Valganciclovir Is Safe and Effective as Pre-Emptive Treatment for CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5300-5300
Author(s):  
Rocco Pastano ◽  
Federica Gigli ◽  
Giovanna Andreola ◽  
Liliana Calabrese ◽  
Fedro Peccatori ◽  
...  
Keyword(s):  
Stem Cell ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Oral Treatment ◽  
Drug Formulation ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Intravenous Ganciclovir ◽  
Hematopoietic Stem

Abstract RATIONALE OF STUDY: Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection still represents an important cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplant (HSCT). The standard pre-emptive treatment is based on intravenous administration of Ganciclovir (GCV). Valganciclovir (VGC), the pro-drug formulation of GCV is characterised by an excellent bio availability, making this drug suitable for oral administration. PATIENTS: Since March 2003 all patients treated with reduced (27 patients) or fully ablative (3 patients) conditioning regimens followed by sibling HSCT, were monitored with bi-weekly CMV/PCR and pp65/assays. Overall 15 episodes of CMV positivity were detected in seven patients. Patients resulted positive (3 cells pp65+ or 1000/100000 PCR +) started oral treatment with VGC 900 mg bid, for the first fourteen days, followed by 900 mg q.d. up to at least seven days after assays normalization. The median duration of therapy was 21 days (range 10–21 days). No significant toxicity was observed. All patients had a normalization of CMV/PCR and pp65/assays within fourteen days, with a response rate (RR) of 100%. In two patients the oral VGC therapy was changed to the intravenous administration of Foscavir, because of concomitant neutropenia and acute GvHD. CONCLUSION: Pre-emptive treatment of CMV infection with VGC is safe, feasible and effective. Furthermore, the oral administration of this drug in an outpatient setting, reduces significantly the costs compared with a therapy that needs hospitalization as intravenous Ganciclovir.

Oral Valganciclovir As Preemptive Therapy for Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5855-5855 ◽  
Author(s):  
Vildan Ozkocaman ◽  
Fahir Ozkalemkas ◽  
Ridvan Ali ◽  
Yasemin Karacan ◽  
Tuba Ersal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
Myeloid Leukemia ◽  
Preemptive Therapy ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Intravenous Ganciclovir ◽  
Hematopoietic Stem ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract Introduction: Cytomegalovirus (CMV) infection remains one of the most important complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). Preemptive therapy with oral VGC or intravenous ganciclovir has replaced universal prophylaxis. We investigated the effect of oral VGC as preemptive therapy on CMV reactivation or infection in AlloHSCT. Patient & Methods: We retrospectively studied 30 consecutive adult recipients of HLA-identical sibling allogeneic peripheral blood stem cell transplant from June 2011 through June 2014 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. Among 30 patients we studied the results of 13 patients with CMV DNA positivity. All 13 recipients and their donors were seropositive for CMV Ig G status. Their diagnosis of pretransplantation were as 8 acute myeloid leukemia (61 %) and 5 acute lymphocytic leukemia (39 %). Median age was 39 years (range 21-54). There were 9 men and 4 women (Table-1). The patients received no prophylaxis against CMV. Blood/serum samples from all patients were routinely monitored for CMV-DNA using PCR twice weekly. We iniciated pre-emptive therapy for CMV as the viral load was above and equal to 500 copies/ml in two consecutive samples. VGC was given twice daily 900 mg for 2 weeks, and maintened at a dose daily 900 mg until viral load is undetectable. Results: The PCR test was persistently negative in 17 patients (57 %) and positive at least once in 13 (43%)patients. All patients with CMV reactivations were on immunsupressive treatment. CMV infection was cleared in most patients within 2 weeks, but for those with stable or increasing CMV levels, the induction period was continued. Twelve patients were treated with oral VGC on an outpatient basis and they all became CMV negative after the first week of treatment. Only one patient received intravenous ganciclovir and he was also CMV negative after the first week of treatment. While no positivity was identified in any of the patients who received VGC on day 21, clinically unimportant low titer CMV positivity was noted in three of these patients. VGC was continued at same dose and no positivity was detected after 2-3 weeks. We were obligated interrupt VGC in only four patients for serious side effects namely neutropenia and thrombocytopenia. We did not observe CMV-related mortality. Conclusions: We concluded that VGC therapy could be safely used at outpatient clinics, with frequent monitorization to prevent severe myelotoxicity. In conclusion, based on our findings, oral VGC is effective and safe in the pre-emptive treatment of CMV disease following allo-HSCT. Therefore, preemptive strategy by oral VGC appears preferable to the prevention of CMV disease in alloHSCT with its advantage of effectiveness and usage in outpatient clinic condition. Table- 1: Management and outcome of the patient characteristics with CMV-reactivation Patients with CMV reactivation/Total number of patient 13/30 Median age, years (range) 39 (21-54) Gender Male Female 9 4 Diagnosis AML ALL 8 5 CMV serologic status Donor+/Recipient + 13 Preperative regimen Bu-Cy CY-TBI Flu/Amsc(FLAMSA) 8 4 1 GVHD propylaxis CSA+MTX CSA+MTX+MM 12 1 GVHD prior to CMV reactivation Acute chronic without GVHD 7 1 5 Prednisolone treatment at the time of starting VCG Yes No 8 5 IST at the time of starting VGC Yes No 13 0 Median duration of CMV reactivation (day) 44 (8-330) Viral load before antivial treament (copies/ml) 1153 (78-12800) Treatment VGC (900 mg, twice daily for induction) GC (5 mg/kg, twice daily for induction) VGC+GC 9 (70 %) 1 (7 %) 3 (23 %) Total treatment duration (day) 24 (10-51) CMV DNA at the end of the treatment Conversion to negative Persistently positive (low titer < 50 copies/ml) 10 (77 %) 3 (23 %) Serious side effects Interruption of therapy due to neutropenia Interruption of therapy due to thrombocytopenia Reactivation 3 (23 %) 1 (7 %) 2 (15 %) Abbreviations: AML: acute myeloid leukemia, ALL: acute lymphoblastic leukemia, CMV: cytomegalovirus,GVHD: graft-versus host disease, CSA: cylosporine, MTX: methotrexate, MMF: mycophenolate mofetil, PDN:prednizolone, IST: Immunosupressive treatment, VGC: valganciclovir, GC: ganciclovir, Bu: Busulfan, Cy: cylophosphamide, TBI: total body irradiation Disclosures No relevant conflicts of interest to declare.

Intravenous Busulfan: Pharmacokinetic Disposition and Clinical Outcomes in Children Undergoing Hematopoietic Stem Cell Transplant.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1760-1760
Author(s):  
Tal Schechter ◽  
Yaron Finkelstein ◽  
John Doyle ◽  
Zulfikaral Verjee ◽  
Gideon Koren ◽  
...  
Keyword(s):  
Stem Cell ◽  
Oral Administration ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Significant Proportion ◽  
Pharmacokinetic Parameters ◽  
Cell Transplant ◽  
Older Children ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Background: Conditioning regimens preceding hematopoietic stem cell transplantation (HSCT) for various malignant and non-malignant diseases in children often include busulfan. Busulfan administration may be complicated by hepatic veno-occlusive disease (HVOD). A relationship has been described between high systemic exposure to busulfan after oral administration, as measured by area under the curve (Bu-AUC) and HVOD. Recently, IV busulfan (IV Bu) administration has been reported to be associated with a much lower incidence of HVOD than oral administration in adults. Objectives: To describe the pharmacokinetics of IVBu in infants (&lt;1 year of age) and children. To determine the incidence of HVOD in children undergoing conditioning with IV Bu, and to correlate IV Bu AUC with the development of HVOD and neutrophil engraftment. Methods: Twenty-four children who underwent HSCT at The Hospital for Sick Children between April 2003 and September 2004 and received IV Bu as part of their conditioning regimen were included in this retrospective study. Diagnoses included: AML (6), metabolic storage disease (6), immune deficiency syndromes (4), histiocytosis (2), beta-thalassemia (2), WAS (1), MDS (1), CML (1), relapsed meduloblastoma (1). Initial IV Bu doses were based on actual patient weight: &lt;9kg =0.95mg/kg/dose; 9–16kg =1.2mg/kg/dose; 16–23kg =1.1mg/kg/dose; 24–34kg =0.95mg/kg/dose; &gt;34kg =0.8mg/kg/dose. Seven blood samples were drawn after the first IV Bu dose for determination of plasma busulfan concentrations. Pharmacokinetic parameters were calculated using 1-compartment analysis (WinNonLin 4.1). The third and subsequent IV Bu doses were adjusted to achieve an AUC of 900–1500μMol•min. HVOD (modified Baltimore criteria) and engraftment (ANC &gt; 0.5 x 109/L) were evaluated. Results: The median patient age was 3.5 years (range 3mo–16.9yrs), including 9 infants. Mean IV Bu pharmacokinetic parameters were: Cmax=4.7±0.9μMol; Vss=0.70±0.22L/kg; ke=0.005±0.001min−1; AUC=1256±320μMol•min. The mean IV Bu AUC of infants was not different from older children (1164μ±331Mol•min vs. 1311±311μMol•min; p=0.35). The mean Vss was higher in infants than older children (0.84±0.29L/kg vs. 0.62±0.10L/kg; p=0.025), but the mean clearance was not different when corrected for body weight. Twenty-three patients (95.8%) engrafted between day +10 to +27. HVOD was diagnosed in 6 patients (25%), including 3 infants. Five patients had moderate HVOD and one had fatal HVOD. Mean IV Bu AUC was 1317±310μMol•min and 1074±299μMol•min in the non- HVOD vs. the HVOD group, respectively (p=0.10). The number of children who did not engraft precluded assessment of the relationship between IV Bu AUC and engraftment. Conclusions: Busulfan Vss differs significantly between infants and older children. A significant proportion of patients developed HVOD. No association was observed between IV Bu AUC and the development of HVOD in children where busulfan doses are adjusted to achieve a target IV Bu AUC.

Haematopoietic Stem Cell Transplantation - An Experience from Developing World.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5036-5036
Author(s):  
Khalil Ullah ◽  
Parvez Ahmed ◽  
Shahid Raza ◽  
Tariq Mahmood ◽  
Badshah Khan
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Stem Cell ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Post Transplant ◽  
Transplant Complications

Abstract One hundred and fifty four patients received allogeneic stem cell transplant from HLA matched siblings for various haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to Sep 2006. Indications for transplant included aplastic anaemia (n=66), b-thalassaemia major (n=40), CML (n=33), acute leukaemia (n=8) and misc disorders (n=7). One hundred and twenty patients were male and thirty four were female. Median age of patient cohort was 14 yrs (range 1 ¼ −54 yrs). Pre-transplant infection surveillance was carried out and strict prophylaxis against infection was observed. The mean mononuclear cell dose was 4.2 x 109/kg of recipient. Post transplant complications encountered in our patients were: acute GvHD (grade II-IV) 28.5%, chronic GvHD 15.5%, haemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, CMV infection 4%, herpes zoster 4%, tuberculosis 2.6%, pneumocytitis jirovici infection 0.6%, malaria 0.6% patient, graft rejection 5.2% patients and relapse in 4%patients. Certain unexpected rare post transplant complications were also observed in our patients. These included hickman catheter embolization, GB syndrome, deep vein thrombosis, haemorrhagic pericarditis with clots leading to cardiac temponade, idiopathic polycythemia, dengue fever and status epilepticus. Mortality was observed in 27.2% patients. Major causes of mortality were GvHD, VOD, relapse, intracranial haemorrhage, acute renal failure, pseudomonas septicemia, tuberculosis, disseminated aspergillosis and CMV infection. At five years, the overall survival (OS) and disease free survival (DFS) was 72.5% & 70.7% respectively.

scholarly journals Incidence and Outcomes of Cytomegalovirus (CMV) Infection among Hematopoietic Stem Cell Transplant (HSCT) Recipients

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S731-S732
Author(s):  
Jon P Furuno ◽  
Miriam R Elman ◽  
Brie N Noble ◽  
Lynne Strasfeld ◽  
Gregory B Tallman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem

Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1655-1662 ◽  
Author(s):  
Jan W. Gratama ◽  
Michael Boeckh ◽  
Ryotaro Nakamura ◽  
Jan J. Cornelissen ◽  
Rik A. Brooimans ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Immune Monitoring ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
Mhc Tetramers

Abstract Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant recipients despite the introduction of posttransplantation viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1400 tetramer/allele results in more than 800 biweekly blood samples from 83 patients monitored for 1 year after transplantation. Major HLA types were included (A*0101, A*0201, B*0702, B*0801, B*3501). iTAg MHC Tetramers (Beckman Coulter) were used to enumerate CMV-specific CD8+ T cells by flow cytometry using a single-platform absolute counting method. Assay variability was 8% or less and results were available within 3 hours. Delayed recovery of CMV-specific T cells (< 7 cells/μL in all blood samples during the first 65 days after transplantation) was found to be a significant risk factor for CMV-related complications; these patients were more likely to develop recurrent or persistent CMV infection (relative risk 2.6, CI 1.2-5.8, P = .01) than patients showing rapid recovery, which was associated with protection from CMV-related complications (P = .004). CMV tetramer–based immune monitoring, in conjunction with virologic monitoring, can be an important new tool to assess risk of CMV-related complications and to guide preemptive therapeutic choices.

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