Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma

被引:72
作者
Hiwase, Devendra K. [1 ,2 ]
Hiwase, Smita [1 ,2 ]
Bailey, Michael [3 ]
Bollard, Geraldine [2 ]
Schwarer, Anthony P. [2 ]
机构
[1] Inst Med & Vet Sci, Dept Haematol, Adelaide, SA 5000, Australia
[2] Alfred Hosp, Bone Marrow Transplant Programme, Melbourne, Vic, Australia
[3] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia
关键词
lymphocyte recovery; autologous stem cell transplantation; multiple myeloma;
D O I
10.1016/j.bbmt.2007.08.051
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) younger than 70 years. However, despite this aggressive therapy most patients will still die of progressive disease. Recent reports have suggested that lymphocyte recovery is an important predictor of relapse or progressive disease in a number of hematologic malignancies including MM. We have conducted retrospective analysis of factors that could predict overall (OS) and progression free survival (PITS) in patients with MM who had ASCT. One hundred nineteen patients with multiple myeloma underwent ASCT. The median OS and PFS were 64 and 32 months, respectively. Univariate and multivariate analysis using Cox proportional hazards regression model showed that absolute lymphocyte count on day 30 following ASCT (ALC-30), international staging system (ISS) stage at diagnosis, and age at diagnosis significantly influenced OS and PFS following ASCT. OS (96 versus 48 months, P = .04) andPFS (43 versus 29 months, P =.03) following ASCT were higher inpatients with ALC-30 >= 1.0 x 10(9)/L compared to patients ALC-30 < 1.0 x 10(9)/L. HigherALC-60, ALC-100, ALC-180, and ALC-365 did not predict superior OS and PITS. Patients with early-stage disease had significantly higher OS (ISS stages 1, 11, and III: 96, 53, and 29 months, respectively; P =.0023) and PITS (ISS stages I, II, and III: 55.5, 31, and 12 months, respectively; P =.027) compared to patients with advanced-stage disease at diagnosis. On univariate analysis, the type of initial chemotherapy (melphalan, VAD, PCAB), lymphocyte count on day of leukapheresis, and the lymphocyte dose infused (LY-DO) significantly influenced lymphocyte recovery following ASCT. Patients who received higher lymphocyte dose (LY-DO) >= 0.2 x 10(9)/kg had higher median ALC-15 (0.25 versus 0.19 x 10(9)/L; P =.3), ALC-30 (1.20 versus 0.99 x 10(9)/L; P =.08), ALC-60 (1.90 versus 1.01 x 10(9)/L; P =.013), ALC-100 (1.58versus 1.03 x 10(9)/L;P=.016), andA-LC-180 (1.33versus 1.01 x 10(9)/L;P =.1), compared to patients who received LY-DO < 0.2 x 10(9)/kg. In summary, our data suggest that infusing large numbers of lymphocytes improves lymphocyte recovery post-ASCT, and that higher ALC-30 is associated with better PFS and OS. These data suggest that a threshold number of CD34(+) cells should not be the only parameter considered for an adequate PBSC collection-perhaps a certain number of lymphocytes should be aimed for as well. (c) 2008 American Society for Blood and Marrow Transplantation.
引用
收藏
页码:116 / 124
页数:9
相关论文
共 27 条
[1]  
ACKERSTEIN A, 1991, BLOOD, V78, P1212
[2]   A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma [J].
Attal, M ;
Harousseau, JL ;
Stoppa, AM ;
Sotto, JJ ;
Fuzibet, JG ;
Rossi, JF ;
Casassus, P ;
Maisonneuve, H ;
Facon, T ;
Ifrah, N ;
Payen, C ;
Bataille, R .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (02) :91-97
[3]  
Blade Joan, 1998, British Journal of Haematology, V102, P1115, DOI 10.1046/j.1365-2141.1998.00930.x
[4]   Early lymphocyte recovery following autologous peripheral stem cell transplantation is associated with better survival in younger patients with lymphoproliferative disorders [J].
Boulassel, M. R. ;
Herr, A. L. ;
Edwardes, M. D. Deb ;
Galal, A. ;
Lachance, S. ;
Laneuville, P. ;
Routy, J. P. .
HEMATOLOGY, 2006, 11 (03) :165-170
[5]   Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia [J].
Dazzi, F ;
Szydlo, RM ;
Craddock, C ;
Cross, NCP ;
Kaeda, J ;
Chase, A ;
Olavarria, E ;
van Rhee, F ;
Kanfer, E ;
Apperley, JF ;
Goldman, JM .
BLOOD, 2000, 95 (01) :67-71
[6]  
Ferrandina G, 2003, CLIN CANCER RES, V9, P195
[7]   Correlation of early lymphocyte recovery and progression-free survival after autologous stem-cell transplant in patients with Hodgkin's and non-Hodgkin's lymphoma [J].
Gordan, LN ;
Sugrue, MW ;
Lynch, JW ;
Williams, KD ;
Khan, SA ;
Moreb, JS .
BONE MARROW TRANSPLANTATION, 2003, 31 (11) :1009-1013
[8]   Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose [J].
Guglielmi, C ;
Arcese, W ;
Dazzi, F ;
Brand, R ;
Bunjes, D ;
Verdonck, LF ;
Schattenberg, A ;
Kolb, HJ ;
Ljungman, P ;
Devergie, A ;
Bacigalupo, A ;
Gomez, M ;
Michallet, M ;
Elmaagacli, A ;
Gratwohl, A ;
Apperley, J ;
Niederwieser, D .
BLOOD, 2002, 100 (02) :397-405
[9]   Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma [J].
Joao, C ;
Porrata, LF ;
Inwards, DJ ;
Ansell, SM ;
Micallef, IN ;
Johnston, PB ;
Gastineau, DA ;
Markovic, SN .
BONE MARROW TRANSPLANTATION, 2006, 37 (09) :865-871
[10]   Immunological and clinical effects of post-transplant G-CSF versus placebo in T-cell replete allogeneic blood transplant patients: results from a randomized double-blind study [J].
Joshi, SS ;
Bishop, MR ;
Lynch, JC ;
Tarantolo, SR ;
Abhyankar, S ;
Bierman, PJ ;
Vose, JM ;
Geller, RB ;
McGuirk, J ;
Foran, J ;
Bociek, RG ;
Hadi, A ;
Day, SD ;
Armitage, JO ;
Kessinger, A ;
Pavletic, ZS .
CYTOTHERAPY, 2003, 5 (06) :542-552