Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Allografting

Second-line age-adjusted International Prognostic Index in patients with advanced non-Hodgkin lymphoma after T-cell depleted allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 45, pages 1408–1416 (2010)Cite this article

Subjects

Abstract

T-cell depleted allogeneic hematopoietic SCT (TCD-HSCT) have shown durable disease-free survival with a low risk of GVHD in patients with AML. We investigated this approach in 61 patients with primary refractory or relapsed non-Hodgkin lymphoma (NHL), who underwent TCD-HSCT from January 1992 through September 2004. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, followed by either thiotepa and cyclophosphamide (45 patients) or thiotepa and fludarabine (16 patients). We determined the second-line age-adjusted International Prognostic Index score (sAAIPI) before transplant transplant. Median follow-up of surviving patients is 6 years. The 10-year OS and EFS were 50% and 43%, respectively. The relapse rate at 10 years was 21% in patients with chemosensitive disease and 52% in those with resistant disease at time of HSCT. Nine of the 18 patients who relapsed entered a subsequent CR. OS (P=0.01) correlated with the sAAIPI. The incidence of grades II–IV acute GVHD was 18%. We conclude that allogeneic TCD-HSCT can induce high rates of OS and EFS in advanced NHL with a low incidence of GVHD. Furthermore, the sAAIPI can predict outcomes and may be used to select the most appropriate patients for this type of transplant.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D et al. 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  PubMed  Google Scholar 

  2. Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med 1987; 316: 1493–1498.

    Article  CAS  PubMed  Google Scholar 

  3. Kewalramani T, Zelenetz AD, Hedrick EE, Donnelly GB, Hunte S, Priovolos AC et al. High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis. Blood 2000; 96: 2399–2404.

    CAS  PubMed  Google Scholar 

  4. Hamlin PA, Zelenetz AD, Kewalramani T, Qin J, Satagopan JM, Verbel D et al. Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2003; 102: 1989–1996.

    Article  CAS  PubMed  Google Scholar 

  5. Kewalramani T, Zelenetz AD, Teruya-Feldstein J, Hamlin P, Yahalom J, Horwitz S et al. Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma. Br J Haematol 2006; 134: 202–207.

    Article  PubMed  Google Scholar 

  6. van Besien K, Sobocinski KA, Rowlings PA, Murphy SC, Armitage JO, Bishop MR et al. Allogeneic bone marrow transplantation for low-grade lymphoma. Blood 1998; 92: 1832–1836.

    CAS  PubMed  Google Scholar 

  7. Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB et al. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 2001; 98: 3595–3599.

    Article  CAS  PubMed  Google Scholar 

  8. Khouri IF, Lee MS, Saliba RM, Jun G, Fayad L, Younes A et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 2003; 21: 4407–4412.

    Article  CAS  PubMed  Google Scholar 

  9. Hosing C, Saliba RM, McLaughlin P, Andersson B, Rodriguez MA, Fayad L et al. Long-term results favor allogeneic over autologous hematopoietic stem cell transplantation in patients with refractory or recurrent indolent non-Hodgkin's lymphoma. Ann Oncol 2003; 14: 737–744.

    Article  CAS  PubMed  Google Scholar 

  10. Levine JE, Harris RE, Loberiza Jr FR, Armitage JO, Vose JM, Van Besien K et al. A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma. Blood 2003; 101: 2476–2482.

    Article  CAS  PubMed  Google Scholar 

  11. Maris MB, Sandmaier BM, Storer BE, Chauncey T, Stuart MJ, Maziarz RT et al. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 2004; 104: 3535–3542.

    Article  CAS  PubMed  Google Scholar 

  12. Faulkner RD, Craddock C, Byrne JL, Mahendra P, Haynes AP, Prentice HG et al. BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. Blood 2004; 103: 428–434.

    Article  CAS  PubMed  Google Scholar 

  13. Escalon MP, Champlin RE, Saliba RM, Acholonu SA, Hosing C, Fayad L et al. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol 2004; 22: 2419–2423.

    Article  PubMed  Google Scholar 

  14. Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100: 3108–3114.

    Article  CAS  PubMed  Google Scholar 

  15. van Besien K, Carreras J, Bierman PJ, Logan BR, Molina A, King R et al. Unrelated donor hematopoietic cell transplantation for non-hodgkin lymphoma: long-term outcomes. Biol Blood Marrow Transplant 2009; 15: 554–563.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kim SW, Tanimoto TE, Hirabayashi N, Goto S, Kami M, Yoshioka S et al. Myeloablative allogeneic hematopoietic stem cell transplantation for non-Hodgkin lymphoma: a nationwide survey in Japan. Blood 2006; 108: 382–389.

    Article  CAS  PubMed  Google Scholar 

  17. Papadopoulos EB, Carabasi MH, Castro-Malaspina H, Childs BH, Mackinnon S, Boulad F et al. T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood 1998; 91: 1083–1090.

    CAS  PubMed  Google Scholar 

  18. Jakubowski AA, Small TN, Young JW, Kernan NA, Castro-Malaspina H, Hsu KC et al. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood 2007; 110: 4552–4559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lister TA, Crowther D, Sutcliffe SB, Glatstein E, Canellos GP, Young RC et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7: 1630–1636.

    Article  CAS  PubMed  Google Scholar 

  20. Kernan NA, Flomenberg N, Collins NH, O’Reilly RJ, Dupont B . Quantitation of T lymphocytes in human bone marrow by a limiting dilution assay. Transplantation 1985; 40: 317–322.

    Article  CAS  PubMed  Google Scholar 

  21. Kernan NA, Bordignon C, Heller G, Cunningham I, Castro-Malaspina H, Shank B et al. Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I Analysis of risk factors and results of secondary transplants. Blood 1989; 74: 2227–2236.

    CAS  PubMed  Google Scholar 

  22. Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997; 97: 855–864.

    Article  CAS  PubMed  Google Scholar 

  23. Shipp MA, Harrington DP, Anderson JR, Armitage JO, Bonadonna G, Brittinger G et al. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 1993; 329: 987–994.

    Article  Google Scholar 

  24. Mantel N . Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50: 163–170.

    CAS  PubMed  Google Scholar 

  25. Ratanatharathorn V, Uberti J, Karanes C, Abella E, Lum LG, Momin F et al. 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 

  26. Schimmer AD, Jamal S, Messner H, Keating A, Meharchand J, Huebsch L et al. Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network, Canada. Bone Marrow Transplant 2000; 26: 859–864.

    Article  CAS  PubMed  Google Scholar 

  27. Peniket AJ, Ruiz de Elvira MC, Taghipour G, Cordonnier C, Gluckman E, de Witte T et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant 2003; 31: 667–678.

    Article  CAS  PubMed  Google Scholar 

  28. van Besien K, Loberiza Jr FR, Bajorunaite R, Armitage JO, Bashey A, Burns LJ et al. Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 2003; 102: 3521–3529.

    Article  CAS  PubMed  Google Scholar 

  29. Juckett M, Rowlings P, Hessner M, Keever-Taylor C, Burns W, Camitta B et al. 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  PubMed  Google Scholar 

  30. Soiffer RJ, Freedman AS, Neuberg D, Fisher DC, Alyea EP, Gribben J et al. CD6+ T cell-depleted allogeneic bone marrow transplantation for non-Hodgkin's lymphoma. Bone Marrow Transplant 1998; 21: 1177–1181.

    Article  CAS  PubMed  Google Scholar 

  31. Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, de Elvira CR et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 2002; 100: 4310–4316.

    Article  CAS  PubMed  Google Scholar 

  32. Kiss TL, Panzarella T, Messner HA, Meharchand J, Reddy V, Schimmer AD et al. Busulfan and cyclophosphamide as a preparative regimen for allogeneic blood and marrow transplantation in patients with non-Hodgkin's lymphoma. Bone Marrow Transplant 2003; 31: 73–78.

    Article  CAS  PubMed  Google Scholar 

  33. Dhedin N, Giraudier S, Gaulard P, Esperou H, Ifrah N, Michallet M et al. Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database. Societ Francaise de Greffe de Moelle. Br J Haematol 1999; 107: 154–161.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the expert care provided to these patients by the fellows, housestaff, and nurses of Memorial Sloan-Kettering Cancer Center. This work is supported in part by P01 CA23766.

Author information

Author notes

  1. A S Wilton

    Present address: 10Current address: Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.,

  2. T Kewalramani

    Present address: 11Current address: Lahey Clinic Medical Center, Burlington, MA 02421, USA.,

  3. J W Young and A A Jakubowski: These authors contributed equally to this work.

Authors and Affiliations

  1. Allogeneic Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    M-A Perales, R Jenq, J D Goldberg, S S E Lee, H R Castro-Malaspina, K Hsu, E B Papadopoulos, M R M van den Brink, F Boulad, N A Kernan, T N Small, M Chiu, R J O'Reilly, J W Young & A A Jakubowski

  2. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    M-A Perales, R Jenq, J D Goldberg, S S E Lee, H R Castro-Malaspina, K Hsu, E B Papadopoulos, M R M van den Brink, T Kewalramani, J W Young & A A Jakubowski

  3. Weill Medical College of Cornell University, New York, NY, USA

    M-A Perales, R Jenq, J D Goldberg, H R Castro-Malaspina, K Hsu, E B Papadopoulos, M R M van den Brink, F Boulad, N A Kernan, T N Small, S Wolden, R J O'Reilly, T Kewalramani, J W Young & A A Jakubowski

  4. Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    A S Wilton & G Heller

  5. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    F Boulad, N A Kernan, T N Small, M Chiu & R J O'Reilly

  6. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    S Wolden

  7. Departement of Clinical Laboratories,

    N H Collins

  8. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    N H Collins

  9. Hematology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    T Kewalramani

Authors
  1. M-A Perales
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Jenq
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J D Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A S Wilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S S E Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H R Castro-Malaspina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E B Papadopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M R M van den Brink
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F Boulad
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. N A Kernan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. T N Small
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S Wolden
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. N H Collins
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M Chiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. G Heller
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. R J O'Reilly
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. T Kewalramani
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. J W Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. A A Jakubowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M-A Perales.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perales, MA., Jenq, R., Goldberg, J. et al. Second-line age-adjusted International Prognostic Index in patients with advanced non-Hodgkin lymphoma after T-cell depleted allogeneic hematopoietic SCT. Bone Marrow Transplant 45, 1408–1416 (2010). https://doi.org/10.1038/bmt.2009.371

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.371

Keywords

This article is cited by

Search

Advanced search

Quick links