CECA Results in Improved Response Rates and Ability to Proceed to Stem Cell Transplantation in Adult Refractory or Relapsed Acute Myeloid Leukemia

Abstract 4299

Despite extensive research in adult acute myeloid leukemia, refractory and relapsed disease remain challenging to treat. The development of CECA (cyclophosphamide, etoposide, carboplatin, cytosine arabinoside) was promising as it provided another therapeutic option for reinduction (Kornblau, et al. Leuk Lymphoma. 1998 Jan;28:371–5). In addition, in this particular subset of patients, at the time of discovery of refractory (PrR) or relapsed (Rel) disease, the next question we face relates to stem cell transplantation. Thus, the importance of achieving complete responses (CR) becomes even more imperative. However, the reported CR rate by Kornblau et al was 12% in a study including 25 patients. We believe that patients treated with CECA at our institution have greater response rates. Furthermore, there has not been any subsequent published study regarding efficacy of CECA in refractory or relapsed AML. With these questions in mind, we performed a retrospective study of adult patients at our institution with AML who have received the CECA regimen for reinduction to determine response rates and ability to proceed to stem cell transplantation.

A total of 50 adult AML patients (14 PrR and 36 Rel) received CECA for reinduction between 1999 and 2009. Median age of patients is 53 (range 24–77). 18 patients (36%) overall achieved CR (defined as less than 5% blasts in a normal or hypercellular marrow lasting at least 28 days after reinduction and peripheral blood count recovery) or CRi (CR without count recovery). Of these 18 patients, 5 had PrR and 13 had Rel. The median number of induction regimens prior to CECA was 2. In the relapsed setting, the median number of days from most recent induction regimen to CECA is 140 days. Of patients who achieved CR, 11 (61%) proceeded to allogeneic stem cell transplantation. Median number of days from CECA to transplant was 65 days. Mean progression-free survival (PFS) of patients who achieved CR was 118 days. Mean overall survival (OS) is 222 days in patients who achieved CR versus 100 days in patients who did not achieve CR. Early toxicity from CECA (defined as an adverse event within 28 days from start of chemotherapy) was fairly common and included bacteremia/sepsis (n=12), fungal pneumonia (n=7), bleeding (n=5, 2 GI, 2 pulmonary, 1 intra-abdominal), acute renal failure (n=5), cutaneous fungal infections (n=2), C. difficile colitis (n=1), and mucositis (n=1). There were 4 deaths within 28 days of therapy.

The CECA regimen for reinduction has activity in patients with refractory or relapsed AML, even after receiving several prior induction cycles. The key factor is the ability of CECA to facilitate stem cell transplantation in greater than half of patients who achieve CR. The toxicity profile appears to be reasonable in this population. Our institutional experience with CECA has shown promising results. Outcomes in a large population of patients and when utilized earlier in the disease course may be even greater and warrants further evaluation.