Main Article Content
Despite recent improvements in the treatment options, adult relapsed/refractory Acute Lymphoblastic Leukaemia (ALL) and lymphoblastic lymphoma (LBL) exhibit poorer cure rates than in childhood. Since, the mainstay difference of childhood multidrug regimens is L-Asparaginase, we sought to salvage adult patients with a protocol containing methotrexate, vincristine, conventional L-asparaginase, and dexamethasone (MOAD). In this study, we aimed to summarize our experience.
Methods: Adult patients with relapsed/refractory ALL and LBL followed-up in our institution between 2017 and 2018 were reviewed and those treated with MOAD protocol were retrospectively included in the study. Clinical data, treatment responses, and adverse events were summarised. The protocol featured 28-day cycles of methotrexate 200 mg/m2 intravenously (IV) on days 1 and 15; vincristine 1.4 mg/m2 IV on days 1, 8, and 15; L-asparaginase 10,000 IU/m2 IV twice weekly; and dexamethasone 40 mg IV or orally on days 1–4 and 15–18.
Results: A total of eight patients were enrolled, of median age 37 years (range: 21–58 years). Four patients were recovered after transplantation. Complete remission was evident in 38%. Two such patients underwent allogeneic hematopoietic stem cell transplantation after the protocol. Another patient with lymphomatous disease achieved partial remission and underwent successful transplantation. L-asparaginase did not trigger any clinically evident hypersensitivity reaction; the most common adverse events associated with the protocol were hypofibrinogenemia, anemia, and febrile neutropenia.
Conclusions: The MOAD protocol was effective and tolerable, enabling to salvage before and after transplantation, particularly in patients with relapsed/refractory T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
2. Fielding AK, Richards SM, Chopra R, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood 2007;109: 944-950. https://doi.org/10.1182/blood-2006-05-018192
3. Tavernier E, Boiron JM, Huguet F, et al. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia 2007;21(9):1907-1914. https://doi.org/10.1038/sj.leu.2404824
4. Thomas DA, Kantarjian H, Smith TL, et al. Primary refractory and relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, and prognosis with salvage therapy. Cancer 1999;86:1216-1230. https://doi.org/10.1002/(sici)1097-0142(19991001)86:7%3C1216::aid-cncr17%3E3.0.co;2-o
5. O’Brien S, Thomas D, Ravandi F, et al. Outcome of adults with acute lymphoblastic leukemia after second salvage therapy. Cancer 2008;113:3186-3191. https://doi.org/10.1002/cncr.23919
6. Saadeh SS, Litzow MR. Hematopoietic stem cell transplant in adults with acute lymphoblastic leukemia: the present state. Expert Rev Hematol 2018; 11(3):195-207. https://doi.org/10.1080/17474086.2018.1433030
7. Bassan R, Maino E, Cortelazzo S. Lymphoblastic lymphoma: an updated review on biology, diagnosis, and treatment. Eur J Haematol 2015; 96:447-460. https://doi.org/10.1111/ejh.12722
8. Thomas DA, Faderl S, O’Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer 2006; 106:1569–1580. https://doi.org/10.1002/cncr.21776
9. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 2004; 103:4396–4407. https://doi.org/10.1182/blood-2003-08-2958
10. DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood 2007; 109:5136-5142. https://doi.org/10.1182/blood-2006-11-056754
11. Kantarjian H, Stein A, Gokbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017;376:836-847. https://doi.org/10.1056/NEJMoa1609783
12. Kantarjian H, De Angelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med 2016;375:740-753. https://doi.org/10.1056/NEJMoa1509277
13. Liu Y, Chen X, Han W, Zhang Y. Tisagenlecleucel, an approved anti-CD 19 chimeric antigen receptor T-cell therapy for the treatment of leukemia. Drugs Today (Barc) 2017;53(11):597-608. https://doi.org/10.1358/dot.2017.53.11.2725754
14. Rytting M. Peg-asparaginase for acute lymphoblastic leukemia. Expert Opin Biol Ther 2010;10:833–839. https://doi.org/10.1517/14712591003769808
15. Kadia TM, Kantarjian HM, Thomas DA, et al. Phase II study of methotrexate, vincristine, pegylated-asparaginase, and dexamethasone (MOpAD) in patients with relpased/refractory acute lymphoblastic leukemia. Am J Hematol 2015;90(2):120-124. https://doi.org/10.1002/ajh.23886
16. Wiernik PH, Dutcher JP, Paietta E, et al. Long-term follow-up of treatment and potential cure of adult acute lymphocytic leukemia with MOAD: a non-anthracycline containing regimen. Leukemia 1993;7(8):1236-1241.
17. National Comprehensive Cancer Network Guidelines. Acute Lymphoblastic Leukemia (Version 1.2019). https://www.nccn.org/professionals/physician_gls/pdf/all.pdf (2019, accessed 28 March 2019)
18. Ronson A, Ariella T, Rowe JM. Treatment of relapsed/refractory acute lymphoblastic leukemia in adults. Curr Oncol Rep 2016;18-39. https://doi.org/10.1007/s11912-016-0519-8
19. Chen R, Campbell JL, Chen B. Prophylaxis and treatment of acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Onco Targets Ther 2015;8:405-412. https://doi.org/10.2147/OTT.S78567
20. Esterhay RJ, Wiernik PH, Grove WR, et al. Moderate dose methotrexate, vincristinei asparaginase, and dexamethasone for treatment of adult acute lymhoblastic leukemia. Blood 1982;59(2):334-345.
21. Aguayo A, Cortes J, Thomas D, Pierce S, Keating M, Kantarjian H. Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia. Cancer 1999;86(7):1203-1209. https://doi.org/10.1002/(sici)1097-0142(19991001)86:7%3C1203::aid-cncr15%3E3.0.co;2-3
22. Van den Berg H. Asparaginase revisited. Leuk Lymphoma 2011;52:168-178. https://doi.org/10.3109/10428194.2010.537796