A standardized approach to the diagnosis, prognosis and therapy of patients with APL and CNS involvement is limited by the rare nature of the complication. We report the incidence, risk factors, management and outcome of APL with CNS involvement at Stanford University and review the published cases in the literature during the prior three decades.
Between 1983 and Jan 2012, 7 cases of APL with CNS involvement were identified at Stanford University and 65 in the literature during the same interval. All pts in the Stanford series received ATRA and anthracycline containing induction regimens followed by consolidation with anthracycline and cytarabine (7 pts), plus ATRA (5 pts), ATO (1 pt), or IT prophylaxis (1 pt). Five pts received maintenance with ATRA containing regimens in all cases (2 pts relapsed prior to starting maintenance). Median follow-up was 6 years.
Seventy-two relapses involving the CNS were seen after 1 to 50 months (median 8 months) and 61 (84.7%) occurred in CR1 with 8 (11.1%) in CR2, 2 (2.8%) in CR3 and 1 (1.4%) in CR4. Forty-seven (66.2%) were accompanied by bone marrow involvement, 14 (29.8%) molecular and 33 (70.2%) hematological. Median age was 35y with 9 pediatric pts (range 1.3 to 20y) and 63 adult pts (range 22 to 69y). Median WBC count was 28,100 cells/mm3 (range 1,100 to 162,000 cells/mm3) with 61.4% >10 and 6.8% >100 cells/mm3. PML/RARα isoform was reported in 29 pts with 37.9% bcr1, 3.4% bcr2, and 58.6% bcr3. Five pts presented with concurrent CNS-localized hemorrhage. Therapy included methotrexate (88.9%), cytarabine (80.6%), arsenic trioxide (ATO, 47.2%), and anthracycline (11.1%) containing regimens with 88.9% receiving intrathecal therapy. Eighty-six percent received cranial radiation with dose ranging 18 to 30 Gy. Autologous or allogeneic transplantation followed salvage therapy in 30.8% and 5.6% of pts, respectively. Fifty-four (75.0%) pts were salvaged successfully, including 88.2% of pts receiving ATO, however 18 (33.3%) pts later relapsed, 4 (22.2%) of which were salvaged with additional treatment.
CNS relapse is a rare complications of APL with the majority of cases occurring in pts with WBC >10 cells/mm3, and in first CR. CNS relapse was frequently associated with concurrent bone marrow relapse and approximately one-third occurred with only molecular involvement. A preventative role of IT prophylaxis could not be determined due to only 1 pt receiving prophylaxis. A high percentage of pts salvaged with ATO achieved CR, supporting its therapeutic efficacy and ability to cross the blood brain barrier. Incorporation of ATO in first line therapy for APL may reduce the risk of CNS relapse.
No relevant conflicts of interest to declare.
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