Promyelocytic leukemia treatment with retinoic acid

A 32-year-old woman with acute promyelocytic leukemia developed severe retinoic acid syndrome after 3 days, with respiratory failure, fever, and bilateral lung infiltrates. Withdrawal of tretinoin and treatment with dexamethasone and antibiotics rapidly ameliorated the syndrome, and on day 10 tretinoin was restarted. However, routine echocardiography showed a 3 cm pedunculated mass in the right ventricle. There was consistent and stable reduction of the mass after 1 year of oral anticoagulant therapy. 

Sun GL. [Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) a report of five-year experience.] Zhonghua Zhong Liu Za Zhi 1993 15(2) 125-9. 

As an alternative to using synthetic analogs for disease treatment, the natural ligand for the retinoic acid receptor, all-irans-retinoic acid (ATRA), is used effectively in the treatment of acute promyelocytic leukemia (APL) (73). Chromosomal translocations in APL patients are responsible for the cellular transformation in this disease. The transformation results in a fusion of the retinoic acid receptor alpha (RARa) with another protein (73). Treatment of APL patients with pharmacologic doses of ATRA induces complete remission by restoring normal granulocytic differentiation (74, 75). 

Shimamoto Y, Suga K, Yamaguchi M, Kuriyama K, Tomonaga M. Prophylaxis of symptoms of hyperhistamine-mia after the treatment of acute promyelocytic leukemia with all-trans retinoic acid. Acta Haematol 1994 92(2) 109-12. 

A 24-year-old woman with acute promyelocytic leukemia took tretinoin, and 2 days later developed dyspnea and general aching (39). Her total leukocyte count was 5.04 x 10 /1, her Pa02 was 42.5 mmHg, and a chest X-ray showed bilateral parenchymal infiltration consistent with respiratory distress syndrome. She recovered within 3 days of treatment with low-dose cytarabine and glucocorticoids, without withdrawal of the retinoic acid. 

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. 

Mann G, Reinhardt D, Ritter J, Hermann J, Schmitt K, Gadner H, Creutzig U. Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children. Ann Hematol 2001 80(7) 417-22. 

Sakamoto O, Yoshinari M, Rikiishi T, Fujiwara I, Imaizumi M, Tsuchiya S, linuma K. Hypercalcemia due to all-trans retinoic acid therapy for acute promyelocytic leukemia a case report of effective treatment with bis-phosphonate. Pediatr Int 2001 43(6) 688-90. 

Tajima K, Sagae M, Yahagi A, Akiba J, Suzuki K, Hayashi T, Satoh S. [Scrotum exfoliative dermatitis with ulcers associated with treatment of acute promyelocytic leukemia with all-trans retinoic acid.) Rinsho Ketsueki 1998 39(l) 48-52. 

Mori A, Tamura S, Katsuno T, Nishimura Y, Itoh T, Saheki K, Takatsuka H, Wada H, Fujimori Y, Okamoto T, Takemoto Y, Kakishita E. Scrotal ulcer occurring in patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid Oncol Rep 1999 6(l) 55-8. 

Doner D, Estey E, Santillana S, Bennett JM, Lopez-Bernstein G, Boehm K, Williams T. Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid. Blood 2001 97(l) 73-80. 

Sanz MA, VellengaE, Rayon C, et al. All-trans retinoic acid and anthra-cycline monochemotherapy for the treatment of elderly patients with acute promyelocytic leukemia Blood 2004 104 3490-3493. 

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. 

Wu X, Wang X, Qien X, Liu H, Ying J, Yang Z, Yaom H. Pour years experience with the treatment of all-trans retinoic acid in acute promyelocytic leukemia. Am J Hematol. 1993 43 183-9. 

Fukutani, H, Naoe, T., Ohno, R., Yoshida, H., Miyawaki, S, Shimazaki, C., Miyake, T, Nakayama, Y, Kobayashi, H., Goto, S., Takeshita, A, Kobayashi, S., Kato, Y., Shiraishi, K., Sasada, M., Ohtake, S., Murakami, H., Kobayashi, M., Endo, N, Shmdo, H, Matsushita, K., Hasegawa, S, Tsuji, K., Ueda, Y, Tominaga, N., Furuya, H, Inoue, Y., Takeuchi, J., Monshita, H, and Iida, H (1995) Isoforms of PML-retmo/c acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all-trans retinoic acid. Leukemia 9, 1478-1482. 

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... 

Tobita T, Takeshita A, Kitamura K, Ohnishi K, Yanagi M, Hiroka A, Karasuno T, Takeuchi M, Miyawaki S, Ueda R et al (1997) Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia relapsed from complete remission induced by all-tra 5-retinoic acid. Blood 90 967-973... 

Treatment of acute promyelocytic leukemia with 2 -trans retinoic acid... 

Fenaux P, Castaigne S, Chomienne C, Dombret H, Degos L (1992) All-tram retinoic acid treatment for patients with acute promyelocytic leukemia. Leukemia 6 64-72... 

Wang ZY, Sun GL, Lu JX, Chen ZH (1990) Treatment of acute promyelocytic leukemia with dHA-trans retinoic acid in China. Nouv Rev Fr Hematol 32 34-36... 

Warrell RP, Maslak P, Eardley A, Heller G, Miller WH, Frankel SR (1994) Treatment of acute promyelocytic leukemia with dW-trans retinoic acid an update of the New York experience. Leukemia 8 926-933... 

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