Safety and Feasibility of Outpatient High Dose Cytarabine for Acute Myeloid Leukemia in the Brazilian Amazon
-
Amanda Lopes Maia Rodrigues
,
Daniel Macêdo do Nascimento
,
Josy Marinho de Lima
,
Marcos Laércio Pontes Reis
,
Lucyana Barbosa Cardoso Leão
,
Murilo Chermont Azavedo
,
Samanta Ribeiro Muccini
,
Polyana Castanha da Silva
,
Thiago Xavier Carneiro
Abstract
Background: The attempt to manage patients with acute myeloid leukemia as outpatients has become increasingly common due to high hospitalization costs, low availability for beds and patient preference. Publications on the subject are scarce, especially in low-income regions and the safety in this population remains to be determined. The present study aims to assess the safety of consolidation with high dose cytarabine in the outpatient setting.
Materials and Methods: We retrospectively analyzed 39 patients who underwent consolidation with high-dose cytarabine, between 2009 and 2018, at Ophir Loyola Hospital, in Belém, Brazil. Patients treated after 2015 were given high-dose cytarabine as outpatients due to the decision of medical staff.
Results: 27 patients received 76 cycles of cytarabine as outpatients; males were 48.14% of the total population, with a median age of approximately 45 years. The occurrence of delay between cycles was significantly lower among outpatients (48.14% vs. 83.33%, p = 0.04). There was no difference between relapse rates, transfusion requirements and non-relapse mortality between both groups. Hospitalization was required in 40.74% of patients during outpatient cycles and 18.51% of blood cultures were positive for pathogens. Non-relapse mortality was significantly higher among patients above 50 years old and treated on an outpatient basis (44.4% vs. 5.60%, p = 0.03).
Conclusion: High-dose cytarabine administration on an outpatient basis appears to be safe and effective in a low-income population at the Brazilian Amazon region, but toxicity seems to be increased for patients older than 50 years.
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2. Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009; 361(13):1235-48.
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9. Cox KM, Goel S, O’Connell RL, et al. A randomized crossover trial comparing inpatient and outpatient administration of high dose cisplatin. Intern Med J. 2011; 41(2):172-8.
10. Halim TY, Song KW, Barnett MJ, et al. Positive impact of selective outpatient management of high-risk acute myelogenous leukemia on the incidence of septicemia. Ann Oncol. 2007; 18(7):1246-52.
11. Gillis S, Dann EJ, Rund D. Selective discharge of patients with acute myeloid leukemia during chemotherapy-induced neutropenia. Am J Hematol. 1996; 51(1):26-31.
12. Walter RB, Lee SJ, Gardner KM, et al. Outpatient management following intensive induction chemotherapy for myelodysplastic syndromes and acute myeloid leukemia: a pilot study. Haematologica. 2011; 96(6):914-7.
13. Vaughn JE, Othus M, Powell MA, et al. Resource Utilization and Safety of Outpatient Management Following Intensive Induction or Salvage Chemotherapy for Acute Myeloid Leukemia or Myelodysplastic Syndrome: A Nonrandomized Clinical Comparative Analysis. JAMA Oncol. 2015; 1(8):1120-7.
14. Savoie ML, Nevil TJ, Song KW, et al. Shifting to outpatient management of acute myeloid leukemia: a prospective experience. Ann Oncol. 2006; 17(5):763-8.
15. Irish W, Ryan M, Gache L, et al. Acute myeloid leukemia: a retrospective claims analysis of resource utilization and expenditures for newly diagnosed patients from first-line induction to remission and relapse. Curr Med Res Opin. 2017; 33(3):519-527.
16. Sopko L, Sabty FA, Rimajova V, et al. The feasibility of an early hospital discharge following chemotherapy for the acute myeloid leukemia. Bratisl Lek Listy. 2012; 113(5):298-300.
17. Cao XX, Wang SJ, Duan MH, et al. Long-term safety and efficacy of high-dose cytarabine consolidation in patients with acute myeloid leukemia. Zhonghua Xue Ye Xue Za Zhi. 2017; 38(4):330-333.
18. Møller T, Nielsen OJ, Welinder P, et al. Safe and feasible outpatient treatment following induction and consolidation chemotherapy for patients with acute leukaemia. Eur J Haematol. 2010; 84(4):316-22.
19. Allen MR, Aljitawi OS, Abhyankar S, et al. Outpatient Cytarabine Administration Is Safe and Effective For Consolidation In Acute Myeloid Leukemia. Blood. 2013; 122: 5030.
20. Halpern AB, Walter RB, Estey EH. Outpatient induction and consolidation care strategies in acute myeloid leukemia. Curr Opin Hematol. 2019; 26(2):65-70.
21. Reid RM, Baran A, Friedberg JW, et al. Outpatient administration of BEAM conditioning prior to autologous stem cell transplantation for lymphoma is safe, feasible, and cost-effective. Cancer Med. 2016; 5(11):3059–3067.
22. O'Donnell O. Access to health care in developing countries: breaking down demand side barriers. Cad Saude Publica. 2007; 23(12):2820-2834.
23. Wetzstein GA, Lancet JE, Kallner JE Sivik JM, et al. Safety, feasibility, and cost-effectiveness with outpatient administration of high-dose cytarabine consolidation in acute myeloid leukemia. Blood. 2008; 112(11):2405.
24. Eisele L, Günther, F, Ebeling P, et al. Outpatient Management of Acute Myeloid Leukemia after Intensive Consolidation Chemotherapy Is Feasible and Reduces Hospital Treatment Costs. Onkologie. 2010; 33(12):658–664.
25. Jarden M, Møller T, Christensen KB, et al. Multimodal intervention integrated into the clinical management of acute leukemia improves physical function and quality of life during consolidation chemotherapy: a randomized trial 'PACE-AL'. Haematologica. 2016;101(7):e316-9.
26. Benke S, Bow EJ, Schacter B, et al. Infectious Morbidity and Hospitalization Requirements of Patients with Acute Myeloid Leukemia Receiving Intensive Outpatient Consolidation. Blood. 2004; 104(11):4524.
27. Saini L, Rostein C, Atenafu EG, et al. Ambulatory consolidation chemotherapy for acute myeloid leukemia with antibacterial prophylaxis is associated with frequent bacteremia and the emergence of fluoroquinolone resistant E. Coli. BMC Infect Dis. 2013;13:284
28. Othus M, Kantarjian H, Petersdorf S, et al. Declining Rates of Treatment-Related Mortality in Patients with Newly-diagnosed AML Given “Intense” Induction Regimens: A Report from SWOG and MD Anderson. Leukemia. 2014; 28(2):289–292.
29. Bittencourt R, Fogliato L, Daudt L, et al. Acute Myelogenous Leukemia: two decades overview – Hematology Service Hospital de Clínicas de Porto Alegre –RS. Ver Bras Hematol Hemoter. 2003;25(1):17-24.
30. Azevedo MC, Velloso EDRP, Buccheri V, et al. Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia. Braz J Med Biol Res. 2015; 48(2):178-85.
31. Saini L, Minden MD, Schuh AC, et al. Feasibility of outpatient consolidation chemotherapy in older versus younger patients with acute myeloid leukemia. Am J Hematol. 2012; 87(3):323-6.
32. Vives S, Oriol A, Piernas S, et al. Feasibility and efficacy of outpatient therapy with intermediate dose cytarabine, fludarabine and idarubicin for patients with acute myeloid leukaemia aged 70 or older. Eur J Haematol. 2015; 95(6):576-82.
2. Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009; 361(13):1235-48.
3. Li W, Gong X, Sun M, et al. High-dose cytarabine in acute myeloid leukemia treatment: a systematic review and meta-analysis. PLoS One. 2014; 9(10):e110-53.
4. Briot T, Roger E, Thépot S, et al. Advances in treatment formulations for acute myeloid leukemia. Drug Discov Today. 2018; 23(12):1936-49.
5. Aw A, Sabloffa M, Shepparda D, et al. Evaluation of an Outpatient Model for Treatment of Acute Myeloid Leukemia. J Haematol. 2016; 5(1):1-7.
6. Walter RB, Taylor LR, Gardner KM, et al. Outpatient management following intensive induction or salvage chemotherapy for acute myeloid leukemia. Clin Adv Hematol Oncol. 2013; 11(9):571-577.
7. Redaelli A, Botteman MF, Stephens JM, et al. Economic burden of acute myeloid leukemia: a literature review. Cancer Treat Rev. 2004; 30(3):237-47.
8. El-Jawahri AR, Traeger LN, Kuzmuk K, et al. Quality of life and mood of patients and family caregivers during hospitalization for hematopoietic stem cell transplantation. Cancer. 2015; 121(6):951-959.
9. Cox KM, Goel S, O’Connell RL, et al. A randomized crossover trial comparing inpatient and outpatient administration of high dose cisplatin. Intern Med J. 2011; 41(2):172-8.
10. Halim TY, Song KW, Barnett MJ, et al. Positive impact of selective outpatient management of high-risk acute myelogenous leukemia on the incidence of septicemia. Ann Oncol. 2007; 18(7):1246-52.
11. Gillis S, Dann EJ, Rund D. Selective discharge of patients with acute myeloid leukemia during chemotherapy-induced neutropenia. Am J Hematol. 1996; 51(1):26-31.
12. Walter RB, Lee SJ, Gardner KM, et al. Outpatient management following intensive induction chemotherapy for myelodysplastic syndromes and acute myeloid leukemia: a pilot study. Haematologica. 2011; 96(6):914-7.
13. Vaughn JE, Othus M, Powell MA, et al. Resource Utilization and Safety of Outpatient Management Following Intensive Induction or Salvage Chemotherapy for Acute Myeloid Leukemia or Myelodysplastic Syndrome: A Nonrandomized Clinical Comparative Analysis. JAMA Oncol. 2015; 1(8):1120-7.
14. Savoie ML, Nevil TJ, Song KW, et al. Shifting to outpatient management of acute myeloid leukemia: a prospective experience. Ann Oncol. 2006; 17(5):763-8.
15. Irish W, Ryan M, Gache L, et al. Acute myeloid leukemia: a retrospective claims analysis of resource utilization and expenditures for newly diagnosed patients from first-line induction to remission and relapse. Curr Med Res Opin. 2017; 33(3):519-527.
16. Sopko L, Sabty FA, Rimajova V, et al. The feasibility of an early hospital discharge following chemotherapy for the acute myeloid leukemia. Bratisl Lek Listy. 2012; 113(5):298-300.
17. Cao XX, Wang SJ, Duan MH, et al. Long-term safety and efficacy of high-dose cytarabine consolidation in patients with acute myeloid leukemia. Zhonghua Xue Ye Xue Za Zhi. 2017; 38(4):330-333.
18. Møller T, Nielsen OJ, Welinder P, et al. Safe and feasible outpatient treatment following induction and consolidation chemotherapy for patients with acute leukaemia. Eur J Haematol. 2010; 84(4):316-22.
19. Allen MR, Aljitawi OS, Abhyankar S, et al. Outpatient Cytarabine Administration Is Safe and Effective For Consolidation In Acute Myeloid Leukemia. Blood. 2013; 122: 5030.
20. Halpern AB, Walter RB, Estey EH. Outpatient induction and consolidation care strategies in acute myeloid leukemia. Curr Opin Hematol. 2019; 26(2):65-70.
21. Reid RM, Baran A, Friedberg JW, et al. Outpatient administration of BEAM conditioning prior to autologous stem cell transplantation for lymphoma is safe, feasible, and cost-effective. Cancer Med. 2016; 5(11):3059–3067.
22. O'Donnell O. Access to health care in developing countries: breaking down demand side barriers. Cad Saude Publica. 2007; 23(12):2820-2834.
23. Wetzstein GA, Lancet JE, Kallner JE Sivik JM, et al. Safety, feasibility, and cost-effectiveness with outpatient administration of high-dose cytarabine consolidation in acute myeloid leukemia. Blood. 2008; 112(11):2405.
24. Eisele L, Günther, F, Ebeling P, et al. Outpatient Management of Acute Myeloid Leukemia after Intensive Consolidation Chemotherapy Is Feasible and Reduces Hospital Treatment Costs. Onkologie. 2010; 33(12):658–664.
25. Jarden M, Møller T, Christensen KB, et al. Multimodal intervention integrated into the clinical management of acute leukemia improves physical function and quality of life during consolidation chemotherapy: a randomized trial 'PACE-AL'. Haematologica. 2016;101(7):e316-9.
26. Benke S, Bow EJ, Schacter B, et al. Infectious Morbidity and Hospitalization Requirements of Patients with Acute Myeloid Leukemia Receiving Intensive Outpatient Consolidation. Blood. 2004; 104(11):4524.
27. Saini L, Rostein C, Atenafu EG, et al. Ambulatory consolidation chemotherapy for acute myeloid leukemia with antibacterial prophylaxis is associated with frequent bacteremia and the emergence of fluoroquinolone resistant E. Coli. BMC Infect Dis. 2013;13:284
28. Othus M, Kantarjian H, Petersdorf S, et al. Declining Rates of Treatment-Related Mortality in Patients with Newly-diagnosed AML Given “Intense” Induction Regimens: A Report from SWOG and MD Anderson. Leukemia. 2014; 28(2):289–292.
29. Bittencourt R, Fogliato L, Daudt L, et al. Acute Myelogenous Leukemia: two decades overview – Hematology Service Hospital de Clínicas de Porto Alegre –RS. Ver Bras Hematol Hemoter. 2003;25(1):17-24.
30. Azevedo MC, Velloso EDRP, Buccheri V, et al. Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia. Braz J Med Biol Res. 2015; 48(2):178-85.
31. Saini L, Minden MD, Schuh AC, et al. Feasibility of outpatient consolidation chemotherapy in older versus younger patients with acute myeloid leukemia. Am J Hematol. 2012; 87(3):323-6.
32. Vives S, Oriol A, Piernas S, et al. Feasibility and efficacy of outpatient therapy with intermediate dose cytarabine, fludarabine and idarubicin for patients with acute myeloid leukaemia aged 70 or older. Eur J Haematol. 2015; 95(6):576-82.
| Files | ||
| Issue | Vol 14, No 3 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v14i3.3722 | |
| Keywords | ||
| Acute myeloid leukemia; High drug dose; Chemotherapy; Outpatient care; Low-income population | ||
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How to Cite
1.
Rodrigues A, do Nascimento D, de Lima J, Reis ML, Leão L, Azavedo M, Muccini S, da Silva P, Carneiro T. Safety and Feasibility of Outpatient High Dose Cytarabine for Acute Myeloid Leukemia in the Brazilian Amazon. Int J Hematol Oncol Stem Cell Res. 2020;14(3):151-156.
