Infectious Complications after Umbilical Cord-Blood Transplantation from Unrelated Donors

Juan Montoro, José Luis Piñana, Federico Moscardó and Jaime Sanz

Hematology Department, University Hospital La Fe and Department of Medicine, University of Valencia, Valencia, Spain.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared with other stem cell sources from adult donors, it has the advantages of immediate availability of cells, absence of risk to the donor and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the use of UCB is limited by the delayed post-transplant hematologic recovery due, at least in part, to the reduced number of hematopoietic cells in the graft and the delayed or incomplete immune reconstitution. As a result, severe infectious complications continue to be a leading cause of morbidity and mortality following UCB transplantation (UCBT). We will address the complex differences in the immune properties of UCB and review the incidence, characteristics, risk factors, and severity of bacterial, fungal and viral infectious complications in patients undergoing UCBT.


Over the past decades, remarkable progress has been made in several areas of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In particular, the use of alternative sources of progenitors stem cells, such as unrelated donors (URD), HLA-haploidentical family donors and umbilical cord-blood (UCB) grafts, has extended the transplant procedure to almost every patient in need of an allo-HSCT. Umbilical cord blood transplantation (UCBT) has rapidly become a valuable alternative for adult patients who lack a well HLA-matched donor providing similar outcomes compared to those allografted from URD in patients with hematological malignancies.[1-3] The lower requirements for HLA-matching between UCB grafts and recipients, the significantly faster availability of banked cryopreserved UCB units compared to other sources of allo-HSCT, the lower incidence of graft-versus-host disease (GVHD) while preserving the graft-versus-leukemia effect, and the lower risks of viral or other infectious disease transmission make UCB an attractive source of stem cells progenitors, particularly pertinent for those patients requiring urgent transplantation.[4] In addition, advances in UCB unit selection citeria, an essential aspect of UCBT, have led to a continuous improvement in the overall survival over the last years.[5]

Unfortunately, UCBT has several limitations, in particular, those associated with the prolonged period of neutropenia and the delayed immune reconstitution that has been related with a high transplantation-related mortality rate, up to 50% in several historical series.[1,2] As a result, infections remain the leading cause of morbidity and mortality during the first six months after transplantation.[6-10]

The infection patterns after an allo-HSCT are classically divided into 3 periods according to the immunodeficiency status of the recipients. These periods show marked differences among the characteristics and incidence of infections.[11] Briefly, the first phase comprised from day 0 to day +30, the intermediate from day +30 to +100 and the later beyond day +100. So far, it has been suggested that UCBT may follow these well-known differentiated patterns.[12] However, intrinsic characteristics related to this procedure such as the naïve immune system status of the recipient or the low nucleated and CD34+ cell dose may vary the pattern of the infectious complications when compared to other stem cell sources. In view of these concerns, several strategies have been explored to enhance engraftment and shorten neutropenia, such as the infusion of double-cord blood units, CD34+ cells ex-vivo expansion or co-infusion of CD34+ cells from a third-party donor. Regrettably, none of these new approaches has shown clear benefits compared with using a single un-manipulated cord blood unit.[13-16]

To date, few studies have analyzed the infectious complications among adult UCBT recipients. Here we review the incidence, characteristics, risk factors, and severity of bacterial, viral and fungal infectious complications in the UCBT setting reported in the literature. 

Particularities of the immune function after UCBT

As compared to allogeneic bone marrow transplantation and peripheral blood stem cell transplantation, UCBT has unique and inherent immunological properties and peculiarities.

First, the transmission of cord-blood-naïve T lymphocytes shows gradual expansion in response to antigens, higher threshold for stimulation by cytoquines and low cytotoxic ability.[17,18] Also, the potential benefit of passively transferring the humoral immunity from the donor to the recipient is lacking and may increase the risk of severe infections in the early period. Reconstitution of the T-cell compartment after UCBT is a slow process that can extend beyond the first year after transplant. T-cell recovery follows 2 different pathways with distinct kinetics: the thymus-independent pathway and the transferred donor T-cell or the recipient T cells that survive conditioning.[19,20] In essence, delayed immune reconstitution after UCBT is characterized by prolonged T-cell lymphopenia, compensatory recovery, and expansion of B and natural killer cells, impaired functional T-cell responses and thymopoietic regenerative failure associated with late memory T-cell skewing.[21] Also, UCB grafts contain relatively more CD4+CD25+ T regulatory cells (Treg) that may exert a more potent suppressor function than those from adult peripheral blood.[22]

Second, the use of anti-thymocyte globulin (ATG) as a component of some preparative regimens to prevent graft rejection influences the number and function of both, the central and the peripheral T cells infused within UCB grafts.[21] In this sense, several studies have observed a higher risk of infection with the use of ATG for UCBT, especially for viral infections.[21,23-26] In contrast, a recent comparative study in children with acute lymphoblastic leukemia showed no increased risk of infection or mortality related to the administration of ATG as a part of the conditioning regimen.[27] A detailed prospective assessment of immune reconstitution was undertaken in adult patients who underwent double UCB-HSCT with ATG or peripheral blood HLA-matched URD transplantation after a reduced-intensity conditioning regimen.[28] They showed that reconstitution of CD3+ T cells, including naive (CD45RO-) and memory (CD45RO+) CD4+ T cells, regulatory (CD4+CD25+) T cells, and CD8+ T cells was significantly delayed in the UCBT group. These findings suggested that increased risk of infections were specifically associated with a delayed reconstitution of all major T cell subsets and, interestingly, without an increased risk of relapse, suggesting that graft-versus-leukemia activity may be maintained by the early reconstitution of B cells and NK cells.

Finally, the low number of hematopoietic stem cells in UCB units has been associated with a higher incidence of infections because of a delayed neutrophil recovery.[2,7,29,30] However, when selecting an adequate single unit (conventionally defined as at least 2.5x107 nucleated cells/kg),[31] episodes, severity and deaths related to infections, seemed similar than with other stem cell sources [1,15]

In conclusion, more studies to improve the understanding of immune recovery after UCBT are needed.

Bacterial Infections

Severe bacterial infections remain a leading cause of morbidity and non-relapse mortality, especially before day 100 in patients undergoing UCBT.[12,32,33] However, few studies have specificaly adressed this issue in the UCBT setting.[30,33-35] Some of these studies have included a relatively small number of patients with few documented infections or have reported bacterial infections together with other severe infections.[6,12-14,32,36,37] It is, therefore, difficult to draw definite conclusions from these studies and efforts to better define the epidemiology, clinical characteristics, outcome and prognostic factors of bacterial infections after UCBT are warranted.

Reported incidence of bacterial infections ranged from 12% to 64% depending on the follow-up and the intensity of the conditioning regimen. Studies that were focused in the early/intermediate period (until day +100) reported an incidence ranging from 30 to 40%.[32,34] However, with longer follow-up, the incidence increased up to 50 to 70% at 4 years.[30,32] Interestingly, a bimodal distribution of baterial infections following UCBT has been proposed, with 25-40% episodes occurring within the first month and 25-30% after 100-180 days postransplant.[32,36] These data suggest an increased predisposition to late infections after UCBTrelated to the delayed immune reconstitution and/or the profound immunosuppression status derived from the GVHD and/or its treatment.[38]

Most studies have demonstrated a predominance of Gram-positive bacteria (GPB) bloodstream infections (BSI) occurring before day +100[6,33-35] and in others within the first year post-transplant.[14] Among the GPB, coagulase-negative staphylococcus (CoNS) were more common, especially before engraftment due to catheter-related infections (66% of CoNS), followed by Enterococcus species. Indeed, we also observed that the type of GPB infections differed significantly with longer follow-up observation time. However, we recently showed that overall Gram-negative rods (GNR) bacteremia in UCBT recipients was more common than GPB, with a ratio of 1.[6.30,32] Among GNR, Escherichia coli and Pseudomonas spp. were the most frequently isolated bacteria (32% and 29% of GNR, respectively).[30] Limited retrospective data suggest higher rates of BSI after UCBT compared to T-cell depleted haploidentical[36] or URD peripheral blood/bone marrow transplants.[32,37] These differences were restricted to the first 100 days after transplantation, however, beyond 100 days the incidence of BSI was comparable without differences in term of bacteremia-related mortality between stem cell sources.[32,37] Several studies have identified risk factors associated with increased risk of infections after UCBT depicts the profound immunosuppression status. The length of neutropenia, the delayed lymphocyte recovery, the low cell dose content of the graft, such as total nucleated cells, CD34+ and CD8+ cells are frequently observed in this scenario.[30,32,37]

BSI in the UCBT has a negative impact on mortality. The death rate of bacterial infections in the early postransplant period is around 25%, mostly due to GNR. Most frequent reported organisms causing fatal BSI were Acinetobacter spp., followed by Stenotrophomonas maltophilia, Klebsiella-Enterobacter-Serratia, Pseudomonas aeruginosa and Escherichia coli.[30,34] Early BSI (before day +7) significantly delayed neutrophil recovery and was an independent risk factor associated with non-relapse mortality.[30,33]

Table 1 summarizes bacterial infections characteristics in the UCBT published series. 

Table 1 Table 1. Bacterial infections characteristics in the UCBT published series. 

The delayed immune recovery, typically associated with the UCBT, is the primary limiting factor. Thus, there is an urgent need for developing strategies that overcome these conditions. To date, the only procedure that has demonstrated to shorten neutropenia is so called “haplo-cord” transplants in which CD34+ selected cells from the mobilized peripheral blood of an HLA-mismatched third-party donor are co-infused with the UCB unit. However, there were no differences in the rate of bacterial infection-related mortality post transplantation suggesting that such a benefit might not be clinically relevant.[13]

As a summary, bacterial infections are a major complication following UCBT particularly in the early/intermediate period. There are few but relevant differences in the incidence and characteristics of BSI in UCBT compared to other stem cell source. As in other procedures, BSI have an adverse impact on NRM in UCBT. Thus, further strategies focused on improving immune reconstitution are of utmost importance in this setting.

Fungal Infections

Again, studies focusing on invasive fungal infections (IFIs), both invasive candidiasis and invasive mold infections after UCBT are scarce. Described incidence varies among different transplantation centers depending on many factors such as the geographical region, patients diagnosis, conditioning, period of neutropenia and type of primary prophylaxis.[7,12-14,21,30,32,36,37,39-43]

Reported incidences of fungal infections ranged from 10% to 38%, of which 33%-100% occurred before day +50. Most common sites of IFI were invasive pulmonary infections followed by brain abscess and disseminated fungal infection. Of the sixty-three documented fungal infections published in the literature, 35 episodes of fungemia were caused by Candida, 19 by Aspergillus, 2 by Scedosporium, 2 by Zygomycetes, 1 by Cryptococcus, 1 by Saccharomyces, 1 by Fusarium, 1 by Trichosporon and 1 by Rhizopus.[6,12-14,30,36,37,41,42] A higher proportion of IFIs before day +100 after UCBT compared to bone marrow or peripheral blood stem cell transplantation has been suggested.[32] However, in the long term, the 3-year cu mulative incidence risk of developing an IFI in 192 patients was 12% and did not differ between stem cell sources. Candida was the most common fungal pathogen during the pre-engraftment period with an incidence of 2% and a median time to onset of 48 days (range, 4-122). Interestingly, all cases were due to non–Candida albicans species. No risk factors were found for Candida infection, except for a trend in cases of prolonged neutropenia beyond day +30. On the other hand, severe aGVHD, use of prednisone and delayed neutrophil recovery have been identified as risk factors for early invasive aspergillosis.[32,41]

More recently, advances in antifungal prophylaxis have diminished the incidence of IFIs in the early postransplant period and have resulted in a delayed onset, associated with GVHD and use of corticosteroids or other immunosuppressive therapies.[40,44] The incidence of late invasive fungal episodes (after day + 100) ranges from 10% to 66% with a time to diagnosis ranging from 148 to 1350 days [37,40,44]. Risk factors for late IFIs were acute and chronic GVHD, use of ATG for the treatment of severe GVHD and the use of nonmyeloablative conditioning regimen. [14,37,40,44]

Finally, no differences have been found in outcome after IFI, with a similar mortality rate after UCBT or transplant with other stem cell sources ranging from 7% to 86%.[13,21,30,32,36,41,43]

Table 2 summarizes fungal infections characteristics in the UCBT published series.

Table 2 Table 2. Fungal infections characteristics in the UCBT published series. 

Viral Infections

The UCB graft is pathogen-naïve, and infused T cells are considered antigen-inexperienced. Therefore UCBT recipients are at increased risk of severe viral infectios when compared with other graft sources, specially due to viral pathogens that require a strong T-cell immunity control such as for the herpes viruses family.[18,45-49] In the current review, we summarize the most relevant viral infections in the UCBT setting: cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus-6 (HHV-6).

CMV: Patients receiving UCBT are at high risk of CMV infection and disease because of the poor T-cell mediated cellular immune reconstitution.[50] Nevertheless, the incidence, outcome, and risk factors for CMV infection and illness after UCBT have been barely addressed and vary considerably across transplantation centers.[48,51-60] Higher rates of CMV infection and disease have been observed in seropositive recipient experiencing acute or chronic extensive GVHD.[52]
Only two retrospective studies have compared CMV infection and illness in UCBT or other stem cell sources.[52,58] Walker and colleagues evaluated episodes of CMV infection in 753 consecutive allo-HSCT patients. The 6-month cumulative incidence of CMV infection and disease in UCBT recipients was 21% and 6%, respectively. These results were very similar to those observed in recipients of peripheral blood or marrow grafts. Interestingly, CMV infection did not have an adverse impact on survival.[52] The study carried out by Mikulska et al., compared CMV infection in 80 UCBT recipients and 85 unrelated matched or mismatched donors. A higher incidence of late CMV infection and a longer duration of infections was seen in UCBT patients when compared with adult donor transplants in which donor and recipient were seropositive. No difference in mortality was observed.[52,58]
The relative efficacy of universal prophylaxis compared to a preemptive approach’s hard to establish. CMV-seropositive patients not receiving prophylaxis had a high incidence of CMV infection, ranging from 70% to 100% at day +100, along with an earlier presentation.[52-55,60] The incidence of CMV infection ranged from 41% to 79% in studies using prophylaxis with high-dose acyclovir, ganciclovir or valganciclovir.[48,52,56,61-63] The incidence of CMV disease after UCBT ranged from 1% to 18% according to differences in conditioning regimens, methods of CMV prevention, patient characteristics, and other variables.[48,52-54,57,60,63] An incidence of CMV disease of 16% at day +100 was reported using preemptive therapy with ganciclovir or foscarnet in a series of 140 UCBT recipients.[55] Another study from our group using prophylaxis, the risk of CMV disease in CMV-seropositive recipients was 3% at day +100 but increased to 12% at 1 year after transplantation.[51] This finding is consistent with previous studies and supports the hypothesis that CMV prophylaxis can delay recovery of CMV-specific T cell immunity.[64] We also showed similar overall survival, non-relapse mortality, and infection-related mortality in CMV-seropositive and -seronegative patients, suggesting that prophylaxis with either intravenous ganciclovir or oral valganciclovir may overcome the survival disadvantage of CMV-seropositive patients in the setting of UCBT.[63]

EBV: EBV reactivation and EBV associated post-transplantation lymphoproliferative disorder (EBV-PTLD) does not seem to be increased in myeloablative UCBT compared to other unrelated donor transplants. The reported incidence of EBV viremia or PTLD in this setting is around 3-5%.[23,49,65] However, EBV related complications increase exponentially after UCBT using ATG in reduced intensity conditioning regimens with a reported incidence of EBV viremia and PTLD of 18% and 13%, respectively.[23,49,65-68] In addition, despite the fact that studies are heterogeneous with respect to patients, disease, and transplant characteristics, a higher incidence of EBV-PTLD has been suggested in patients with Hodgkin’s disease.[65,68] The clinical presentation of PTLD may also be somewhat different showing early onset (median time of 75 days), frequent disseminated disease and extranodal involvement commonly affecting liver and spleen.[49,65,66] The clinical course was aggressive with high mortality despite the administration of rituximab or chemo-immunotherapy when feasible.[65,67-69]

HHV-6: HHV-6 reactivation is frequent after UCBT and can be detected in over 80% of patients early after transplantation.[45,70-74] The clinical significance of viral reactivation is unknown, although it has been associated with many complications including encephalitis, marrow suppression and delayed engraftment, skin rash, hepatitis, interstitial pneumonia and an increased risk of developing aGVHD. A recent meta-analysis showed an increased prevalence of HHV-6 reactivation and severity of HHV-6 associated disease in patients receiving UCBT in comparison to other stem cell sources, recommending a closely monitoring for HHV-6 reactivation in this setting.[75] A more recent study investigated HHV-6 reactivation within 60 days of transplantation in stem cell transplants using single UCB, double UCB, or UCB plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source. Indeed, they did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. However, HHV-6 reactivation was associated with subsequent development of acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4; p = 0.004).[76]


Over the past three decades, remarkable progress has been made in the use of UCB as an alternative stem cell source for allogeneic transplantation for patients lacking a suitable HLA-matched donor. However, UCBT is still limited by the low cell dose of the graft and the slow or incomplete immune reconstitution, resulting in a high transplantation-related mortality (TRM) due to infections. It’s hard to compare the impact on infection risk of UCB with other transplant strategies since there are no randomized studies. The sequential post-transplant periods: early (<30 days), intermediate (days +30 to +100) and late (days > +100) are associated with characteristic patterns of infectious complications after UCBT. Efforts to improve graft selection, shorten neutropenia, enhance immune reconstitution and develop prevention and supportive care measures are wanted and should be the primary focus of clinical research in the field.


  1. Rocha V, Labopin M, Sanz G, et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med. 2004;351(22):2276-2285. PMid:15564544    
  2. Laughlin MJ, Eapen M, Rubinstein P, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med. 2004;351(22):2265-2275. PMid:15564543  
  3. Takahashi S. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood. 2004;104(12):3813-3820. PMid:15280199   
  4. Ruggeri A, Ciceri F, Gluckman E, et al. Alternative donors hematopoietic stem cells transplantation for adults with acute myeloid leukemia: Umbilical cord blood or haploidentical donors? Best Practice & Research Clinical Haematology. 2010;23(2):207-216. PMid:20837332    
  5. Barker JN, Byam C, Scaradavou A. How I treat: the selection and acquisition of unrelated cord blood grafts. Blood. 2011;117(8):2332-2339. PMid:21149636 PMCid:PMC3062405 
  6. Saavedra S, Sanz GF, Jarque I, et al. Early infections in adult patients undergoing unrelated donor cord blood transplantation. Bone Marrow Transplantation. 2002;30(12):937-943. PMid:12476288    
  7. Long GD, Laughlin M, Madan B, et al. Unrelated umbilical cord blood transplantation in adult patients. Biol. Blood Marrow Transplant. 2003;9(12):772-780. PMid:14677117    
  8. Cornetta K, Laughlin M, Carter S, et al. Umbilical cord blood transplantation in adults: results of the prospective Cord Blood Transplantation (COBLT). Biol. Blood Marrow Transplant. 2005;11(2):149-160. PMid:15682076    
  9. Sanz GF, Saavedra S, Planelles D, et al. Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Blood. 2001;98(8):2332-2338. PMid:11588027    
  10. Ruggeri A, Labopin M, Sormani MP, et al. Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen. Haematologica. 2014;99(9):1509-1515. PMid:24972767 PMCid:PMC4562541 
  11. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. Biol. Blood Marrow Transplant. 2009;15(10):1143-1238. PMid:19747629 PMCid:PMC3103296 
  12. Cahu X, Rialland F, Touzeau C, et al. Infectious Complications after Unrelated Umbilical Cord Blood Transplantation in Adult Patients with Hematologic Malignancies. Biology of Blood and Marrow Transplantation. 2009;15(12):1531-1537. PMid:19896076    
  13. Martino R, Bautista G, Parody R, et al. Severe infections after single umbilical cord blood transplantation in adults with or without the co-infusion of CD34+ cells from a third-party donor: results of a multicenter study from the Grupo Espa-ol de Trasplante Hematopoyético (GETH). Transplant infectious disease : an official journal of the Transplantation Society. 2015;17(2):221-233. PMid:25652036    
  14. Sauter C, Abboud M, Jia X, et al. Serious Infection Risk and Immune Recovery after Double-Unit Cord Blood Transplantation Without Antithymocyte Globulin. Biol. Blood Marrow Transplant. 2011;17(10):1460-1471. PMid:21310254 PMCid:PMC3165093 
  15. Wagner JE Jr., Eapen M, Carter S, et al. One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers. N Engl J Med. 2014;371(18):1685-1694. PMid:25354103 PMCid:PMC4257059 
  16. Mehta RS, Rezvani K, Olson A, et al. Novel Techniques for Ex Vivo Expansion of Cord Blood: Clinical Trials. Front Med (Lausanne). 2015;2:89.  
  17. Szabolcs P. T-lymphocyte recovery and function after cord blood transplantation. Immunologic research. 2011;49(1-3):56-69. PMid:21128006 PMCid:PMC3684067 
  18. Szabolcs P, Niedzwiecki D. Immune reconstitution after unrelated cord blood transplantation. Cytotherapy. 2007;9(2):111-122. PMid:17453963 PMCid:PMC2203410 
  19. Politikos I, Boussiotis VA. The role of the thymus in T-cell immune reconstitution after umbilical cord blood transplantation. Blood. 2014;124(22):3201-3211. PMid:25287708 PMCid:PMC4239330 
  20. Williams KM, Hakim FT, Gress RE. T cell immune reconstitution following lymphodepletion. Semin. Immunol. 2007;19(5):318-330. PMid:18023361 PMCid:PMC2180244 
  21. Komanduri KV, St John LS, de Lima M, et al. Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing. Blood. 2007;110(13):4543-4551. PMid:17671230 PMCid:PMC2234787 
  22. Godfrey WR, Spoden DJ, Ge YG, et al. Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function. Blood. 2005;105(2):750-758. PMid:15374887    
  23. Brunstein CG, Weisdorf DJ, DeFor T, et al. Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood. 2006;108(8):2874-2880. PMid:16804113 PMCid:PMC1895580 
  24. Cohen J, Gandhi M, Naik P, et al. Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning. Br. J. Haematol. 2005;129(2):229-239. PMid:15813851    
  25. Robin M, Marque-Juillet S, Scieux C, et al. Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome. Haematologica. 2007;92(9):1254-1257. PMid:17666361    
  26. Brown JA, Stevenson K, Kim HT, et al. Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis. Blood. 2010;115(20):4111-4119. PMid:20107229 PMCid:PMC3372946 
  27. Ponce DM, Eapen M, Sparapani R, et al. In Vivo T Cell Depletion with Myeloablative Regimens on Outcomes after Cord Blood Transplantation for Acute Lymphoblastic Leukemia in Children. Biol. Blood Marrow Transplant. 2015;21(12):2173-2179. PMid:26327630    
  28. Jacobson CA, Turki AT, McDonough SM, et al. Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation. Biol. Blood Marrow Transplant. 2012;18(4):565-574. PMid:21875503 PMCid:PMC3288552 
  29. Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001;97(10):2962-2971. PMid:11342418    
  30. Sanz J, Cano I, González-Barberá EM, et al. Bloodstream infections in adult patients undergoing cord blood transplantation from unrelated donors after myeloablative conditioning regimen. Biol. Blood Marrow Transplant. 2015;21(4):755-760. PMid:25585274    
  31. Bart T, Boo M, Balabanova S, et al. Impact of selection of cord blood units from the United States and swiss registries on the cost of banking operations. Transfus Med Hemother. 2013;40(1):14-20. PMid:23637645 PMCid:PMC3635979 
  32. Parody R, Martino R, Rovira M, et al. Severe Infections after Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation in Adults: Comparison of Cord Blood Transplantation with Peripheral Blood and Bone Marrow Transplantation. Biology of Blood and Marrow Transplantation. 2006;12(7):734-748. PMid:16785063    
  33. Yazaki M, Atsuta Y, Kato K, et al. Incidence and risk factors of early bacterial infections after unrelated cord blood transplantation. Biol. Blood Marrow Transplant. 2009;15(4):439-446. PMid:19285631    
  34. Narimatsu H, Matsumura T, Kami M, et al. Bloodstream Infection after Umbilical Cord Blood Transplantation Using Reduced-Intensity Stem Cell Transplantation for Adult Patients. Biology of Blood and Marrow Transplantation. 2005;11(6):429-436. PMid:15931631    
  35. Tomonari A, Takahashi S, Ooi J, et al. Bacterial bloodstream infection in neutropenic adult patients after myeloablative cord blood transplantation: experience of a single institution in Japan. Int. J. Hematol. 2007;85(3):238-241. PMid:17483061    
  36. Mulanovich VE, Jiang Y, de Lima M, et al. Infectious complications in cord blood and T-cell depleted haploidentical stem cell transplantation. Am J Blood Res. 2011;1(1):98-105. PMid:22432070 PMCid:PMC3301419 
  37. Hamza NS, Lisgaris M, Yadavalli G, et al. Kinetics of myeloid and lymphocyte recovery and infectious complications after unrelated umbilical cord blood versus HLA-matched unrelated donor allogeneic transplantation in adults. Br. J. Haematol. 2004;124(4):488-498. 
  38. Szabolcs P, Cairo MS. Unrelated umbilical cord blood transplantation and immune reconstitution. Semin. Hematol. 2010;47(1):22-36. PMid:20109609 PMCid:PMC3684393 
  39. Ito J, Kriengkauykiat, Dadwal S, Kriengkauykiat. Epidemiology and treatment approaches in management of invasive fungal infections. CLEP. 2011;175. PMCid:PMC3130903 
  40. Narimatsu H, Matsumura T, Kami M, et al. Bloodstream Infection after Umbilical Cord Blood Transplantation Using Reduced-Intensity Stem Cell Transplantation for Adult Patients. Biology of Blood and Marrow Transplantation. 2005;11(6):429-436. PMid:15931631    
  41. Miyakoshi S, Kusumi E, Matsumura T, et al. Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases. Biol. Blood Marrow Transplant. 2007;13(7):771-777. PMid:17580255    
  42. Ferrá C, Sanz J, la Cámara de R, et al. Unrelated transplantation for poor-prognosis adult acute lymphoblastic leukemia: long-term outcome analysis and study of the impact of hematopoietic graft source. Biol. Blood Marrow Transplant. 2010;16(7):957-966. PMid:20144909    
  43. Montesinos P, Rodríguez-Veiga R, Boluda B, et al. Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis. Bone Marrow Transplantation. 2015;50(11):1465-1472. PMid:26281032    
  44. Almyroudis NG, Fabian J, Hahn T, et al. Late infectious complications after cord blood stem cell transplantation. Eur J Clin Microbiol Infect Dis. 2009;28(11):1405-1408. PMid:19672638    
  45. Hill JA, Koo S, Guzman Suarez BB, et al. Cord-blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus-6-associated acute limbic encephalitis: a cohort analysis. Biol. Blood Marrow Transplant. 2012;18(11):1638-1648. PMid:22564265 PMCid:PMC3816521 
  46. Silva L de P, Patah PA, Saliba RM, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica. 2010;95(7):1183-1190. PMid:20410183 PMCid:PMC2895044 
  47. Vandenbosch K, Ovetchkine P, Champagne MA, et al. Varicella-zoster virus disease is more frequent after cord blood than after bone marrow transplantation. Biol. Blood Marrow Transplant. 2008;14(8):867-871. PMid:18640569    
  48. Beck JC, Wagner JE, DeFor TE, et al. Impact of cytomegalovirus (CMV) reactivation after umbilical cord blood transplantation. Biol. Blood Marrow Transplant. 2010;16(2):215-222. PMid:19786112 PMCid:PMC2819578 
  49. Dumas PY, Ruggeri A, Robin M, et al. Incidence and risk factors of EBV reactivation after unrelated cord blood transplantation: a Eurocord and Société Française de Greffe de Moelle-Therapie Cellulaire collaborative study. Bone Marrow Transplantation. 2013;48(2):253-256. PMid:22773124    
  50. Brown JA, Boussiotis VA. Umbilical cord blood transplantation: basic biology and clinical challenges to immune reconstitution. Clin. Immunol. 2008;127(3):286-297. PMid:18395491 PMCid:PMC2468219 
  51. Montesinos P, Sanz J, Cantero S, et al. Incidence, risk factors, and outcome of cytomegalovirus infection and disease in patients receiving prophylaxis with oral valganciclovir or intravenous ganciclovir after umbilical cord blood transplantation. Biol. Blood Marrow Transplant. 2009;15(6):730-740. PMid:19450758    
  52. Walker CM, van Burik J-AH, De For TE, Weisdorf DJ. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biology of Blood and Marrow Transplantation. 2007;13(9):1106-1115. PMid:17697973    
  53. Tomonari A, Takahashi S, Ooi J, et al. Impact of cytomegalovirus serostatus on outcome of unrelated cord blood transplantation for adults: a single-institute experience in Japan. Eur. J. Haematol. 2008;80(3):251-257. PMid:18081702    
  54. Takami A, Mochizuki K, Asakura H, et al. High incidence of cytomegalovirus reactivation in adult recipients of an unrelated cord blood transplant. Haematologica. 2005;90(9):1290-1292. PMid:16154862    
  55. Matsumura T, Narimatsu H, Kami M, et al. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients. Biol. Blood Marrow Transplant. 2007;13(5):577-583. PMid:17448917   
  56. Milano F, Pergam SA, Xie H, et al. Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients. Blood. 2011;118(20):5689-5696. PMid:21937692 PMCid:PMC3217367 
  57. Park M, Lee YH, Lee SH, et al. Cytomegalovirus infection in seropositive unrelated cord blood recipients: a study of 349 Korean patients. Ann Hematol. 2015;94(3):481-489. PMid:25417830    
  58. Mikulska M, Raiola AM, Bruzzi P, et al. CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus. Biol. Blood Marrow Transplant. 2012;18(1):92-99. PMid:21689774    
  59. Tong J, Sun Z, Liu H, et al. Risk factors of CMV infection in patients after umbilical cord blood transplantation: a multicenter study in China. Chin. J. Cancer Res. 2013;25(6):695-703. PMid:24385697 PMCid:PMC3872544 
  60. Dahi PB, Perales MA, Devlin SM, et al. Incidence, nature and mortality of cytomegalovirus infection after double-unit cord blood transplant. Leukemia & Lymphoma. 2015;56(6):1799-1805. PMid:25224458 PMCid:PMC4405462 
  61. Tomonari A, Iseki T, Ooi J, et al. Cytomegalovirus infection following unrelated cord blood transplantation for adult patients: a single institute experience in Japan. Br. J. Haematol. 2003;121(2):304-311. 
  62. Tong J, Sun Z, Liu H, et al. Risk factors of CMV infection in patients after umbilical cord blood transplantation: a multicenter study in China. Chin. J. Cancer Res. 2013;25(6):695-703. PMid:24385697 PMCid:PMC3872544 
  63. Montesinos P, Sanz J, Cantero S, et al. Incidence, Risk Factors, and Outcome of Cytomegalovirus Infection and Disease in Patients Receiving Prophylaxis with Oral Valganciclovir or Intravenous Ganciclovir after Umbilical Cord Blood Transplantation. Biology of Blood and Marrow Transplantation. 2009;15(6):730-740. PMid:19450758    
  64. Boeckh M, Leisenring W, Riddell SR, et al. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2003;101(2):407-414. PMid:12393659   
  65. Sanz J, Arango M, Senent L, et al. EBV-associated post-transplant lymphoproliferative disorder after umbilical cord blood transplantation in adults with hematological diseases. Bone Marrow Transplantation. 2014;49(3):397-402. PMid:24292521    
  66. Barker JN, Martin PL, Coad JE, et al. Low incidence of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorders in 272 unrelated-donor umbilical cord blood transplant recipients. Biol. Blood Marrow Transplant. 2001;7(7):395-399. 
  67. Blaes AH, Cao Q, Wagner JE, et al. Monitoring and preemptive rituximab therapy for Epstein-Barr virus reactivation after antithymocyte globulin containing nonmyeloablative conditioning for umbilical cord blood transplantation. Biol. Blood Marrow Transplant. 2010;16(2):287-291. PMid:19835968 PMCid:PMC4113553 
  68. Piñana JL, Sanz J, Esquirol A, et al. Umbilical cord blood transplantation in adults with advanced hodgkin's disease: high incidence of post-transplant lymphoproliferative disease. Eur. J. Haematol. 2016;96(2):128-135. PMid:25845981    
  69. Brunstein CG, Fuchs EJ, Carter SL, 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(2):282-288. PMid:21527516 PMCid:PMC3138683 
  70. Chevallier P, Hebia-Fellah I, Planche L, et al. Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source. Bone Marrow Transplantation. 2010;45(7):1204-1211. PMid:19935727    
  71. Sashihara J, Tanaka-Taya K, Tanaka S, et al. High incidence of human herpesvirus 6 infection with a high viral load in cord blood stem cell transplant recipients. Blood. 2002;100(6):2005-2011. PMid:12200359    
  72. Yamane A, Mori T, Suzuki S, et al. Risk factors for developing human herpesvirus 6 (HHV-6) reactivation after allogeneic hematopoietic stem cell transplantation and its association with central nervous system disorders. Biol. Blood Marrow Transplant. 2007;13(1):100-106. PMid:17222758    
  73. Zerr DM. Human herpesvirus 6 (HHV-6) disease in the setting of transplantation. Curr. Opin. Infect. Dis. 2012;25(4):438-444. PMid:22710317    
  74. Olson AL, Dahi PB, Zheng J, et al. Frequent human herpesvirus-6 viremia but low incidence of encephalitis in double-unit cord blood recipients transplanted without antithymocyte globulin. Biol. Blood Marrow Transplant. 2014;20(6):787-793. PMid:24548875 PMCid:PMC4097025 
  75. Scheurer ME, Pritchett JC, Amirian ES, et al. HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis. Bone Marrow Transplantation. 2012;48(4):574-580. PMid:23000642    
  76. Cirrone F, Ippoliti C, Wang H, et al. Early human herpes virus type 6 reactivation in umbilical cord blood allogeneic stem cell transplantation. Leukemia & Lymphoma. 2016;1-5.    


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