Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution

Saavedra, Silvana; Jarque, Isidro; Sanz, Guillermo; Moscardó, Federico; Jiménez, Carmen; Martı́n, Guillermo; Plumé, Gema; Regadera, Anabel; Martı́nez, Jesús; Rubia, Javier de la; Acosta, Beatriz; Pemán, Javier; Pérez-Bellés, C; Gobernado, M; Sanz, MA

doi:10.1046/j.1469-0691.2002.00458.x

Cited by 28 publications

(21 citation statements)

References 39 publications

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“…Half of all infectious complications occur during the first 4-6 weeks following hematopoietic grafting, and most of them are bacterial in origin. [1][2][3][4] In spite of prophylaxis with oral antibiotics (mainly fluoroquinolones) used by some groups, most of the patients (90-100%) who receive myeloablative hematopoietic transplantation develop fever 22 and need initiating empirical antibiotic therapy that usually continues until neutropenia resolves. The use of empirical intravenous antibiotic therapy may actually prevent subsequent infections as reported in some studies by Table 3 Pathogens isolated in patients with bacteremia during FFE, according to treatment group All patients Study group patients (Pip-Tazo) Control group patients (Quinolone)…”

Section: Discussionmentioning

confidence: 99%

“…1 In spite of the reduction in post transplant aplasia associated with the use of peripheral blood stem cells and myeloid growth factors, more than 80% of patients develop fever and infections that are the leading cause of transplant-related mortality (TRM). [2][3][4] The most frequent approach to reducing the incidence of infection is the administration of oral antibiotic regimens, which aim to eliminate aerobic bacteria while maintaining colonization resistance by preserving the anaerobic flora. [5][6][7] In neutropenic patients, antibacterial chemoprophylaxis with fluorinated quinolones has reduced the incidence of Gram negative bacteremia.…”

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confidence: 99%

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Prophylaxis of early bacterial infections after autologous peripheral blood stem cell transplantation (PBSCT): a matched-pair study comparing oral fluoroquinolones and intravenous piperacillin–tazobactam

Solano

Gutiérrez

Martínez

et al. 2005

Bone Marrow Transplant

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Summary:The safety and efficacy of early bacterial prophylaxis with piperacillin-tazobactam were prospectively evaluated in 51 autologous peripheral blood stem cell transplantation (PBSCT) recipients. The results were compared with those obtained in 51 control patients receiving oral fluoroquinolones in a retrospective matched-pair control study. Overall, 76% of the study group and 98% of the control group developed at least one febrile episode during neutropenia (P ¼ 0.002). Time from neutropenia to the first febrile episode (FFE) was significantly longer in the study group than in the control group (P ¼ 0.04). Once a febrile episode appeared, the duration of fever was significantly longer in cases than in controls (median of 5 and 2 days respectively, Po0.001), and led to a more frequent use of empirical amphotericin B (AmB), not statistically significant (P ¼ 0.13). However, the total time of antibiotic administration was significantly greater in the control than in the study group (P ¼ 0.05). The duration of AmB treatment shows a trend toward a longer duration in the control than in study group (P ¼ 0.2). Overall, 86% of the Gram-positive bacteremia and 85% of the Gram-negative bacteria were susceptible to the tested antibiotics. Our study suggests that a subgroup of patients could benefit from prophylaxis with piperacillintazobactam without increasing toxicity or bacterial resistance. Bone Marrow Transplantation (2005) 36, 59-65.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Prophylaxis of early bacterial infections after autologous peripheral blood stem cell transplantation (PBSCT): a matched-pair study comparing oral fluoroquinolones and intravenous piperacillin–tazobactam

Solano

Gutiérrez

Martínez

et al. 2005

Bone Marrow Transplant

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“…Ten patients (37%) died prior to day 100. Infection was a direct cause of death in 4 patients [74]. Investigators from Japan reported cytomegalovirus (CMV) infection following UCB in 28 adults compared with sibling matched (R-BMT) and URD BM recipients.…”

Section: Ucb Basic Biology and Implications For Immune Reconstitutionmentioning

confidence: 99%

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Brown

Boussiotis

2008

Clinical Immunology

152

112

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Allogeneic stem cell transplantation has continued to evolve as a common procedure for the treatment of hematological malignancies and bone marrow failure. Donor bone marrow and mobilized peripheral stem cells are routinely employed for the reconstitution of immune function in leukemia and lymphoma patients following radiation and/or chemotherapy. Unfortunately, only 30% of patients have an HLA identical sibling donor and the identification of matched unrelated donors, particularly for minorities, can present an exceptional challenge. The transplantation of umbilical cord blood (UCB) represents the most recent strategy to expand the potential donor pool while maintaining an acceptable level of treatment related complications. First utilized in children, UCB transplantation permits a higher degree of HLA disparity while demonstrating a reduction in the incidence and severity of graft versus host disease (GvHD) compared to previous transplantation modalities. Despite the apparent decrease in GvHD, relapse rates remain comparable to transplantation with bone marrow or mobilized peripheral blood suggesting a strong graft versus leukemia/lymphoma (GvL) effect. However, several issues complicate the use of UCB transplantation and its extension to the treatment of adults. Many infections that afflict transplant patients are particularly frequent and more severe in the context of UCB transplantation. UCB T cells are naïve and therefore display less proliferation and IFN-γ production in response to cognate antigen and also appear to demonstrate defects in signal transduction mechanisms. In addition, UCB contain T regulatory cells (Treg) with more potent suppressor function than adult Treg. Furthermore, adult patients often require more total cells and CD34+ progenitors for transplantation than a single UCB unit can provide. Thus, strategies to expand selected subpopulations from UCB and the use of multiunit transplantation are areas of active research. This review will provide a condensed summary of the clinical history of UCB transplantation and emphasize the advantages and disadvantages of this approach to hematological malignancies in comparison to other methods of hematopoietic stem cell transplantation. Subsequently, it will mainly focus on the current challenges to immune reconstitution presented by UCB transplantation, recent research into their cellular and molecular mechanisms, and experimental approaches to overcome them.

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“…7 Third, allogeneic HSCT requires post-HSCT pharmacologic immunosuppression. The ensuing immunodeficient state renders HSCT recipients particularly susceptible to opportunistic infections that require T-cell control, such as caused by viruses [8][9][10][11] and fungi. 12 The profound alteration of T-cell immunity thus represents a still-unsolved core problem of HSCT (reviewed in Storek and Witherspoon 13 ).…”

Section: Introductionmentioning

confidence: 99%

Monocyte-mediated T-cell suppression and augmented monocyte tryptophan catabolism after human hematopoietic stem-cell transplantation

Hainz

Obexer

Winkler

et al. 2005

Blood

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IntroductionHematopoietic stem-cell transplantation (HSCT) profoundly alters host immunity by several mechanisms. First, a state of transient immunodeficiency is induced by the lymphocytotoxic effects of myeloablative and even nonmyeloablative preparative regimens. [1][2][3] Second, the transfusion of hematopoietic stem cells (HSCs) will modulate the recipient immune system, by eliciting host-versusgraft or graft-versus-host reactions in the allogeneic setting 4-6 and through immunomodulatory effects of the cytokines used to prepare HSCs in the autologous setting. 7 Third, allogeneic HSCT requires post-HSCT pharmacologic immunosuppression. The ensuing immunodeficient state renders HSCT recipients particularly susceptible to opportunistic infections that require T-cell control, such as caused by viruses [8][9][10][11] and fungi. 12 The profound alteration of T-cell immunity thus represents a still-unsolved core problem of HSCT (reviewed in Storek and Witherspoon 13 ). It occurs on the basis of discordant regeneration kinetics, a skewed T-cell receptor (TCR) repertoire, 14,15 and unbalanced function of individual T-cell subpopulations. [16][17][18] Dysfunction of T cells, frequently observed as a decreased lymphoproliferative response to activation, 16 has been attributed to numerous defects intrinsic to T cells. These include inappropriate cellular activation 19,20 and disturbed cytokine production, 21,22 especially of interleukin 2 (IL-2), 23,24 and increased susceptibility to apoptosis. 25,26 Here, we show that an impaired T-cell proliferative capacity early after HSCT may be mediated by potent suppressor activity of monocytes. Monocytes obtained from HSCT recipients (autologous and allogeneic) 1 to 6 months after HSCT, when cocultured with highly enriched T cells, had a profound inhibitory effect on the T-cell proliferative response to polyclonal stimulation in contrast to the effect of monocytes from healthy controls. In efforts to trace the mechanism, we discovered enhanced kynurenine production and release into cell culture supernatants by post-HSCT monocytes, particularly upon stimulation. Kynurenine, the first stable downstream metabolite of tryptophan, is generated through the enzymatic activity of indoleamine 2,3-dioxygenase (IDO; reviewed in Moffett and Namboodiri 27 ). Its release correlates to the rate of tryptophan catabolism, 28 which has been recently described to represent a key mechanism regulating T-cell responses in vitro and in vivo (reviewed in Mellor and Munn 29 ). The studies reported here suggest that after HSCT monocytes are dysfunctional, generating Patients, materials, and methods PatientsPeripheral blood samples of 31 recipients of HSCT were included in the study, which was approved by the institutional review boards of the participating institutions. Informed consent was obtained from all patients and/or their parents. Blood sampling was performed upon routine examinations to minimize harm to the patients. There were 21 pediatric and 10 adult patients; 16 males and 15 females. The m...

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Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution

Abstract: A high incidence of life-threatening infections and infection-related mortality was observed. A high rate of CMV infection in the early period, and death caused by multiresistant Gram-negative microorganisms in the late period, were the main findings in this series.

Cited by 28 publications

References 39 publications

Prophylaxis of early bacterial infections after autologous peripheral blood stem cell transplantation (PBSCT): a matched-pair study comparing oral fluoroquinolones and intravenous piperacillin–tazobactam

Prophylaxis of early bacterial infections after autologous peripheral blood stem cell transplantation (PBSCT): a matched-pair study comparing oral fluoroquinolones and intravenous piperacillin–tazobactam

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Monocyte-mediated T-cell suppression and augmented monocyte tryptophan catabolism after human hematopoietic stem-cell transplantation

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