Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Abstract

We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26 950/mm 3 (7700-162 000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age o45 years (P ¼ 0.05), bcr3 PML-RARa isoform (P ¼ 0.0003) and high WBC counts (X10 000/ mm 3 ) (Po0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P ¼ 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P ¼ 0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (X10 000/mm 3 ) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC X10 000/mm 3 at diagnosis remains to be established.

How to manage acute promyelocytic leukemia

“…At present, the relapse rate is more than 1% in a 5-year follow-up, especially in patients with initial WBC greater than 10 Â 10 9 /l, in which the recurrence rate could exceed 5%. 49,93 Once a CNS relapse is recognized, we recommend intrathecal therapy with methotrexate (10 --15 mg), dexamethasone (5 mg) (or Prednisolone 40 mg) and Ara-C (40 --50 mg) 2 --3 times per week until complete clearance of blasts in the cerebrospinal fluid. At the same time, systemic medication, including ATO and ATRA, should be started.…”

Granulocytic Sarcoma of Colon in a Patient with Acute Promyelocytic Leukemia

“…One case of APML presenting as colonic ulcer has been described [7] and one case report of a tumor in a supraclavicluar lymph node has been described when the marrow was in remission [8]. Central nervous system involvement is the commonest site that has been reported [9,10]. Leukemia cutis is also a rare occurrence in APML.…”

Promyelocytic sarcoma presenting with spinal cord compression and treated successfully with surgical debulking and the PETHEMA regimen for acute promyelocytic leukemia

“…In the six patients who relapsed with extramedullary APL, 2 (of 61 patients) had received chemotherapy plus ATRA and 4 (of 59 patients) had received chemotherapy alone, leading the authors to conclude that ATRA does not appear to predispose to the development of extramedullary APL any more than other types of treatment for APL. De Botton et al analyzed 169 relapses of 740 patients with APL treated in 3 multicenter trials [5] . Ten of the 169 relapses were extramedullary, involving the CNS (9 cases) and skin (1 case).…”