A Comparison of Dexamethasone plus Vincristine versus Standard Regimen in Induction Therapy of Adult Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplantation
-
Mohammad Vaezi
,
Amirhoushang Pourkhani
,
Amir Kasaeian
,
Maryam Souri
,
Marjan Yaghmaie
,
Kamran Alimoghaddam
,
Ardeshir Ghavamzadeh
Abstract
Background: Current treatment options of acute lymphoblastic leukemia(ALL) include chemotherapy alone or hematopoietic stem cell transplantation (HSCT) following induction chemotherapy both along with CNS prophylaxis. The usual and standard induction regimens currently administered could have severe complications and mortality.
Materials and Methods: To lessen induction regimen complications in ALL patients who undergo HSCT, we used a cytoreduction induction regimen including dexamethasone (8 mg, IV, three times a day, for 28 days) and vincristine(1.4 mg/m2, IV, on days 1,8,15 and 22) for 49 newly diagnosed adult ALL patients followed by an early sibling donor HSCT within two months. The results were matched with outcomes of HSCT in 172 ALL patients inducted by standard induction regimen.
Results: Median follow-up time was 5.41 years in the standard group and 5.27 years in the other. All patients of the case group (100%) achieved complete remission. Landmark analyses were performed to scrutinize the effect of treatments on different time intervals: first two years and 2nd to end years. Type of treatment had no significant effect on the hazard of death in the first landmark (HR=0.87, P=0.64). Cytoreduction regimen amplified the hazard of death 3.43 times more than the standard regimen in the second landmark (HR=3.43 P=0.035). Multivariate analysis showed that the cytoreduction regimen reduced the hazard of relapse about 22%, but not statistically significant (HR=0.78, P-value=0.24).
Conclusion: Overall, it seems despite achieving complete remission in induction therapy, depth of response is a critical predictor for long-term outcomes of HSCT in ALL patients, and the use of multiple agents may be necessary to decrease tumor cell burden and minimal residual disease(MRD).
1. Katz AJ, Chia VM, Schoonen WM, et al. Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden. Cancer Causes Control. 2015; 26(11):1627-42.
2. Larson RA, Dodge RK, Burns CP, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995; 85(8):2025-37.
3. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005; 106(12):3760-7.
4. Thomas X, Boiron JM, Huguet F, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004; 22(20):4075-86.
5. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004; 101(12):2788-801.
6. Imamura M, Shigematsu A. Allogeneic hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: potential benefit of medium-dose etoposide conditioning. Exp Hematol Oncol. 2015; 4: 20.
7. Wassmann B, Pfeifer H, Goekbuget N, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL). Blood. 2006; 108(5):1469-77.
8. Curran E, Stock W. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood. 2015; 125(24):3702-10.
9. Ribera JM. Allogeneic stem cell transplantation for adult acute lymphoblastic leukemia: when and how. Haematologica. 2011; 96(8): 1083–6.
10. Kako S, Morita S, Sakamaki H, et al. A decision analysis of allogeneic hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission who have an HLA-matched sibling donor. Leukemia. 2011; 25(2):259–65.
11. Ram R, Gafter-Gvili A, Vidal L, et al. Management of adult patients with acute lymphoblastic leukemia in first complete remission: systematic review and meta-analysis. Cancer. 2010; 116(14):3447–57.
12. Arnold R, Terwey T, Vuong L, et al. Allogeneic Stem Cell Transplantation in High Risk ALL Patients: Influence of ALL Subtypes. Bio Blood Marrow Transplant. 2014(20) S151-S164.
13. Forman SJ. Allogenic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults. Hematol Oncol Clin North Am. 2009; 23(5):1011-1031.
14. Wintrobe's clinical hematology.Greer, John P.13th edition.Philadelphia : Wolters Kluwer Lippincott Williams & Wilkins Health,2014 .P 1565-1567.
15. Fielding A. The Treatment of Adults with Acute Lymphoblastic Leukemia. ASH Education Book January 1, 2008 vol. 2008 no. 1. P 381-389.
16. Gökbuget N. How I treat older patients with ALL. Blood. 2013; 122(8):1366-75.
17. Lee S, Cho BS, Kim SY, et al. Allogeneic stem cell transplantation in first complete remission enhances graft-versus-leukemia effect in adults with acute lymphoblastic leukemia: antileukemic activity of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2007; 13(9):1083-94.
18. Kolb H-J, Schmetzer H, Schmid C, et al. Mechanisms of graft-versus-leukemia effects after allogeneic stem cell transplantation: effects on the leukemia stem cell? Leuk Suppl. 2014; 3(Suppl 1): S16–7.
19. Hess CE, Zirkle JW. Results of induction therapy with vincristine and prednisone alone in adult acute lymphoblastic leukemia: report of 43 patients and review of the literature. Am J Hematol. 1982; 13(1):63-71.
20. Scavino HF, George JN, Sears DA. Remission induction in adult acute lymphocytic leukemia. Use of vincristine and prednisone alone. Cancer. 1976; 38(2):672-7.
21. Takahashi I, Uchida K, Ohmoto E, et al. [Clinical management of acute lymphocytic leukemia in adults. 1. Treatment of acute lymphocytic leukemia with VP (vincristine, prednisolone)--DVMP (daunorubicin, vincristine 6-mercaptopurine, prednisolone) regimen].Gan To Kagaku Ryoho. 1982; 9(6):1091-6.
22. Pullarkat V, Slovak ML, Kopecky KJ, et al. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008; 111(5):2563-72.
23. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11(12):945-56.
24. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958; 53(282):457-481.
25. Cox DR. Regression models and life tables (with discussion). J R Statist Soc B.1972; 34(2):187-220.
26. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966; 50(3):163-170.
27. 0 Gökbuget N, Hoelzer D. Treatment of Adult Acute Lymphoblastic Leukemia. ASH Education Book January 1, 2006 vol. 2006 no. 1 133-141.
28. Inaba H, Pui CH. Glucocorticoid use in acute lymphoblastic leukemia: comparison of prednisone and dexamethasone. Lancet Oncol. 2010; 11(11): 1096–106.
29. Teuffel O, Kuster SP, Hunger SP, et al. Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. Leukemia. 2011; 25(8):1232-8.
30. Shen Z, Gu X, Mao W, et al. Influence of pre-transplant minimal residual disease on prognosis after Allo-SCT for patients with acute lymphoblastic leukemia: systematic review and meta-analysis. BMC Cancer. 2018; 18(1):755.
31. Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008; 111(4):1827–33.
32. Cornelissen JJ, van der Holt B, Verhoef GE, et al. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a pro-spective sibling donor versus no-donor comparison. Blood. 2009; 113(6):1375-82.
2. Larson RA, Dodge RK, Burns CP, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995; 85(8):2025-37.
3. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005; 106(12):3760-7.
4. Thomas X, Boiron JM, Huguet F, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004; 22(20):4075-86.
5. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004; 101(12):2788-801.
6. Imamura M, Shigematsu A. Allogeneic hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: potential benefit of medium-dose etoposide conditioning. Exp Hematol Oncol. 2015; 4: 20.
7. Wassmann B, Pfeifer H, Goekbuget N, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL). Blood. 2006; 108(5):1469-77.
8. Curran E, Stock W. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood. 2015; 125(24):3702-10.
9. Ribera JM. Allogeneic stem cell transplantation for adult acute lymphoblastic leukemia: when and how. Haematologica. 2011; 96(8): 1083–6.
10. Kako S, Morita S, Sakamaki H, et al. A decision analysis of allogeneic hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission who have an HLA-matched sibling donor. Leukemia. 2011; 25(2):259–65.
11. Ram R, Gafter-Gvili A, Vidal L, et al. Management of adult patients with acute lymphoblastic leukemia in first complete remission: systematic review and meta-analysis. Cancer. 2010; 116(14):3447–57.
12. Arnold R, Terwey T, Vuong L, et al. Allogeneic Stem Cell Transplantation in High Risk ALL Patients: Influence of ALL Subtypes. Bio Blood Marrow Transplant. 2014(20) S151-S164.
13. Forman SJ. Allogenic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults. Hematol Oncol Clin North Am. 2009; 23(5):1011-1031.
14. Wintrobe's clinical hematology.Greer, John P.13th edition.Philadelphia : Wolters Kluwer Lippincott Williams & Wilkins Health,2014 .P 1565-1567.
15. Fielding A. The Treatment of Adults with Acute Lymphoblastic Leukemia. ASH Education Book January 1, 2008 vol. 2008 no. 1. P 381-389.
16. Gökbuget N. How I treat older patients with ALL. Blood. 2013; 122(8):1366-75.
17. Lee S, Cho BS, Kim SY, et al. Allogeneic stem cell transplantation in first complete remission enhances graft-versus-leukemia effect in adults with acute lymphoblastic leukemia: antileukemic activity of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2007; 13(9):1083-94.
18. Kolb H-J, Schmetzer H, Schmid C, et al. Mechanisms of graft-versus-leukemia effects after allogeneic stem cell transplantation: effects on the leukemia stem cell? Leuk Suppl. 2014; 3(Suppl 1): S16–7.
19. Hess CE, Zirkle JW. Results of induction therapy with vincristine and prednisone alone in adult acute lymphoblastic leukemia: report of 43 patients and review of the literature. Am J Hematol. 1982; 13(1):63-71.
20. Scavino HF, George JN, Sears DA. Remission induction in adult acute lymphocytic leukemia. Use of vincristine and prednisone alone. Cancer. 1976; 38(2):672-7.
21. Takahashi I, Uchida K, Ohmoto E, et al. [Clinical management of acute lymphocytic leukemia in adults. 1. Treatment of acute lymphocytic leukemia with VP (vincristine, prednisolone)--DVMP (daunorubicin, vincristine 6-mercaptopurine, prednisolone) regimen].Gan To Kagaku Ryoho. 1982; 9(6):1091-6.
22. Pullarkat V, Slovak ML, Kopecky KJ, et al. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008; 111(5):2563-72.
23. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11(12):945-56.
24. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958; 53(282):457-481.
25. Cox DR. Regression models and life tables (with discussion). J R Statist Soc B.1972; 34(2):187-220.
26. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966; 50(3):163-170.
27. 0 Gökbuget N, Hoelzer D. Treatment of Adult Acute Lymphoblastic Leukemia. ASH Education Book January 1, 2006 vol. 2006 no. 1 133-141.
28. Inaba H, Pui CH. Glucocorticoid use in acute lymphoblastic leukemia: comparison of prednisone and dexamethasone. Lancet Oncol. 2010; 11(11): 1096–106.
29. Teuffel O, Kuster SP, Hunger SP, et al. Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. Leukemia. 2011; 25(8):1232-8.
30. Shen Z, Gu X, Mao W, et al. Influence of pre-transplant minimal residual disease on prognosis after Allo-SCT for patients with acute lymphoblastic leukemia: systematic review and meta-analysis. BMC Cancer. 2018; 18(1):755.
31. Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008; 111(4):1827–33.
32. Cornelissen JJ, van der Holt B, Verhoef GE, et al. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a pro-spective sibling donor versus no-donor comparison. Blood. 2009; 113(6):1375-82.
| Files | ||
| Issue | Vol 16, No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v16i1.8439 | |
| Keywords | ||
| Acute lymphoblastic leukemia (ALL); Induction, Hematopoietic stem cell transplantation (HSCT); Cytoreduction | ||
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How to Cite
1.
Vaezi M, Pourkhani A, Kasaeian A, Souri M, Yaghmaie M, Alimoghaddam K, Ghavamzadeh A. A Comparison of Dexamethasone plus Vincristine versus Standard Regimen in Induction Therapy of Adult Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplantation. Int J Hematol Oncol Stem Cell Res. 2022;16(1):22-33.
