Autologous Transplant, and Not ATO Alone, Remains the Preferred Therapy for Relapsed APL: A Report from the CIBMTR, EBMT and Two Specialized Centers
Authors: Ganzel Chezi , Mathews Vikram , Alimoghaddam Kamran , Ghavamzadeh Ardeshir , Kuk Deborah , Devlin Sean , Wang Hailin , Weisdorf Daniel , Douer Dan , Rowe Jacob M. , Nagler Arnon , Mohty Mohamad , Tallman Martin S. , Estev Jordi , Zhang Mei-Jie 
Published: October 2019

Introduction: Despite its favorable prognosis, 10-20% of APL patients relapse with contemporary therapeutic strategies. At relapse, reinduction therapy is often followed by autologous hematopoietic cell transplantation (auto-HCT). In the last two decades, arsenic trioxide (ATO) has become part of the standard reinduction regimens. Such an approach is often followed successfully by auto-HCT. However, long-term survivors have also been reported after ATO treatment alone without HCT. We retrospectively compared the outcome of auto-HCT, with or without ATO, and ATO-based therapy given alone following relapse in patients with APL.

Patients and Methods: Data on APL patients in first relapse were collected from the two largest transplant registries (CIBMTR, EBMT) and two specialty referral centers (Hematology-Oncology & Stem Cell Transplantation Research Center, Shariati Hospital, Tehran and Christian Medical College & Hospital, Vellore, India). The outcome of patients who received ATO at relapse and did not undergo transplantation was compared to that of patients who received any reinduction therapy, including ATO and subsequent auto-HCT. Overall survival was calculated from two months post relapse with left truncation at date of CR2 for patients receiving ATO alone and date of transplant for those receiving auto-HCT. Cox proportional hazard regression was used to estimate the univariate and multivariate associations with overall survival. Potential prognostic factors included age, disease risk based on WBC >10,000/µl, the presence of extramedullary disease, and duration of CR1, in addition to the primary comparison of auto-HCT and ATO-based reinduction therapy.

Results: 242 patients were identified, of whom 34 were excluded due to missing relapse date (n = 25), death or lost to follow-up before 2 months after relapse (n = 7), or receiving auto-HCT within two months of relapse (n = 2). The median age was 31, 63% of the patients were males and median WBC count at diagnosis was 4,750/µl. The final cohort of 208 patients included 68 receiving ATO alone and 140 receiving auto-HCT. The groups were comparable in terms of age, gender, duration of CR1 and risk group. Fifty-six percent of the auto-HCT patients received ATO-based treatment as salvage therapy and the others received various combinations of chemotherapy and ATRA.

There is a statistically significant survival advantage for the HCT group (HR = 0.34 (0.27-0.42), p<0.001) compared to the ATO only group. At 5 years, OS was 42% (95% CI: 31% - 58%) and 78% (95% CI: 71% - 86%) for the ATO-only and HCT groups, respectively. In addition, there was a significant OS association with longer duration of CR1 (p=0.002) and presence of extramedullary disease (p = 0.041); which remained significant in a multivariate model (p < 0.001). Disease risk at diagnosis was not associated with OS.

Conclusions: These data suggest that auto-HCT results in improved OS after APL relapse, better than ATO-based therapy alone. Further studies to identify improvements in auto-HCT and which patients treated with ATO alone may be cured are needed.

Disclosures

Douer: Gilead: Consultancy. Rowe:Amgen: Consultancy; BioLineRx Ltd.: Consultancy; BioSight Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees.