Long-term results of allogeneic stem cell transplantation in 533 patients: a single centre experience
Authors:
M. Krejčí; M. Doubek; M. Tomíška; Z. Ráčil; A. Janíková; Y. Brychtová; B. Robešová; J. Procházková; A. Žmijáková; K. Kšeňáková; P. Kouřilová; Z. Král; J. Mayer
Authors‘ workplace:
Interní hematologická a onkologická klinika LF MU a FN Brno
Published in:
Transfuze Hematol. dnes,24, 2018, No. 4, p. 284-296.
Category:
Original Papers
Overview
Allogeneic stem cell transplantation (SCT) is considered to be the treatment of choice for many haematological disorders, especially haematological malignancies. We present here our long-term experience with allogeneic SCT in cohort of 533 pts.
We analysed 533 pts who underwent allogeneic SCT at our centre from November 1996 to June 2017. The diagnoses were as follows: AML (187 pts; 35%), ALL (73 pts, 14%), lymphomas (66 pts, 12%), MDS + MPN (52 pts, 10%), CML (74 pts, 14%), CLL (47 pts, 9%), other diagnoses (34 pts, 6%). The median age was 45 years (range 18–64). The types of donors and grafts used were as follows: HLA identical sibling, n = 257 (48%); unrelated donor, n = 276 (52%); PBSCs, n = 492 (92%); BM, n = 41 (8%). Median follow-up from SCT was 26.6 months, median follow-up from SCT for surviving pts was 83.2 months. Myeloablative conditioning (MAC) was used in 253 pts (47%), reduced intensity conditioning (RIC) was used in 280 pts (53%). Disease status at SCT was remission in 351 pts (66%) and active disease in 182 pts (34%). Median time from diagnosis to SCT was 7.4 months.
The overall response rate after allogeneic SCT was 82%, including CR in 78% of pts and PR in 4% of pts. The incidence of acute and chronic GvHD was 42% and 40% resp. Non-relapse mortality (NRM) was 18%, 19% and 20% at 1 year, 2 years and 4 years from SCT resp. Relapse incidence was 22%, 27% and 31% at 1 year, 2 years and 4 years from SCT resp. Median PFS was 31.5 months, median OS was 85.6 months. Gender, type of donor, type of graft, time from diagnosis to SCT and type of conditioning did not significantly influence PFS and OS in our cohort of pts. Patients with AML had significantly shorter PFS compared to pts with other diagnoses (median PFS 18.9 months versus 43.2 months, p = 0.031, HR 1.32). Patients with active disease at SCT had significantly shorter PFS compared to pts in remission at SCT (median PFS 9.6 months versus 73.7 months, p < 0.001, HR 1.79). On multivariate analysis, diagnosis of AML versus other diagnoses (median OS 29.7 months versus 197.2 months, p < 0.001, HR 1.63) and active disease at SCT versus remission at SCT (median OS 25.0 months versus 186.5 months, p < 0.001, HR 1.93) were significant predictors of poor OS.
Allogeneic transplantation remains the standard treatment option predominantly for various haematological malignancies. According to our results, the type of diagnosis and disease status at allogeneic SCT are important prognostic factors for PFS and OS. Patients in remission of their disease at the time of allogeneic SCT have significantly longer PFS and OS.
Key words:
allogeneic stem cell transplantation – haematological malignancies – acute leukaemi
Sources
1. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med 2006;354:1813–1826.
2. Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med 2007;357:1472–1475.
3. Ljungman P, Bregni M, Brune M, et al. European Group for Blood and Marrow. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant 2010;45:219–234.
4. Gratwohl A, Baldomero H, Aljurf M, et al. Hematopoietic stem cell transplantation: a global perspective. JAMA 2010;303:1617–1624.
5. Sureda A, Bader P, Cesaro S, et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant 2015;50:1037–1056.
6. Krejčí M, Sedláček P, Jindra P, et al. Indikace k alogenním a autologním transplantacím krvetvorných buněk v ČR v roce 2016: doporučení Transplantační sekce České hematologické společnosti ČLS JEP a České onkologické společnosti ČLS JEP. Transfuze Hematol dnes 2016;22:127–150.
7. Koza V, Cetkovský P, Faber E, et al. Indikace k alogenním a autologním transplantacím krvetvorných buněk. Doporučení České hematologické společnosti ČLS JEP a České onkologické společnosti ČLS JEP. Transfuze Hematol dnes 2006;12:223–231.
8. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2015;21:1863–1869.
9. Ruutu T, Grathwohl A, T de Witte, et al. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standartized practice. Bone Marrow Transplant 2014;49:168–173.
10. Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant diseases. Blood 1998;91:756–763.
11. Or R, Shapira MY, Resnick I, et al. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood 2003;101:441–445.
12. Krejci M, Brychtova Y, Doubek M, et al. Long-term results of allogeneic hematopoietic stem cell transplantation after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin. Neoplasma 2011;58:406–414.
13. Schmid C, Schleuning M, Ledderose G, et al. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005;23:5675–5687.
14. Krejci M, Doubek M, Dusek J, et al. Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia. Ann Hematol 2013;92:1397–1403.
15. Krejci M, Doubek M, Brychtova Y, et al. Fludarabine with cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with poor-risk chronic lymphocytic leukemia. Ann Hematol 2013;92:249–254.
16. Przepiorka D, Weisdorf D, Martin P, et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995;15:825–828.
17. Rowlings PA, Przepiorka D, Klein JP, et al. IBMTR severity index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997;97:855–864.
18. Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopatologic study of 20 Seattle patients. Am J Med 1980;60:204–217.
19. 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;11:945–956.
20. Krejci M, Doubek M, Buchler T, et al. Mycophenolate mofetil for the treatment of acute and chronic steroid-refractory graft-versus-host disease. Ann Hematol 2005;84:681–685.
21. Mayer J, Krejci M, Doubek M, et al. Pulse cyclophosphamide for corticosteroid-refractory graft-versus-host disease. Bone Marrow Transplant 2005;35:699–705.
22. Lion T. Summary: reports on quantitative analysis of chimerim after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection. Leukemia 2003;17:232–254.
23. Passweg JR, Baldomero H, Bader P, et al. Impact of drug development on the use of stem cell transplantation: a report by the European society for blood and marrow transplantation (EBMT). Bone Marrow Transplant 2017;52:191–196.
24. Passweg JR, Baldomero H, Bader P, et al. Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant 2015;50:476–482.
25. Barret A, Savani BN. Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years´ experience with new transplant concepts and new therapeutic agents. Leukemia 2006;20:1661–1672.
26. Finke J, Bethge WA, Schmoor C, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomized, open-label, multicenter phase 3 trial. Lancet Oncol 2009;10:855–864.
27. Vítek A, Vydra J, Marková-Šťastná M, et al. Transplantace krvetvorných buněk v Ústavu hematologie a krevní transfúze (1986–2016). Transfuze Hematol dnes 2017;23:54–66.
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Haematology Internal medicine Clinical oncologyArticle was published in
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