Conditioning Regimens in Allogeneic Hematopoietic Stem Cell Transplantation Do Not Fit All: Adjusting BuCy2 in Mexico to Improve Outcomes in AML and MDS
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Abstract
Background: Conditioning regimens are critical for allogeneic hematopoietic cell transplantation (allo-HCT). After unfavorable results using BuCy2 at the beginning of our HCT Program, a restructuring was made with the consequent development of a modified HCT method including a reduced conditioning regimen. The objective of this study was to describe the outcomes using Reduced BuCy2 (rBuCy2) in allo-HCT.
Materials and Methods: Data from 38 consecutive patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT conditioned with rBuCy2 in a 21-year period were retrospectively analyzed.
Results: Most patients were males (53%) and the median age was 35 years. The most common disease was myelodysplastic syndrome (55%). Toxicity grades III-IV were observed in 44%; and acute and chronic graft-versus-host disease were observed in 26% and 34%, respectively; the median follow-up was 26 months; 30-day non-relapse mortality (NRM) was 3%, and 1 and 2-year NRM were 8%. Ten-year overall survival (OS) was 60%, and 86%, for AML and MDS, respectively.
Conclusion: Our rBuCy2 maintains a myeloablative effect, along with immunosuppression for fast engraftment and more importantly, this regimen reduces grades III-IV acute GVHD and NRM in allo-HCT and improves the OS and it appears to be an option for low and middle-income countries
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2. Giralt S, Ballen K, Rizzo D, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 2009; 15(3):367-9.
3. Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009; 15(12):1628–33.
4. Santos GW, Tutschka PJ, Brookmeyer R, et al. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983; 309(22):1347–53.
5. Gratwohl A, Carreras E. Principles of Conditioning. In: ESH-EBMT Handbook on Haematopoietic Stem Cell Transplantation 2012, 6th edition, Apperley J, Carreras E, Gluckman E, Masszi T (Eds), European School of Haematology, Paris 2012. p.126.
6. Tutschka PJ, Copelan EA, Klein JP. Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood. 1987; 70(5):1382–8.
7. Lucarelli G, Clift RA, Galimberti M, et al. Bone Marrow Transplantation in Adult Thalassemic Patients. Blood. 1999; 93 (4): 1164-7.
8. Leon Rodriguez E, Rivera Franco MM, Campos Castro A. Is Day +1 Omission of Methotrexate associated with higher incidence of Acute Graft-Versus-Host-Disease in Hematopoietic Stem Transplantation? Bone Marrow Transplant. 2017; 52(5):772-774.
9. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant. 2015; 21(3): 389–401.e1.
10. Vigorito A, Campregher P, Storer B, et al. Evaluation of NIH consensus criteria for classification of late acute and chronic GVDH. Blood. 2009; 114 (3): 702-8.
11. Armand P, Kim HT, Logan BR, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014; 123(23):3664-71.
12. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8):2912-19.
13. Clift RA, Buckner CD, Thomas ED, et al. Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood. 1994; 84(6):2036-43.
14. Grochow LB. Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. Semin Oncol. 1993; 20(4 Suppl 4):18-25; quiz 26.
15. Tanaka Y, Kurosawa S, Tajima K, et al. Analysis of non-relapse mortality and causes of death over 15 years following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2016; 51(4): 553-9.
16. Rubio MT, Labopin M, Blaise D, et al. The Impact Of Graft-Versus-Host Disease Prophylaxis In Reduced-Intensity Conditioning Allogeneic Stem Cell Transplant In Acute Myeloid Leukemia: A Study From The Acute Leukemia Working Party Of The European Group For Blood And Marrow Transplantation. Haematologica. 2015; 100(5): 683-9.
17. Malard F, Chevallier P, Guillaume T, et al. Continuous reduced nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: a single-institution's three-decade experience. Biol Blood Marrow Transplant. 2014; 20(8):1217-23.
18. Kurosawa S, Yakushijin K, Yamaguchi T, et al. Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia. Bone Marrow Transplant. 2013; 48(9): 1198–204.
19. Kurosawa S, Yakushijin K, Yamaguchi T, et al. Changes in incidence and causes of non-relapse mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia/myelodysplastic syndrome: an analysis of the Japan Transplant Outcome Registry. Bone Marrow Transplant. 2013; 48(4): 529–36.
20. Chaudhry HM, Bruce AJ, Wolf RC, et al. The Incidence and Severity of Oral Mucositis among Allogeneic Hematopoietic Stem CellTransplantation Patients: A Systematic Review. Biol Blood Marrow Transplant. 2016; 22(4):605-616.
21. Chae YS, Sohn SK, Kim JG, et al. New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Bone Marrow Transplantat. 2007; 40(6): 541-7.
22. Ottinger HD, Ferencik S, Beelen DW, et al. Hematopoietic stem cell transplantation: contrasting the outcome of transplantations from HLA-identical siblings, partially HLA mismatched related donors, and HLA-matched unrelated donors. Blood. 2003; 102(3): 1131-7.
23. Masouridi-Levrat S, Simonetta F, Chalandon Y. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2016; 7:362.
24. Ozdemir ZN, Civriz Bozdağ S. Graft failure after allogeneic hematopoietic stem cell transplantation. Transfus Apher Sci. 2018; 57(2):163-167.
25. Han HS, Reis IM, Zhao W, et al. Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer. Eur J Cancer. 2011; 47(17): 2537-45.
26. Sharib JM, Cyrus J, Horvai A, et al. Predictors of acute chemotherapy-associated toxicity in patients with Ewing sarcoma. Pediatr Blood Cancer. 2012; 59(4):611-6.
27. Bandera EV, Lee VS, Rodriguez-Rodriguez L, et al. Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival. Clin Cancer Res. 2016; 22(23):5909-5914.
2. Giralt S, Ballen K, Rizzo D, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 2009; 15(3):367-9.
3. Bacigalupo A, Ballen K, Rizzo D, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009; 15(12):1628–33.
4. Santos GW, Tutschka PJ, Brookmeyer R, et al. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983; 309(22):1347–53.
5. Gratwohl A, Carreras E. Principles of Conditioning. In: ESH-EBMT Handbook on Haematopoietic Stem Cell Transplantation 2012, 6th edition, Apperley J, Carreras E, Gluckman E, Masszi T (Eds), European School of Haematology, Paris 2012. p.126.
6. Tutschka PJ, Copelan EA, Klein JP. Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood. 1987; 70(5):1382–8.
7. Lucarelli G, Clift RA, Galimberti M, et al. Bone Marrow Transplantation in Adult Thalassemic Patients. Blood. 1999; 93 (4): 1164-7.
8. Leon Rodriguez E, Rivera Franco MM, Campos Castro A. Is Day +1 Omission of Methotrexate associated with higher incidence of Acute Graft-Versus-Host-Disease in Hematopoietic Stem Transplantation? Bone Marrow Transplant. 2017; 52(5):772-774.
9. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant. 2015; 21(3): 389–401.e1.
10. Vigorito A, Campregher P, Storer B, et al. Evaluation of NIH consensus criteria for classification of late acute and chronic GVDH. Blood. 2009; 114 (3): 702-8.
11. Armand P, Kim HT, Logan BR, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014; 123(23):3664-71.
12. Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8):2912-19.
13. Clift RA, Buckner CD, Thomas ED, et al. Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood. 1994; 84(6):2036-43.
14. Grochow LB. Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens. Semin Oncol. 1993; 20(4 Suppl 4):18-25; quiz 26.
15. Tanaka Y, Kurosawa S, Tajima K, et al. Analysis of non-relapse mortality and causes of death over 15 years following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2016; 51(4): 553-9.
16. Rubio MT, Labopin M, Blaise D, et al. The Impact Of Graft-Versus-Host Disease Prophylaxis In Reduced-Intensity Conditioning Allogeneic Stem Cell Transplant In Acute Myeloid Leukemia: A Study From The Acute Leukemia Working Party Of The European Group For Blood And Marrow Transplantation. Haematologica. 2015; 100(5): 683-9.
17. Malard F, Chevallier P, Guillaume T, et al. Continuous reduced nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: a single-institution's three-decade experience. Biol Blood Marrow Transplant. 2014; 20(8):1217-23.
18. Kurosawa S, Yakushijin K, Yamaguchi T, et al. Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia. Bone Marrow Transplant. 2013; 48(9): 1198–204.
19. Kurosawa S, Yakushijin K, Yamaguchi T, et al. Changes in incidence and causes of non-relapse mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia/myelodysplastic syndrome: an analysis of the Japan Transplant Outcome Registry. Bone Marrow Transplant. 2013; 48(4): 529–36.
20. Chaudhry HM, Bruce AJ, Wolf RC, et al. The Incidence and Severity of Oral Mucositis among Allogeneic Hematopoietic Stem CellTransplantation Patients: A Systematic Review. Biol Blood Marrow Transplant. 2016; 22(4):605-616.
21. Chae YS, Sohn SK, Kim JG, et al. New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Bone Marrow Transplantat. 2007; 40(6): 541-7.
22. Ottinger HD, Ferencik S, Beelen DW, et al. Hematopoietic stem cell transplantation: contrasting the outcome of transplantations from HLA-identical siblings, partially HLA mismatched related donors, and HLA-matched unrelated donors. Blood. 2003; 102(3): 1131-7.
23. Masouridi-Levrat S, Simonetta F, Chalandon Y. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2016; 7:362.
24. Ozdemir ZN, Civriz Bozdağ S. Graft failure after allogeneic hematopoietic stem cell transplantation. Transfus Apher Sci. 2018; 57(2):163-167.
25. Han HS, Reis IM, Zhao W, et al. Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer. Eur J Cancer. 2011; 47(17): 2537-45.
26. Sharib JM, Cyrus J, Horvai A, et al. Predictors of acute chemotherapy-associated toxicity in patients with Ewing sarcoma. Pediatr Blood Cancer. 2012; 59(4):611-6.
27. Bandera EV, Lee VS, Rodriguez-Rodriguez L, et al. Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival. Clin Cancer Res. 2016; 22(23):5909-5914.
| Files | ||
| Issue | Vol 16, No 4 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v16i4.10876 | |
| Keywords | ||
| Hematopoietic cell transplantation; Conditioning regimen; Non-relapse mortality; Developing country | ||
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How to Cite
1.
Leon Rodriguez E, Rivera Franco M. Conditioning Regimens in Allogeneic Hematopoietic Stem Cell Transplantation Do Not Fit All: Adjusting BuCy2 in Mexico to Improve Outcomes in AML and MDS. Int J Hematol Oncol Stem Cell Res. 2022;16(4):189-197.
