Remobilization of hematopoietic stem cells with high-dose methotrexate and cytarabine in patients with non-Hodgkin's lymphoma and multiple myeloma after failure to mobilize with chemotherapy and cytokines
Seong Joon Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorDok Hyun Yoon
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorShin Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorKyungmin Lee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorJung Sun Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorSeongsoo Jang
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorChan-Jeoung Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorHuyn-Sook Chi
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorChan-Sik Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorJooryung Huh
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Cheolwon Suh
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Address reprint requests to: Cheolwon Suh, MD, PhD, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea; e-mail: [email protected].Search for more papers by this authorSeong Joon Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorDok Hyun Yoon
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorShin Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorKyungmin Lee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorJung Sun Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorSeongsoo Jang
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorChan-Jeoung Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorHuyn-Sook Chi
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorChan-Sik Park
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorJooryung Huh
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Cheolwon Suh
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Address reprint requests to: Cheolwon Suh, MD, PhD, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea; e-mail: [email protected].Search for more papers by this authorAbstract
Background
High-dose chemotherapy supported by autologous stem cell transplantation is an effective treatment for patients with relapsed or refractory non-Hodgkin's lymphomas (NHLs) and fit patients with multiple myeloma (MM). However, failure rates of hematopoietic stem cell mobilization are estimated to be between 5 and 30%, respectively. Thus, we investigated the efficacy of the combination chemotherapy of high-dose methotrexate (MTX) and cytarabine with granulocyte-colony-stimulating factor (G-CSF) as a remobilization method in those who failed a prior mobilization and collection with chemotherapy and G-CSF.
Study Design and Methods
Mobilization failure was defined as a collection of fewer than 5 × 106 CD34+ cells after three to five apheresis procedures. MTX (3500 mg/m2 in a 120-min infusion) on Day 1 and cytarabine (3000 mg/m2 infusion for 120 min) on Day 4 and Day 5 were followed by G-CSF (10 μg/kg daily).
Results
A total of eight patients (six NHL and two MM; median age, 55 years) who had failed in prior mobilization with conventional chemotherapy and G-CSF underwent the second mobilization as described in the method. Successful collection of CD34+ cells (> 5 × 106/kg) was achieved in six patients (75%) with three to five apheresis procedures. The total yield of CD34+ cells/kg body weight was 6.28 × 106/kg (median; range, 1.53 × 106-10.09 × 106/kg).
Conclusions
This preliminary result warrants further investigation of high-dose MTX and cytarabine plus G-CSF as a means to remobilize stem cells in those with prior failure to mobilize stem cells with chemotherapy and G-CSF.
References
- 1 Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875-1883.
- 2 Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin 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.
- 3 Schmitz N, Linch DC, Dreger P, Goldstone AH, Boogaerts MA, Ferrant A, Demuynck HM, Link H, Zander A, Barge A. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet 1996; 347: 353-357.
- 4 Bensinger W, DiPersio JF, McCarty JM. Improving stem cell mobilization strategies: future directions. Bone Marrow Transplant 2009; 43: 181-195.
- 5 Lee JL, Kim SB, Lee GW, Ryu MH, Kim EK, Kim S, Kim WK, Lee JS, Suh C. Collection of peripheral blood progenitor cells: analysis of factors predicting the yields. Transfus Apher Sci 2003; 29: 29-37.
- 6 Haas R, Mohle R, Fruhauf S, Goldschmidt H, Witt B, Flentje M, Wannenmacher M, Hunstein W. Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. Blood 1994; 83: 3787-3794.
- 7 DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E, Nademanee A, McCarty J, Bridger G, Calandra G. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol 2009; 27: 4767-4773.
- 8 DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, Maziarz RT, Hosing C, Fruehauf S, Horwitz M, Cooper D, Bridger G, Calandra G. 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: 5720-5726.
- 9 Calandra G, McCarty J, McGuirk J, Tricot G, Crocker SA, Badel K, Grove B, Dye A, Bridger G. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data. Bone Marrow Transplant 2008; 41: 331-338.
- 10 Jantunen E, Kvalheim G. Mobilization strategies in hard-to-mobilize patients with lymphoid malignancies. Eur J Haematol 2010; 85: 463-471.
- 11 Kim H, Sohn HJ, Kim S, Lee JS, Kim WK, Suh C. Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma. Bone Marrow Transplant 2006; 37: 1037-1042.
- 12 Kim JE, Yoo C, Kim S, Lee DH, Kim SW, Lee JS, Suh C. Optimal timing of G-CSF administration for effective autologous stem cell collection. Bone Marrow Transplant 2011; 46: 806-812.
- 13 Kim S, Kim HJ, Park JS, Lee J, Chi HS, Park CJ, Huh J, Suh C. Prospective randomized comparative observation of single- vs split-dose lenograstim to mobilize peripheral blood progenitor cells following chemotherapy in patients with multiple myeloma or non-Hodgkin's lymphoma. Ann Hematol 2005; 84: 742-747.
- 14 Suh C, Kim S, Kim SH, Kim EK, Lee JL, Park KU, Park JS, Lee J, Kim MW, Chi HS, Park CJ, Kim SW. Initiation of peripheral blood progenitor cell harvest based on peripheral blood hematopoietic progenitor cell counts enumerated by the Sysmex SE9000. Transfusion 2004; 44: 1762-1768.
- 15 Jillella AP, Ustun C. What is the optimum number of CD34+ peripheral blood stem cells for an autologous transplant? Stem Cells Dev 2004; 13: 598-606.
- 16 Siena S, Schiavo R, Pedrazzoli P, Carlo-Stella C. Therapeutic relevance of CD34 cell dose in blood cell transplantation for cancer therapy. J Clin Oncol 2000; 18: 1360-1377.
- 17 Tricot G, Jagannath S, Vesole D, Nelson J, Tindle S, Miller L, Cheson B, Crowley J, Barlogie B. Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood 1995; 85: 588-596.
- 18 Jantunen E, Lemoli RM. Preemptive use of plerixafor in difficult-to-mobilize patients: an emerging concept. Transfusion 2012; 52: 906-914.
- 19 Duarte RF, Shaw BE, Marin P, Kottaridis P, Ortiz M, Morante C, Delgado J, Gayoso J, Goterriz R, Martinez-Chamorro C, Mateos-Mazon JJ, Ramirez C, de la Rubia J, Achtereekte H, Gandhi PJ, Douglas KW, Russell NH. Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data. Bone Marrow Transplant 2011; 46: 52-58.
- 20 Damon L, Damon LE, Gaensler K, Kaplan L, Martin T 3rd, Rubenstein J, Linker C. Impact of intensive PBSC mobilization therapy on outcomes following auto-SCT for non-Hodgkin's lymphoma. Bone Marrow Transplant 2008; 42: 649-657.
- 21 Blystad AK, Delabie J, Kvaloy S, Holte H, Valerhaugen H, Ikonomou I, Kvalheim G. Infused CD34 cell dose, but not tumour cell content of peripheral blood progenitor cell grafts, predicts clinical outcome in patients with diffuse large B-cell lymphoma and follicular lymphoma grade 3 treated with high-dose therapy. Br J Haematol 2004; 125: 605-612.
- 22 Shpall EJ, Champlin R, Glaspy JA. Effect of CD34+ peripheral blood progenitor cell dose on hematopoietic recovery. Biol Blood Marrow Transplant 1998; 4: 84-92.
- 23 Toor AA, Ayers J, Strupeck J, Parthasarathy M, Creech S, Rodriguez T, Stiff PJ. Favourable results with a single autologous stem cell transplant following conditioning with busulphan and cyclophosphamide in patients with multiple myeloma. Br J Haematol 2004; 124: 769-776.
- 24 Canellos GP, Skarin AT, Rosenthal DS, Moloney WC, Frei E 3rd. Methotrexate as a single agent and in combination chemotherapy for the treatment of non-Hodgkin's lymphoma of unfavorable histology. Cancer Treat Rep 1981; 65(Suppl 1): 125-129.
- 25 Skarin AT, Zuckerman KS, Pitman SW, Rosenthal DS, Moloney W, Frei E 3rd, Canellos GP. High-dose methotrexate with folinic acid in the treatment of advanced non-Hodgkin lymphoma including CNS involvement. Blood 1977; 50: 1039-1047.
- 26 Kremer WB. Drugs five years later: cytarabine. Ann Intern Med 1975; 82: 684-688.
- 27 Kantarjian H, Barlogie B, Plunkett W, Velasquez W, McLaughlin P, Riggs S, Cabanillas F. High-dose cytosine arabinoside in non-Hodgkin's lymphoma. J Clin Oncol 1983; 1: 689-694.
- 28 Patriarca F, Zaja F, Silvestri F, Sperotto A, Scalise A, Gigli G, Fanin R. Meningeal and cerebral involvement in multiple myeloma patients. Ann Hematol 2001; 80: 758-762.
- 29 D'Sa S, Yong K, Kyriakou C, Bhattacharya S, Peggs KS, Foulkes B, Watts MJ, Ings SJ, Ardeshna KM, Goldstone AH, Williams CD. Etoposide, methylprednisolone, cytarabine and cisplatin successfully cytoreduces resistant myeloma patients and mobilizes them for transplant without adverse effects. Br J Haematol 2004; 125: 756-765.
- 30 Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol 2003; 21: 4151-4156.
- 31 Cheng T, Forsyth P, Chaudhry A, Morris D, Gluck S, Russell JA, Stewart DA. High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant 2003; 31: 679-685.
- 32 Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broet S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant 2006; 38: 417-420.
- 33 Kiefer T, Kruger WH, Montemurro M, Schuler F, Hirt C, Pasold R, Niederwieser D, Schwenke M, Dolken G. Mobilization of hemopoietic stem cells with high-dose methotrexate plus granulocyte-colony-stimulating factor in patients with primary central nervous system lymphoma. Transfusion 2008; 48: 2624-2628.
- 34 Reiser M, Josting A, Draube A, Mapara MY, Scheid C, Chemnitz J, Tesch H, Wolf J, Diehl V, Sohngen D, Engert A. Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization. Bone Marrow Transplant 1999; 23: 1223-1228.