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Lymphoma

Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma

Leukemia volume 15, pages 635–641 (2001)Cite this article

Abstract

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European–American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3–12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatment-related mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered.

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References

  1. Devasa SS, Fears T . Non-Hodgkin's lymphoma time trends: United States and international data Cancer Res 1992 52: (Suppl.) 5432–5440

    Google Scholar 

  2. Sarris A, Richard F . Recent advances in the molecular pathogenesis of lymphomas Curr Opin Oncol 1999 11: 351–363

    Article  CAS  Google Scholar 

  3. International Non-Hodgkin's Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin's lymphoma N Engl J Med 1993 329: 987–994

  4. Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G . High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma N Engl J Med 1997 336: 1290–1297

    Article  CAS  Google Scholar 

  5. Philip T, Guglielmi C, Hagenbeek A, Somers R, van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn J-Y, Harousseau J-L, Coiffier B, Biron P, Mandelli F, Ghauvin F . Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma N Engl J Med 1995 333: 1540–1545

    Article  CAS  Google Scholar 

  6. Lazarus HM, Crilley P, Ciobanu N, Creger RJ, Fox RM, Shina DC, Bulova SI, Gucalp R, Cooper BW, Topolsky D, Soegiarso W, Brodsky I . High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma J Clin Oncol 1992 10: 1682–1689

    Article  CAS  Google Scholar 

  7. Gulati S, Yahalom J, Acaba L, Reich L, Motzer R, Crown J, Toia M, Igarashi T, Lemoli R, Hanninen E . Treatment of patients with relapsed and resistent non-Hodgkin's lymphoma using total body irradiation, etoposide, and cyclophosphamide and autologous bone marrow transplantation J Clin Oncol 1992 10: 936–941

    Article  CAS  Google Scholar 

  8. Freedman AS, Neuberg D, Gribben JG, Mauch P, Soiffer RJ, Fisher DC, Andersen N, Schlossman R, Kroon M, Ritz J, Aster J, Nadler LM . High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission J Clin Oncol 1998 16: 13–18

    Article  CAS  Google Scholar 

  9. Haas R, Moos M, Mohle R, Dohner H, Witt B, Goldschmidt H, Murea S, Flentje M, Wannenmacher M, Hunstein W . High-dose therapy with peripheral blood progenitor cell transplantation in low-grade non-Hodgkin's lymphoma Bone Marrow Transplant 1996 17: 149–155

    CAS  Google Scholar 

  10. Gribben JG, Freedman A, Woo SD, Blake K, Shu RS, Freeman G, Longtine JA, Pinkus GS, Nadler LM . All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment Blood 1991 78: 3275–3280

    CAS  PubMed  Google Scholar 

  11. Stone RM, Neuberg D, Soiffer R, Takvorian T, Whelan M, Rabinowe SN, Aster JC, Leavitt P, Mauch P, Freedman AS . Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma J Clin Oncol 1994 12: 2535–2542

    Article  CAS  Google Scholar 

  12. Ratanatharathorn V, Uberti J, Karanes C, Abella E, Lum LG, Momin F, Cummings G, Sensenbrenner LL . Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma Blood 1994 84: 1050–1055

    CAS  PubMed  Google Scholar 

  13. Jones RJ, Ambinder RF, Piantadosi S, Santos GW . Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation Blood 1991 77: 649–653

    CAS  PubMed  Google Scholar 

  14. Appelbaum FR, Sullivan KM, Buckner CD, Clift RA, Deeg HJ, Fefer A, Hill R, Mortimer J, Neiman PE, Sanders JE, Singer J, Stewart P, Storb R, Thomas ED . Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation, and marrow transplantation J Clin Oncol 1987 5: 1340–1347

    Article  CAS  Google Scholar 

  15. Chopra R, Goldstone AH, Pearce R, Philip T, Petersen F, Appelbaum F, De Vol E, Ernst P . Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European bone marrow transplant group registry data J Clin Oncol 1992 10: 1690–1695

    Article  CAS  Google Scholar 

  16. Bernard M, Dauriac C, Drenou B, Leberre C, Branger B, Fauchet R, Le Prise PY, Lamy T . Long-term follow-up of allogeneic bone marrow transplantation in patients with poor prognosis non-Hodgkin's lymphoma Bone Marrow Transplant 1999 23: 329–333

    Article  CAS  Google Scholar 

  17. Van Besien K, Champlin IK, McCarthy P . Allogeneic transplantation for low-grade lymphoma: long-term follow-up J Clin Oncol 2000 18: 702–703

    Article  CAS  Google Scholar 

  18. Juckett M, Rowlings P, Hessner M, Keever-Taylor C, Burns W, Camitta B, Casper J, Drobyski WR, Hanson G, Horowitz M, Lawton C, Margolis J, Peitryga D, Vesole d . T cell-depleted allogeneic bone marrow transplantation for high-risk non-Hodgkin's lymphoma: clinical and molecular follow up Bone Marrow Transplant 1998 21: 893–899

    Article  CAS  Google Scholar 

  19. Mandigers CM, Raemaekers JM, Schattenberg AV, Roovers EA, Bogman MJ, van der Maazen RW, De Pauw BE, De Witte T . Allogeneic bone marrow transplantation with T-cell-depleted marrow grafts for patients with poor-risk relapsed low-grade non Hodgkin's lymphoma Br J Haematol 1998 100: 198–206

    Article  CAS  Google Scholar 

  20. Toze CL, Shepherd JD, Connors JM, Voss NJ, Gascoyne RD, Hogge DE, Klingemann HG, Nantel SH, Nevill TJ, Phillips GL, Reece DE, Sutherland HJ, Barnett MJ . Allogeneic bone marrow transplantation for low-grade lymphoma and chronic lymphatic leukemia Bone Marrow Transplant 2000 25: 605–612

    Article  CAS  Google Scholar 

  21. Födinger M, Winkler K, Mannhalter C, Chott A . Combined polymerase chain reaction approach for clonality detection in lymphoid neoplasms Diagn Mol Pathol 1999 8: 80–91

    Article  Google Scholar 

  22. Yunis JJ, Oken MM, Kaplan ME, Ensrud KM, Howe RR, Theologides A . Distinctive chromosomal abnormalities in histological subtypes of non-Hodgkin's lymphoma N Engl J Med 1982 307: 1231–1236

    Article  CAS  Google Scholar 

  23. Greinix HT, Reiter E, Keil F, Fischer G, Lechner K, Dieckmann K, Leitner G, Schulenburg A, Hoecker P, Haas OA, Knoebl P, Mannhalter C, Fonatsch C, Hinterberger W, Kalhs P . Leukemia-free survival and mortality in patients with refractory or relapsed acute leukemia given marrow transplants from sibling and unrelated donors Bone Marrow Transplant 1998 21: 673–678

    Article  CAS  Google Scholar 

  24. Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Neiman PE, Lerner KG, Glucksberg H, Buckner CD . Bone marrow transplantation N Engl J Med 1975 292: 832–843, 895–902

    Article  CAS  Google Scholar 

  25. Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, Hansen J, Hill R, Lum L, Martin P, McGuffin R, Sanders J, Stewart P, Sullivan K, Witherspoon R, Yee G, Thomas ED . Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia N Engl J Med 1986 314: 729–735

    Article  CAS  Google Scholar 

  26. Przepiorka D, Shapiro S, Schwinghammer TL, Bloom EJ, Rosenfeld CS, Shadduck RK, Venkataramanan R . Cyclosporine and methylprednisolone after allogeneic marrow transplantation: association between low cyclosporine concentration and risk of acute graft-versus-host disease Bone Marrow Transplant 1991 7: 461–465

    CAS  PubMed  Google Scholar 

  27. Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ, Cahn JY, Calderwood S, Gratwohl A, Socie G, Abecasis MM, Sobocinski KA, Zhang MJ, Horowitz MM . IBMTR severity index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade Br J Haematol 1997 97: 855–864

    Article  CAS  Google Scholar 

  28. Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB, Schubert MM, Atkinson K, Thomas ED . Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression Blood 1981 57: 267–276

    CAS  PubMed  Google Scholar 

  29. Winston DJ, Gale RP . Prevention and treatment of cytomegalovirus infection and disease after bone marrow transplantation in the 1990s Bone Marrow Transplant 1991 8: 7–11

    CAS  PubMed  Google Scholar 

  30. ISCN . An International System for Human Cytogenetic Nomenclature. Harnden DG, Klinger HP (eds) Karger: Basel 1985

    Google Scholar 

  31. Gaiger A, Mannhalter C, Hinterberger W, Haas O, Marosi C, Kier P, Eichinger S, Funovic M, Lechner K . Detection of engraftment and mixed chimerism following bone marrow transplantation using PCR amplification of a highly variable region-variable number of tandem repeats (VNTR) in the von Willebrand factor gene Ann Hematol 1991 63: 227–228

    Article  CAS  Google Scholar 

  32. Peake IR, Bowen D, Bignell P, Sadler JE, Standen G, Bloom AL . Family studies and prenatal diagnosis in severe von Willebrands disease by polymerase chain reaction amplification of variable number of tandem repeat region of the von Willebrand factor gene Blood 1990 76: 555–561

    CAS  PubMed  Google Scholar 

  33. Nishimura DY, Murray JC . A tetranucleotide repeat for the F13B locus Nucleic Acids Res 1992 20: 1167

    PubMed  PubMed Central  Google Scholar 

  34. Weber JL, May PE . Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction Am J Hum Genet 1989 44: 388–396

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations J Am Stat Assoc 1958 53: 457–481

    Article  Google Scholar 

  36. Sambrook J, Fritsch EF, Maniatis T . Molecular Cloning. A Laboratory Manual Cold Spring Harbor Laboratory Press: New York 1989

    Google Scholar 

  37. Voso MT, Hohaus S, Moos M, Haas R . Lack of t(14;18) polymerase chain reaction-positive cells in highly purified CD34+ cells and their CD19 subsets in patients with follicular lymphoma Blood 1997 89: 3763–3768

    CAS  PubMed  Google Scholar 

  38. Dhedin N, Giraudier S, Gaulard P, Esperou H, Ifrah N, Michallet M, Milpied N, Rio B, Cahn JY, Molina L, Laporte JL, Guilhot F, Kuentz M . Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoblastic lymphoma): a series of 73 patients from the SFGM data base Br J Haematol 1999 107: 154–161

    Article  CAS  Google Scholar 

  39. Mendoza E, Territo M, Schiller G, Lill M, Kunkel L, Wolin M . Allogeneic bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma Bone Marrow Transplant 1995 15: 299–303

    CAS  PubMed  Google Scholar 

  40. Shepherd JD, Barnett MJ, Connors JM, Spinelli JJ, Sutherland HJ, Kingemann HG, Nantel SH, Reece DE, Currie CJ, Phillips GL . Allogeneic bone marrow transplantation for poor-prognosis non-Hodgkin's lymphoma Bone Marrow Transplant 1993 12: 591–596

    CAS  PubMed  Google Scholar 

  41. Verdonck LF, Dekker AW, Lokhorst HM, Petersen EJ, Nieuwenhuis HK . Allogeneic versus autologous bone marrow transplantation for refractory and recurrent low-grade non-Hodgkin's lymphoma Blood 1997 90: 4201–4205

    CAS  Google Scholar 

  42. Khouri IF, Keating M, Korbling M, Przepiorka D, Anderlini P, O'Brien S, Giralt S, Ippoliti C, von Wolff B, Gajewski J, Donato M, Claxton D, Ueno N, Andersson B, Gee A, Champlin R . Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancies J Clin Oncol 1998 16: 2817–2824

    Article  CAS  Google Scholar 

  43. Khouri IF, Lee MS, Romaguera J, Mirza N, Kantarjian H, Korbling M, Albitar M, Giralt S, Samuels B, Anderlini P, Rodriguez J, von Wolff B, Gajewski J, Cabanillas F, Champlin R . Allogeneic hematopoietic tranplantation for mantle-cell lymphoma: molecular remissions and evidence of graft versus-malignancy Ann Oncol 1999 10: 1293–1299

    Article  CAS  Google Scholar 

  44. Van Besien KW, de Lima M, Giralt SA, Moore Jr DF, Khouri IF, Rondon G, Mehra R, Andersson BS, Dyer C, Cleary K, Przepiorka D, Gajewski JL, Champlin RE . Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect Bone Marrow Transplant 1997 19: 977–982

    Article  CAS  Google Scholar 

  45. Apostolidis J, Gupta RK, Grenzelias D, Johnson PW, Pappa VI, Summers KE, Salam A, Adams K, Norton AJ, Amess JA, Matthews J, Bradburn M, Lister TA, Rohatiner AZ . High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up J Clin Oncol 2000 18: 527–536

    Article  CAS  Google Scholar 

  46. Zwicky CS, Maddocks AB, Andersen N, Gribben JG . Eradication of polymerase chain reaction immunoglobulin rearrangement in non-Hodgkin's lymphoma is associated with decreased relapse after autologous bone marrow transplantation Blood 1996 88: 3314–3322

    CAS  Google Scholar 

  47. Gribben JG, Neuberg D, Freedman AS, Gimmi CD, Pesek KW, Barber M, Saporito L, Woo SD, Coral F, Spector N, Rabinowe SN, Grossbard ML, Ritz J, Nadler LM . Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma Blood 1993 81: 3449–3457

    CAS  Google Scholar 

  48. Corradini P, Ladotto M, Astolfi M, Voena C, Tarella C, Bacigalupo A, Pileri A . Clinical and molecular remission after allogeneic blood cell transplantation in a patient with mantle-cell lymphoma Br J Haematol 1996 94: 376–378

    Article  CAS  Google Scholar 

  49. Masuda R, Teshima T, Ishimaru F, Shinagawa K, Nakayama H, Shimono M, Asakura S, Ohmoto E, Harada M . Allogeneic peripheral blood stem cell transplantation for the treatment of refractory follicular lymphoma Intern Med 1998 37: 1050–1054

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the dedicated nurses of our stem cell transplant program, our fellows and housestaff, the medical technicians, and the physicians who referred patients to our unit. We are indebted to the staff of the bloodbank for technical assistance in marrow harvesting, peripheral blood stem cell collection and support of blood products.

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Authors and Affiliations

  1. Department of Medicine I, Bone Marrow Transplantation Unit, University Hospital of Vienna, Vienna, Austria

    M Mitterbauer, P Kalhs, S Brugger, W Hinterberger & HT Greinix

  2. Department of Medicine, Division of Hematology, University of Graz, Graz, Austria

    P Neumeister & W Linkesch

  3. Department of Blood Group Serology and Transfusion Medicine, University Hospital of Vienna, Vienna, Austria

    G Fischer & P Hoecker

  4. Department of Radiotherapy, University Hospital of Vienna, Vienna, Austria

    K Dieckmann

  5. Institute of Clinical Pathology, University Hospital of Vienna, Vienna, Austria

    I Simonitsch

  6. Department of Medicine I, Division of Hematology and Hemostaseology, University Hospital of Vienna, Vienna, Austria

    U Jaeger & K Lechner

  7. Department of Laboratory Medicine, Division of Molecular Biology, University Hospital of Vienna, Vienna, Austria

    C Mannhalter & G Mitterbauer

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  1. M Mitterbauer
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Mitterbauer, M., Neumeister, P., Kalhs, P. et al. Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma. Leukemia 15, 635–641 (2001). https://doi.org/10.1038/sj.leu.2402053

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