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Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2225-2229
Therapy of Molecular Relapse in Acute Promyelocytic Leukemia
Francesco Lo Coco,
Daniela Diverio,
Giuseppe Avvisati,
Maria C. Petti,
Giovanna Meloni,
Enrico M. Pogliani,
Andrea Biondi,
Giuseppe Rossi,
Carmelo Carlo-Stella,
Carmine Selleri,
Bruno Martino,
Giorgina Specchia, and
Franco Mandelli
From the Dipartimento di Biotecnologie Cellulari ed Ematologia,
Università "La Sapienza," Rome; Clinica Pediatrica and
Divisione di Ematologia, Ospedale S.Gerardo, Monza; Sezione Ematologia,
Spedali Civili, Brescia; Cattedra di Ematologia, Università di
Parma; Divisione di Ematologia, Università Federico II, Napoli;
Dipartimento di Ematologia, Azienda Ospedaliera di Reggio Calabria; and
Cattedra di Ematologia, Università di Bari, Bari, Italy.
Fourteen patients with PML/RAR -positive acute promyelocytic
leukemia (APL) were given salvage therapy at the time of first molecular relapse. All patients had achieved first molecular remission after the AIDA protocol (all-trans retinoic acid [ATRA] + idarubicin) and were being prospectively monitored by reverse
transcriptase-polymerase chain reaction (RT-PCR). Molecular relapse was
defined as reappearance of RT-PCR-positivity for the PML/RAR fusion
(sensitivity 10 4) in 2 successive marrow samples
collected during postconsolidation monitoring. The median duration of
first molecular remission was 7.5 months (range, 2 to 25). Salvage
therapy consisted of oral ATRA for 30 days followed by 4 daily courses
of chemotherapy (CHT) with cytarabine 1 g/m2/d and
mitoxantrone 6 mg/m2/d. Second molecular remission was
obtained in 12 of 14 patients (86%). Seven of these 12 attained
molecular remission after ATRA alone. Of the 2 patients who persisted
PCR+ after CHT, 1 died in remission and 1 progressed to
hematologic relapse. Of 12 patients PCR, 8 received
consolidation with autologous bone marrow transplantation (ABMT), and 4 received ATRA-containing maintenance. Ten patients in this group are in
sustained second molecular remission at a median time of 9.5+ months
(range, 4 to 22+) and 2 underwent hematologic relapse 6 and 13 months, respectively, after transient second molecular remission. The
2-year Kaplan and Meier survival estimate from time of relapse was 92%
(95% confidence interval [CI]: 61% to 98%) in this
series, and 44% (95% CI: 35% to 52%) in a previous series of 37 patients who received the same treatment at the time of hematologic
recurrence (P < .05, by log-rank test). This study suggests
that early administration of salvage therapy is advantageous in APL and
represents the first experience on therapy of molecular relapse in
acute leukemia.
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