Mitoxantrone is a conventional agent for relapsed or refractory acute lymphoblastic leukemia (ALL). However, an effective combination with other drugs and a feasible dosage has not been identified. A retrospective study of 46 patients with relapsed or refractory ALL was conducted to determine the efficacy of mitoxantrone and Ara-C treatment with (MEC) and or without etoposide (MC). Twenty-seven and 19 patients received MC and MEC chemotherapy, respectively. Twenty-two (48%) patients showed overall response [complete response (CR), 33%; CR with incomplete platelet recovery (CRp), 15%], and 10 of 22 responders received allogeneic stem cell transplantation (SCT). Median overall survival (OS) was 6.2 months (95% confidence interval, 3.41-9.0). Thirteen (48%) patients in the MC group and 9 (47%) in the MEC group achieved CR/CRp (p = 0.96). Treatment-related mortalities in the MC and MEC groups were 3 (11%) and 4 (21%), respectively (p = 0.36). However, the MEC group frequently presented with grade 3 or higher bacteremia/candidemia (p = 0.013). No difference in OS was observed between the two groups (p = 0.769). In conclusion, salvage therapy consisting of mitoxantrone and Ara-C without etoposide appeared to be an effective bridge therapy to allogeneic SCT for patients with refractory or relapsed ALL.

1.
Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lheritier V, Macintyre E, Bene MC, Ifrah N, Dombret H: Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol 2009;27:911-918.
2.
Al-Khabori M, Minden MD, Yee KW, Gupta V, Schimmer AD, Schuh AC, Xu W, Brandwein JM: Improved survival using an intensive, pediatric-based chemotherapy regimen in adults with T-cell acute lymphoblastic leukemia. Leuk Lymphoma 2010;51:61-65.
3.
Tavernier E, Boiron JM, Huguet F, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lheritier V, Vernant JP, Dombret H, Thomas X, GET-LALA Group, Swiss Group for Clinical Cancer Research SAAK, Australasian Leukaemia and Lymphoma Group: Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia 2007;21:1907-1914.
4.
Oriol A, Vives S, Hernandez-Rivas JM, Tormo M, Heras I, Rivas C, Bethencourt C, Moscardo F, Bueno J, Grande C, del Potro E, Guardia R, Brunet S, Bergua J, Bernal T, Moreno MJ, Calvo C, Bastida P, Feliu E, Ribera JM, Programa Español de Tratamiento en Hematologia Group: Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA study group. Haematologica 2010;95:589-596.
5.
Kantarjian HM, Thomas D, Ravandi F, Faderl S, Jabbour E, Garcia-Manero G, Pierce S, Shan J, Cortes J, O'Brien S: Defining the course and prognosis of adults with acute lymphocytic leukemia in first salvage after induction failure or short first remission duration. Cancer 2010;116:5568-5574.
6.
Gökbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Huttmann A, Kobbe G, Kreuzer KA, Leimer L, Reichle A, Schaich M, Schwartz S, Serve H, Starck M, Stelljes M, Stuhlmann R, Viardot A, Wendelin K, Freund M, Hoelzer D, German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia: Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood 2012;120:2032-2041.
7.
Liew E, Atenafu EG, Schimmer AD, Yee KW, Schuh AC, Minden MD, Gupta V, Brandwein JM: Outcomes of adult patients with relapsed acute lymphoblastic leukemia following frontline treatment with a pediatric regimen. Leuk Res 2012;36:1517-1520.
8.
Kozlowski P, Astrom M, Ahlberg L, Bernell P, Hulegardh E, Hagglund H, Karlsson K, Markuszewska-Kuczymska A, Tomaszewska-Toporska B, Smedmyr B, Hallbook H: High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007. Haematologica 2012;97:1414-1421.
9.
Parker BS, Buley T, Evison BJ, Cutts SM, Neumann GM, Iskander MN, Phillips DR: A molecular understanding of mitoxantrone-DNA adduct formation: effect of cytosine methylation and flanking sequences. J Biol Chem 2004;279:18814-18823.
10.
Kohrt HE, Patel S, Ho M, Owen T, Pollyea DA, Majeti R, Gotlib J, Coutre S, Liedtke M, Berube C, Alizadeh AA, Medeiros BC: Second-line mitoxantrone, etoposide, and cytarabine for acute myeloid leukemia: a single-center experience. Am J Hematol 2010;85:877-881.
11.
Di Bona E, Pogliani E, Rossi G, Lerede T, D'Emilio A, Vespignani M, Rodeghiero F, Barbui T, Bassan R: Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients. Leuk Lymphoma 2005;46:879-884.
12.
Rosen PJ, Rankin C, Head DR, Boldt DH, Luthardt FW, Norwood T, Pugh RP, Karanes C, Appelbaum FR: A phase II study of high dose ARA-C and mitoxantrone for treatment of relapsed or refractory adult acute lymphoblastic leukemia. Leuk Res 2000;24:183-187.
13.
Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M, Pierce S, Huh Y, Andreeff M, Koller C, Ha CS, Keating MJ, Murphy S, Freireich EJ: Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 2000;18:547-561.
14.
Faderl S, Thomas DA, O'Brien S, Ravandi F, Garcia-Manero G, Borthakur G, Ferrajoli A, Verstovsek S, Ayoubi M, Rytting M, Feliu J, Kantarjian HM: Augmented hyper-CVAD based on dose-intensified vincristine, dexamethasone, and asparaginase in adult acute lymphoblastic leukemia salvage therapy. Clin Lymphoma Myeloma Leuk 2011;11:54-59.
15.
Kako S, Kanamori H, Kobayashi N, Shigematsu A, Nannya Y, Nakamae M, Shigeno K, Suzukawa K, Takeuchi M, Tsuzuki M, Usuki K, Hatanaka K, Ogawa K, Mitani K, Nawa Y, Hatta Y, Mizuno I, Kanda Y: Outcome after first relapse in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia. Br J Haematol 2013;161:95-103.
16.
Loike JD: VP16-213 and podophyllotoxin. A study on the relationship between chemical structure and biological activity. Cancer Chemother Pharmacol 1982;7:103-111.
17.
Bishop JF: Etoposide in the treatment of leukemias. Semin Oncol 1992;19:33-38.
18.
Gore M, Powles R, Lakhani A, Milan S, Maitland J, Goss G, Nandi A, Perren T, Forgeson G, Treleaven J, Zuitable A, Porta F: Treatment of relapsed and refractory acute leukaemia with high-dose cytosine arabinoside and etoposide. Cancer Chemother Pharmacol 1989;23:373-376.
19.
Abromowitch M, Bowman WP, Ochs J, Rivera G: Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia. J Clin Oncol 1985;3:789-792.
20.
Esumi N, Todo S, Arakawa S, Imashuku S: Etoposide and cytosine arabinoside combination chemotherapy for refractory acute lymphocytic leukemia in childhood. J Clin Oncol 1986;4:1089-1093.
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