This study explored the effect of thalidomide and cyclophosphamide on stem cell collection, in addition to assessing their efficacy as induction therapy for myeloma patients destined for autologous stem cell transplantation (ASCT). We analyzed newly diagnosed myeloma patients who received TCD (thalidomide 100 mg/day for 28 days, oral cyclophosphamide 150 mg/m2/day and dexamethasone 40 mg/day on days 1-4) as induction therapy prior to ASCT. Peripheral stem cells were mobilized with granulocyte colony-stimulating factor and cyclophosphamide. Thirty-six patients (median age 54 years) received TCD chemotherapy (median 4 cycles). The overall response rate to TCD was 77.8% (28/36). The median number of CD34+ cells was 6.5 × 106/kg, and 2 patients failed to achieve the optimal number of CD34+ cells, i.e. 4.0 × 106/kg, although they were able to attain >2.0 × 106/kg. The overall response rate increased up to 94.4% (34/36) after ASCT; this included 9 patients with a stringent complete response without transplantation-related mortality. Four patients died due to disease progression and 17 were found to have progressed after ASCT (the median progression-free survival after ASCT was 19.6 months). TCD chemotherapy can be an effective and feasible induction regimen prior to ASCT for myeloma patients.

Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R: A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe francais du myelome. N Engl J Med 1996;335:91-97.
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.
Kumar S: Stem cell transplantation for multiple myeloma. Curr Opin Oncol 2009;21:162-170.
Garcia-Sanz R, Gonzalez-Porras JR, Hernandez JM, Polo-Zarzuela M, Sureda A, Barrenetxea C, Palomera L, Lopez R, Grande-Garcia C, Alegre A, Vargas-Pabon M, Gutierrez ON, Rodriguez JA, San Miguel JF: The oral combination of thalidomide, cyclophosphamide and dexamethasone (Thacydex) is effective in relapsed/refractory multiple myeloma. Leukemia 2004;18:856-863.
Wu P, Davies FE, Horton C, Jenner MW, Krishnan B, Alvares CL, Saso R, McCormack R, Dines S, Treleaven JG, Potter MN, Ethell ME, Morgan GJ: The combination of cyclophosphamide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide - vincristine - doxorubicin - methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis. Leuk Lymphoma 2006;47:2335-2338.
Roussou M, Anagnostopoulos A, Kastritis E, Matsouka C, Barmparousi D, Koutsoukou V, Dimopoulos MA: Pulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously treated patients with multiple myeloma: Long-term follow up and disease control after subsequent treatments. Leuk Lymphoma 2007;48:754-758.
Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA: Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood 2011;118:1231-1238.
Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA: Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC myeloma IX randomized trial results. Haematologica 2012;97:442-450.
Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H: Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005;105:2862-2868.
Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B: Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end-stage cancer patients. Cancer Immunol Immunother 2007;56:641-648.
Boccadoro M, Palumbo A, Bringhen S, Merletti F, Ciccone G, Richiardi L, Rus C, Bertola A, Giaccone L, Omede P, Musto P: Oral melphalan at diagnosis hampers adequate collection of peripheral blood progenitor cells in multiple myeloma. Haematologica 2002;87:846-850.
Popat U, Saliba R, Thandi R, Hosing C, Qazilbash M, Anderlini P, Shpall E, McMannis J, Korbling M, Alousi A, Andersson B, Nieto Y, Kebriaei P, Khouri I, de Lima M, Weber D, Thomas S, Wang M, Jones R, Champlin R, Giralt S: Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant 2009;15:718-723.
Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG, Zepeda VH, Mikhael JR, Leis JF, Bergsagel PL, Fonseca R, Stewart AK: Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia 2009;23:1337-1341.
de la Rubia J, Blade J, Lahuerta JJ, Ribera JM, Martinez R, Alegre A, Garcia-Larana J, Fernandez P, Sureda A, de Arriba F, Carrera D, Besalduch J, Garcia Boyero R, Palomera Bernal L, Hernandez MT, Garcia PR, Perez-Calvo J, Alcala A, Casado LF, San Miguel J: Effect of chemotherapy with alkylating agents on the yield of CD34+ cells in patients with multiple myeloma. Results of the Spanish Myeloma Group (GEM) Study. Haematologica 2006;91:621-627.
Mellqvist UH, Lenhoff S, Johnsen HE, Hjorth M, Holmberg E, Juliusson G, Tangen JM, Westin J: Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of a randomized comparison with vincristine, doxorubicin, and dexamethasone. Cancer 2008;112:129-135.
Auner HW, Mazzarella L, Cook L, Szydlo R, Saltarelli F, Pavlu J, Bua M, Giles C, Apperley JF, Rahemtulla A: High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma. Bone Marrow Transplant 2011;46:364-367.
Jung SH, Park H, Ahn JS, Yang DH, Kim MY, Kim YK, Kim HJ, Lee JJ: Efficacy of stem cell mobilization in patients with newly diagnosed multiple myeloma after a CTD (cyclophosphamide, thalidomide, and dexamethasone) regimen. Int J Hematol 2013;97:92-97.
Palumbo A, Sezer O, Kyle R, Miguel JS, Orlowski RZ, Moreau P, Niesvizky R, Morgan G, Comenzo R, Sonneveld P, Kumar S, Hajek R, Giralt S, Bringhen S, Anderson KC, Richardson PG, Cavo M, Davies F, Blade J, Einsele H, Dimopoulos MA, Spencer A, Dispenzieri A, Reiman T, Shimizu K, Lee JH, Attal M, Boccadoro M, Mateos M, Chen W, Ludwig H, Joshua D, Chim J, Hungria V, Turesson I, Durie BGM, Lonial S: International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation. Leukemia 2009;23:1716-1730.
Bensinger W, Appelbaum F, Rowley S, Storb R, Sanders J, Lilleby K, Gooley T, Demirer T, Schiffman K, Weaver C, Clift R, Chauncey T, Klarnet J, Montgomery P, Petersdorf S, Weiden P, Witherspoon R, Buckner CD: Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol 1995;13:2547-2555.
Desikan KR, Tricot G, Munshi NC, Anaissie E, Spoon D, Fassas A, Toor A, Zangari M, Badros A, Morris C, Vesole DH, Siegel D, Jagannath S, Barlogie B: Preceding chemotherapy, tumour load and age influence engraftment in multiple myeloma patients mobilized with granulocyte colony-stimulating factor alone. Br J Haematol 2001;112:242-247.
Gratama JW, Kraan J, Keeney M, Sutherland DR, Granger V, Barnett D: Validation of the single-platform ISHAGE method for CD34(+) hematopoietic stem and progenitor cell enumeration in an international multicenter study. Cytotherapy 2003;5:55-65.
Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV: International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467-1473.
Kapoor P, Rajkumar SV: Update on risk stratification and treatment of newly diagnosed multiple myeloma. Int J Hematol 2011;94:310-320.
Dimopoulos MA, Terpos E: Multiple myeloma. Ann Oncol 2010;21(suppl 7):VII143-VII150.
Park HJ, Park EH, Jung KW, Kong HJ, Won YJ, Lee JY, Yoon JH, Park BK, Lee H, Eom HS, Park S: Statistics of hematologic malignancies in Korea: incidence, prevalence and survival rates from 1999 to 2008. Korean J Hematol 2012;47:28-38.
Kim SJ, Kim K, Kim BS, Jo DY, Kang HJ, Kim JS, Mun YC, Kim CS, Sohn SK, Eom HS, Kwak JY, Shim H, Yoon HJ, Jin JY, Min CK, Shin H, Won JH, Lee JJ, Kwon JH, Joo YD, Do YR, Kim SH, Oh S, Suh C, Lee J, Yoon SS, Kim MK, Bang SM, Ryoo HM, Kim H, Kim HJ, Kim YS, Park CW, Lee GW, Shin HJ, Park SK, Park JS, Kim HY, Lee DS, Lee JH: Clinical features and survival outcomes in patients with multiple myeloma: analysis of Web-based data from the Korean myeloma registry. Acta Haematol 2009;122:200-210.
Kropff MH, Lang N, Bisping G, Domine N, Innig G, Hentrich M, Mitterer M, Sudhoff T, Fenk R, Straka C, Heinecke A, Koch OM, Ostermann H, Berdel WE, Kienast J: Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Br J Haematol 2003;122:607-616.
Kyriakou C, Thomson K, D'Sa S, Flory A, Hanslip J, Goldstone AH, Yong KL: Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well-tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. Br J Haematol 2005;129:763-770.
Morris CL, Siegel E, Barlogie B, Cottler-Fox M, Lin P, Fassas A, Zangari M, Anaissie E, Tricot G: Mobilization of CD34+ cells in elderly patients (>/= 70 years) with multiple myeloma: influence of age, prior therapy, platelet count and mobilization regimen. Br J Haematol 2003;120:413-423.
Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B, Fonseca R, Stewart AK, Harousseau JL, Dimopoulos M, Jagannath S, Hajek R, Sezer O, Kyle R, Sonneveld P, Cavo M, Rajkumar SV, San Miguel J, Crowley J, Avet-Loiseau H: Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 2011;117:4696-4700.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG: Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906-917.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.