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928 Autologous Transplant, and Not ATO Alone, Remains the Preferred Therapy for Relapsed APL: A Report from the CIBMTR, EBMT and Two Specialized Centers

Clinical Autologous Transplantation: Results
Program: Oral and Poster Abstracts
Type: Oral
Session: 731. Clinical Autologous Transplantation: Results III
Monday, December 7, 2015: 7:00 PM
W314, Level 3 (Orange County Convention Center)

Chezi Ganzel1*, Vikram Mathews, DM2, Kamran Alimoghaddam, MD3, Ardeshir Ghavamzadeh, MD3, Deborah Kuk, ScM4*, Sean Devlin, PhD4*, Hailin Wang5*, Daniel Weisdorf, MD6, Dan Douer, MD7, Jacob M. Rowe, MD1,8, Arnon Nagler, MD, MSc9, Mohamad Mohty10, Martin S. Tallman, MD11, Jordi Estev12* and Mei-Jie Zhang13*

1Hematology, Shaare Zedek Medical Center, Jerusalem, Israel
2Department of Haematology, Christian Medical College, Vellore, India
3Shariati Hospital, Tehran, Iran
4Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
5CIBMTR Statistical Center, Minneapoiis
6Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
7Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
8Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
9Hematology Division, Chaim Sheba Medical Center and Tel Aviv University, Tel-Hashomer, Ramat-Gan, Israel
10Saint-Antoine Hospital and University Pierre & Marie Curie, Paris, France
11Memorial Sloan-Kettering Cancer Center, New York, NY
12Hospital Clinic, Institut d' investigacions biomediques August Pi Sunyer, Barcelona, Spain
13Medical College of Wisconsin, Milwaukee

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 .

*signifies non-member of ASH