Acute promyelocytic leukemia chemotherapy

Other organoarsenicals, most notably lewisite (dichloro[2-chlorovinyl]arsine), were developed in the early twentieth century as chemical warfare agents. Arsenic trioxide was reintroduced into the United States Pharmacopeia in 2000 as an orphan drug for the treatment of relapsed acute promyelocytic leukemia (Chapter 55 Cancer Chemotherapy). 

Katayama I, Kitabayashi T, Yanai M, Sekiguchi N, Egi S. Acute promyelocytic leukemia with t(15 17) abnormality after chemotherapy containing etoposide for Langerhans cell histiocytosis. Cancer 1993 72(12) 3723-6. 

Although the retinoic acid syndrome involves the lungs, pulmonary hemorrhage has only rarely been reported. Two patients with acute promyelocytic leukemia developed severe lung hemorrhage during the first 3 weeks of treatment with tretinoin, shortly after the administration of chemotherapy (40). 

Extramedullary relapse of acute promyelocytic leukemia, which is rare after chemotherapy alone, was more common after tretinoin, but it is not clear whether it truly increases the risk of extramedullary recurrence and what the risk factors are. In a retrospective analysis of the incidence of extramedullary relapse in patients after prior treatment with tretinoin and in patients previously treated with chemotherapy alone (68) three of the 13 patients who received tretinoin had extramedullary involvement compared with none of the 11 patients previously treated with chemotherapy alone (RR = 2.1 Cl = 1.34, 3.29). The retinoic acid syndrome during prior induction treatment was significantly associated with extramedullary relapse (three of five patients with the retinoic acid syndrome versus none of eight without the syndrome (RR = 5.0 Cl = 1.4,17)). Thus, tretinoin may predispose patients with acute promyelocytic leukemia to extramedullary involvement at relapse and the retinoic acid syndrome is a risk factor. 

Eenaux P, Chastang C, Chevret S, et al. A randomized comparison of all-trans-retinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. Blood 1999 94 1192-1200. 

Kanlarjian H, Keating M, Walters RS, et al. Role of maintenance chemotherapy in acute promyelocytic leukemia. Cancer 1987 59 1258— 1263. 

Laczika, K., Mitterbauer, G., Korninger, L. et al. (1994) Rapid achievment of PML-RARa polymerase chain reaction (PCR)-negativity by combined treatment with Al-trans-retinoic acid and chemotherapy in acute promyelocytic leukemia a pilot study. Leukemia, 8, 1-5. 

Vahdat, L., Maslak, P., Miller, W H, Eardley, A., Heller, G., Schemberg, D A, and Warrell, R P (1994) Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia Impact of leukocytosis, low-dose chemotherapy, PML-RAR-a isoform, and CD 13 expression in patients treated with All-Tr n5 retinoic acid. Blood 84, 3843-3849... 

Pei R, Cao J, Ma J, Zhang P, Liu X, Du X, et al. Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia. Hematology 2012 17(6) 311-6. 

Ding W, Li YP, Nobile LM, Grills G, Carrera I, Paietta E, Tallman MS, Wiemik PH, Gallagher RE (1998) Leukemic cellular retinoic acid resistance and missense mutations in the PML-RARa fusion gene after relapse of acute promyelocytic leukemia from treatment with dW-trans retinoic acid and intensive chemotherapy [In Process Citation]. Blood 92 1172-1183... 

Acute promyelocytic leukemia (APL) is a specific type of acute myeloid leukemia (AML) characterized by the morphology of blast cells (M3 in the French American British classification of AML) [1, 2], the t [15, 17] translocation [3] which fuses the promyelocytic leukemia (PML) gene on chromosome 15 to the retinoic acid receptor (RARa) a gene on chromosome 17 [4, 5], and by a coagulopathy combining disseminated intravascular coagulation (DIC) and fibrinolysis [6, 7]. Until recently, intensive chemotherapy, usually combining an anthracycHne and cytosine arabinoside (AraC) was the only effective treatment of APL [8-22]. 

Dombret H, Sutton L, Duarte M, Daniel MT, Leblond V, Castaigne S, Degos L (1992) Combined therapy with diW-trans retinoic acid and high-dose chemotherapy in patients with hyperleukocytic acute promyelocytic leukemia and severe visceral hemorrhage. Leukemia 6 1237-1244... 

Fenaux P, Wattel E, Archimbaud E, Sanz M, Hecquet B, Guerci A, Link H, Fegueux N, Fey M, Castaigne S et al (1994) Prolonged follow up confirms that all-tran retinoic acid (ATRA) followed by chemotherapy reduces the risk of relapse in newly diagnosed acute promyelocytic leukemia (APL). Blood 84 666-667... 

Eardley AM, Heller G, Warrell RP (1994) Morbidity and costs of remission induction therapy with all-trans retinoic acid compared with standard chemotherapy in acute promyelocytic leukemia. Leukemia 8 934-939... 

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