Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients

Milano, Filippo; Pergam, Steven A.; Xie, Hu; Leisenring, Wendy; Gutman, Jonathan A.; Riffkin, Ivy; Chow, Victor A.; Boeckh, Michael; Delaney, Colleen

doi:10.1182/blood-2011-06-361618

Cited by 96 publications

(87 citation statements)

References 48 publications

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“…Saavedra S [34] reported that all of their patients (100%) experienced at least 1 infectious episode, and 66% of them suffered from severe infections. Bloodstream infections occurred in 10% of the patients in our study, and the rate of CMV reactivation in the overall series was 56.7% (17 of 30), which was similar to the reports in the literature [35,36], but the number of CMV-DNA copies decreased significantly compared to that in other reports. None of the patients developed CMV disease, whereas Milano F [36] reported an incidence of CMV disease of 5-28%.…”

Section: Discussionsupporting

confidence: 90%

“…Bloodstream infections occurred in 10% of the patients in our study, and the rate of CMV reactivation in the overall series was 56.7% (17 of 30), which was similar to the reports in the literature [35,36], but the number of CMV-DNA copies decreased significantly compared to that in other reports. None of the patients developed CMV disease, whereas Milano F [36] reported an incidence of CMV disease of 5-28%. Sauter C [14] reported that UCBT without ATG was associated with prompt T cell recovery, which might have led to the reduction in CMV infection.…”

Section: Discussionsupporting

confidence: 90%

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A myeloablative conditioning regimen with fludarabine demonstrates good results in UCBT for 30 pediatric patients with hematologic malignancies, especially acute lymphoblastic leukemia

Tong¹,

Sun²,

Liu³

et al. 2014

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We retrospectively analyzed the safety and efficacy of a myeloablative conditioning regimen with fludarabine (FLU) in unrelated cord blood transplantation (UCBT) of 30 pediatric patients with hematologic malignancies. The conditioning regimen consisted of FLU, busulfan (BU) and cyclophosphamide (CY). All of the patients received Cyclosporine (CSA) and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prophylaxis. We achieved high engraftment rates (96.7%) and rapid hematopoietic reconstitution. Acute GVHD occurred in 12 cases of the 29 engraftment patients (41.4%), and 6 cases (20.7%) were of grade III-IV. Chronic GVHD only occurred in 1 of 28 evaluable patients (3.6%). Twenty-three patients (76.7%) became infected, and 3 cases (10.0%) died of severe infections. Cytomegalovirus (CMV) reactivation occurred in 70.0% of the patients, but no CMV diseases were observed, nor did any patients die of CMV infection. The cumulative incidence of relapse (6.7%) was significantly reduced, and none of the acute lymphoblastic leukemia (ALL) patients relapsed. The 3-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 70.0%, respectively. The 3-year OS and EFS of the ALL patients was 75.0%. This conditioning regimen demonstrates good results and security in UCBT, especially in acute lymphoblastic leukemia. Key words: conditioning regimen, cord blood transplant, fludarabine, hematologic malignanciesUmbilical cord blood transplantation (UCBT) has increasingly been used as a therapeutic option for patients affected by many disorders of either hematologic or non-hematologic origin [1][2][3]. In comparison to bone marrow transplantation (BMT), UCBT offers the advantage of easier procurement with no risk for the donor. In addition, there are lower risks of transmitting infections and of developing both acute and chronic GVHD. Despite the lower incidence of acute and chronic GVHD in UCB transplant recipients, the risk of leukemia relapse is not increased [4,5]. UCBT allows also transplantation in the absence of full HLA compatibility in the donor/recipient pair. Moreover, UCBT from unrelated donors offers the advantage of rapid availability of cryopreserved cells, and the median time for a successful donor search is less than 1 month [6]. However, there are also some drawbacks with UCBT in comparison with BMT. The nucleated cells contained in umbilical cord blood constitute only 1/10 of the number of nucleated cells in the peripheral blood stem cells or bone marrow. Additionally, the T and B lymphocytes contained in umbilical cord blood are in their naïve state [7]. The limited number of cells and low immunogenicity of the nucleated cells could lead to the high incidence of engraftment failure and might slow hematopoietic and immune reconstitution, which could result in the high incidence of early opportunistic infections [8,9].How to increase the UCBT engraftment rate and reduce the incidence of infections is an important area of study. Researchers have attempted to solve both of these problems ...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

A myeloablative conditioning regimen with fludarabine demonstrates good results in UCBT for 30 pediatric patients with hematologic malignancies, especially acute lymphoblastic leukemia

Tong¹,

Sun²,

Liu³

et al. 2014

neo

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“…1,6,[17][18][19] The improved immune reconstitution in the group not receiving ATG prior to transplantation was associated with a lower incidence of reactivation of EBV, CMV, and/or adenovirus. Various reports have shown that UCBT recipients are at increased risk of viral reactivation because of the delayed immune recovery, [2][3][4][20][21][22] and early initiation of preemptive antiviral therapy is frequently used to prevent viral disease using a lower cutoff quadruplex DNA value in CB recipients. 5,6,23,24 Although we did not find MAC or RIC regimens to be predictors in this cohort, others have found ATG used in association with RIC regimens to further increase the risk of viral reactivation and specifically the risk of EBV posttransplantation lymphoproliferative disorder (PTLD).…”

Section: Discussionmentioning

confidence: 99%

Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome

Lindemans

Chiesa

Amrolia

et al. 2014

Blood

156

125

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Key Points• For good immune reconstitution and fewer viral reactivations, thymoglobulin should be omitted in cord blood transplants.• Because omission of thymoglobulin is associated with higher acute GVHD rates, further improvement of outcome may require individualized dosing.In vivo T-cell depletion might contribute to the delayed immune reconstitution observed after unrelated umbilical cord blood transplantation (UCBT). We studied the impact of early, late, and no antithymocyte globulin (ATG) on immune reconstitution and outcome. One hundred twenty seven children receiving UCBT in London or Utrecht were divided into 3 groups: early ATG (days 29 to 25; n 5 33), late ATG (days 25 to 0; n 5 48), and no ATG (n 5 46). The no-ATG group received mycophenolate mofetile 1 cyclosporin A as graft-versus-host disease (GVHD) prophylaxis, while the ATG groups received cyclosporin A 1 prednisone. End points studied were survival, immune recovery, infections, and GVHD. The probability of survival was similar in all groups: no ATG, 71% 6 8%; early ATG, 68% 6 9%; and late ATG, 61% 6 7%. CD3 1 , CD4 1 , and CD4 1-naive T-cell counts were significantly higher (P < .001) in the no-ATG group at 1, 2, 3, 6, and 12 months post-UCBT. In the no-ATG group, significantly fewer viral reactivations (P 5 .021) were noted. A higher probability of severe acute GVHD (aGVHD; 31%) was found in the no-ATG group compared with 18% (P 5 .018) for early-ATG and 5% (P < .001) for late-ATG groups. This was not associated with more chronic GVHD (cGVHD). (Blood. 2014;123(1):126-132)

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“…[13][14][15][16] At our institution, nearly 100% of CMV-seropositive UCBT patients reactivate CMV early posttransplant and require antiviral drug therapy. 17 Previous studies suggest that CMV-specific CD8 1 T cells cannot reliably be detected in UCBT recipients until .100 days after transplant, when thymopoiesis recovers. 14,18 In the few cases where CMV-specific T cells were detected before 100 days, the origin (cord blood or recipient) of these T cells and the breadth of viral antigens recognized were not determined.…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo

McGoldrick

Bleakley

Guerrero

et al. 2013

Blood

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Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients

Cited by 96 publications

References 48 publications

A myeloablative conditioning regimen with fludarabine demonstrates good results in UCBT for 30 pediatric patients with hematologic malignancies, especially acute lymphoblastic leukemia

A myeloablative conditioning regimen with fludarabine demonstrates good results in UCBT for 30 pediatric patients with hematologic malignancies, especially acute lymphoblastic leukemia

Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome

Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo

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