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Relapse of Leukaemia

High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant

Bone Marrow Transplantation volume 26, pages 333–338 (2000)Cite this article

Abstract

Patients with acute leukemias relapsing within 1 year of an allogeneic BMT have a poor prognosis. We studied the use of melphalan 180 mg/m2 followed by allogeneic peripheral blood stem cells (PBSC) as salvage treatment for patients relapsing after related (n = 7) or matched unrelated transplants (n = 3). Diagnoses were AML (n = 4), ALL (n = 3), biphenotypic acute leukemia (n = 2) and CML in blast crisis (n = 1). Eight patients were beyond first relapse and none were in remission. The median time from previous transplant to relapse was 146 days (range 66–206). The melphalan dose was 90 mg/m2 intravenously on days −4 and −3 with pbsc infusion on day 0. gvhd prophylaxis consisted of cyclosporine and methylprednisolone. the median time to an absolute neutrophil count >0.5 × 109/l and to a platelet count >20 × 109/l was 11 and 13 days, respectively. All engrafting patients (n = 8) had 100% donor cells. Two patients died before day 30, but no other grade 3 or 4 toxicity occurred. Acute GVHD grades II–III occurred in two subjects, and chronic GVHD in four. Seven patients achieved CR, but relapsed at a median of 116 days (range 56–614). Leukemia was the cause of death in eight patients. Median survival was 149 days (range 6–614). This treatment produced responses in the majority of this poor prognosis group. However, durable remissions were not observed, and new treatments to consolidate the responses achieved in this setting are needed. This regimen could be considered for short-term disease control to facilitate donor lymphocyte infusion-based immunotherapy or other measures to prevent disease recurrence. Bone Marrow Transplantation (2000) 26, 333–338.

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References

  1. Bortin M, Horowitz M, Gale R et al. Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s JAMA 1992 268: 607–612

    Article  CAS  PubMed  Google Scholar 

  2. Giralt S, Champlin R . Leukemia relapse after allogeneic bone marrow transplantation: a review Blood 1994 84: 3603–3612

    CAS  PubMed  Google Scholar 

  3. Frassoni F, Barrett J, Granena A et al. Relapse after allogeneic bone marrow transplantation for acute leukemia. A survey of the EBMTR of 117 cases Br J Haematol 1988 70: 317–322

    Article  CAS  PubMed  Google Scholar 

  4. Mortimer J, Binder M, Schulman S et al. Relapse of acute leukemia after marrow transplantation. Natural history and results of subsequent therapy J Clin Oncol 1989 7: 50–54

    Article  CAS  PubMed  Google Scholar 

  5. Bostrom B, Woods W, Nesbit M et al. Successful reinduction of patients with acute lymphoblastic leukemia who relapse following bone marrow transplantation J Clin Oncol 1987 5: 376–381

    Article  CAS  PubMed  Google Scholar 

  6. Mrsic M, Horowitz M, Atkinson K et al. Second HLA-identical sibling transplants for leukemia recurrence Bone Marrow Transplant 1992 9: 269–275

    CAS  PubMed  Google Scholar 

  7. Odom L, Githers J, Morse H et al. Remission of relapsed leukemia during a graft-versus-host reaction A graft-versus-leukemia reaction in man? Lancet 1978 2: 537–538

    CAS  Google Scholar 

  8. Higano C, Brixey M, Bryant E et al. Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marrow transplantation. A case report of a probable graft-versus-leukemia effect Transplantation 1990 50: 175–176

    Article  CAS  PubMed  Google Scholar 

  9. Collins R, Rogers Z, Bennett M et al. Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression Bone Marrow Transplant 1992 10: 391–392

    PubMed  Google Scholar 

  10. Kolb H, Mittermuller J, Clemm C et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients Blood 1990 76: 2462–2465

    CAS  PubMed  Google Scholar 

  11. Porter D, Roth M, McGarigle C et al. Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia New Engl J Med 1994 330: 100–103

    Article  CAS  PubMed  Google Scholar 

  12. Drobyski W, Keever C, Roth M et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose Blood 1993 82: 2310–2314

    CAS  PubMed  Google Scholar 

  13. Szer J, Grigg A, Phillips G, Sheridan W . Donor leukocyte infusions after chemotherapy for patients relapsing with acute leukemia following allogeneic BMT Bone Marrow Transplant 1993 11: 109–113

    CAS  PubMed  Google Scholar 

  14. Helg C, Roux E, Beris P et al. Adoptive immunotherapy for recurrent CML after BMT Bone Marrow Transplant 1993 12: 125–129

    CAS  PubMed  Google Scholar 

  15. van Rhee F, Lin F, Cullis J et al. Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse Blood 1994 83: 3377–3380

    CAS  PubMed  Google Scholar 

  16. Bar B, Schattenberg A, Mensink E et al. Donor leukocyte infusions for chronic myelogenous leukemia after allogeneic bone marrow transplantation J Clin Oncol 1993 11: 513–517

    Article  CAS  PubMed  Google Scholar 

  17. Kolb H, Schattenberg A, Goldman JM et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients Blood 1995 86: 2041–2050

    CAS  PubMed  Google Scholar 

  18. Collins R, Shpilberg O, Drobyski W et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation J Clin Oncol 1997 15: 433–444

    Article  PubMed  Google Scholar 

  19. Giralt S, Escudier S, Kantarjian H et al. Treatment with filgrastim for relapse of leukemia and myelodysplasia after allogeneic bone marrow transplantation. Preliminary observations New Engl J Med 1993 329: 757–761

    Article  CAS  PubMed  Google Scholar 

  20. Giralt S, Hester J, Talpaz M et al. Cytokine therapy for patients relapsing after allogeneic bone marrow transplantation J Cell Biochem 1994 (Suppl. 18B) 88a (Abstr.)

  21. Arcese W, Mauro F, Alimena G et al. Interferon therapy for Ph-positive CML patients relapsing after T cell-depleted allogeneic bone marrow transplantation Bone Marrow Transplant 1991 5: 309–311

    Google Scholar 

  22. Higano C, Raskind W, Singer J . Use of alpha interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation Blood 1992 80: 1437–1442

    CAS  PubMed  Google Scholar 

  23. Maraninchi D, Blaise D, Viens P et al. High dose recombinant interleukin-2 and acute myeloid leukemias in relapse Blood 1991 78: 2182–2187

    CAS  PubMed  Google Scholar 

  24. Sarosy G, Leyland-Jones B, Soochan P, Cheson B . The systemic administration of intravenous melphalan J Clin Oncol 1988 6: 1768–1782

    Article  CAS  PubMed  Google Scholar 

  25. Moreau P, Kergueris M, Milpied N et al. A pilot study of 220 mg/m2 melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity Br J Haematol 1996 95: 527–530

    Article  CAS  PubMed  Google Scholar 

  26. Singhal S, Powles R, Treleaven J et al. Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women Bone Marrow Transplant 1996 18: 1049–1055

    CAS  PubMed  Google Scholar 

  27. Yam P, Petz LD, Ali S et al. Development of a single probe for documentation of chimerism following bone marrow transplantation Am J Hum Genet 1987 41: 867–869

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Yam P, Petz L, Knowlton R et al. Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation Transplantation 1987 43: 399–401

    Article  CAS  PubMed  Google Scholar 

  29. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen related toxicities in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 1562–1566

    Article  CAS  PubMed  Google Scholar 

  30. Przepiorka D, Weisdorf D, Martin P et al. Report of the 1994 consensus conference on acute GVHD grading Bone Marrow Transplant 1995 15: 825–828

    CAS  PubMed  Google Scholar 

  31. Shulman HM, Sullivan KM, Weiden P et al. Chronic graft-versus-host disease syndrome in man. A long term clinical pathologic study of 20 Seattle patients Am J Med 1980 69: 204–217

    Article  CAS  PubMed  Google Scholar 

  32. Kaplan E, Meier P . Non parametric estimation from incomplete observations J Am Stat Assoc 1958 53: 457–462

    Article  Google Scholar 

  33. Atkinson K, Biggs J, Concannon A et al. Second marrow transplants for recurrence of hematological malignancy Bone Marrow Transplant 1986 1: 159–166

    CAS  PubMed  Google Scholar 

  34. Mehta J, Powles R, Treleaven J et al. Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy Bone Marrow Transplant 1997 19: 709–719

    Article  CAS  PubMed  Google Scholar 

  35. Levine JE, Penza S, Topolsky D et al. Prospective trial of chemotherapy plus donor lymphocyte infusions to treat relapsed advanced myeloid leukemia after related bone marrow transplantation Blood 1999 94: 2964a (Abstr.)

    Google Scholar 

  36. Przepiorka D, Ippolitti C, Khouri I et al. Allogeneic transplantation for advanced leukemia: improved short-term outcome with blood stem cell grafts and tacrolimus Blood 1996 62: 1806–1810

    CAS  Google Scholar 

  37. Appelbaum FR . Choosing the source of stem cells for allogeneic transplantation: no longer a peripheral issue Blood 1999 94: 381–383

    CAS  PubMed  Google Scholar 

  38. Bensinger W, Martin P, Clift R et al. A prospective, randomized trial of peripheral blood stem cells (PBSC) or marrow (BM) for patients undergoing allogeneic transplantation for hematologic malignancies Blood 1999 94: 368a (Abstr.)

    Google Scholar 

  39. Storek J, Gooley T, Siadak M et al. Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease Blood 1997 90: 4705–4711

    CAS  PubMed  Google Scholar 

  40. Sandoval A, Consoli U, Plunkett W . Fludarabine-mediated inhibition of nucleotide excision repair induces apoptosis in quiescent human lymphocytes Clin Cancer Res 1996 2: 1731–1741

    CAS  PubMed  Google Scholar 

  41. Giralt S, Khouri I, Braunschweig I et al. Melphalan and purine analog containing preparative regimens. Less intensive conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation Blood 1999 94: 564a (Abstr.)

    Google Scholar 

  42. Spitzer TR, McAfee S, Sackstein R et al. Mixed lymphohematopoietic chimerism following non-myeloablative conditioning and HLA-matched allogeneic bone marrow transplantation: the effects of chimerism and anti-tumor response of prophylactic donor lymphocyte infusions Blood 1999 94: 709a (Abstr.)

    Google Scholar 

  43. de Lima M, Bonamino M, Vasconcelos Z et al. Moderately ablative chemotherapy, hematopoietic stem cell transplantation, and prophylactic donor lymphocyte infusions for poor prognosis patients with hematological malignancies Blood 1999 94: 349a (Abstr.)

    Google Scholar 

  44. Falkenburg JHF, Wafelman AR, Joosten P et al. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes Blood 1999 94: 1201–1208

    CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M de Lima, K van Besien, J Gajewski, I Khouri, B Andersson, M Korbling, R Champlin & S Giralt

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  1. M de Lima
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  2. K van Besien
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de Lima, M., van Besien, K., Gajewski, J. et al. High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant. Bone Marrow Transplant 26, 333–338 (2000). https://doi.org/10.1038/sj.bmt.1702521

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