Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines

Jácomo, Rafael H.; Melo, Raul Antônio Morais; Souto, Fernanda Ribeiro; Mattos, E.R.; Oliveira, Claudia; Fagundes, Evandro M.; Bittencourt, Henrique; Bittencourt, Rosane; Bortolheiro, Teresa Cristina; Paton, Eduardo; Bendlin, Rodrigo Miguel; Ismael, Sebastião José; Chauffaille, Maria de Lourdes Lopes Ferrari; Silva, Dirceu da; Pagnano, Kátia Bórgia Barbosa; Ribeiro, Raul C.; Rego, Eduardo Magalhães

doi:10.3324/haematol.10874

Cited by 127 publications

(92 citation statements)

References 6 publications

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“…This is similar to what was reported from Brazil, 22 but considerably higher compared with recent European and North American clinical trials. 3,4,[8][9][10] The main reason for the higher ED in the Swedish Registry compared with clinical trials is probably the inclusion of patients with very early deaths, as well as of patients who were not fit or too old for inclusion in clinical trials.…”

Section: Discussionsupporting

confidence: 78%

“…ED in this study was defined as death within 30 days from diagnosis. Although some reports define ED as deaths within 10 or 14 days, 12,22 other studies show that typical APL-dependent deaths, such as hemorrhagic deaths due to coagulopathy and death from differentiation syndrome, can occur during the third and fourth week after start of treatment. 11 Still, only two of the 30 deaths occurred more than 14 days after diagnosis, and the ED rate within day 14 was still as high as 27%.…”

Section: Discussionmentioning

confidence: 99%

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Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry

et al. 2011

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9Swedish Acute Myeloid Leukemia Group, SwedenOur knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the populationbased Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100 000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients o40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry

et al. 2011

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“…Our analysis of blood counts at the time of diagnosis for individual types of leukemia roughly corresponded to findings in previously published studies [9,11,[17][18][19][20][21][22]. Nevertheless, it is important to note that even though the total leukocyte (LEU) counts were highest in CML cases (median 93 3 10 9 /l), these values only represent 40-50% of the median LEU counts in the analyses published two to four decades ago [9,20].…”

supporting

confidence: 86%

Clinical and laboratory features of leukemias at the time of diagnosis: An analysis of 1,004 consecutive patients

et al. 2011

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“…Despite the incorporation of ATRA, hemorrhage remains the major cause of early death (4.5 %); other causes of early death include infection (1.9 %) and differentiation syndrome (1.2 %) [20] (Table 1). Moreover, population-based studies have shown that the early death rate during induction chemotherapy remains extremely high (30 %), and the most common cause of death is associated with hemorrhage [24][25][26] (Table 1). Thus, development of a novel treatment strategy to alleviate coagulopathy in APL patients is urgently required.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin

Ikezoe

2013

Int J Hematol

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Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhagerelated death during the early phase of therapy remains a serious problem. Moreover, population-based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients.

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Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines

Cited by 127 publications

References 6 publications

Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry

Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry

Clinical and laboratory features of leukemias at the time of diagnosis: An analysis of 1,004 consecutive patients

Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin

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