Cord blood transplant (CBT) is characterized by the limited amount of hematopoietic stem cells (H... more Cord blood transplant (CBT) is characterized by the limited amount of hematopoietic stem cells (HSCs), and exhibits higher incidence of engraftment failure. Transplant using two (double) CB units (DCBT) is the most promising strategy to date to augment the total transplanted HSC dose. DCBT increases the availability of transplant to adults, for whom there is only a small chance of finding a matched CB suitable for a single unit transplant. Better selection of CB units, optimization of conditioning regimen, and GVHD prophylaxis are important to further improve DCBT outcomes. In this review we attempt to summarize recent progress in the field of DCBT, to present the strategies applied, and to point out directions for the future.
We show here that the anti-T lymphocyte immunoglobulin (ATG) can induce Treg cells following 24-h... more We show here that the anti-T lymphocyte immunoglobulin (ATG) can induce Treg cells following 24-h incubation in human peripheral blood mononuclear cells (PBMCs). The ATG-induced Treg cells express known cell surface markers (e.g., CD25, FoxP3) and suppress the proliferation of autologous responder PBMCs, stimulated with allogeneic PBMCs, when added into the mixed lymphocyte culture (MLC) at zero time point or 48 h later. We expanded the characteristics of the ATG-induced human Treg cells by showing that they express a novel biomarker designated "activated CD44". ATG-induced Treg cells retain their suppressor function after freezing and thawing or irradiation. Suppression of MLC by ATG-induced Treg cells is consistently seen when the Treg cells and the responder cells were derived from the same donor, but not when they derived from different donors. Finally, patients undergoing stem cell transplantation and conditioned with ATG generate in vivo Treg cells that suppress MLC.
This review provides an update on recently explored therapies in systemic lupus erythematosus and... more This review provides an update on recently explored therapies in systemic lupus erythematosus and introduces novel therapeutic approaches under consideration. Recent advances in our understanding of systemic lupus are highlighted as well, as these must now inform consideration of therapeutics. Many therapeutic strategies have been shown to be beneficial in murine models of lupus. Compounds that inhibit cellular signaling in response to autoantigens or other triggers and protocols that reconstitute the immune repertoire to diminish autoreactivity are now entering clinical trials. Requirements for novel approaches in lupus include improved efficacy and lower toxicity than current therapies, with the goal to reduce tissue damage while preserving immunocompetence.
Imatinib (IM) is the current first line treatment for chronic myeloid leukemia (CML). However, th... more Imatinib (IM) is the current first line treatment for chronic myeloid leukemia (CML). However, the disease will progress in the majority of patients pausing IM. IFN-α may intensify the response and increase the percentage of patients maintaining remission after IM cessation. Eleven patients with stable (≥ 2 years) complete cytogenetic responses (CCyR) on IM therapy were recruited to the study. They were administered Peg-IFN-α for 9 months before and for 3 months following IM discontinuation. During the 12 months of Peg-IFN-α therapy the remission status improved in five (45%) of the patients. Six (55%) of the patients experienced cytogenetic relapses at a median period of 8 months (range 2-33) after IM withdrawal. All six patients regained CCyR following IM restart. With a median follow up of 47 months (range 35-50), five (45%) out of the 11 studied patients maintain cytogenetic response off IM therapy. The role of Peg-IFN-α in patients pausing IM is to be further evaluated.
Cord blood transplant (CBT) is characterized by the limited amount of hematopoietic stem cells (H... more Cord blood transplant (CBT) is characterized by the limited amount of hematopoietic stem cells (HSCs), and exhibits higher incidence of engraftment failure. Transplant using two (double) CB units (DCBT) is the most promising strategy to date to augment the total transplanted HSC dose. DCBT increases the availability of transplant to adults, for whom there is only a small chance of finding a matched CB suitable for a single unit transplant. Better selection of CB units, optimization of conditioning regimen, and GVHD prophylaxis are important to further improve DCBT outcomes. In this review we attempt to summarize recent progress in the field of DCBT, to present the strategies applied, and to point out directions for the future.
We show here that the anti-T lymphocyte immunoglobulin (ATG) can induce Treg cells following 24-h... more We show here that the anti-T lymphocyte immunoglobulin (ATG) can induce Treg cells following 24-h incubation in human peripheral blood mononuclear cells (PBMCs). The ATG-induced Treg cells express known cell surface markers (e.g., CD25, FoxP3) and suppress the proliferation of autologous responder PBMCs, stimulated with allogeneic PBMCs, when added into the mixed lymphocyte culture (MLC) at zero time point or 48 h later. We expanded the characteristics of the ATG-induced human Treg cells by showing that they express a novel biomarker designated "activated CD44". ATG-induced Treg cells retain their suppressor function after freezing and thawing or irradiation. Suppression of MLC by ATG-induced Treg cells is consistently seen when the Treg cells and the responder cells were derived from the same donor, but not when they derived from different donors. Finally, patients undergoing stem cell transplantation and conditioned with ATG generate in vivo Treg cells that suppress MLC.
This review provides an update on recently explored therapies in systemic lupus erythematosus and... more This review provides an update on recently explored therapies in systemic lupus erythematosus and introduces novel therapeutic approaches under consideration. Recent advances in our understanding of systemic lupus are highlighted as well, as these must now inform consideration of therapeutics. Many therapeutic strategies have been shown to be beneficial in murine models of lupus. Compounds that inhibit cellular signaling in response to autoantigens or other triggers and protocols that reconstitute the immune repertoire to diminish autoreactivity are now entering clinical trials. Requirements for novel approaches in lupus include improved efficacy and lower toxicity than current therapies, with the goal to reduce tissue damage while preserving immunocompetence.
Imatinib (IM) is the current first line treatment for chronic myeloid leukemia (CML). However, th... more Imatinib (IM) is the current first line treatment for chronic myeloid leukemia (CML). However, the disease will progress in the majority of patients pausing IM. IFN-α may intensify the response and increase the percentage of patients maintaining remission after IM cessation. Eleven patients with stable (≥ 2 years) complete cytogenetic responses (CCyR) on IM therapy were recruited to the study. They were administered Peg-IFN-α for 9 months before and for 3 months following IM discontinuation. During the 12 months of Peg-IFN-α therapy the remission status improved in five (45%) of the patients. Six (55%) of the patients experienced cytogenetic relapses at a median period of 8 months (range 2-33) after IM withdrawal. All six patients regained CCyR following IM restart. With a median follow up of 47 months (range 35-50), five (45%) out of the 11 studied patients maintain cytogenetic response off IM therapy. The role of Peg-IFN-α in patients pausing IM is to be further evaluated.
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