Acute promyelocytic leukemia: from highly fatal to highly curable

Abstract

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia. Morphologically, it is identified as the M3 subtype of acute myeloid leukemia by the French-American-British classification and cytogenetically is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion between promyelocytic leukemia (PML) gene and retinoic acid receptor ␣ (RAR␣). It seems that the disease is the most malignant form of acute leukemia with a severe bleeding tendency and a fatal course of only weeks. Chemotherapy (CT; daunorubicin, idarubicin and cytosine arabinoside) was the front-line treatment of APL with a complete remission (CR) rate of 75% to 80% in newly diagnosed patients. Despite all these progresses, the median duration of remission ranged from 11 to 25 months and only 35% to 45% of the patients could be cured by CT. Since the introduction of all-trans retinoic acid (ATRA) in the treatment and optimization of the ATRA-based regimens, the CR rate A historical view of acute promyelocytic leukemia (APL)Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML; Figure 1). Morphologically, it is identified as AML-M3 by the French-American-British (FAB) classification. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion between the promyelocytic leukemia (PML) gene and retinoic acid receptor ␣ (RAR␣). Variant chromosomal translocations (eg, t(11;17), t(5;17)) can be detected in no more than 2% of APL patients. As a special entity, APL was first described in 1957 by a Swedish author, Hillestad, 1 when he reported 3 patients characterized by "a very rapid fatal course of only a few weeks'duration," with a white blood cell (WBC) picture dominated by promyelocytes and a severe bleeding tendency. He concluded that the disease "seems to be the most malignant form of acute leukemia." More detailed features of APL were described by Bernard et al 2 in 1959, and the severe hemorrhagic diathesis has been ascribed to disseminated intravascular coagulation (DIC) or hyperfibrinolysis.In 1973, Bernard et al 3 demonstrated that APL leukemic cells were relatively sensitive to chemotherapy (CT: daunorubicin) that yielded a complete remission (CR) rate of 19 (55%) in 34 patients with APL. From then on, CT composed of an anthracycline (daunorubicin, idarubicin, or others) and cytosine arabinoside (Ara-C) was the frontline treatment of APL, and the CR rates could reach 75% to 80% 4,5 in newly diagnosed patients. However, the frequently observed aggravation of bleeding syndrome by CT, leading to high early death rate, necessitated intensive platelet and fibrinogen support. Despite such progress, the median duration of remission ranged from 11 to 25 months and only 35% to 45% of the patients could be cured by CT alone as judged by the criterion of 5-year disease-free survival (5-year DFS). 6,39 In 1985, the introduction of all-trans retinoic acid (ATRA) opened a new...

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy

“…Increased bone marrow FDG uptake at PET/CT is not a sufficient proof of bone marrow involvement in diffuse large B-cell lymphoma Consequently, they suggest that BMB can be omitted in case of unequivocal bone marrow involvement at FDG-PET/CT. Although the results of the study by Chen-Liang et al [1] underline the results of our previous study [2] that FDG-PET has a suboptimal sensitivity for the identification of bone marrow involvement in DLBCL, we cannot agree with their conclusion that bone marrow abnormalities at FDG-PET/CT can confidently designate advanced-stage disease. Increased focal FDG uptake in the marrow is not sufficient evidence to confirm bone marrow involvement.…”

“…This concern is reflected by the fact that although bone marrow involvement according to BMB has been established as an important adverse prognostic factor in DLBCL [7], this is not the case for FDG-PET/CT-based bone marrow involvement. Of the five studies that reported the prognostic value of bone marrow involvement at FDG-PET/CT in DLBCL [2,[8][9][10][11], four showed that FDG-PET/CTbased bone marrow status did not have any prognostic value at all [2,[8][9][10]. These observations suggest that false-positive FDG-PET/CT results occur in a considerable proportion of patients with DLBCL and that increased FDG uptake of the marrow is not sufficient evidence to designate advanced-stage disease.…”

“…Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy To the Editor: With the current ATRA and chemotherapeutic regimens, over 80% of patients with de novo acute promyelocytic leukemia (APL) can be cured [1,2]. The PETHEMA group stratified APL patients into three different subgroups (low, intermediate, and high risk), by using upfront WBC count (> or <10 3 10 9 /L) and platelet count (> or <40 3 10 9 /L) [3].…”

Severe Aplastic Anemia Manifesting After Complete Remission of Acute Promyelocytic Leukemia: Is it a Fortuitous Association?

“…It is a morphologically unique subtype of AML that is classified as AML M3 by the old French-American-British (FAB) system and APL with t(15;17)(q22;q21) by the World Health Organization (WHO) [1]. The resultant PML/RARa fusion protein inhibits differentiation at the promyelocyte stage [7].…”

“…Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) that harbors a unique balanced reciprocal translocation between chromosomes 15 and 17 resulting in the generation of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARa) fusion gene [1]. Untreated, it runs a fatal course of only weeks, with most succumbing to severe hemorrhagic diathesis.…”