1. ¹Hospital Clínic, Barcelona, Spain
2. ²Hospital Joan XXIII, Tarragona, Spain
3. ³Hospital La Fe, Valencia, Spain
4. ⁴Hospital General de Jerez de la Frontera, Jerez de la Frontera, Spain
5. ⁵Hospital Clínico San Carlos, Madrid, Spain
6. ⁶Hospital Universitario, Salamanca, Spain
7. ⁷Hospital General, Alicante, Spain
8. ⁸Hospital de Cruces, Baracaldo, Spain
9. ⁹Hospital Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain
10. ¹⁰Hospital de Sant Pau, Barcelona, Spain
11. ¹¹Fundación Jiménez Díaz, Madrid, Spain
12. ¹²Hospital Clínico, Valencia, Spain
13. ¹³Hosp. Dr Pesset, Valencia, Spain
14. ¹⁴Hospital Severo Ochoa, Leganés, Spain
15. ¹⁵Department of Medical Biopathology, Hospital La Fe, Valencia, Spain

Correspondence: Dr J Esteve, Department of Hematology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. E-mail: jesteve@clinic.ub.es

¹⁶These two authors contributed equally to this study

Received 20 June 2006; Revised 12 September 2006; Accepted 13 October 2006; Published online 4 January 2007.

Abstract

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3–72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 6414 vs 248%, P=0.01) and lower relapse risk (5-year relapse risk: 3013 vs 649%; P=0.044). Additionally, age40 and male gender were favorable variables for survival, whereas molecular response predicted longer leukemia-free survival. In conclusion, early institution of salvage therapy at molecular failure, before onset of hematological relapse, is beneficial in APL. Moreover, given the poor outcome of HEMrel managed with ATRA and HDAC, use of alternative therapeutic strategies in this setting is warranted.