Graft Source

PBSC vs BM grafts with myeloablative conditioning for unrelated donor transplantation in adults with high-risk ALL

Article metrics

Abstract

Few studies are available that compare PBSC and BM from unrelated donors, especially in adult high-risk ALL. To determine which graft source is superior in adult high-risk ALL, we analyzed the long-term outcomes of 106 consecutive transplants from 8/8-matched or 7/8-matched unrelated donors (38 PBSC vs 68 BM). All patients received a uniform strategy of pre-transplant therapy, myeloablative conditioning and GVHD prophylaxis. At 5 years, PBSC transplants showed higher incidence of chronic GVHD than did BM transplants (74.3% vs 46.7%, P=0.001). PBSC transplants showed outcomes comparable to those of BM transplants for relapse (23.7% vs 28.1%), non-relapse mortality (18.4% vs 25.0%), disease-free survival (57.9% vs 46.9%) and OS (57.9% vs 50.0%). In a separate comparison of outcomes between the two graft sources according to the presence of a Ph chromosome, no significant advantage of PBSC over BM was found in both subgroups of patients. Our data suggest that the outcomes of unrelated donor transplantation are similar between PBSC and BM in adult high-risk ALL. Whether PBSC should be the preferred graft source for a specific subgroup of adult ALL needs to be further investigated.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1
Figure 2
Figure 3

References

  1. 1

    Linker C, Damon L, Ries C, Navarro W . Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia. J Clin Oncol 2002; 20: 2464–2471.

  2. 2

    Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood 2002; 99: 863–871.

  3. 3

    Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S et al. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia 2002; 16: 1259–1266.

  4. 4

    Kantarjian H, Thomas D, O'Brien S, Cortes J, Giles F, Jeha 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: 2788–2801.

  5. 5

    Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 2004; 104: 3028–3037.

  6. 6

    Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004; 22: 4075–4086.

  7. 7

    Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM 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: 3760–3767.

  8. 8

    Cornelissen JJ, van der Holt B, Verhoef GE, van't Veer MB, van Oers MH, Schouten HC et al. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 2009; 113: 1375–1382.

  9. 9

    Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK 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: 1827–1833.

  10. 10

    Yanada M, Matsuo K, Suzuki T, Naoe T . Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis. Cancer 2006; 106: 2657–2663.

  11. 11

    Blaise D, Kuentz M, Fortanier C, Bourhis JH, Milpied N, Sutton L et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Societe Francaise de Greffe de Moelle. J Clin Oncol 2000; 18: 537–546.

  12. 12

    Powles R, Mehta J, Kulkarni S, Treleaven J, Millar B, Marsden J et al. Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial. Lancet 2000; 355: 1231–1237.

  13. 13

    Heldal D, Tjonnfjord G, Brinch L, Albrechtsen D, Egeland T, Steen R et al. A randomised study of allogeneic transplantation with stem cells from blood or bone marrow. Bone Marrow Transplant 2000; 25: 1129–1136.

  14. 14

    Morton J, Hutchins C, Durrant S . Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells. Blood 2001; 98: 3186–3191.

  15. 15

    Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. New Engl J Med 2001; 344: 175–181.

  16. 16

    Schmitz N, Beksac M, Hasenclever D, Bacigalupo A, Ruutu T, Nagler A et al. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia. Blood 2002; 100: 761–767.

  17. 17

    Couban S, Simpson DR, Barnett MJ, Bredeson C, Hubesch L, Howson-Jan K et al. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood 2002; 100: 1525–1531.

  18. 18

    Stem Cell Trialists' Collaborative G. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol 2005; 23: 5074–5087.

  19. 19

    Friedrichs B, Tichelli A, Bacigalupo A, Russell NH, Ruutu T, Shapira MY et al. Long-term outcome and late effects in patients transplanted with mobilised blood or bone marrow: a randomised trial. Lancet Oncol 2010; 11: 331–338.

  20. 20

    Ringden O, Remberger M, Runde V, Bornhauser M, Blau IW, Basara N et al. Peripheral blood stem cell transplantation from unrelated donors: a comparison with marrow transplantation. Blood 1999; 94: 455–464.

  21. 21

    Remberger M, Ringden O, Blau IW, Ottinger H, Kremens B, Kiehl MG et al. No difference in graft-versus-host disease, relapse, and survival comparing peripheral stem cells to bone marrow using unrelated donors. Blood 2001; 98: 1739–1745.

  22. 22

    Remberger M, Beelen DW, Fauser A, Basara N, Basu O, Ringden O . Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors. Blood 2005; 105: 548–551.

  23. 23

    Remberger M, Ringden O . Similar outcome after unrelated allogeneic peripheral blood stem cell transplantation compared with bone marrow in children and adolescents. Transplantation 2007; 84: 551–554.

  24. 24

    Meisel R, Laws HJ, Balzer S, Bernbeck B, Kramm C, Schonberger S et al. Comparable long-term survival after bone marrow versus peripheral blood progenitor cell transplantation from matched unrelated donors in children with hematologic malignancies. Biol Blood Marrow Transplant 2007; 13: 1338–1345.

  25. 25

    Eapen M, Logan BR, Confer DL, Haagenson M, Wagner JE, Weisdorf DJ et al. Peripheral blood grafts from unrelated donors are associated with increased acute and chronic graft-versus-host disease without improved survival. Biol Blood Marrow Transplant 2007; 13: 1461–1468.

  26. 26

    Bertz H, Spyridonidis A, Ihorst G, Engelhardt M, Grullich C, Wasch R et al. Marrow versus blood-derived stem cell grafts for allogeneic transplantation from unrelated donors in patients with active myeloid leukemia or myelodysplasia. Biol Blood Marrow Transplant 2012; 18: 894–902.

  27. 27

    Nagler A, Labopin M, Shimoni A, Niederwieser D, Mufti GJ, Zander AR et al. Mobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2012; 18: 1422–1429.

  28. 28

    Ringden O, Labopin M, Beelen DW, Volin L, Ehninger G, Finke J et al. Bone marrow or peripheral blood stem cell transplantation from unrelated donors in adult patients with acute myeloid leukaemia, an Acute Leukaemia Working Party analysis in 2262 patients. J Intern Med 2012; 272: 472–483.

  29. 29

    Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. New Engl J Med 2012; 367: 1487–1496.

  30. 30

    Lee S, Kim YJ, Min CK, Kim HJ, Eom KS, Kim DW et al. The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 2005; 105: 3449–3457.

  31. 31

    Lee S, Kim YJ, Chung NG, Lim J, Lee DG, Kim HJ et al. The extent of minimal residual disease reduction after the first 4-week imatinib therapy determines outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer 2009; 115: 561–570.

  32. 32

    Lee S, Kim DW, Cho BS, Yoon JH, Shin SH, Yahng SA et al. Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia. Leukemia 2012; 26: 2367–2374.

  33. 33

    Lee S, Cho BS, Kim SY, Choi SM, Lee DG, Eom KS 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: 1083–1094.

  34. 34

    Lee S, Chung NG, Cho BS, Eom KS, Kim YJ, Kim HJ et al. Donor-specific differences in long-term outcomes of myeloablative transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia. Leukemia 2010; 24: 2110–2119.

  35. 35

    Cho BS, Lee S, Kim YJ, Chung NG, Eom KS, Kim HJ et al. Reduced-intensity conditioning allogeneic stem cell transplantation is a potential therapeutic approach for adults with high-risk acute lymphoblastic leukemia in remission: results of a prospective phase 2 study. Leukemia 2009; 23: 1763–1770.

  36. 36

    Eom KS, Shin SH, Yoon JH, Yahng SA, Lee SE, Cho BS et al. Comparable long-term outcomes after reduced-intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high-risk acute lymphoblastic leukemia in complete remission. Am J Hematol 2013; 88: 634–641.

  37. 37

    Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

  38. 38

    Lee SJ, Vogelsang G, Flowers ME . Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003; 9: 215–233.

  39. 39

    Pidala J, Anasetti C, Kharfan-Dabaja MA, Cutler C, Sheldon A, Djulbegovic B . Decision analysis of peripheral blood versus bone marrow hematopoietic stem cells for allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2009; 15: 1415–1421.

  40. 40

    Signori A, Crocchiolo R, Oneto R, Sacchi N, Sormani MP, Fagioli F et al. Chronic GVHD is associated with lower relapse risk irrespective of stem cell source among patients receiving transplantation from unrelated donors. Bone Marrow Transplant 2012; 47: 1474–1478.

  41. 41

    Elmaagacli AH, Basoglu S, Peceny R, Trenschel R, Ottinger H, Lollert A et al. Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia. Blood 2002; 99: 1130–1135.

Download references

Acknowledgements

This research was supported by the Seoul St Mary’s Clinical Medicine Research Program in 2010 at the Catholic University of Korea. Statistical analyses performed in this article were supervised by the Catholic Medical Center Clinical Research Coordinating Center.

Author information

Correspondence to S Lee.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shin, S., Yoon, J., Yahng, S. et al. PBSC vs BM grafts with myeloablative conditioning for unrelated donor transplantation in adults with high-risk ALL. Bone Marrow Transplant 49, 773–779 (2014) doi:10.1038/bmt.2014.54

Download citation

Further reading