HHV-6 Encephalitis in Pediatric Unrelated Umbilical Cord Blood Transplantation: Role for Ganciclovir Prophylaxis?

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4667-4667
Author(s):  
Frankie Wai Tsoi Cheng ◽  
Vincent Lee ◽  
Wing Kwan Leung ◽  
Paul Kay Sheung Chan ◽  
Ting Fan Leung ◽  
...  

Abstract Abstract 4667 Background The role of ganciclovir as HHV-6 prophylaxis in unrelated hematopoietic stem cell transplant (HSCT) setting remains controversial. Methods We performed a 8-year retrospective review of patients received unrelated HSCT from January 2000 to September 2008. From January 2002, ganciclovir prophylaxis 5mg/kg twice daily for 7 days for all unrelated HSCT before transplant was adopted. The other transplant policies including antibacterial, antifungal, antiviral and graft-versus-host disease control policies remained unchange in that period. The prevalence of HHV-6 encephalitis was studied before and after the change in policy. Result Fifty-four unrelated HSCT were performed from January, 2000 to September, 2008. Total four cases (7.4%) of HHV-6 encephalitis were diagnosed. Two cases out of 16 cases (12.5%) diagnosed before adoption of the policy; 2 cases out of 38 cases (5.3%) diagnosed afterward. All of them were unrelated umbilical cord blood (UCB) transplant recipients. Two cases had significant residual neurological deficit and refractory seizure. The other two cases died of other transplant-related mortalities. Conclusion We conclude that HHV-6 encephalitis is still a rare complication of unrelated HSCT and may be more common in unrelated UCB transplantation. Routine use of ganciclovir as HHV-6 prophylaxis in all unrelated HSCT recipients may not be justified. Disclosures: No relevant conflicts of interest to declare.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 272-272 ◽  
Author(s):  
Jennifer Crombie ◽  
Laura Michelle Spring ◽  
Shuli Li ◽  
Robert Soiffer ◽  
Joseph Harry Antin ◽  
...  

272 Background: Readmission within 30 days of discharge has been perceived by the Centers for Medicare and Medicaid Services to be an indicator of poor healthcare quality, however it is unclear how accurately this applies to oncology patients. Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of readmission, but the incidence following umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence, reasons, and risk factors for readmission following UCBT. Methods: A retrospective review of patients receiving an UCBT at Dana-Farber/Brigham and Women’s Hospital between January 1, 2004 and December 31, 2013 was performed. The 30-day and the day +100, a traditional assessment point in transplantation, readmission rates were examined. Reasons for readmission, as well as sociodemographic and disease and stem cell transplant related variables were evaluated. Predictors of readmission were identified using multivariate regression analysis. Results: 33.6% (42/125) of patients were readmitted within 30 days of discharge. Of patients who survived until day +100, 46.7% (57/122) were readmitted within 100 days of UCBT. The most common cause for readmission was infection (38.3%), followed by fever without a source (14.8%) and graft vs. host disease (GVHD) (8.6%) (Table). A multivariate logistic regression model of the probability of being readmitted within 30 days and by day +100 suggested that infection during transplant admission was a significant risk factor for readmission (OR: 5.1, p=0.003 and OR: 2.9, p=0.014, respectively). Conclusions: There is a high rate of readmission within 30 days and by day +100 following UCBT. The most common causes of readmission were infection and fever without a source. Infection during the transplant admission predicted a higher risk of readmission, suggesting a possible group to target for interventions aimed at reducing readmissions and improving quality of care. [Table: see text]


Author(s):  
Liangliang Ren ◽  
Ling Li ◽  
Lei Zhang ◽  
Xin Li ◽  
xiaorui Fu ◽  
...  

Umbilical cord blood allogeneic hematopoietic stem cell transplantation(UCBT) has been gradually applied in the treatment of patients with blood system diseases. This paper reports a case of a child patient with highly invasive T-cell lymphoma who underwent UCBT after chemotherapy and developed minimal change glomerulopathy after transplantation.


Blood ◽  
2010 ◽  
Vol 116 (4) ◽  
pp. 649-652 ◽  
Author(s):  
Shinsuke Takagi ◽  
Yasunori Ota ◽  
Naoyuki Uchida ◽  
Koichi Takahashi ◽  
Kazuya Ishiwata ◽  
...  

Abstract Although allogeneic hematopoietic stem cell transplantation has recently been applied to patients with myelofibrosis with reproducible engraftment and resolution of marrow fibrosis, no data describe the outcomes of umbilical cord blood transplantation. We describe 14 patients with primary (n = 1) and secondary myelofibrosis (n = 13) who underwent reduced-intensity umbilical cord blood transplantation. Conditioning regimens included fludarabine and graft-versus-host disease prophylaxis composed cyclosporine/tacrolimus alone (n = 6) or a combination of tacrolimus and mycophenolate mofetil (n = 8). Thirteen patients achieved neutrophil engraftment at a median of 23 days. The cumulative incidence of neutrophil and platelet engraftment was 92.9% at day 60 and 42.9% at day 100, respectively. Posttransplantation chimerism analysis showed full donor type in all patients at a median of 14 days. The use of umbilical cord blood could be feasible even for patients with severe marrow fibrosis, from the viewpoint of donor cell engraftment.


Author(s):  
Juan Montoro ◽  
Jaime Sanz

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.


1993 ◽  
Vol 16 (5_suppl) ◽  
pp. 113-115 ◽  
Author(s):  
R. Miniero ◽  
U. Ramenghi ◽  
N. Crescenzio ◽  
L. Perugini ◽  
A. Busca ◽  
...  

Human umbilical cord blood as an alternative source of hematopoietic stem cells for bone marrow reconstitution, has recently been demonstrated to yield successful HLA-matched placental blood grafts in children. It has been shown that cord blood contains sufficient progenitor cells to effect hematological reconstitution. Since then, more than 25 cord blood stem cells (CBSCs) transplants have been performed worldwide for the treatment of a variety of malignant and nonmalignant diseases. The majority of the grafts performed thus far have utilized CBSCs from HLA-identical siblings. However, much of the interest in this setting is devoted to the potential use of CBSCs for HLA-mismatched and unrelated transplants. Preliminary results suggest that allorecognition and graft-versus-host disease may be less intense in CBSCs transplants than in recipients of similarly compatible bone marrow. This review summarizes the results and potential future applications of cord blood transplantation.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 225-225 ◽  
Author(s):  
Pablo A. Ramirez ◽  
John E. Wagner ◽  
Todd Defor ◽  
Bruce R. Blazar ◽  
Michael Verneris ◽  
...  

Abstract Abstract 225 Double umbilical cord blood (dUCB) transplantation (dUCBT) is a strategy to overcome dose limitation in adult recipients. It is established that after dUCBT, one unit will predominate by day +100 after transplant in >95%. While in some studies order of infusion has been associated with unit predominance, this has not been reproduced in an analysis at our center. However, significant differences in UCB infusion between these two analysis were present. In particular, at our center, unit order of infusion is random and the second infusion is within minutes of the first, while this prior study separated infusion time by 6 hours. Between 2001 and 2009, 262 patients with hematologic malignancies underwent a dUCBT and engrafted. Of these, 233 were >18 years of age with 39% conditioned with cyclophosphamide (CY) 60 mg/kg, fludarabine (FLU) 75 mg/m2 and total body irradiation (TBI) 1320–1375 cGy and 61% with CY 50 mg/kg, FLU 200 mg/m2 and TBI 200 cGy with 1/3 also receiving antithymocyte globulin (ATG); 100% received cyclosporine and mycophenolate mofetil posttransplant immunosuppression. Median recipient weight was 78 kg and median follow-up was 2.7 years (0.5-7.2). The following factors were considered in the logistic regression model: total nucleated cell (TNC), CD34+ and CD3+ cell and colony forming units-granulocyte macrophage (CFU-GM) doses, HLA match, sex and ABO-match, CXCR4 expression on CD34+ cells, order of infusion and cell viability. Cell viability, infused TNC, CD34+ and CD3+ cell and CFU-GM doses were remarkably similar between the predominating and non-predominating unit. By day 21, the predominating unit (i.e., representing >70% of hematopoiesis) was achieved in 73 of 90 (81%) patients after MA conditioning and in 88 of 145 (61%) patients after reduced dose conditioning (p<0.01). Subsequently, predominant unit chimerism in the bone marrow between MA and NMA was similar by day 100 (95% vs. 97%, p=0.35), day 180 (97% vs. 100%, p=0.3), day 365 (97% vs. 98%, p=0.84) and day 730 (94% vs. 93%, p=0.81). Notably, CD3+ cell dose and HLA were strongly associated with unit predominance. In the MA setting, CD3+ cell dose was the most significant factor that predicted unit predominance [OR 4.4 (95% CI, 1.8–10.6, p<0.01)]; while CD3+ cell dose [OR 2.1 (95%CI, 1.0–4.2, p=0.05)] and HLA-match [OR 3.4 (95%CI 1.0–11.4, p=0.05)] were independent predictors in the reduced intensity setting. In summary, immunological graft-graft interactions are likely responsible for unit predominance. While the combined CD34 dose and CFU-GM dose from the two UCB units are critical for rate of neutrophil recovery (data previously reported), CD3 dose and HLA match after reduced intensity conditioning are important in determining which unit will ultimately predominate. These findings have potential implications in the algorithm of graft selection. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2643-2652 ◽  
Author(s):  
Lisa Marie Serrano ◽  
Timothy Pfeiffer ◽  
Simon Olivares ◽  
Tontanai Numbenjapon ◽  
Jennifer Bennitt ◽  
...  

AbstractDisease relapse is a barrier to achieving therapeutic success after unrelated umbilical cord-blood transplantation (UCBT) for B-lineage acute lymphoblastic leukemia (B-ALL). While adoptive transfer of donor-derived tumor-specific T cells is a conceptually attractive approach to eliminating residual disease after allogeneic hematopoietic stem cell transplantation, adoptive immunotherapy after UCBT is constrained by the difficulty of generating antigen-specific T cells from functionally naive umbilical cord-blood (UCB)–derived T cells. Therefore, to generate T cells that recognize B-ALL, we have developed a chimeric immunoreceptor to redirect the specificity of T cells for CD19, a B-lineage antigen, and expressed this transgene in UCB-derived T cells. An ex vivo process, which is compliant with current good manufacturing practice for T-cell trials, has been developed to genetically modify and numerically expand UCB-derived T cells into CD19-specific effector cells. These are capable of CD19-restricted cytokine production and cytolysis in vitro, as well as mediating regression of CD19+ tumor and being selectively eliminated in vivo. Moreover, time-lapse microscopy of the genetically modified T-cell clones revealed an ability to lyse CD19+ tumor cells specifically and repetitively. These data provide the rationale for infusing UCB-derived CD19-specific T cells after UCBT to reduce the incidence of CD19+ B-ALL relapse.


Blood ◽  
2014 ◽  
Vol 124 (22) ◽  
pp. 3201-3211 ◽  
Author(s):  
Ioannis Politikos ◽  
Vassiliki A. Boussiotis

Abstract Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for patients without HLA-matched adult donors. UCB contains a low number of nucleated cells and mostly naive T cells, resulting in prolonged time to engraftment and lack of transferred T-cell memory. Although the first phase of T-cell reconstitution after UCB transplantation (UCBT) depends on peripheral expansion of transferred T cells, permanent T-cell reconstitution is mediated via a central mechanism, which depends on de novo production of naive T lymphocytes by the recipient’s thymus from donor-derived lymphoid-myeloid progenitors (LMPs). Thymopoiesis can be assessed by quantification of recent thymic emigrants, T-cell receptor excision circle levels, and T-cell receptor repertoire diversity. These assays are valuable tools for monitoring posttransplantation thymic recovery, but more importantly they have shown the significant prognostic value of thymic reconstitution for clinical outcomes after UCBT, including opportunistic infections, disease relapse, and overall survival. Strategies to improve thymic entry and differentiation of LMPs and to accelerate recovery of the thymic stromal microenvironment may improve thymic lymphopoiesis. Here, we discuss the mechanisms and clinical implications of thymic recovery and new approaches to improve reconstitution of the T-cell repertoire after UCBT.


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