conditioning regimen

Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

LYMPHOID TUMORS , , , ,

SV Gritsaev1, II Kostroma1, AA Zhernyakova1, IM Zapreeva1, EV Karyagina2, ZhV Chubukina1, SA Tiranova1, IS Martynkevich1, SS Bessmeltsev1, AV Chechetkin1

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA, et al. Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2019;12(3):282–8 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-282-288

ABSTRACT

Background. In multiple myeloma (MM) treatment a single autologous hematopoietic stem cell transplantation (auto-HSCT) is preceded by conditioning regimens aimed at intensifying cytoreductive effect. In the course of ongoing search for combined conditioning regimens an attractive option proved to be thiotepa/melphalan combination.

Aim. Data analysis of a pilot study of the efficacy of conditioning regimens including administration of two alkylating agents (thiotepa and melphalan) with subsequent auto-HSCT.

Materials & Methods. 9 patients received 10 auto-HSCTs with conditioning regimen including administration of 250 mg/m2 of thiotepa on Day –5 and 140 mg/m2 of melphalan on Day –2. After auto-HSCT pegylated filgrastim was administered in 8 patients. Engraftment period was calculated on the basis of absolute neutrophil count ≥ 0,5 × 109/L and thrombocyte level ≥ 20 × 109/L. Regimen toxicity was assessed according to CTCAE v5.0. Survival rates were estimated by Kaplan-Meier curves.

Results. The use of thiotepa did not require administration of any additional drugs. The incidence of mucositis and enteropathy of grade 1–2 was 100 % and 70 %, respectively. Pyrexia was reported in 7 auto-HSCTs. Pneumonia occurred in 1 patient. The infusion of 1–3 doses of platelet concentrate (median of 2 doses) was required in all patients except for one. Donor erythrocytes were transfused to 3 patients. Engraftment was reported in all patients within the period of 10–14 days. Median hospitalization duration from Day 0 to hospital discharge was 16 patient-days. After auto-HSCT the quality of response improved in 6 out of 9 patients. MM progression was reported in one patient with complex karyotype. Further follow-up showed progression in 2 patients. By December 2018 median follow-up of 9 patients from the date of auto-HSCT was 9 months (range 3–20 months), median progression-free survival was 17 months, median overall survival was not reached.

Conclusion. Acceptable toxicity, improvement of response quality, and maintenance of it for up to 20 months allow to consider combined conditioning regimen Thio/Mel to be a possible alternative to the standard Mel200 regimen.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, conditioning regimen, thiotepa, melphalan.

Received: December 26, 2018

Accepted: May 25, 2019

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REFERENCES

  1. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: СИМК, 2016. 512 с.

    [Bessmeltsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: SIMK Publ.; 2016. 512 p. (In Russ)]

  2. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24.

    [Mendeleeva LP, Votyakova OM, Pokrovskaya OS, et al. National clinical guidelines on diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24. (In Russ)]

  3. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60. doi: 10.1056/NEJMra1011442.

  4. Cavo M, Rajkumar SV, Palumbo A, et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. 2011;117(23):6063–73. doi: 10.1182/blood-2011-02-297325.

  5. Engelhardt M, Terpos E, Kleber M, et al. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica. 2014;99(2):232–42. doi: 10.3324/haematol.2013.099358.

  6. Sidiqi MH, Aljama MA, Bin Riaz I, et al. Bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplant for multiple myeloma. Blood Cancer J. 2018;8(8):106. doi: 10.1038/s41408-018-0147-7.

  7. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311–20. doi: 10.1056/NEJMoa1611750.

  8. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996;335(2):91–7.

  9. Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905. doi: 10.1056/NEJMoa1402888.

  10. Thoennissen GB, Gorlich D, Bacher U, et al. Autologous stem cell transplantation in multiple myeloma in the era of novel drug induction: a retrospective single-center analysis. Acta Haematol. 2017;137(3):163–72. doi: 10.1159/000463534.

  11. Ozaki S, Harada T, Saitoh T, et al. Survival of multiple myeloma patients aged 65–70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network. Acta Haematol. 2014;132(2):211–9. doi: 10.1159/000357394.

  12. Cavo M, Salwender H, Rosinol L, et al. Double vs single autologous stem cell transplantation after bortezomib-based induction regimens for multiple myeloma: an integrated analysis of patient-level data from phase III European studies. Blood. 2013;122(21):767.

  13. Cavo M, Beksac M, Dimopoulos M, et al. Intensification therapy with bortezomib-melphalan-prednisone versus autologous stem cell transplantation for newly diagnosed multiple myeloma: an intergroup, multicenter, phase III study of the European Myeloma Network (EMN02/HO95 MM trial). 2016;128(22):673.

  14. Sonneveld P, Beksac M, van der Holt B, et al. Consolidation followed by maintenance therapy versus maintenance alone in newly diagnosed, transplant eligible patients with multiple myeloma (MM): a randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM Trial). 2016;128(22):242.

  15. Stadtmauer EA, Pasquini MC, Blackwell B, et al. Comparison of autologous hematopoietic cell transplant (autoHCT), bortezomib, lenalidomide and dexamethasone (RVD) consolidation with lenalidomide maintenance (ACM), tandem autoHCT with lenalidomide maintenance (TAM), and autoHCT with lenalidomide maintenance (AM) for upfront treatment of patients with multiple myeloma (MM): primary results from the randomized phase III trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 – StaMINA Trial). 2016;128(22):LBA-1.

  16. Yhim HY, Kim K, Kim JS, et al. Matched-pair analysis to compare the outcomes of a second salvage auto-SCT to systemic chemotherapy alone in patients with multiple myeloma who relapsed after front-line auto-SCT. Bone Marrow Transplant. 2013;48(3):425–32. doi: 10.1038/bmt.2012.164.

  17. Olin RL, Vogl DT, Porter DL, et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transplant. 2009;43(5): 417–22. doi: 10.1038/bmt.2008.334.

  18. Abbi KKS, Zheng J, Devlin SM, et al. Second autologous stem cell transplant: an effective therapy for relapsed multiple myeloma. Biol Blood Marrow Transplant. 2015;21(3):468–72. doi: 10.1016/j.bbmt.2014.11.677.

  19. Cook G, Williams C, Brown JM, et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(8):874–85. doi: 10.1016/S1470-2045(14)70245-1.

  20. Benson DM, Panzner K, Hamadani M, et al. Effects of induction with novel agents versus conventional chemotherapy on mobilization and autologous stem cell transplant outcomes in multiple myeloma. Leuk Lymphoma. 2010;51(2):243–51. doi: 10.3109/10428190903480728.

  21. Kumar SK, Lacy MQ, Dispenzieri A, et al. Early versus delayed autologous transplantation following IMiD-based induction therapy in patients with newly diagnosed multiple myeloma. Cancer. 2012;118(6):1585–92. doi: 10.1002/cncr.26422.

  22. Ashcroft J, Judge D, Dhanasiri S, et al. Chart review across EU5 in MM post-ASCT patients. Int J Hematol Oncol. 2018;7(1):IJH05. doi: 10.2217/ijh-2018-0004.

  23. McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35(29):3279–89. doi: 10.1200/JCO.2017.72.6679.

  24. Kumar S, Lacy MQ, Dispenzieri A, et al. High-dose therapy and autologous stem cell transplantation for multiple myeloma poorly responsive to initial therapy. Bone Marrow Transplant. 2004;34(2):161–7. doi: 10.1038/sj.bmt.1704545.

  25. Kim JS, Kim K, Cheong JW, et al. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation. Biol Blood Marrow Transplant. 2009;15(4):463–70. doi: 10.1016/j.bbmt.2008.12.512.

  26. Gertz MA, Kumar S, Lacy MQ, et al. Stem cell transplantation in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction. Blood. 2010;115(12):2348–53. doi: 10.1182/blood-2009-07-235531.

  27. Грицаев С.В., Кузяева А.А., Бессмельцев С.С. Отдельные аспекты аутологичной трансплантации гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2017;10(1):7–12. doi: 21320/2500-2139-2017-10-1-7-12.

    [Gritsaev SV, Kuzyaeva AA, Bessmeltsev SS. Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma. Clinical oncohematology. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12. (In Russ)]

  28. Musso M, Messina G, Marcacci G, et al. High-dose melphalan plus thiotepa as conditioning regimen before second autologous stem cell transplantation for “de novo” multiple myeloma patients: a phase II study. Biol Blood Marrow Transplant. 2015;21(11):1932–8. doi: 10.1016/j.bbmt.2015.06.011.

  29. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328–46. doi: 10.1016/S1470-2045(16)30206-6.

  30. Schiffman KS, Bensinger WI, Appelbaum FR, et al. Phase II study of high-dose busulfan, melphalan and thiotepa with autologous peripheral blood stem cell support in patients with malignant disease. Bone Marrow Transplant. 1996;17(6):943–50.

  31. Zaid AB, Abdul-Hai A, Grotto I, et al. Autologous transplant in multiple myeloma with an augmented conditioning protocol. Leuk Lymphoma. 2013;54(11):2480–4. doi: 10.3109/10428194.2013.782608.

  32. Anagnostopoulos A, Aleman A, Ayers G, et al. Comparison of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma. Cancer. 2004;100(12):2607–12. doi: 10.1002/cncr.20294.

  33. Hari P, Reece DE, Randhawa J, et al. Final outcomes of escalated melphalan 280 mg/m2 with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival. Bone Marrow Transplant. 2019;54(2):293–9. doi: 10.1038/s41409-018-0261-y.

  34. Auner HW, Iacobelli S, Sbianchi G, et al. Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma: results from the collaboration to collect autologous transplant outcomes in lymphoma and myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party. Haematologica. 2018;103(3):514–21. doi: 10.3324/haematol.2017.181339.

  35. Dimopoulos M, Wang M, Maisnar V, et al. Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study. J Hematol Oncol. 2018;11(1):49. doi: 10.1186/s13045-018-0583-7.

  36. Costa LJ, Landau HJ, Chhabra S, et al. Phase 1/2 trial of carfilzomib plus high-dose melphalan preparative regimen for salvage autologous hematopoietic cell transplantation followed by maintenance carfilzomib in patients with relapsed/refractory multiple myeloma. Biol Blood Marrow Transplant. 2018;24(7):1379–85. doi: 10.1016/j.bbmt.2018.01.036.

Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

REVIEWS , , ,

SV Gritsaev, AA Kuzyaeva, SS Bessmel’tsev

Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Sergei Vasil’evich Gritsaev, DSci, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel: +7(812)717-58-57; e-mail: gritsaevsv@mail.ru

For citation: Gritsaev SV, Kuzyaeva AA, Bessmel’tsev SS. Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma. Clinical oncohematology. 2017;10(1):7–12 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-7-12

ABSTRACT

The review dwells on certain problems of mobilization and conditioning regimens, as well as autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma. The aim of the review is to determine new approaches to improve the effectiveness of the auto-HSCT.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, mobilization regimen, conditioning regimen.

Received: July 13, 2016

Accepted: November 12, 2016

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REFERENCES

  1. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: МК, 2016. 504 с.
    [Bessmel’tsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: MK Publ.; 2016. 504 p. (In Russ)]
  2. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2014;1(Приложение № 3):1–24.
    [Mendeleeva LP, Votyakova OM, Pokrovskaya OS, et al. National guidelines for diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2014;1(Suppl 3):1–24. (In Russ)]
  3. Reece DE. Management of multiple myeloma: The changing landscape. Blood Rev. 2007;21(6):301–14. doi: 10.1016/j.blre.2007.07.001.
  4. Cavo M, Tosi P, Zamagni E, et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol. 2007;25(17):2434–41. doi: 10.1200/jco.2006.10.2509.
  5. Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349(26):2495–502. doi: 10.1056/nejmoa032290.
  6. Allan DS, Keeney M, Howson-Jan K, et al. Number of viable CD34(+) cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation. Bone Marrow Transplant. 2002;29(12):967–72. doi: 10.1038/sj.bmt.1703575.
  7. Michaelis LC, Saad A, Zhong X, et al. Salvage second hematopoietic cell transplantation in myeloma. Biol Blood Marrow Transplant. 2013;19(5):760–6. doi: 10.1016/j.bbmt.2013.01.004.
  8. Cook G, Williams C, Brown JM, et al. High dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(14):874–85. doi: 10.1016/s1470-2045(14)70245-1.
  9. Musto P, Simeon V, Grossi A, et al. Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie Ematologiche dell’Adulto Multiple Myeloma Working Party study. Stem Cell Res Ther. 2015;6:64. doi: 10.1186/s13287-015-0033-1.
  10. Olivieri A, Marchetti M, Lemoli R, et al. Proposed definition of “poor mobilizer” in lymphoma and multiple myeloma: an analytic hierarchy process by ad hoc working group Gruppo ItalianoTrapianto di Midollo Osseo. Bone Marrow Transplant. 2012;47(3):342–51. doi: 10.1038/bmt.2011.82.
  11. To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. Blood. 2011;118(17):4530–40. doi: 10.1182/blood-2011-06-318220.
  12. Gertz MA. Current status of stem cell mobilization. Br J Haematol. 2010;150(6):647–62. doi: 10.1111/j.1365-2141.2010.08313.x.
  13. Popat U, Saliba R, Thandi R, et al. Impairment of filgrastim induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant. 2009;15(6):718–23. doi: 10.1016/j.bbmt.2009.02.011.
  14. Mazumder A, Kaufman J., Niesvizky R, et al. Effect of lenalidomide therapy on mobilization of peripheral blood stem cells in previously untreated multiple myeloma patients (letter). Leukemia. 2008;22(60):1280–1. doi: 10.1038/sj.leu.2405035.
  15. Giralt S, Costa L, Schriber J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant. 2014;20(3):295–308. doi: 10.1016/j.bbmt.2013.10.013.
  16. Duong HK, Savani BN, Copelan E, et al. Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2014;20(9):1262–73. doi: 10.1016/j.bbmt.2014.05.003.
  17. Sung AD, Grima DT, Bernard LM, et al. Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone. Bone Marrow Transplant. 2013;48(11):1444–9. doi: 10.1038/bmt.2013.80.
  18. Gertz MA, Kumar SK, Lacy MQ, et al. Comparison of high-dose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma. Bone Marrow Transplant. 2009;43(8):619–25. doi: 10.1038/bmt.2008.369.
  19. Arora M, Burns LJ, Barker JN, et al. Randomized comparison of granulocyte colony-stimulating factor versus granulocyte-macrophage colony-stimulating factor plus intensive chemotherapy for peripheral blood stem cell mobilization and autologous transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2004;10(6):395–404. doi: 10.1016/s1083-8791(04)00068-0.
  20. Nakasone H, Kanda Y, Ueda T, et al. Retrospective comparison of mobilization methods for autologous stem cell transplantation in multiple myeloma. Am J Hematol. 2009;84(12):809–14. doi: 10.1002/ajh.21552.
  21. Mark T, Stern J, Furst JR, et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant. 2008;14(7):795–8. doi: 10.1016/j.bbmt.2008.04.008.
  22. Costa LJ, Miller AN, Alexander ET, et al. Growth factor and patient-adapted use of plerixafor is superior to CY and growth factor for autologous hematopoietic stem cells mobilization. Bone Marrow Transplant. 2011;46(4):523–8. doi: 10.1038/bmt.2010.170.
  23. DiPersio J., Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113(23):5720–6. doi: 10.1182/blood-2008-08-174946.
  24. Покровская О.С. Механизм действия и клиническая эффективность антагониста хемокинового рецептора CXCR4 плериксафора при мобилизации гемопоэтических стволовых клеток. Клиническая онкогематология. 2012;5(4):371–9.
    [Pokrovskaya OS. Mechanism of action and clinical activity of CXCR4 antagonist Plerixafor in stem cell mobilization. Klinicheskaya onkogematologiya. 2012;5(4):371–9. (In Russ)]
  25. Кучер М.А., Моталкина М.С., Климова О.У. и др. Плериксафор у пациентов со сниженной мобилизационной способностью аутологичных гемопоэтических стволовых клеток. Клиническая онкогематология. 2016;9(2):155–61. doi: 10.21320/2500-2139-2016-9-2-155-61.
    [Kucher MA, Motalkina MS, Klimova OU, et al. Plerixafor in Patients with Decreased Mobilizing Ability of Autologous Hematopoietic Stem Cells. Clinical oncohematology. 2016;9(2):155–61. doi: 10.21320/2500-2139-2016-9-2-155-61. (In Russ)]
  26. Levesque JP, Takamatsu Y, Nilsson SK, et al. Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood. 2001;98(5):1289–97. doi: 10.1182/blood.V98.5.1289.
  27. Levesque JP, Hendy J, Takamatsu Y, et al. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 2003;111(2):187–96. doi: 10.1172/jci15994.
  28. Petit I, Szyper-Kravitz M, Nagler A, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and upregulating CXCR4. Nat Immunol. 2002;3(7):687–94. doi: 10.1038/ni813.
  29. Cesana C, Carlo-Stella C, Regazzi E, et al. CD34+ cells mobilized by cyclophosphamide and granulocyte colonystimulating factor (G-CSF) are functionally different from CD34+ cells mobilized by G-CSF. Bone Marrow Transplant. 1998;21(6):561–8. doi: 10.1038/sj.bmt.1701133.
  30. Bruns I, Steidl U, Fischer JC, et al. Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor. Haematologica. 2008;93(3):347–55. doi: 10.3324/haematol.12081.
  31. Kim MG, Han N, Lee EK, Kim T. Pegfilgrastim vs filgrastim in PBSC mobilization for autologous hematopoietic SCT: a systematic review and meta-analysis. Bone Marrow Transplant. 2015;50(4):523–30. doi: 10.1038/bmt.2014.297.
  32. Tuchman SA, Bacon WA, Huang LW, et al. Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma. J Clin Apher. 2015;30(3):176–82. doi: 10.1002/jca.21360.
  33. Dingli D, Nowakowski GS, Dispenzieri A, et al. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma. Clin Lymphoma Myeloma. 2006;6(5):384–8. doi: 10.3816/clm.2006.n.014.
  34. Hamadani M, Kochuparambil ST, Osman S, et al. Intermediate-dose versus low-dose cyclophosphamide and granulocyte colony-stimulating factor for peripheral blood stem cell mobilization in patients with multiple myeloma treated with novel induction therapies. Biol Blood Marrow Transplant. 2012;18(7):1128–35. doi: 10.1016/j.bbmt.2012.01.005.
  35. Hiwase DK, Bollard G, Hiwase S. Intermediate-dose CY and G-CSF more efficiently mobilize adequate numbers of PBSC for tandem autologous PBSC transplantation compared with low-dose CY in patients with multiple myeloma. Cytotherapy. 2007;9(6):539–47. doi: 10.1080/14653240701452800.
  36. Jantunen E, Putkonen M, Nousiainen T, Low-dose or intermediate-dose cyclophosphamide plus granulocyte colonystimulating factor for progenitor cell mobilisation in patients with multiple myeloma. Bone Marrow Transplant. 2003; 31(5):347–51. doi: 10.1038/sj.bmt.1703840.
  37. Nazha A, Cook R, Vogl DT, et al. Stem cell collection in patients with multiple myeloma: impact of induction therapy and mobilization regimen. Bone Marrow Transplant. 2011;46(1):59–63. doi: 10.1038/bmt.2010.63.
  38. Brioli A, Perrone G, Patriarca F, et al. Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation. Bone Marrow Transplant. 2015;50(5):673–8. doi: 10.1038/bmt.2014.322.
  39. Samaras P, Pfrommer S, Seifert B, et al. Efficacy of vinorelbine plus granulocyte colonye-stimulation factor for CD34+ hematopoietic progenitor cell mobilization in patients with multiple myeloma. Biol Blood Marrow Transplant. 2015;21(1):74–80. doi: 10.1016/j.bbmt.2014.09.020.
  40. Heizmann M, O’Meara AC, Moosmann PR, et al. Efficient mobilization of PBSC with vinorelbine/G-CSF in patients with malignant lymphoma. Bone Marrow Transplant. 2009;44(2):75–9. doi: 10.1038/bmt.2008.434.
  41. Annunziata M, Celentano M, Pocali B, et al. Vinorelbine plus intermediate dose cyclophosphamide is an effective and safe regimen for the mobilization of peripheral blood stem cells in patients with multiple myeloma. Ann Hematol. 2006;85(6):394–9. doi: 10.1007/s00277-005-0058-0.
  42. Bargetzi MJ, Passweg J, Baertschi E, et al. Mobilization of peripheral blood progenitor cells with vinorelbine and granulocyte colony-stimulating factor in multiple myeloma patients is reliable and cost effective. Bone Marrow Transplant. 2003;31(2):99–103. doi: 10.1038/sj.bmt.1703787.
  43. Schmid A, Friess D, Taleghani BM, et al. Role of plerixafor in autologous stem cell mobilization with vinorelbine chemotherapy and granulocyte-colony stimulating factor in patients with myeloma: a phase II study (PAV-trial). Leuk Lymphoma. 2015;56(3):608–14. doi: 10.3109/10428194.2014.927454.
  44. Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood. 2002;99(3):731–5. doi: 10.1182/blood.v99.3.731.
  45. Palumbo A, Bringhen S, Bruno B, et al. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood. 2010;115(10):1873–9. doi: 10.1182/blood-2010-08-301085.
  46. Giralt S. 200mg/m2 melphalan – the gold standard for multiple myeloma. Nat Rev. 2010;7(9):490–1. doi: 10.1038/nrclinonc.2010.104.
  47. Philips GL, Meisenberg BR, Reece DE, et al. Activity of single-agent melphalan 220 to 300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma. Bone Marrow Transplant. 2004;33(8):781–7. doi: 10.1038/sj.bmt.1704424.
  48. Moreau P, Milpied N, Mahe B. Melphalan 220 mg/m2 followed by peripheral blood stem cell transplantation in 27 patients with advanced multiple myeloma. Bone Marrow Transplant. 1999;23(10):1003–6. doi: 10.1038/sj.bmt.1701763.
  49. Reece D., Song K., Leblanc R., et al. Efficacy and safety of busulfan-based conditioning regimens for multiple myeloma. Oncologist. 2013;18:611–8. doi: 10.1634/theoncologist.2012-0384.
  50. Roussel M, Moreau P, Huynh A, et al. Bortezomib ad high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010;115(1):32–7. doi: 10.1182/blood-2009-06-229658.
  51. Nishihori T, Alekshun TJ, Shain K, et al. Bortezomib salvage followed by a phase I/II study of bortezomib plus high-dose melphalan and tandem autologous transplantation for patients with primary resistant myeloma. Br J Haematol. 2012;157(5):553–63. doi: 10.1111/j.1365-2141.2012.09099.x.
  52. Huang W, Li J, Li H, et al. High-dose melphalan with bortezomib as conditioning regimen for autologous stem cell transplant in patients with newly diagnosed multiple myeloma who exhibited at least very good partial response to bortezomib-based induction therapy. Leuk Lymphoma. 2012;53(12):2507–10. doi: 10.3109/10428194.2012.685735.
  53. Mark TM, Reid W, Niesvizky R, et al. A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplant in multiple myeloma. Biol Blood Marrow Transplant. 2013;19(5):831–7. doi: 10.3109/10428194.2012.685735.
  54. Martino M, Tripepi G, Messina G, et al. A phase II, single-arm, prospective study of bendamustine plus melphalan conditioning for second autologous stem cell transplantation in de novo multiple myeloma patients through a tandem transplant strategy. Bone Marrow Transplant. 2016;51(9):1197–203. doi: 10.1038/bmt.2016.94.
  55. Visani G, Malerba L, Stefani PM, et al. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011;118(12):3419–25. doi: 10.1182/blood-2011-04-351924.
  56. Veeraputhiran M, Jain T, Deol A, et al. BEAM conditioning regimen has higher toxicity compared with high-dose melphalan for salvage autologous hematopoietic stem cell transplantation in multiple myeloma. Clin Lymph Myeloma Leuk. 2015;15(9):531–5. doi: 10.1016/j.clml.2015.05.008.
  57. Abu Zaid B, Abdul-Hai A, Grotto I, et al. Autologous transplant in multiple myeloma with an augmented conditioning protocol. Leuk Lymphoma. 2013;54(11):2480–4. doi: 10.3109/10428194.2013.782608.
  58. Musso M, Messina G, Marcacci G, et al. High-dose melphalan plus thiotepa as conditioning regimen before second autologous stem cell transplantation for “de novo” multiple myeloma patients: a phase II study. Biol Blood Marrow Transplant. 2015;21(11):1932–8. doi: 10.1016/j.bbmt.2015.06.011.

 

Bone Marrow Transplantation in Patients with Acute Lymphoblastic Leukemia with Extremely Poor Prognosis: Literature Review and Case Report

BONE MARROW TRANSPLANTATION , , ,

NN Subbotina, AV Popa, IS Dolgopolov, VK Boyarshinov, RI Pimenov, VV Dailidite, GL Mentkevich

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Natal’ya Nikolaevna Subbotina, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-45-08; e-mail: natik-23@yandex.ru

For citation: Subbotina N.N., Popa A.V., Dolgopolov I.S., Boyarshinov V.K., Pimenov R.I., Dailidite V.V., Mentkevich G.L. Bone Marrow Transplantation in Patients with Acute Lymphoblastic Leukemia with Extremely Poor Prognosis: Literature Review and Case Report. Klin. Onkogematol. 2015; 8(3): 331-6. (In Russ.)

ABSTRACT

The difference in the survival rate between patients receiving the chemotherapy alone and those receiving the chemotherapy with hematopoietic stem cell transplantation (HSCT) becomes more significant with the increased number of acute lymphoblastic leukemia (ALL) risk factors. Myeloablative conditioning regimens remain a gold standard before HSCT in children and young adults with ALL. The traditional TBI-CPM based conditioning regimen followed by HSCT from related HLA identical donor demonstrates the highest survival rates. The survival rate of patients with ALL relapses after allogeneic HSCT remains low. The second HSCT is the only possible therapeutic option that provides a longer survival rate for not more than 10–15 % of patients. Delayed relapses after the first HSCT and patient’s age less than 10 y.o. are statistically significant factors of a better prognosis. The article describes author’s own experience in the management of an ALL high-risk group patients who have undergone chemotherapy, 3 allogeneic related HSCT with involvement of several donors, as well as an additional transfusion of peripheral blood stem cells obtained from the second HLA matching donor. The patient remains under medical supervision in the N.N. Blokhin Russian Cancer Research Center by the date of composition of this paper (23 months after a haploidentical HSCT).

Keywords: acute lymphoblastic leukemia, extremely poor prognosis, hematopoietic stem cell transplantation, conditioning regimen.

Received: March 3, 2015

Accepted: June 3, 2015

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REFERENCES

  1. Favre C, Foa R, Locatelli F, et al. Hematopoietic stem cell transplantation for children with high-risk acute lymphoblastic leukemia in first complete remission: a report from the AIEOP registry. Haematologica. 2013;98(8):1273–81. doi: 10.3324/haematol.2012.079707.
  2. Silverman LB, Gelber RD, Clavell LA, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood. 2001;97(5):1211–8. doi: 10.1182/blood.v97.5.1211.
  3. Arico M, Valsecchi MG, Messina C, et al. Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone poor response treated with double Berlin-Frankfurt-Muenster protocol II. Blood. 2002;100(2):420–6. doi: 10.1182/blood.v100.2.420.
  4. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. The Lancet. 2008;371(9617):1030–43. doi: 10.1016/s0140-6736(08)60457-2.
  5. Pulte D, Gondos A, Brenner H. Trends in 5-and 10-year survival after diagnosis with childhood hematologic malignancies in the United States 1990–2004. J Natl Cancer Inst. 2008;100(18):1271–3. doi: 10.1093/jnci/djn276.
  6. Burke PW, Douer D. Acute lymphoblastic leukemia in adolescents and young adults. Acta Haematol. 2014;132(3–4):264–73. doi: 10.1159/000360204.
  7. Barry EV, Silverman LB. Acute lymphoblastic leukemia in adolescents and young adults. Curr Hematol Malig Rep. 2008;3(3):161–6. doi: 10.1007/s11899-008-0023-9.
  8. Balduzzi A, Klingebiel T, Peters C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomization in an international prospective study. The Lancet. 2005;366(9486):635–42. doi: 10.1016/s0140-6736(05)66998-x.
  9. Kato M, Horikoshi Y, Okamoto Y, et al. Second allogeneic hematopoietic SCT for relapsed ALL in children. Bone Marrow Transplant. 2012;47(10):1307–11. doi: 10.1038/bmt.2012.29.
  10. Poon LM, Bassett R. Jr, Kebriaei P, et al. Outcomes of second allogeneic hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia. Bone Marrow Transplant. 2013;48(5):666–70. doi: 10.1038/bmt.2012.195.
  11. Spyridonidis A, Labopin M, Rocha V, et al. Immunotherapy Subcommittee of Acute Leukemia Working Party. Outcomes and prognostic factors of adults with acute lymphoblastic leukemia who relapse after allogeneic hematopoietic cell transplantation. An analysis on behalf of the Acute Leukemia Working Party of EBMT. Leukemia. 2012;26(6):1211–7. doi: 10.1038/leu.2011.351.
  12. Mohty M, Nagler A, Rocha V, et al. Acute Leukemia Working Party of EBMT. Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood. 2010;116(22):4439–43. doi: 10.1182/blood-2010-02-266551.
  13. Eom KS, Shin SH, Lee S, et al. Comparable long-term outcomes after reduced-intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high-risk acute lymphoblastic leukemia in complete remission. Am J Hematol. 2013;88(8):634–41. doi: 10.1002/ajh.23465.
  14. Verneris MR, Eapen M, Davies SM, et al. Reduced-Intensity Conditioning Regimens for Allogeneic Transplantation in Children with Acute Lymphoblastic Leukemia. Biol Blood Marrow Transplant. 2010;16(9):1237–44. doi: 10.1016/j.bbmt.2010.03.009.
  15. Bunin N, Cnaan A, Simms S, et al. Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant. 2003;32(6):543–8. doi: 10.1038/sj.bmt.1704198.
  16. Davies SM, Ramsay NK, Horowitz MM, et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol. 2000;18(2):340–7.
  17. Blaise D, Maraninchi D, Archimbaud E, et al. Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: A randomized trial of a busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen. A report from the Groupe d’Etudes de la Greffe de Moelle Osseuse. Blood. 1992;79:2578–82.
  18. Dusenbery KE, Daniels KA, McClure JS, et al. Randomized comparison of cyclophosphamide-total body irradiation versus busulfan-cyclophosphamide conditioning in autologous bone marrow transplantation for acute myeloid leukemia. Int J Radiat Oncol Biol Phys. 1995;31(1):119–28. doi: 10.1016/0360-3016(94)00335-i.
  19. Ringden O, Ruutu T, Remberger M, et al. A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: A report from the Nordic Bone Marrow Transplantation Group. Blood. 1994;83(9):2723–30.
  20. Ringden O, Labopin M, Tura S, et al. A comparison of busulfan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukemia. Br J Haematol. 1996;93(3):637–45. doi: 10.1046/j.1365-2141.1996.d01-1681.x.
  21. Rozman C, Carreras E, Qian C, et al. Risk factors for hepatic veno-occlusive disease following HLA-identical sibling bone marrow transplantation for leukemia. Bone Marrow Transplant. 1996;17(1):75–80.
  22. Bhatia S, Ramsay NK, Neglia JP, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87(9):3633–9.
  23. Deeg HJ, Gluckman E, Storb R, et al. Malignancies after marrow transplantation for aplastic anemia and Fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood. 1996;87(1):386–92.
  24. Chou RH, Wong GB, Wara WM, et al. Toxicities of total-body irradiation for pediatric bone marrow transplantation. Int J Radiat Oncol Biol Phys. 1996;34(4):843–51.