Cytomegalovirus Infection after Unrelated Cord Blood Transplantation (CBT) for Adults with Hematological Diseases.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5101-5101
Author(s):  
Tomohiro Myojo ◽  
Tomoko Matsumura ◽  
Hiroto Narimatsu ◽  
Kazuhiro Masuoka ◽  
Chiho Inokuchi ◽  
...  
Keyword(s):  
Cord Blood ◽  
Antiviral Treatment ◽  
Cord Blood Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Major Complication ◽  
Cmv Infection ◽  
Blood Transplantation ◽  
Cmv Reactivation ◽  
Cmv Antigenemia

Abstract Backgrounds: Cytomegalovirus (CMV) infection is a major complication after allogeneic transplantation; however clinical significance of CMV reactivation after cord blood transplantation remains unclear. Objective: We retrospectively investigated the incidence of CMV antigenemia, and CMV diseases, and its prognosis in adult patients who underwent reduced-intensity cord blood transplantation (RI-CBT) Patients/ Methods: We reviewed medical records of 77 patients who received RICBT at Toranomon Hospital between January 2002 and March 2004. Median age of the patients was 55 years (range 17–79). Underlying diseases were chemorefractory hematologic diseases (n=76) and severe aplastic anemia (n=4). Conditioning regimen comprised fludarabine (125 mg/m2), melphalan (80 mg/m2), and TBI 4-8Gy. GVHD prophylaxis was cyclosporine (n=69) or tacrolimus (n=11). Median total nucleated cells and CD34+ cells was 2.4×106 cells/kg (0.39–4.3), and 0.81×105 cells/kg (0.05–5.7) respectively. HLA disparity was 6/6 (n=3), 5/6 (n=12), 4/6 (n=63), and 3/6 (n=2). All patients were monitored CMV-antigenemia weekly and received pre-emptive gancyclovir or foscarnet. Results CMV antigenemia tested positive in 47 patients on a median of day 32 (range, 12–55) after RICBT. The cumulative incidence of CMV reactivation at day 100 was 0.70. Seven and 29 patients were treated with preemptive ganciclovir and foscarnet, respectively. Adverse events of them were myelosuppression in 3 patients given ganciclovir, and mild hyponatremia in a patient given foscarnet. CMV diseases developed in 15 patients on a median of day 39 (range 15–92); enterocolitis (n=13), pneumonia (n=1), and encephalitis (n=1). Seven of 15 patients were resolved with antiviral treatment, and the other patients were fatal with CMV infection. Univariate analysis showed any risk factors for CMV reactivation. Discussion CMV reactivation and diseases develop early after cord blood transplantation. Opitimal strategy for preventing CMV disease should be established in RICBT.

High Incidence of Cytomegalovirus Reactivation and Diseases Following Reduced-Intensity Cord Blood Transplantation for Adult Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2846-2846
Author(s):  
Hisashi Yamamoto ◽  
Naoyuki Uchida ◽  
Tomoko Matsumura ◽  
Shinsuke Takagi ◽  
Daisuke Kato ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Adult Patients ◽  
The Other ◽  
Haematopoietic Stem Cell ◽  
Cmv Infection ◽  
Blood Transplantation ◽  
Cmv Disease ◽  
Cmv Antigenemia ◽  
Reduced Intensity

Abstract Backgrounds: Although cytomegalovirus (CMV) infection is one of the major complication after allogeneic haematopoietic stem-cell transplantation, there is little information on the incidence and clinical features of CMV infection after reduced-intensity cord blood transplantation (RI-CBT) for Adult Patients. Patients/methods: We reviewed medical records of 166 patients who received RI-CBT at Toranomon Hospital between January 2002 and December 2005. Fifty Patients were excluded due to early death before engraftment, primary graft failure, and those who CMV antigenemia was not properly monitored. The remaining 116 patients were included in the analysis. Median age of the patients was 52 years (range 17–79). Underlying diseases were AML (n=34), ALL (n=13), MDS(n=15), ATL (n=13), CML (n=5), NHL (n=20), and others (n=16). Ninety-four of those were chemo-refractory, and the other were chemo-sensitive. Conditioning regimens comprised of fludarabine 125 mg/m2, melphalan 80 mg/m2 and total body irradiation (TBI) of (2–4 Gy)(n=107) and others(n=9). Graft-versus-host disease (GVHD) prophylaxis was cyclosporine (n=59) or tacrolimus (n=57). Median number of total nucleated cells and CD34+ cells was 2.6×106 cells/kg (range, 1.8–4.8), and 0.72×105 cells/kg (range, 0.1–4.4) respectively. HLA disparity was 6/6 (n=2), 5/6 (n=17), 4/6 (n=95), and 3/6 (n=2). All the patients were monitored weekly for CMV-antigenemia and received pre-emptive ganciclovir or foscarnet therapy. Results: Positive antigenemia was observed in 81 patients (70%) at a median of 34 days (range, 0–87) after RI-CBT. Median of maximal numbers of CMV antigen positive cell was 15 per 50,000 leukocytes (range, 1–848). CMV diseases developed in 22 patients (19%) at a median of 45 days (range, 20–350); enterocolitis (n=20), pneumonia (n=2), and adrenalitis (n=1). CMV-antigenemia remained negative in five patients with enterocolitis, even when CMV disease was diagnosed. Twenty of the 22 patients were improved using ganciclovir or foscarnet with only one recurrence. The other two had fatal outcome from CMV disease. Despite improvement of CMV disease, thirteen of the remaining 20 patients died due to infection (n=6 bacterial sepsis: 4, bacterial pneumonia: 1, gas gangrene:1), GVHD (n=2), disease progression (n=3), and others (n=2). Multivariate analysis revealed that grade II–IV acute GVHD were associated with on increased risk and developing CMV disease (p<0.05). Discussion: CMV reactivation and diseases develop at high frequency and at early period after RI-CBT. Once the disease has established, many of them had poor prognosis despite effective antiviral therapy. Further preventive strategy, such as development of more sensitive monitoring methods, or better prevention and control of GVHD, are warranted.

Higher Risk Of HHV6 Reactivation Among Patients Undergoing Umbilical Cord Blood Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. s4649-s4649
Author(s):  
Paulo Guilherme Alvarenga Gomes de Oliveira ◽  
Miriam Ueda ◽  
Juliana Monte Real ◽  
Eloisa de Sá Moreira ◽  
Ana Paula Vaz Carvalho ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Primary Infection ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Umbilical Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Human Herpesviruses ◽  
Cmv Reactivation

Introduction Human herpesviruses may cause severe complications after allogeneic hematopoietic stem cell transplantation (HSCT) such as interstitial pneumonia, encephalitis, delayed engraftment and post-transplant lymphoproliferative disease. A prospective survey on the incidence of primary infection or reactivation and clinical features of the eight human herpesviruses after HSCT has not yet been performed in Brazilian patients. Additionally, the impact of most of these infections on the transplant outcome is still unclear. Methods Between August 2010 and December 2012, peripheral blood samples from 99 allogeneic HSCT recipients were collected weekly after transplant until day +100, totalizing 824 samples. Median age was 15 years (range: 2-72), 60% were male, and acute leukemias were the most frequent diagnosis (54%). Stem cell sources were bone marrow in 62%, umbilical cord blood in 22% and mobilized peripheral blood in 16%. Fifty–one percent of donors were related. In a semi-automated workflow, the DNA was extracted from plasma in the QIAcube robot. A test based on quantitative real-time PCR (Taqman®) was optimized to screen and quantify all known human herpesviruses (CMV, EBV, HSV1, HSV2, VZV, HHV6, HHV7 and HHV8). The PCR reactions were set up using QIAgility robot for high-precision pipetting, and have been performed in a 7900HT (Life Technologies). Infected cell cultures and plasma specimens with a known viral load/amplicon copy number have been used as controls. The limit of detection of the qPCR was 5 copies per reaction, representing 250 copies/mL of plasma for all of the viruses. Results The incidences of primary infection or reactivation of herpesviruses were as follows: CMV=41%, HHV6=11%, HHV8=5.5%, EBV=3%, HSV1=3%, VZV=3%, HHV7=2%, and HSV2=1%. CMV reactivation was significantly more frequent in adults (72% vs. 27% for children, p<0.0001), and in those or receiving fludarabine (60% vs. 29%, p=0.03) and TBI (68% vs. 32%, p=0.01) in the conditioning regimen, but in a multivariate analysis, only age greater than 18 years remained significant (HR 3.4, 95%CI 1.7-6.7). HHV6 reactivation was significantly more frequent after umbilical cord blood transplant than after transplant from other sources (41% vs. 6%, respectively, p<0.0001) and in those receiving TBI in the conditioning regimen (19% vs. 3%, p=0.01) and in those receiving mycophenolate mofetil as GVHD prophylaxis (22% vs. 2%, p=0.004). In a multivariate analysis, only the use of cord blood remained significantly associated with the risk of HHV6 reactivation (HR 5.7, 95%CI 1.2-26.2). CMV reactivation was associated with a higher risk of acute graft-versus-host disease (GVHD), with a cumulative incidence at 100 days of 37% vs. 17% (p=0.02), but had no impact on the other outcomes. HHV6 reactivation had no significant impact on outcomes. HHV8 reactivation was associated with an increased risk of chronic GVHD (83% vs. 49%, p=0.001). Conclusion HHV6 primary infection or reactivation is more frequent after umbilical cord blood transplantation. CMV and HHV6 primary infection or reactivation are frequent after HSCT, but had no significantly impact on the transplant outcomes, possibly due to monitoring and preemptive measures. Monitoring these viruses constitute an essential measure to improve outcomes. Disclosures: No relevant conflicts of interest to declare.

Reactivation of Cytomegalovirus Following Reduced-Intensity Cord Blood Transplantation for Adult Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5454-5454
Author(s):  
Tomoko Matsumura ◽  
Masahiro Kami ◽  
Eiji Kusumi ◽  
Tomohiro Myojo ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Adult Patients ◽  
Hematopoietic Stem ◽  
Hematologic Diseases ◽  
Blood Transplantation ◽  
Cmv Disease ◽  
Cmv Reactivation ◽  
Cmv Antigenemia ◽  
Reduced Intensity

Abstract Backgrounds: Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem-cell transplantation. We and other groups recently reported the feasibility of cord blood transplantation using reduced-intensity regimens (RI-CBT) for adult patients with advanced hematologic diseases. We have little information on the clinical features of CMV reactivation after RI-CBT. Patients/methods: We reviewed medical records of 142 patients who received RI-CBT at Toranomon Hospital between January 2002 and March 2005. Median age of the patients was 55 years (range 17–79). Underlying diseases were chemorefractory hematologic diseases (n=136) and severe aplastic anemia (n=6). Conditioning regimens comprised fludarabine 125 mg/m2, melphalan 80 mg/m2 and total body irradiation (TBI) (4–8 Gy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporine (n=86) or tacrolimus (n=56). Median number of total nucleated cells and CD34+ cells was 2.7×106 cells/kg (0.39–4.8), and 0.73×105 cells/kg (0.03–5.7) respectively. HLA disparity was 6/6 (n=3), 5/6 (n=21), 4/6 (n=116), and 3/6 (n=2). All the patients were monitored CMV-antigenemia weekly and received pre-emptive ganciclovir or foscarnet. Results: CMV antigenemia tested positive in 77 patients on a median of day 36 (range, 4–87) after RI-CBT. Median of maximal CMV antigenemia was 22 per 50,000 leukocytes (range, 1–1806). CMV diseases developed in 18 patients on a median of day 40 (range 15–99); enterocolitis (n=18), and adrenalitis (n=1). CMV-antigenemia remained negative in two patients, when CMV disease was diagnosed. CMV disease was successfully treated using ganciclovir or foscarnet in 17 patients, and the other patient died of septic shock. Multivariate analysis revealed grade II–IV acute GVHD as a risk factor (odds, 95% CI). Discussion: CMV reactivation and diseases develop early after RI-CBT. Optimal strategy for preventing CMV disease should be established in RICBT.

Low Incidence of Cytomegalovirus Infection Associated with Rapid Cell-Mediated Immune Reconstitution after Cord Blood Transplantation Using Full Conditioning Regimen Containing 12Gy Total Body Irradiation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2926-2926
Author(s):  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Nobuhiro Tsukada ◽  
Takaaki Konuma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Cd8 T Cells ◽  
Immune Reconstitution ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Total Body ◽  
Cmv Reactivation ◽  
Cmv Antigenemia

Abstract The one of crucial questions in cord blood transplantation (CBT) is whether naïvity of cord blood lymphocytes could gain antigen-specific cellular immunity during early phase of transplant. Cytomegalovirus (CMV) infection is serious clinical problem in allogeneic transplant recipients and T cell immunity has known to have an important role in control of virus replication and prevention. During 1998 and 2006, 111 adults has received myeloablative regimens including 12 Gy of total body irradiation followed by CBT and a standard cyclosporine and methotrexate combination as GVHD prophylaxis in our institute. Patients also received intravenous immunoglobulin from day −3 to day 120 if the immunoglobulin level in the serum was less than 500 mg/dl. CMV antigenemia assay was performed twice a week after neutrophil recovery until day 120. Once CMV antigenemia is positive, patients received 5 mg/kg ganciclovir (GCV) once daily for at least 2 weeks as preemptive therapy. Ninety-two patients achieved engraftment with full donor chimerism and survived without disease relapse at the time of 120 days after CBT (82.8%). None of these 92 recipients had CMV disease during first 4 months after CBT. We have investigated the association of CMV reactivation status and their immune reconstitution process for 4 months after CBT in 39 patients who received CBT from 2002 to 2006 in our institute. CMV-specific CD4+ and CD8+ T cell recoveries were assessed by detection of interferon-g (IFN-g) producing cells with CMV antigen stimulation using intracellular cytokine staining. The positive was defined as more than 0.1% IFN-g positive cells among CD4+ or CD8+ T cell population. Six of 39 patients were CMV sero-negative and 33 patients were sero-positive. None of 6 CMV sero-negative receipients and 31 of 33 CMV sero-positive recipients observed CMV reactivation and received GCV therapy within the first 4 months. CMV-specific CD4+ T cells were detected in 30 of 31 recipients with positive CMV antigenemia (% positive: 55% at 1 month and 85% at 2 month), on the other hand, CMV-specific CD8+ T cells were detected in 14 out of 31 cases (% positive: 14% at 1 month and 22% at 2 month), both of which were comparable to post-bone marrow or peripheral blood transplants (CMV-specific CD4+ T cells were detected 18 of 21 recipients with positive CMV antigenemia and CMV-specific CD8+ T cells were detected in 12 out of 21). These data suggest that post-thymic naive T lymphocytes in cord blood might obtain memory and effector function in vivo with antigen-specific manner during early phase of post-transplant.

Blood Stream Infection after Reduced- Intensity Unrelated Cord Blood Transplantation for Adults with Hematologic Diseases.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5097-5097
Author(s):  
Hiroto Narimatsu ◽  
Masahiro Kami ◽  
Tomoko Matsumura ◽  
Tomohiro Myojo ◽  
Kazuhiro Masuoka ◽  
...  
Keyword(s):  
Cord Blood ◽  
Blood Stream Infection ◽  
Cord Blood Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Blood Stream ◽  
Hematologic Diseases ◽  
Blood Transplantation ◽  
Toranomon Hospital ◽  
Reduced Intensity

Abstract <Introduction> Blood stream infection (BSI) is a major problem after cord blood transplantation (CBT). However we have little information on it after reduced-intensity cord blood transplantation (RICBT). <Objective> This study aims to investigate clinical characteristics of BSI within 100 days of RICBT, and to identify its risk factors in the patient who received RICBT between January 2002 and March 2004 in Toranomon hospital. <Characteristics of patients and cord blood units/ Transplantation> We reviewed medical records of 77 patients with advanced hematologic diseases who underwent RICBT at Toranomon Hospital between January 2002 and June 2004. Median age of the patients was 55 years (17-79). Median number of infused cells and CD34+ cells were 0.86 x 10E7 (range; 1.73–4.31) and 0.8x10E7/kg (range; 0.01–46.1), respectively. Conditioning regimen consisted of fludarabine (125–150 mg/m2), melphalan (80–140 mg/m2), and TBI 2–8 Gy. GVHD prophylaxis was cyclosporine or tacrolimus. BSI must have met at least one of the following criteria previously described. (O’Grady, NP et al., Infect Control Hosp Epidemiol 2002) Mortality was considered to be directly attributable to a bloodstream pathogen if the patient died within 7 day after the last positive blood culture without any other probable cause of death, The patient’s characteristics were compared between those with or without BSI by univariate analysis. <Results> 149 episodes of BSI were observed in 31 patients. Cumulative incidence within 100 days was 0.40. Median onset was day 13 (1–98) after RICBT. The causative organisms were P. aeruginosa (47), S. epidermidis (44), E. faecium (13), T. beigelii (6), S. maltophilia (6), E. faecalis (5), E. coli (3), A. xylosoxidans (3) and others (22). 8 patients died of septicemia directly associated with BSI. A mortality rate was 26%. The causative organism included P. aeruginosa, A. xylosoxidans, S. maltophilia, S, aureus and gram-positive rod. Use of corticosteroid (p=0.012) and time to engraftment (p=0.003) were associated with the development of BSI. <Discussion/ Conclusion > BSI is a major complication in our series of RICBT. Use of corticosteroid and prolonged neutropenia might have increased the risk of incidence of BSI.

scholarly journals Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040467
Author(s):  
Seitaro Terakura ◽  
Takaaki Konuma ◽  
Masatsugu Tanaka ◽  
Yukiyasu Ozawa ◽  
Makoto Onizuka ◽  
...  
Keyword(s):  
Cord Blood ◽  
Study Protocol ◽  
Total Body Irradiation ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
Blood Transplantation ◽  
Total Body ◽  
Randomised Controlled

IntroductionA better long-term quality of life after umbilical cord blood transplantation (CBT) is observed compared with transplants from other alternative donors, whereas graft failure and relapses after CBT are still major issues. To minimise graft failure and relapse after CBT, intensification of conditioning by the addition of high-dose cytosine arabinoside (CA) and concomitant continuous use of granulocyte-colony stimulating factor (G-CSF) are reported to convey a significantly better survival after CBT in some retrospective studies. To confirm the effect of G-CSF plus CA combination, in addition to the standard conditioning regimen, cyclophosphamide (CY)/total body irradiation (TBI), we design a randomised controlled study comparing CA/CY/TBI with versus without G-CSF priming (G-CSF combined conditioned cord blood transplantation [G-CONCORD] study).Methods and analysisThis is a multicentre, open-label, randomised phase III study that aimed to compare G-CSF+CA/CY/TBI as a conditioning regimen for CBT with CA/CY/TBI. Patients with acute myeloid leukaemia or myelodysplastic syndrome, aged 16–55 years, are eligible. The target sample size is 160 and the registration period is 4 years. The primary endpoint is the 2-year disease-free survival rate after CBT. The secondary endpoints are overall survival, relapse, non-relapse mortality, acute and chronic graft-versus-host disease, engraftment rate, time to neutrophil recovery, short-term adverse events, incidence of infections and causes of death.This study employs a single one-to-one web-based randomisation between the with-G-CSF versus without-G-CSF groups after patient registration. Combination of high-dose CA and CY/TBI in both groups is used for conditioning.Ethics and disseminationThe study protocol was approved by the central review board, Nagoya University Certified Review Board, after the enforcement of the Clinical Trials Act in Japan. The manuscripts presenting data from this study will be submitted for publication in quality peer-reviewed medical journals. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journals.Trial registration numbersUMIN000029947 and jRCTs041180059.

scholarly journals Treosulfan-based conditioning is feasible and effective for cord blood recipients: a phase 2 multicenter study

2020 ◽  
Vol 4 (14) ◽  
pp. 3302-3310
Author(s):  
Filippo Milano ◽  
Jonathan A. Gutman ◽  
H. Joachim Deeg ◽  
Eneida R. Nemecek ◽  
Joachim Baumgart ◽  
...  
Keyword(s):  
Cord Blood ◽  
Clinical Outcomes ◽  
Hematopoietic Cell Transplantation ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Phase 2 ◽  
Acute Leukemias ◽  
Blood Transplantation

Abstract Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.

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