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past three decades have brought major therapeutic advances in treating
acute promyelocytic leukemia (APL) both in adults and children. The
current state-of-the-art treatment with all-trans retinoic acid (ATRA)
and arsenic trioxide (ATO) in combination or not with chemotherapy
results in long-lasting remission and cure in more than 90% of newly
diagnosed patients. These treatments have made relapse a rare event.
The detection of PML-RARA transcript by polymerase chain reaction (PCR)
during treatment and follow-up can predict a hematological relapse. All
studies have suggested a survival benefit in patients with molecular
relapse given pre-emptive therapy compared with those treated at the
time of overt hematological relapse. ATO-based regimens seem to be
effective for achieving a second molecular complete remission (CR).
Patients in second molecular CR are generally considered candidates for
autologous hematopoietic stem cell transplant (HSCT), while for those
with a persistent molecular disease, allogeneic HSCT should be offered
if a suitable donor is identified.
Hematopoietic Stem Cell Transplantation as Part of APL Salvage Therapy (Allogeneic and Autologous)
|Table 1. Results of hematopoietic stem cell transplantation in pediatric APL patients in second complete remission.|
|Figure 1. ECOG E2491 and CALGB C9710 trials. Event-free survival following hematopoietic stem cell transplant for childhood relapsed/refractory acute promyelocytic leukemia.|
|Figure 2. Center for International Blood and Marrow Transplantation Research (CIBMTR). Treatment-related mortality in patients undergoing allogeneic and autologous transplant for acute promyelocytic leukemia in second complete remission.|
|Figure 3. Center for
International Blood and Marrow Transplantation Research (CIBMTR).
Overall survival in patients undergoing allogeneic and autologous
transplant for acute promyelocytic leukemia in second complete
|Table 2. Italian Experience. Patients with relapsed/refractory APL re-induced with ATRA + chemotherapy or ATO: outcome by type of consolidation.|
|Figure 4. Overall survival for Italian children/adolescents undergoing allogeneic- or autologous-hematopoietic stem cell transplant in second complete remission.|
|Figure 5. Event-free survival for Italian children/adolescents undergoing allogeneic- or autologous-hematopoietic stem cell transplant in second complete remission.|
|Figure 6. C) Overall
survival, D) Event-free survival of adult and pediatric patients with
acute promyelocytic leukemia in second complete remission consolidated
with autologous-stem cell transplant versus arsenic trioxide-based
|Figure 7. Treatment
algorithm for relapsed pediatric APL. *TTR=time to relapse;
**mos=months; ˜ATO=arsenic trioxide; ˜˜ATRA=all-trans retinoic acid;
^mCR=molecular complete remission; ^^GO=gentuzumab ozogamicin;
°CT=chemotherapy; °°HSC=hematopoietic stem cells; ˤHSCT=hematopoietic
stem cell transplant.
Very Late Relapse
Comments and Conclusions