In Vivo DPP-4 Inhibition to Enhance Engraftment of Single-Unit Cord Blood Transplants in Adults with Hematological Malignancies

Farag, Sherif; Srivastava, Shivani; Messina-Graham, Steven; Schwartz, Jae C.; Robertson, Michael J.; Abonour, Rafat; Cornetta, Kenneth; Wood, Lisa; Secrest, Angie; Strother, Robert Matthew; Jones, David R.; Broxmeyer, Hal E.

doi:10.1089/scd.2012.0636

Cited by 119 publications

(122 citation statements)

References 46 publications

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“…[35][36][37] Additional strategies to increase homing and migration of cord blood cells are also under development using prostaglandin E2, CD 26/dipeptidyl peptidase (DPP-IV) and Fucosylation. [38][39][40] All of these approaches are in early clinical trials and are showing promising results. 41 Strategies to support immune reconstitution are more challenging but the emergence of new antivirals (Chimerix CMX001) and third-party cytotoxic T lymphocytes appear to have benefit in pilot clinical trials.…”

Section: Ucbt In Pediatricsmentioning

confidence: 99%

Umbilical cord blood donation: public or private?

Ballen

Verter²,

Kurtzberg

2015

Bone Marrow Transplant

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Umbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and ∼ 35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing ∼ 4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released ∼ 30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn's cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking.

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Section: Ucbt In Pediatricsmentioning

confidence: 99%

Umbilical cord blood donation: public or private?

Ballen

Verter²,

Kurtzberg

2015

Bone Marrow Transplant

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“…A number of strategies have been proposed to reduce the risk of graft failure after UCBT, including the use of multiple units, 27 intrabone infusion of the UCB unit, 28 co-infusion of purified stem cells from a haploidentical family donor, 29,30 administration of molecules facilitating stem cell homing, 31 and the co-infusion of ex-vivo expanded progenitor cells 32,33 or mesenchymal stromal cells. All the above strategies were reported to give promising results, but so far no definitive conclusion can be drawn on their long-term outcome or reproducibility.…”

mentioning

confidence: 99%

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Ruggeri¹,

Labopin²,

Sormani³

et al. 2014

Haematologica

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on behalf of Eurocord, Cord Blood Committee EBMT and NetcordInternational audienceUmbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42

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“…Additional approaches not covered in this review that are under investigation to accelerate hematopoietic and/or cellular immune reconstitution following UCBT include ex vivo expansion of UCB with nicotinamide and the non-altered T-cell fraction, ex vivo enforced fucosylation with fucosyltransferase IV and guanosine diphosphate fucose, inhibition of dipeptidyl peptidase (DDP-4) by sitagliptin, ex vivo expansion with cytokines and StemRegenin 1 and the use of UCB-derived anti-viral CTLs are just a few of the newer contemporary approaches for ex vivo CB graft engineering being investigated at the present time. [51][52][53][54][55][56] CONFLICT OF INTEREST DAL has financial or ownership interest relating to ex vivo expansion of NK cells in Intrexon Corporation, Ziopharm Oncology and Cyto-Sen Therapeutics. The remaining authors declare no conflict of interest.…”

Section: Discussionmentioning

confidence: 99%

Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients

Cairo

Tarek

Lee

et al. 2015

Bone Marrow Transplant

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Cord blood (CB) transplantation is an alternate source of human hematopoietic progenitor cells for allogeneic stem cell transplantation in children and adolescents with both malignant and nonmalignant diseases. Current limitations included delay in hematopoietic reconstitution, increased incidence of primary graft failure and slow cellular immunoreconstitution. These limitations lead to a significant increase in primary graft failure, infectious complications and increased transplant-related mortality. There is a number of experimental approaches currently under investigation including cellular engineering to circumvent these limitations. In this review, we summarize the recent findings of utilizing ex vivo CB expansion with Notch1 ligand Delta 1, mesenchymal progenitor cells, the use of human placenta-derived stem cells and CB-derived natural killer cells. Early and preliminary results suggest some of these experimental cellular strategies may in part ameliorate the incidence of primary graft failure, delays in hematopoietic reconstitution and/or slowness in cellular immune reconstitution following unrelated CB transplantation.

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In Vivo DPP-4 Inhibition to Enhance Engraftment of Single-Unit Cord Blood Transplants in Adults with Hematological Malignancies

Cited by 119 publications

References 46 publications

Umbilical cord blood donation: public or private?

Umbilical cord blood donation: public or private?

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients

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