents that hold promise in improving outcomes in our patients."
One of those newer therapeutic options is CPX-351 (cytarabine and daunorubicin liposome), said Boddu, "which is believed to be more effective than the standard 7+3."
For example, in published in the Journal of Clinical Oncology, researchers determined that CPX-351, compared to standard cytarabine plus daunorubicin, significantly improved overall survival among older patients with secondary AML.
Median overall survival was 9.56 months in the CPX-351 group vs 5.95 months in the 7+3 group (HR 0.69, P=0.003). Estimated overall survival was 41.5% vs 27.6% at 1 year and 31.1% vs 12.3% at 2 years.
In 2017, the under the brand name Vyxeos for adult patients with newly diagnosed t-AML or AML with myelodysplasia-related changes.
"But, even with CPX-351, some patients do poorly," Boddu said. "That's why there is so much interest in exploring new therapeutic approaches for these patients."