Results of treatment of relapsed promyelocytic leukemia in children using chemotherapy and arsenic trioxide (ATO) followed by autologous SCT (ASCT)
Dina D. Baidildina, Elena V. Samochatova, Michail A. Maschan, Alexey A. Maschan
On behalf of the Russian-Byelorussian Pediatric APL study group
Correspondence:
Elena V. Samochatova, Research Institute for Pediatric Hematology, 117, Leninsky prosp, Moscow, 105062, Russia
E-mail: samochatova@
niidg.ru
Summary
The Russian multicenter APL-2003 protocol for pediatric APL demonstrated a non–inferior outcome compared with the APL-93/98 studies despite a reduction of ATRA to 25 mg/m2 and cumulative anthracycline dose to 405 mg/m2: at a median follow up of 35 mo the EFS and OS were 0.79±0.6 and 0.93±0.3. Seven relapses (11.9%) occurred out of 61 patients (pts) at a median of 21 (4–35) mo. Second remission was induced with diverse therapy (Table 1) and consolidated with 14 ATO at 0.15 mg/kg per day;
in 1 pt gemtuzumab ozogamicin (GO) at 6 mg/m2 was added to ATO. All pts achieved 2nd hematological remission and PML/RARα negativity in bone marrow either after induction (3 pts) or after consolidation (4 pts). HDAraC + G–CSF were used for additional “in-vivo purging” and PBSC mobilization. Harvesting was successful in all pts: а median of CD34+ dose 17 (8–40) х 106/kg was achieved after single apheresis. In all cases, apheresis product proved to be PML/RARα negative. AHSCT was performed in 6 pts after conditioning with HDAraC + Mel180 mg/m2 in 4 pts, Bu12mg/kg + Mel 140 mg/m2 in 1 pt and Treosulfan 42 mg/m2 + Mel140 mg/m2 in 1 pt. All pts engrafted at a median of 16 (12–25) d with minimal transplant-related toxicity. Three pts received GO on day +100 after ASCT with minimal toxicity. Two pts with skin involvement received complementary electron beam skin irradiation. At a median of 26 mo 6 pts continued in molecular remission and 1 pt experienced 2nd relapse. We conclude that children with relapsed APL can be treated effectively with chemotherapy, ATO, and ASCT.
Keywords: promylocytic leukemia, arsenic trioxide, autologous hematopoietic stem cell transplantation
Case № | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
Age in years | 14 | 13 | 1 | 14 | 7 | 12 | 13 |
WBC at Dx mm3 | 1.400 | 3.900 | 57.000 | 15.700 | 2.600 | 40.000 | 0.900 |
Rx start – relapse, mo | 21 | 29 | 9 | 35 | 23 | 4 | 12 |
PML/RARα before maintenance | + | + | - | + | - | + | - |
Relapse site | bone marrow | bone marrow | bone marrow | bone marrow skin | bone marrow | bone marrow skin | bone marrow |
2nd remission induction | АТRА АТО | АТRА 7+3 | АТRА HDAraC Mitox | АТRА AraC, Ida | АТRА АТО Mitox | АТО | АТО |
Post 2nd remission therapy | АТО 2 courses | АТО 3 courses | АTО 3 courses | АТО 3 courses | АТО 3 courses | АТО GO | АТО 1 course |
Autо-HSCT | + | + | + | + | + | + | |
Duration of 2nd mol remission mo | + 35 | + 27 | + 26 | + 26 | + 18 | + 8 | + 1 |