Repopulation of circulating T, B and NK lymphocytes following bone marrow and blood stem cell transplantation

Parrado, Antonio; Casares, Sofía; Prieto, J.; Carmona, María Teresa Padilla; Vaquero, Almudena Fernández; Rodríguez-Fernández, J. M.

doi:10.1007/s00282-997-0301-3

Cited by 17 publications

(13 citation statements)

References 18 publications

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“…B-cell recovery was also highly variable, whereas NK cells recovered relatively early, consistent with other HCT studies (38)(39)(40). Anti-third-party alloreactivity generally recovered quite early when measured via LDA, and was frequently associated with a 'suppressive' pattern, possibly explaining the frequently weak simultaneous bulk culture alloresponses.…”

Section: Tolerance In Patients With Combined Kidney and Marrow Transpsupporting

confidence: 76%

Myeloma Responses and Tolerance Following Combined Kidney and Nonmyeloablative Marrow Transplantation: In Vivo and In Vitro Analyses

Fudaba

Spitzer

Shaffer

et al. 2006

American Journal of Transplantation

242

207

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Six patients with renal failure due to multiple myeloma (MM) received simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical sibling donors following nonmyeloablative conditioning, including cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic irradiation. Cyclosporine (CyA) was given for approximately 2 months posttransplant, followed by donor leukocyte infusions. All six patients accepted their kidney grafts long-term. Three patients lost detectable chimerism but accepted their kidney grafts off immunosuppression for 1.3 to >7 years. One such patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in association with marrow rejection. Two patients achieved full donor chimerism, but resumed immunosuppression to treat graft-versus-host disease. Only one patient experienced rejection following CyA withdrawal. He responded to immunosuppression, which was later successfully withdrawn. The rejection episode was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness to cultured donor renal tubular epithelial cells. Initially recovering T cells were memory cells and were enriched for CD4 + CD25 + cells. Three patients are in sustained complete remissions of MM, despite loss of chimerism in two. Combined kidney/BMT with nonmyeloablative conditioning can achieve renal allograft tolerance and excellent myeloma responses, even in the presence of donor marrow rejection and antidonor alloresponses in vitro.

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Section: Tolerance In Patients With Combined Kidney and Marrow Transpsupporting

confidence: 76%

Myeloma Responses and Tolerance Following Combined Kidney and Nonmyeloablative Marrow Transplantation: In Vivo and In Vitro Analyses

Fudaba

Spitzer

Shaffer

et al. 2006

American Journal of Transplantation

242

207

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“…[13][14][15][16][17] This same phenomenon of delayed B and T cell recovery post-ASCT has been reported in patients with metastatic breast cancer. Avigan et al 18 demonstrated abnormalities in T cell phenotype and function in patients followed up to 12 months post-ASCT.…”

Section: Discussionmentioning

confidence: 57%

Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer

et al. 2001

Bone Marrow Transplant

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Summary:Early absolute lymphocyte count (ALC) recovery at day 15 post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival in multiple myeloma and non-Hodgkin's lymphoma. The relationship of ALC with clinical outcomes in metastatic breast cancer is unknown. We evaluated all 29 patients with metastatic breast cancer who underwent ASCT at the Mayo Clinic, Rochester, Minnesota, from 1994 to 1999. The ALC threshold was set at 500 cells/l on day 15 post-ASCT based on previous experience with hematologic malignancies. All patients were followed for a minimum of 2 years or until death, with a median follow-up for living patients of 2.25 years. Of the 29 patients, 17 have died with disease progression, two are alive and have progressed, and 10 are alive without progression. The median overall and progression-free survival times were significantly better for the 20 patients with ALC у500 cells/l compared with the nine patients with ALC Ͻ500 cells/l (not reached vs 14 months, P Ͻ 0.0001; 24 vs 7 months, P Ͻ 0.0015, respectively). In conclusion, ALC у500 cells/l on day 15 post-ASCT was associated with significantly better survival in patients with metastatic breast cancer, suggesting the importance of early immune recovery post-ASCT in these patients. Bone Marrow Transplantation (2001) 28, 865-871. Keywords: absolute lymphocyte count recovery; autologous stem cell transplantation; metastatic breast cancer Randomized studies between high-dose therapy (HDT) and conventional chemotherapy for metastatic breast cancer have shown no difference in survival. 1 The largest of the four metastatic breast cancer trials, the Philadelphia Intergroup study (PBT1), 2 entered a total of 535 patients. With a median follow-up of 37 months, there was no significant difference in the overall survival (OS) at 3 years (32% in the transplant group and 38% in the conventionalchemotherapy group, P = 0.23). There was also no significant difference in the median time to diverse progression (9.6 months for the transplant group and 9 months for conventional-dose chemotherapy, P = 0.31).High relapse rates post-ASCT have been attributed to the inability of HDT to eradicate minimal residual disease. Lower relapse rates observed after allogeneic bone marrow transplantation (ABMT) in malignant hematological conditions have been attributed to the adoptive graft-versustumor (GVT) immune response.3 Studies in ABMT have demonstrated that early absolute lymphocyte count (ALC) recovery post-ABMT is associated with prolonged survival. Using an ALC cut-off value of 200 cells/l at day 29 post-ABMT in 188 acute myelogenous leukemia (AML) patients, Powles et al 4 demonstrated a 3-year relapse probability of 42% for ALC Ͻ200 cells/l vs 16% for ALC 200 cells/l (P Ͻ 0.004). Pavletic et al 5 analyzed ALC in 41 patients post-ABMT (AML, chronic myelogenous leukemia, myelodysplastic syndrome, Hodgkin's disease, chronic lymphocytic leukemia). The OS at 1 year with an ALC at day 17 post-ABMT of у500 cells/l was 79% vs 19% for ALC Ͻ500 cel...

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“…[8][9][10][11][12][13] NK cells comprise 5% to 8% of human peripheral blood lymphocytes and morphologically resemble large granular lymphocytes.…”

mentioning

confidence: 99%

Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-α in autologous stem cell transplantation

Porrata

Inwards

Lacy

et al. 2001

Bone Marrow Transplant

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suggests that lack of post-ASCT immunosurveillance may contribute to the risk of tumor relapse.Overwhelming evidence from several post-ASCT immunorecovery studies demonstrated normal quantitative reconstitution of natural killer (NK) cells within 1 month after ASCT.8-13 NK cells comprise 5% to 8% of human peripheral blood lymphocytes and morphologically resemble large granular lymphocytes.14 NK cells are capable of dual cytolytic activity. First, they are capable of spontaneous, antibody-independent, non-major histocompatibility complexrestricted cytotoxicity mediated by the binding of NK cell surface leukocyte function-associated antigen 1 (clusters of differentiation [CD]11aCD18) and CD2 to their target cell ligands, CD54 and CD58, respectively.15 Second, they can mediate antibody-dependent cellular cytotoxicity by the binding of NK cell surface CD16 to their target cell ligands. 15Several studies have shown the presence of infiltrating NK cells in solid tumors and lymphomas. [16][17][18][19][20] Preclinical studies have shown that NK cells eradicate and control tumor cell growth of leukemias and lymphoma. [21][22][23] Because NK cells recover early during the period when most tumor relapses occur post ASCT, our interest focused on regulation of NK cells as a method of immunotherapy to improve remission and cure rates by eradicating minimal residual disease by means of stimulated NK cells.IL-2 is a 15-kDa glycoprotein that promotes proliferation and differentiation of helper T cells, cytotoxic T cells, and B cells and is necessary for acute and anamnestic adaptive immune responses.24 IL-2 is an excellent candidate to be an immunomodulator for post-ASCT up-regulation of NK cells, because NK cells are unique in that they constitutively express IL-2 receptors; thus, they always react to IL-2.25 NK cells have also interferon receptors in their cell membrane, and interferons have been shown to be effective up-regulators of NK-cell activity. [26][27][28][29] Results of previous studies have demonstrated that IL-2 and IFN-␣ augment NK cell cytotoxicity. [30][31][32][33][34] The aim of our study was to determine whether IL-2 or IFN-␣ can up-regulate NK cell activity in vitro as early as 14 days after ASCT.

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Repopulation of circulating T, B and NK lymphocytes following bone marrow and blood stem cell transplantation

Cited by 17 publications

References 18 publications

Myeloma Responses and Tolerance Following Combined Kidney and Nonmyeloablative Marrow Transplantation: In Vivo and In Vitro Analyses

Myeloma Responses and Tolerance Following Combined Kidney and Nonmyeloablative Marrow Transplantation: In Vivo and In Vitro Analyses

Prolonged survival associated with early lymphocyte recovery after autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer

Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-α in autologous stem cell transplantation

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