Prognostic impact of pre-transplantation computed tomography and 67gallium scanning in chemosensitive diffuse large B cell lymphoma patients undergoing hematopoietic stem-cell transplantation

  • Ignacio G. Escobar
  • Pilar T. Alonso
  • Dolores C. Barrigon
  • Jose A. Perez-Simon
  • Maria V. Mateos Manteca
  • Jesus F. San Miguel Izquierdo
Original Article



In the present study, we evaluated computed tomography (CT) and 67gallium scanning (67Ga scan) pre-transplant as prognostic factors for overall survival (OS) and event-free survival (EFS) in patients with diffuse large B cell lymphoma, undergoing high-dose chemotherapy and stem-cell transplantation.

Patients and methods

Forty-two patients were included. Of these, 9 (21%) had both positive CT and 67Ga scans, 17 (41%) negative results with both techniques, and 16 (38%) positive CT/negative 67Ga scan. Whole-body planar imaging and single-photon emission computed tomography (SPECT) were performed 72 h after an intravenous administration of 67Ga citrate measuring between 7 mCi and 10 mCi (259–370 MBq).


Patients with positive CT/positive 67Ga scan had a significantly worse EFS and OS at 5 years than those with negative 67Ga scan regardless of whether it was associated with a positive or a negative CT scan (29% and 16% vs. 81% and 93% vs. 88% and 100%, respectively, P < 0.001). After a median follow-up of 43 months (range 4–130 months), no differences were observed between patients with negative CT/negative 67Ga scan and those with positive CT/negative 67Ga scan, with an EFS and OS at 5 years of 88% versus 81% and 100% versus 93%, respectively. In multivariate analysis, the presence of a pre-transplant positive CT/67Ga scans adversely influenced both EFS and OS [HR 8, 95% confidence interval (CI) (1.4–38), P = 0.03 and HR 2; 95% CI (1.3–8), P = 0.02, respectively].


67Ga scan helps to identify, in the pre-transplant evaluation, two groups with a different outcome: one group of patients with positive CT and negative 67Ga scans pre-transplant, who showed a favorable outcome with a low rate of relapse, and the other group of patients with both positive CT and 67Ga scans pre-transplant, who showed a poor prognosis and did not benefit from autologous stem-cell transplantation. They should have been offered other therapeutic strategies.


Chemosensitive diffuse large B cell lymphoma Hematopoietic stem-cell transplantation Prognostic factors CT and 67Ga scan 


  1. 1.
    De Vita VT Jr, Canellos GP, Chapner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma: a potentially curable disease. Lancet 1975;1:248–250.Google Scholar
  2. 2.
    Armitage JO. Drug therapy: treatment of non-Hodgkin’s lymphoma. N Engl J Med 1993;328:1023–1030.PubMedCrossRefGoogle Scholar
  3. 3.
    Fisher RI, Gainor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 1993;328:1002–1006.PubMedCrossRefGoogle Scholar
  4. 4.
    Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M, et al. International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin’s lymphomas: report of the jury (review). J Clin Oncol 1999;17:423–429.PubMedGoogle Scholar
  5. 5.
    Bosly A, Coiffier B, Gisselbrecht C, Tilly H, Auzanneau G, Adrien F, et al. Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients with LNH-84 regimen. J Clin Oncol 1992;10:1615–1623.PubMedGoogle Scholar
  6. 6.
    Vose JM, Anderson JR, Kessinger A, Bierman PJ, Coccia P, Reed EC, et al. High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin’s lymphoma. J Clin Oncol 1993;11:1846–1851.PubMedGoogle Scholar
  7. 7.
    Rahmouni A, Tempany C, Jones R, Mann R, Yang A, Zerhouni E. Lymphoma: monitoring tumor size and signal intensity with MR imaging. Radiology 1993;188:445–451.PubMedGoogle Scholar
  8. 8.
    Vose JM, Bierman PJ, Anderson JR, Harrison KA, Dalrymple GV, Byar K, et al. Single-photon emission computed tomography gallium imaging versus computed tomography: predictive value in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin’s lymphoma. J Clin Oncol 1996;14:2473–2479.PubMedGoogle Scholar
  9. 9.
    Anderson KC, Leonard RCF, Canellos GP, Skarin AT, Kaplan WD. High-dose gallium imaging in lymphoma. Am J Med 1983;75:327–331.PubMedCrossRefGoogle Scholar
  10. 10.
    Kaplan WD, Jochelson MS, Herman TS, Nadler LM, Stomper PC, Takvorian T, et al. Gallium-67 imaging: a predictor of residual tumor viability and clinical outcome of patients with diffuse large-cell lymphoma. J Clin Oncol 1990;8:1966–1970.PubMedGoogle Scholar
  11. 11.
    Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 1999;17:1244–1253.PubMedGoogle Scholar
  12. 12.
    Martín A, Pérez-Simón J-A, Caballero MD, Lopez N, García-Sanz R, Vázquez L, et al. Effect of cumulative etoposide doses on the outcome of autologous peripheral-blood progenitorcell transplantation for lymphoma. Bone Marrow Transplant 2004;33:579–587.PubMedCrossRefGoogle Scholar
  13. 13.
    Bar-Shalom R, Israel O, Haim N, Leviov M, Epelbaum R, Frenkel A, et al. Diffuse lung uptake of 67Ga after treatment of lymphoma: is it of clinical importance. Radiology 1996;199:473–476.PubMedGoogle Scholar
  14. 14.
    Even-Sapir E, Bar-Shalom R, Israel O, Frenkel A, Iosilevsky G, Haim N, et al. Single-photon emission computed tomography quantitation of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake. J Clin Oncol 1995;13:942–946.PubMedGoogle Scholar
  15. 15.
    Sureda A, Arranz R, Iriondo A, Carreras E, Lahuerta JJ, García-Conde J, et al. Autologous stem-cell transplantation for Hodgkin’s disease: results and prognostic factors in 494 patients from the Grupo Español de LInfomas/Trasplante Autólogo de Médula Ósea Spanish Cooperative Group. J Clin Oncol 2001;19:1395–1404.PubMedGoogle Scholar
  16. 16.
    Vose JM, Zhang MJ, Rowlings PA, Lazarus HM, Bolwell BJ, Freytes CO, et al. Autologous transplantation for diffuse aggressive non-Hodgkin’s lymphoma in patients never achieving remission: a report from the Autologus Blood and Marrow Transplant Registry. J Clin Oncol 2001;19:406–413.PubMedGoogle Scholar
  17. 17.
    Vose JM, Anderson JR, Kessinger A, Bierman PJ, Coccia P, Reed EC, et al. High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin’s lymphoma. J Clin Oncol 1993;11:1846–1851.PubMedGoogle Scholar
  18. 18.
    Vose JM, Sharp G, Chan WC, Nichols C, Loh K, Inwards D, et al. Autologous transplantation for aggressive non-Hodgkin’s lymphoma: results of a randomized trial evaluating graft source and minimal residual disease. J Clin Oncol 2002;20:2344–2352.PubMedCrossRefGoogle Scholar
  19. 19.
    Chen CI, Roitman D, Tsang R, Stewart AK, Keating A, Crump M. “Relative” chemotherapy sensitivity: the impact of number of salvage regimens prior to autologous stem cell transplant for relapsed and refractory aggressive non-Hodgkin’s lymphoma. Bone Marrow Transplant 2002;30:885–891.PubMedCrossRefGoogle Scholar
  20. 20.
    De Kreuk M, Ossenkoppele GJ, Meijer CJ, Huijgens PC. Prognostic factors for survival of non-Hodgkin’s lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation. Bone Marrow Transplant 1996;17:963–971.PubMedGoogle Scholar
  21. 21.
    Caballero MD, Perez-Simon JA, Iriondo A, Lahuerta JJ, Sierra J, Marín J, et al. High-dose therapy in diffuse large cell lymphoma: results and prognostic factors in 452 patients from the GEL-TAMO Spanish Cooperative Group. Ann Oncol 2003;14:140–151.PubMedCrossRefGoogle Scholar
  22. 22.
    Mills W, Chopra R, McMillan A, Pearce R, Linch DC, Goldstone AH. BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin’s lymphoma. J Clin Oncol 1995;13:588–595.PubMedGoogle Scholar
  23. 23.
    Prince HM, Imrie K, Crump M, Stewart AK, Girouard C, Colwill R, et al. The role of intensive therapy and autologous blood and marrow transplantation for chemotherapy-sensitive relapsed and primary refractory non-Hodgkin’s lymphoma: identification of major prognostic groups. Br J Haematol 1996;92:880–889.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    Caballero MD, Rubio V, Rifon J, Heras I, García-Sanz R, Vázquez L, et al. BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Bone Marrow Transplant 1997;20:451–458.PubMedCrossRefGoogle Scholar
  26. 26.
    Hamlin PA, Zelenetz AD, Kewalramani T, Quin 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Kewalramani T, Zelenetz AD, Hendrick 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.PubMedGoogle Scholar
  28. 28.
    Moskowitz CH, Nimer SD, Glassman JR, Portlock CS, Yahalom J, Straus DJ, et al. The International Prognostic Index predicts outcome following autologous stem cell transplantation in patients with relapsed and primary refractory intermediate-grade lymphoma. Bone Marrow Transplant 1999;23:561–567.PubMedCrossRefGoogle Scholar
  29. 29.
    Front D, Bar-Shalom R, Mor M, Haim N, Epelbaum R, Frankel A, et al. Aggressive non-Hodgkin lymphoma: early prediction of outcome with 67Ga scintigraphy. Radiology 2000;214:253–257.PubMedGoogle Scholar
  30. 30.
    Israel O, Mor M, Epelbaum R, Frenkel A, Haim N, Dann EJ, et al. Clinical pretreatment risk factors and Ga-67 scintigraphy early during treatment for prediction of outcome of patients with aggressive non-Hodgkin lymphoma. Cancer 2002;94:873–878.PubMedCrossRefGoogle Scholar
  31. 31.
    Escobar IG, Caballero Barrigón MD, Alonso PT, Pérez-Simón JA, Mateos MV, García JR, et al. Prognostic impact of pre-transplant computed tomography and gallium scan in poor prognosis Hodgkin’s lymphoma patients undergoing hematopoietic stem-cell transplantation. Clin Lymphoma Myeloma 2006;6:217–225.Google Scholar
  32. 32.
    Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin’s disease. J Nucl Med 2002;43:1018–1027.PubMedGoogle Scholar
  33. 33.
    Haioun C, Itti E, Rahmouni A, Brice P, Rain JD, Belhadj K, et al. [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood 2005;106:1376–1381.PubMedCrossRefGoogle Scholar
  34. 34.
    Hutchings M, Loft A, Hansen M, Pedersen L, Buhl T, Jurlander J, et al. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 2006;107:52–59.PubMedCrossRefGoogle Scholar
  35. 35.
    Kostakoglu L, Goldsmith SJ, Leonard JP, Christos P, Furman RR, Atasever T, et al. FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease. Cáncer 2006;107:2678–2687.PubMedCrossRefGoogle Scholar
  36. 36.
    Schot BW, Zijlstra JM, Stuiter WJ, van Imhoff GW, Pruim J, Vaalburg W, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood 2007;109:486–491.PubMedCrossRefGoogle Scholar
  37. 37.
    Bar-Shalom R, Yefremov N, Haim N, Dann EJ, Epelbaum R, Keidar Z, et al. Camera-based FDG PET and 67Ga SPECT in evaluation of lymphoma: comparative study. Radiology 2003;227:353–360.PubMedCrossRefGoogle Scholar
  38. 38.
    Yamamoto F, Tsukamoto E, Nakada K, Takei T, Zhao S, Asaka M, et al. 18F-FDG PET is superior to 67Ga SPECT in the staging of non-Hodgkin’s lymphoma. Ann Nucl Med 2004;18:519–526.PubMedCrossRefGoogle Scholar
  39. 39.
    Mody RJ, Bui C, Hutchinson RJ, Fray KA, Shulkin BL. Comparison of (18) F fluorodeoxyglucose PET with Ga-67 scintigraphy and conventional imaging modalities in pediatric lymphoma. Leuk Lymphoma 2007;48:699–707.PubMedCrossRefGoogle Scholar
  40. 40.
    Fruchart C, Reman O, Le Stang N, Musafiri D, Cheze S, Macro M, et al. Prognostic value of early 18 fluorodeoxyglucose positron emission tomography and gallium scintigraphy in aggressive lymphoma: a prospective comparative study. Leuk Lymphoma 2006;47:2547–2557.PubMedCrossRefGoogle Scholar
  41. 41.
    Cremerius U, Fabry U, Wildberger JE, Zimny M, Reinartz P, Nowak B, et al. Pre-transplant positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose (FDG) predicts outcome in patients treated with high-dose chemotherapy and autologous stem cell transplantation for non-Hodgkin’s lymphoma. Bone Marrow Transplant 2002;30:103–111.PubMedCrossRefGoogle Scholar
  42. 42.
    Filmont JE, Czernin J, Yap C, Silverman DH, Quon A, Phelps ME, et al. Value of F-18 fluorodeoxyglucose positron emission tomography for predicting the clinical outcome of patients with aggressive lymphoma prior to and after autologous stem-cell transplantation. Chest 2003;124:608–613.PubMedCrossRefGoogle Scholar
  43. 43.
    Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Maertens J, Bormans G, et al. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood 2003;102:53–59.PubMedCrossRefGoogle Scholar
  44. 44.
    Svoboda J, Andreadis C, Elstrom R, Chong EA, Downs LH, Berkowitz A, et al. Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant 2006;38:211–216.PubMedCrossRefGoogle Scholar
  45. 45.
    Jabbour E, Hosing C, Ayers G, Nuñez R, Anderlini P, Pro B, et al. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cáncer 2007;109:2481–2489.PubMedCrossRefGoogle Scholar
  46. 46.
    Chajari M, Lacroix J, Peny AM, Chesnay E, Batalla A, Henry-Amar M, et al. Gallium-67 scintigraphy in lymphoma: is there a benefit of image fusion with computed tomography? Eur J Nucl Med Mol Imaging 2002;29:380–387.PubMedCrossRefGoogle Scholar
  47. 47.
    Allen-Auerbach M, Quon A, Weber WA, Obrzut S, Crawford T, Silverman DH, et al. Comparison between 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography and positron emission tomography/computed tomography hardware fusion for staging of patients with lymphoma. Mol Imaging Biol 2004;6:411–416.PubMedCrossRefGoogle Scholar
  48. 48.
    Raanani P, Shasha Y, Perry C, Metser U, Naparstek E, Apter S, et al. Is CT scan still necessary for staging in Hodgkin and non-Hodgkin lymphoma pa tients in the PET/CT era? Ann Oncol 2006;17:117–122.PubMedCrossRefGoogle Scholar
  49. 49.
    Juweid ME, Wiseman GA, Vose JM, Ritchie JM, Menda Y, Wooldridge JE, et al. Response assessment of aggressive non-Hodgkin’s lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography. J Clin Oncol 2005;23:4652–4661.PubMedCrossRefGoogle Scholar
  50. 50.
    Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittiee of International Harmonization Project in Lymphoma. J Clin Oncol 2007;25:571–578.PubMedCrossRefGoogle Scholar
  51. 51.
    Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579–586.PubMedCrossRefGoogle Scholar
  52. 52.
    Even Sapir E, Israel O. Gallium-67 scintigraphy: a cornerstone in functional imaging of lymphoma (review). Eur J Nucl Med Mol Imaging 2003;30Suppl 1:S65–S81.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2008

Authors and Affiliations

  • Ignacio G. Escobar
    • 1
  • Pilar T. Alonso
    • 2
  • Dolores C. Barrigon
    • 1
  • Jose A. Perez-Simon
    • 1
  • Maria V. Mateos Manteca
    • 1
  • Jesus F. San Miguel Izquierdo
    • 1
  1. 1.Department of HematologyUniversity Clínic Hospital of SalamancaSalamancaSpain
  2. 2.Department of Nuclear MedicineUniversity Clinic Hospital of SalamancaSalamancaSpain

Personalised recommendations