Treatment of Acute Promyelocytic Leukemia

Abstract

Cure of acute promyelocytic leukemia (APL) is now a possibility for most patients through the use of state-of-the-art treatments, which include simultaneous administration of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy for induction and consolidation, as well as ATRA-based maintenance. Risk-adapted strategies to modulate treatment intensity may be an effective approach to minimize therapy-related morbidity and mortality while maintaining the potential of cure. In this context, there is no role for hematopoietic stem cell transplantation (HSCT) in front-line therapy, except for the small fraction of patients with persistent minimal residual disease at the end of consolidation. However, HSCT plays an important role for patients in second complete remission. In contrast, an increasing role of arsenic trioxide (ATO) is emerging. Given the high antileukemic efficacy observed with ATO in patients relapsing after ATRA-containing regimens, this agent is currently regarded as the best treatment option in this setting. However, until a randomized comparison between the standard therapy and ATO-based regi-mens in front-line therapy is available, this latter approach should only be recommended for unfit patients for whom chemotherapy is contraindicated. In addition to reviewing current consensus and controversial issues on antileukemic strategies, this review addresses other aspects that can be crucial for the outcome of individual patients. These aspects include supportive care, recognition and treatment of life-threatening complications, evaluation of response, and, finally, management of the disease in special conditions such as older patients, children and pregnant women.

Seventeen years of experience with ATRA-based therapy for acute promyelocytic leukaemia: Long-term follow-up of patients treated at S. Martino Hospital, Genoa

“…The percentage of haematologic and cytogenetic response after induction, as well as the long-term molecular results in our series confirm the previously established high efficacy of ATRA-containing therapy in APL patients of all ages (1)(2)(3)(4)(5)(6)(7)(8)11,12). Furthermore, our retrospective analysis highlights that achieving a persistently negative PML/RAR status as assessed by RT-PCR is associated with favourable DFS and OS (4,10) and that maintenance therapy might be beneficial.…”

“…The favourable outcome that was observed upon longterm evaluation in our subgroup of patients aged 60 years or older confirms the good results that have already been reported in this particular subset of patients (6,11,12). On the other hand, the non-optimal feasibility of consolidation therapy indicates the need for post-induction regimens specifically designed for elderly patients.…”

“…Although myelotoxicity was milder than what is induced by chemotherapy in other AML subtypes, in some patients infectious complications were life threatening events. Thus, in order to reduce the risk, the most recent approaches tailor post-induction therapy to the patient's individual risk (7,8,12).…”

“…The inclusion of new specific and selective drugs, such as ATO and GO in front-line therapy, together with improved prognostic characterisation might further improve the quality of response (12,17,18), thus reducing the likelihood of disease recurrence.…”

Diagnostic Characterization of Acute Promyelocytic Leukemia and Targeted Therapy in this Leukemia

“…ATRA induces differentiation of leukemic promyelocytes into mature granulocytes. All-trans retinoic acid (ATRA) as a highly effective therapy in acute promyelocytic leukemia (APL) The patients receiving ATRA followed by chemotherapy did significantly better compared with patients treated with ATRA alone or chemotherapy alone [5]. With this combination the CR rate ranges from 90 to 96 percent (Figure 1 & 2).…”