Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma

VG Potapenko1,2, NB Mikhailova1, BI Smirnov4, IA Skorokhod2, DA Chaginskaya2, VV Ryabchikova2, IA Samorodova2, EI Podol’tseva2, VV Ipatov3, IV Boikov3, VN Semelev3, DA Gornostaev3, TG Potapenko5, TG Kulibaba5, NV Medvedeva2, BV Afanas’ev1

1 Academician IP Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

2 Municipal Hematological Center, Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

3 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

4 VI Ul’yanov (Lenin) St. Petersburg State Electrotechnical University LETI, 5 Professora Popova str., Saint Petersburg, Russian Federation, 197376

5 St. Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Vsevolod Gennad’evich Potapenko, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)230-19-33; е-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Mikhailova NB, Smirnov BI, et al. Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma. Clinical oncohematology. 2016;9(4):406–12 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-406-412


ABSTRACT

Aim. To perform a comparative analysis of the prognostic significance of positron-emission tomography (PET) with other prognostic factors of the efficacy of high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with Hodgkin’s lymphoma.

Methods. Data on 84 patients with Hodgkin’s lymphoma receiving treatment over the period from October 2007 till November 2015 were analyzed. The median age was 26.6 years (range: 10–62). The median follow-up was 25 months (range: 1–81 months). The prognostic significance of sex, response to the initial chemotherapy, time to relapse, second-line chemotherapy regimen type, B-symptoms, tumor size (>5 cm in cases of relapse prior to the HDCT), serum LDH and albumin levels, CT findings, the number of chemotherapy lines, conditioning regimen before the auto-HSCT, and the metabolic activity before the HDCT (PET1, n = 82) and after auto-HSCT (PET2, n = 57) was analyzed.

Results. The two-year overall (OS) and event-free (EFS) survival rates were 70.6 % and 58.7%, respectively. Prognosis was the worst in patients with CT-confirmed lymphoma progression by the initiation of HDCT. In the presence of a CT-response, the PET status of lymphoma has a prognostic significance. The 2-year OS and EFS rates of PET1-negative and PET1-positive patients were 82 % vs. 62 % (= 0.056) and 74 % vs. 44 % (= 0.003), respectively. In PET2-negative and PET2-positive patients, the OS and EFS rates were 90 % vs. 65 % (= 0.013) and 72 % vs. 52 % (= 0.014), respectively. From the prognostic point of view, PET2 findings prevailed over PET1 findings. The multivariate analysis confirmed only PET2 significance for OS prediction.

Conclusion. The tumor sensitivity to the chemotherapy assessed by the CT is the most important prognostic factor. In case of a positive CT dynamics, the achievement of PET1 or PET2 negativity before or after HDCT/auto-HSCT is a favorable prognostic factor. The worst prognosis was observed in patients with tumor metabolic activity before or after HDCT/auto-HSCT.


Keywords: positron-emission tomography (PET), Hodgkin’s lymphoma, high-dose chemotherapy, auto-HSCT.

Received: June 23, 2016

Accepted: August 29, 2016

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REFERENCES

  1. Жуков Н.В., Румянцев А.Г., Усс А.Л. и др. Эффективность и безопасность высокодозной химиотерапии с аутологичной трансплантацией гемопоэтических стволовых клеток у больных с неблагоприятным течением лимфомы Ходжкина. Опыт трансплантационных центров России, Украины и республики Беларусь. Вопросы гематологии, онкологии и иммунопатологии в педиатрии. 2014;13(1): 22–31. [Zhukov NV, Rumyantsev AG, Uss AL, et al. Efficacy and safety of high-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with unfavorable course of Hodgkin’s lymphoma. Experience of transplantation centers in Russia, Ukraine, and Belarus. Voprosy gematologii, onkologii i immunopatologii v pediatrii. 2014;13(1):22–31. (In Russ)]
  2. Федоренко Д.А., Мельниченко В.Я., Ионова Т.И. и др. Клиническая оценка эффективности аутологичной трансплантации кроветворных стволовых клеток при лимфомах. Вестник Национального медико-хирургического центра им. Н.И. Пирогова. 2013;8(4):62–5. [Fedorenko DA, Mel’nichenko VYa, Ionova TI, et al. Clinical evaluation of efficacy of autologous hematopoietic stem cell transplantation in lymphomas. Vestnik Natsional’nogo mediko-khirurgicheskogo tsentra im. N.I. Pirogova. 2013;8(4):62–5. (In Russ)]
  3. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048–58. doi: 10.1200/jco.2013.53.5229.
  4. Асланиди И.П., Мухортова О.В., Шурупова И.В. и др. Позитронно-эмиссионная томография: уточнение стадии болезни при злокачественных лимфомах. Клиническая онкогематология. 2010;3(2):119–29. [Aslanidis IP, Mukhortova OV, Shurupova IV, et al. Positron emission tomography for staging of patients with malignant lymphomas. Klinicheskaya onkogematologiya. 2010;3(2):119–29. (In Russ)]
  5. Moskowitz СH, Yahalom J, Zelenetz AD. High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol. 2010;148(6):890–7. doi: 10.1111/j.1365-2141.2009.08037.x.
  6. Nieto Y, Popat U, Anderlini P, et al. Autologous stem cell transplantation for refractory or poor-risk relapsed Hodgkin’s lymphoma: effect of the specific high-dose chemotherapy regimen on outcome. Biol Blood Marrow Transplant. 2013;19(3):410–7. doi: 10.1016/j.bbmt.2012.10.029.
  7. Schot BW, Zijlstra JM, Sluiter WJ, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood. 2007;109(2):486–91. doi: 10.1182/blood-2005-11-006957.
  8. Spaepen K, Stroobants S, Dupont P, 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(1):53–9. doi: 10.1182/blood-2002-12-3842.
  9. Svoboda J, Andreadis C, Elstrom R, et al. Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant. 2006;38(3):211–6. doi: 10.1038/sj.bmt.1705416.
  10. Becherer A, Mitterbauer M, Jaeger U, et al. Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation. Leukemia. 2002;16(2):260–7. doi: 10.1038/sj.leu.2402342.
  11. Filmont JE, Czernin J, Yap C, 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(2):608–13. doi: 10.1378/chest.124.2.608.
  12. Devillier R, Coso D, Castagna L, et al. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy. Haematologica. 2012;97(7):1073–9. doi: 10.3324/haematol.2011.056051.
  13. Arai S, Letsinger R, Wong RM, et al. Phase I/II trial of GN-BVC, a gemcitabine and vinorelbine-containing conditioning regimen for autologous hematopoietic cell transplantation in recurrent and refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2010;16(8):1145–54. doi: 10.1016/j.bbmt.2010.02.022.
  14. Castagna L, Bramanti S, Balzarotti M, et al. Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy. Br J Haematol. 2009;145(3):369–72. doi: 10.1111/j.1365-2141.2009.07645.x.
  15. Akhtar S, Al-Sugair AS, Abouzied M, et al. Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high-dose chemotherapy and auto-SCT. Bone Marrow Transplant. 2013;48(12):1530–6. doi: 10.1038/bmt.2013.88.
  16. Crocchiolo R, Canevari C, Assanelli A, et al. Pre-transplant 18FDG-PET predicts outcome in lymphoma patients treated with high-dose sequential chemotherapy followed by autologous stem cell transplantation. Leuk Lymphoma. 2008;49(4):727–33. doi: 10.1080/10428190701885545.
  17. Gentzler RD, Evens AM, Rademaker AW, et al. F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Br J Haematol. 2014;165(6):793–800. doi: 10.1111/bjh.12824.
  18. Jabbour E, Hosing C, Ayers G, et al. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cancer. 2007;109(12):2481–9. doi: 10.1002/cncr.22714.
  19. Cohen JB, Hall NC, Ruppert AS, et al. Association of pre-transplantation positron emission tomography/computed tomography and outcome in mantle-cell lymphoma. Bone Marrow Transplant. 2013;48(9):1212–7. doi: 10.1038/bmt.2013.46.
  20. Dickinson M, Hoyt R, Roberts AW, et al. Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre-transplant FDG-PET scan following salvage chemotherapy. Br J Haematol. 2010;150(1):39–45. doi: 10.1111/j.1365-2141.2010.08162.x.
  21. Palmer J, Goggins T, Broadwater G, et al. Early post transplant (F-18) 2-fluoro-2-deoxyglucose positron emission tomography does not predict outcome for patients undergoing auto-SCT in non-Hodgkin and Hodgkin lymphoma. Bone Marrow Transplant. 2011;46(6):847–51. doi: 10.1038/bmt.2010.203.
  22. Alousi AM, Saliba RM, Okoroji GJ, et al. Disease staging with positron emission tomography or gallium scanning and use of rituximab predict outcome for patients with diffuse large B-cell lymphoma treated with autologous stem cell transplantation. Br J Haematol. 2008;142(5):786–92. doi: 10.1111/j.1365-2141.2008.07277.x.
  23. Bondly C, Johnston PB, Lowe V, et al. Positive positron emission tomography (PET) pre-autologous stem cell transplant (ASCT) in non-Hodgkin lymphoma (NHL) does not preclude successful outcome. Biol Blood Marrow Transplant. 2006;12(2):18–9. doi: 10.1016/j.bbmt.2005.11.060.
  24. Qiao W, Zhao J, Xing Y. Predictive value of [18F]fluoro-2-deoxy-D-glucose positron emission tomography for clinical outcome in patients with relapsed/refractory diffuse large B-cell lymphoma prior to and after autologous stem cell transplant. Leuk Lymphoma. 2014;55(2):276–82. doi: 10.3109/10428194.2013.797974.
  25. Sucak GT, Ozkurt ZN, Suyani E, et al. Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival. Ann Hematol. 2011;90(11):1329–36. doi: 10.1007/s00277-011-1209-0.
  26. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  27. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–86. doi: 10.1200/jco.2006.09.2403.
  28. David G, Kleinbaum MK. Survival Analysis. A Self-Learning Text. 2nd edition. Springer; 2002. рр. 583. doi: 10.1111/j.1541-0420.2006.00540_18.x.
  29. Петрова Г.Д., Мелкова К.Н., Чернявская Т.З. и др. Первично-рефрактерное течение лимфомы Ходжкина и аутологичная трансплантация гемопоэтических стволовых клеток. Результаты одноцентрового проспективного исследования. Российский онкологический журнал. 2015;20(3):4–11. [Petrova GD, Melkova KN, Chernyavskaya TZ, et al. Primary refractory Hodgkin’s lymphoma and autologous stem cell transplantation: results of the single-center prospective study. Rossiiskii onkologicheskii zhurnal. 2015;20(3):4–11. (In Russ)]
  30. Crocchiolo R, Fallanca F, Giovacchini G, et al. Role of 18FDG-PET/CT in detecting relapse during follow-up of patients with Hodgkin’s lymphoma. Ann Hematol. 2009;88(12):1229–36. doi: 10.1007/s00277-009-0752-4.
  31. Gupta D, Lis ChG. Pretreatment Serum Albumin as a Predictor of Cancer Survival: A Systematic Review of the Epidemiological Literature. Nutrition J. 2010;9(1):69–116. doi: 10.1186/1475-2891-9-69.
  32. Демина Е.А. Лимфома Ходжкина: прогностические признаки сегодня. Современная онкология. 2006;4:4–7. [Demina EA. Hodgkin’s lymphoma: prognostic factors today. Sovremennaya onkologiya. 2006;4:4–7. (In Russ)]
  33. Czyz A, Lojko-Dankowska A, Dytfeld D, et al. Prognostic factors and long-term outcome of autologous haematopoietic stem cell transplantation following a uniform-modified BEAM-conditioning regimen for patients with refractory or relapsed Hodgkin lymphoma: a single-center experience. Med Oncol. 2013;30(3):611. doi: 10.1007/s12032-013-0611-y.
  34. Villa D, Seshadri T, Puig N, et al. Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin’s lymphoma resistant to platinum-containing first-line salvage chemotherapy. Haematologica. 2012;97(5):751–7. doi: 10.3324/haematol.2011.047670.
  35. Colpo A, Hochberg E, Chen YB. Current status of autologous stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma. Oncologist. 2012;17(1):80–90. doi: 10.1634/theoncologist.2011-0177.