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1.
Bone Marrow Transplant ; 49(1): 138-44, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23933765

RESUMO

Depletion of naive T cells from donor leukapheresis products (LPs) aims at the reduction of alloreactivity, while preserving memory T-cell reactivity (for example, to pathogens). This study established the immunomagnetic depletion procedure under clean room conditions using CD45RA beads and analyzed LPs of six donors for cell composition and functional immune responses. CD45RA depletion resulted in 3.4-4.7 log (median 4.4) reduction of CD45RA(+) T cells, thereby eliminating naive and late effector T cells. B cells were also completely removed, whereas significant proportions of NK cells, monocytes and granulocytes persisted. CD45RA-depleted LPs contained effector and central memory CD4(+) and CD8(+) T cells that showed sustained IFN-γ secretion to CMV, EBV, Aspergillus and Candida Ags. Alloreactivity was measured in MLRs between donors with complete HLA-mismatch. Alloreactive CD8(+) T cells were strongly reduced (median >1-log) upon CD45RA depletion, whereas alloreactive CD4(+) T cells persisted in significant numbers. In conclusion, clinical grade depletion of CD45RA(+) naive T cells from donor LPs is feasible and highly efficient. The depleted products show sustained CD4(+) and CD8(+) T-cell reactivity to pathogens and effectively reduced CD8-mediated alloreactivity. Prophylactic and preemptive infusions after allogeneic SCT may improve T-cell reconstitution and pathogen-specific immunosurveillance, along with lower risk of inducing GVHD.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Separação Imunomagnética/métodos , Antígenos Comuns de Leucócito/metabolismo , Depleção Linfocítica/métodos , Linfócitos T/imunologia , Adulto , Antígenos de Neoplasias/metabolismo , Aspergillus , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Candida , Citomegalovirus , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Herpesvirus Humano 4 , Humanos , Imunofenotipagem , Interferon gama/metabolismo , Leucaférese/métodos , Depleção Linfocítica/instrumentação , Masculino
2.
Bone Marrow Transplant ; 46(8): 1045-52, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20972470

RESUMO

The CXCR4-inhibitor plerixafor mobilizes hematopoietic stem cells amplifying the effects of granulocyte-CSF (G-CSF). Before approval plerixafor was used in a compassionate use program (CUP) for patients who failed a previous mobilization. In the German CUP 60 patients from 23 centers (median age 56.5 years (2-75)) were given 240 µg/kg plerixafor SC 9-11 h before apheresis. A total of 78.3% (47/60) received G-CSF for 4 days before plerixafor administration; 76.6% of those (36/47) yielded at least 2.0 × 10(6) CD34(+) cells/µL. The median cell yield was 3.35 × 10(6) CD34+ cells/kg (0-29.53). Nine patients received plerixafor alone or with G-CSF for less than 4 days mobilizing a median of 3.30 × 10(6) CD34+ cells/kg (1.6-5.6). There was no significant difference between G-CSF application for 4 days and for a shorter period of time (P=0.157). A total of 47 patients received plerixafor plus G-CSF combined with chemotherapy yielding a median of 3.28 × 10(6) CD34+ cells/kg (0-24.79). In all, 40 of 60 patients (66.7%) proceeded to transplantation, and achieved a timely and stable engraftment. Side effects were rare and manageable. In conclusion, mobilization with plerixafor in poor mobilizers is safe and results in a sufficient stem cell harvest in the majority of patients.


Assuntos
Ensaios de Uso Compassivo , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Benzilaminas , Remoção de Componentes Sanguíneos/métodos , Criança , Pré-Escolar , Terapia Combinada , Ciclamos , Feminino , Alemanha , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/efeitos adversos , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/cirurgia , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Resultado do Tratamento , Adulto Jovem
3.
Bone Marrow Transplant ; 45(4): 668-74, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19684624

RESUMO

Donor lymphocyte infusions (DLI) are used to resolve mixed T-cell chimerism (TCC) after allo-SCT despite a substantial risk of GVHD. We analyzed the impact of prophylactic CD8-depleted (CD8(depl)) DLI in 20 recipients of anti-CD52 alemtuzumab in vivo T-cell-depleted allografts with declining donor TCC after day +60. A total of 13 patients received CD8(depl) DLI and 7 patients did not. All but one of the DLI patients converted to complete donor T-cell chimeras, whereas only one non-DLI patient converted spontaneously. DLI induced transient acute GVHD in five and extensive chronic GVHD in two patients. These data suggest the use of CD8(depl) DLI as an effective treatment for mixed TCC, particularly in patients at high risk for GVHD. We also observed that the majority of reconstituting donor-derived T cells after alemtuzumab conditioning were CD52-negative. CD8(depl) DLI significantly increased the proportion of CD52-positive CD4 T cells, whereby their beneficial effect on reconstituting the post-transplant T-cell repertoire was shown.


Assuntos
Antígenos CD , Antígenos de Neoplasias , Linfócitos T CD4-Positivos/transplante , Glicoproteínas , Depleção Linfocítica , Transfusão de Linfócitos/métodos , Transplante de Células-Tronco de Sangue Periférico , Quimeras de Transplante/imunologia , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno CD52 , Proliferação de Células , Transplante de Células-Tronco Hematopoéticas , Humanos , Pessoa de Meia-Idade , Subpopulações de Linfócitos T
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