AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR ACUTE PROMYELOCYTIC LEUKEMIA IN 2ND REMISSION - PROGNOSTIC RELEVANCE OF PRETRANSPLANT MINIMAL RESIDUAL DISEASE ASSESSMENT BY REVERSE-TRANSCRIPTION POLYMERASE CHAIN-REACTION OF THE PML RAR-ALPHA FUSION GENE/

Reverse-transcription polymerase chain reaction (RT-PCR) of the PML/RA R alpha fusion gene may predict relapse in acute promyelocytic leukemi a (APL) patients in hematologic complete remission (CR), We have prosp ectively studied by RT-PCR 15 PML/RAR alpha(+) APL patients undergoing autologous bone marrow transplantation (ABMT) in second CR. The media n time of first CR duration was 12 months (range, 6 to 40). All patien ts were reinduced with all-trans retinoic acid (ATRA), followed in 12 of 15 cases by mitoxantrone and Ara-C as consolidation, Fourteen patie nts received the BAVC (BCNU, Ara-C, m-AMSA, and VP-16) schedule as con ditioning regimen. Unpurged marrows were collected immediately before conditioning treatment, analyzed by RT-PCR, and reinfused at median of 2 months (range, 2 to 7) from the achievement of second CR. Seven pat ients were PCR+ and eight PCR- for PML/RAR alpha in their pretransplan t marrows. All seven patients of the former group remained PCR+ during the followup and relapsed at a median time of 5 months (range, 2 to 9 ) from ABMT and 9 months (range, 4 to 14) from second CR. Of the eight PCR- patients, all remained PCR- during the follow-up controls. One p atient relapsed at 10 months from ABMT, one died of a secondary (PML/R AR alpha(-)) leukemia, and six are in hematologic and molecular remiss ion at a median time of 28 months (range, 15 to 60) after ABMT and 32 months (range, 17 to 62) from second CR. Our results indicate that, in APL patients in second CR, ABMT with PML/RAR alpha(-) marrow cells is likely to result in prolonged clinical and molecular remissions. Conv ersely, patients who test PCR+ after reinduction necessitate the use o f alternative aggressive approaches, including unrelated allogeneic tr ansplant. (C) 1997 by The American Society of Hematology.