Abstract
The utilization of cord blood as a source of stem cells for transplantation has decreased in recent years. Although cord blood transplantation (CBT) is an established practice for the treatment of adult and pediatric patients with hematological malignancies, the high acquisition cost of CB units along with high transplant-related mortality due to delayed hematopoietic recovery and immune reconstitution have contributed to the slowing in widespread adoption of CBT. Strategies aimed to enhance speed of engraftment and ongoing clinical trials are investigating ways to make CBT more widely available. Meanwhile, the recent clinical data suggest that the choice of CBT might be preferable for patients with pre-transplant minimal residual disease. We review here the background data on the utilization of CB for the treatment of hematological malignancies, and discuss the current challenges and future directions in the field of CBT.
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References
Laughlin MJ, Barker J, Bambach B, Koc O, Rizzieri D, Wagner J et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 2001; 344: 1815–1822.
Laughlin MJ, Eapen M, Rubinstein P, Wagner J, Zhang M, Champlin R et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.
Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.
Kurtzberg J, Laughlin M, Graham M, Smith C, Olson J, Halperin E et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med 1996; 335: 157–166.
Barker J, Byam C, Kernan N, Lee S, Hawke R, Doshi K et al. Availability of cord blood extends allogeneic hematopoietic stem cell transplant access to racial and ethnic minorities. Biol Blood Marrow Transplant 2010; 16: 1541–1548.
Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 2014; 371: 339–348.
Eapen M, Rubinstein P, Zhang M, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.
Brunstein C, Gutman J, Weisdorf D, Woolfrey A, Defor T, Gooley T et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116: 4693–4699.
Atsuta Y, Morishima Y, Suzuki R, Nagamura-Inoue T, Taniquchi S, Takahashi S et al. Comparison of unrelated cord blood transplantation and HLA-mismatched unrelated bone marrow transplantation for adults with leukemia. Biol Blood Marrow Transplant 2012; 18: 780–787.
Ponce D, Gonzales A, Lubin M, Castro-Malaspina H, Giralt S, Goldberg J et al. Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match. Biol Blood Marrow Transplant 2013; 19: 904–911.
Newell L, Flowers M, Gooley T, Milano F, Carpenter P, Martin P et al. Characteristics of chronic GVHD after cord blood transplantation. Bone Marrow Transplant 2013; 48: 1285–1290.
Broxmeyer H, Kurtzberg J, Gluckman E, Auerbach A, Douglas G, Cooper S et al. Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplantation. Blood Cells 1991; 17: 313–329.
Broxmeyer HE, Hangoc G, Cooper S, Ribeiro R, Graves V, Yoder M et al. Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc Natl Acad Sci USA 1992; 89: 4109–4113.
Gluckman E, Broxmeyer H, Auerbach A, Friedman H, Douglas G, Devergie A et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 1989; 321: 1174–1178.
Brunstein C, Fuchs E, Carter S, Karanes C, Costa L, Devine S et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood 2011; 118: 282–288.
Majhail N, Mothukuri J, Brunstein C, Weisdorf D . Costs of hematopoietic cell transplantation: comparison of umbilical cord blood and matched related donor transplantation and the impact of posttransplant complications. Biol Blood Marrow Transplant 2009; 15: 564–573.
Barker J, Weisdorf D, DeFor T, Blazar B, McGlave P, Miller J et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 2005; 105: 1343–1347.
Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S et al. Pluripotent cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med 2000; 6: 1278–1281.
Varnum-Finney B, Wu L, Yu M, Brashem-Stein C, Staats S, Flowers D et al. Immobilization of Notch ligand, Delta-1 is required for induction of notch signaling. J Cell Sci 2000; 113: 4313–4318.
Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger R, Bernstein I . Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 2010; 16: 232–236.
Milano F, Heimfeld S, Riffkin I, Nicoud I, Appelbaum F, Bernstein I et al. Infusion of a non HLA-matched off-the-shelf ex-vivo expanded cord blood progenitor cell product following myeloablative cord blood transplantation is safe, decreases the time to hematopoietic recovery, and results in excellent overall survival. Blood 2014; 124: 46.
Thompson P, Rezvani K, Hosing C, Oran B, Olson A, Popat U et al. Umbilical cord blood graft engineering: challenges and opportunities. Bone Marrow Transplant 2015; 50: S55–S62.
Ballen KK, Gluckman E, Broxmeyer HE . Umbilical cord blood transplantation: the first 25 years and beyond. Blood 2013; 122: 491–498.
Dahlberg A, Delaney C, Bernstein ID . ex vivo expansion of human hematopoietic stem and progenitor cells. Blood 2011; 117: 6083–6090.
Cutler C, Multani P, Robbins D, Kim H, Hoggat J, Pelus L et al. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 2013; 122: 3074–3081.
Farag S, Srivastava S, Messina-Graham S, Schwartz J, Robertson M, Abonour R et al. In vivo DPP-4 inhibition to enhance engraftment of single-unit cord blood transplants in adults with hematological malignancies. Stem Cells Dev 2013; 22: 1007–1015.
Capitano M, Hangoc G, Cooper S, Broxmeyer H . Mild heat treatment primes human CD34+ cord blood cells for migration towards SDF-1α and enhances engraftment in an NSG mouse model. Stem Cells 2015; 33: 1975–1984.
Popat U, Mehta R, Rezvani K, Fox P, Kondo K, Marin D et al. Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation. Blood 2015; 125: 2885–2892.
de Lima M, McNiece I, Robinson S, Munsell M, Eapen M, Horowitz M et al. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med 2012; 367: 2305–2315.
Horwitz M, Chao N, Rizzieri D, Long G, Sullivan K, Gasparetto C et al. Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment. J Clin Invest 2014; 124: 3121–3128.
Boitano A, Wang J, Romeo R, Bouchez L, Parker A, Sutton S et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 2010; 329: 1345–1348.
Wagner J, Brunstein C, Boitano A, DeFor T, McKenna D, Sumstad D et al. Phase I/II trial of StemRegenin-1 expanded umbilical cord blood hematopoietic stem cells supports testing as a stand-alone graft. Cell Stem Cell 2016; 18: 144–155.
Wagner J, Eapen M, Carter S, Wang Y, Schultz K, Wall D et al. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med 2014; 371: 1685–1694.
Milano F, Gooley T, Wood B, Woolfrey A, Flowers M, Doney K et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med 2014; 375: 944–953.
Verneris M, Brunstein C, Barker J, MacMillan M, Defor T, McKenna D et al. Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood 2009; 114: 4293–4299.
Sun J, Kurtzberg J . Cord blood for brain injury. Cytotherapy 2015; 17: 775–785.
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Dahlberg, A., Milano, F. Cord blood transplantation: rewind to fast forward. Bone Marrow Transplant 52, 799–802 (2017). https://doi.org/10.1038/bmt.2016.336
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DOI: https://doi.org/10.1038/bmt.2016.336
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