CD34+ selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation

被引:40
作者
Mainardi, Chiara [1 ,2 ]
Ebinger, Martin [2 ]
Enkel, Sigrid [3 ]
Feuchtinger, Tobias [4 ]
Teltschik, Heiko-Manuel [2 ]
Eyrich, Matthias [5 ]
Schumm, Michael [2 ]
Rabsteyn, Armin [2 ]
Schlegel, Patrick [2 ]
Seitz, Christian [2 ]
Schwarze, Carl-Phillip [2 ]
Mueller, Ingo [6 ]
Greil, Johann [7 ]
Bader, Peter [8 ]
Schlegel, Paul-Gerhardt [5 ]
Martin, David [2 ,9 ]
Holzer, Ursula [2 ]
Doering, Michaela [2 ]
Handgretinger, Rupert [2 ]
Lang, Peter [2 ]
机构
[1] Univ Padua, Childrens Univ Hosp, Dept Paediat Oncol, Padua, Italy
[2] Childrens Univ Hosp, Dept Paediat Haematol Oncol, Dublin, Ireland
[3] Univ Tubingen, Univ Tubingen Hosp, Transfus Med Dept, Tubingen, Germany
[4] Ludwig Maximilians Univ Munchen, Dr Von Hauner Childrens Hosp, Munich, Germany
[5] Univ Wurzburg, Univ Childrens Hosp, Dept Paediat Oncol, Wurzburg, Germany
[6] Univ Hosp Eppendorf, Dept Paediat Haematol & Oncol, Hamburg, Germany
[7] Heidelberg Univ, Dept Paediat Oncol Haematol & Immunol, Heidelberg, Germany
[8] Univ Hosp Frankfurt, Clin Paediat & Adolescent Med, Frankfurt, Germany
[9] Filderklinik, Filderstadt Bonlanden, Germany
关键词
stem cell boost; poor graft function; haematopoietic stem cell transplantation; haematopoietic recovery; COLONY-STIMULATING FACTOR; BONE-MARROW; UNRELATED DONORS; IMMUNE RECONSTITUTION; RECIPIENTS; MOBILIZATION; FAILURE;
D O I
10.1111/bjh.15012
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Poor graft function (PGF) is a severe complication of haematopoietic stem cell transplantation (HSCT) and administration of donor stem cell boosts (SCBs) represents a therapeutic option. We report 50 paediatric patients with PGF who received 61 boosts with CD34(+) selected peripheral blood stem cells (PBSC) after transplantation from matched unrelated (n=25) or mismatched related (n=25) donors. Within 8weeks, a significant increase in median neutrophil counts (0.6 vs. 1.516x10(9)/l, P<0.05) and a decrease in red blood cell and platelet transfusion requirement (median frequencies 1 and 7 vs. 0, P<0.0001 and <0.001), were observed, and 78.8% of patients resolved one or two of their cytopenias. 36.5% had a complete haematological response. Median lymphocyte counts for CD3(+), CD3(+)CD4(+), CD19(+) and CD56(+) increased 8.3-, 14.2-, 22.- and 1.6-fold. The rate of de novo acute graft-versus-host disease (GvHD) grade I-III was only 6% and resolved completely. No GvHD grade IV or chronic GvHD occurred. Patients who responded to SCB displayed a trend toward better overall survival (OS) (P=0.07). Thus, administration of CD34(+) selected SCBs from alternative donors is safe and effective. Further studies are warranted to clarify the impact on immune reconstitution and survival.
引用
收藏
页码:90 / 99
页数:10
相关论文
共 23 条
[1]   Treatment of poor graft function after allogeneic hematopoietic cell transplantation with a booster of CD34-selected cells infused without conditioning [J].
Askaa, B. ;
Fischer-Nielsen, A. ;
Vindelov, L. ;
Haastrup, E. K. ;
Sengelov, H. .
BONE MARROW TRANSPLANTATION, 2014, 49 (05) :720-721
[2]   Granulocyte colony-stimulating factor for poor graft function after allogeneic stem cell transplantation: 3 days of G-CSF identifies long-term responders [J].
Bittencourt, H ;
Rocha, V ;
Filion, A ;
Ionescu, I ;
Herr, AL ;
Garnier, F ;
Ades, L ;
Esperou, H ;
Devergie, A ;
Ribaud, P ;
Socie, G ;
Gluckman, E .
BONE MARROW TRANSPLANTATION, 2005, 36 (05) :431-435
[3]  
DONSKOY E, 1992, J IMMUNOL, V148, P1604
[4]   A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors [J].
Eyrich, M ;
Leiler, C ;
Lang, P ;
Schilbach, K ;
Schumm, M ;
Bader, P ;
Greil, J ;
Klingebiel, T ;
Handgretinger, R ;
Niethammer, D ;
Schlegel, PG .
BONE MARROW TRANSPLANTATION, 2003, 32 (04) :379-390
[5]   A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigen-disparate haematopoietic stem cells from parental donors [J].
Eyrich, M ;
Lang, P ;
Lal, S ;
Bader, P ;
Handgretinger, R ;
Klingebiel, T ;
Niethammer, D ;
Schlegel, PG .
BRITISH JOURNAL OF HAEMATOLOGY, 2001, 114 (02) :422-432
[6]   CLINICAL MANIFESTATIONS OF GRAFT VERSUS HOST DISEASE IN HUMAN RECIPIENTS OF MARROW FROM HL-A-MATCHED SIBLING DONORS [J].
GLUCKSBERG, H ;
STORB, R ;
FEFER, A ;
BUCKNER, CD ;
NEIMAN, PE ;
CLIFT, RA ;
LERNER, KG ;
THOMAS, ED .
TRANSPLANTATION, 1974, 18 (04) :295-304
[7]   Cyclical mobilization and gated importation of thymocyte progenitors in the adult mouse: evidence for a thymus-bone marrow feedback loop [J].
Goldschneider, I .
IMMUNOLOGICAL REVIEWS, 2006, 209 :58-75
[8]   CD34+-Selected Stem Cell Boost without Further Conditioning for Poor Graft Function after Allogeneic Stem Cell Transplantation in Patients with Hematological Malignancies [J].
Klyuchnikov, Evgeny ;
El-Cheikh, Jean ;
Sputtek, Andreas ;
Lioznov, Michael ;
Calmels, Boris ;
Furst, Sabine ;
Chabannon, Christian ;
Crocchiolo, Roberto ;
Lemarie, Claude ;
Faucher, Catherine ;
Bacher, Ulrike ;
Alchalby, Haefaa ;
Stuebig, Thomas ;
Wolschke, Christine ;
Ayuk, Francis ;
Reckhaus, Marie-Luise ;
Blaise, Didier ;
Kroeger, Nicolaus .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2014, 20 (03) :382-386
[9]   Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age [J].
Kollman, C ;
Howe, CWS ;
Anasetti, C ;
Antin, JH ;
Davies, SM ;
Filipovich, AH ;
Hegland, J ;
Kamani, N ;
Kernan, NA ;
King, R ;
Ratanatharathorn, V ;
Weisdorf, D ;
Confer, DL .
BLOOD, 2001, 98 (07) :2043-2051
[10]   Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia [J].
Lang, P ;
Handgretinger, R ;
Niethammer, D ;
Schlegel, PG ;
Schumm, M ;
Greil, J ;
Bader, P ;
Engel, C ;
Scheel-Walter, H ;
Eyrich, M ;
Klingebiel, T .
BLOOD, 2003, 101 (04) :1630-1636