scholarly journals Factors Influencing Pharmacokinetics of Prophylactic Posaconazole in Patients Undergoing Allogeneic Stem Cell Transplantation

2009 ◽  
Vol 54 (1) ◽  
pp. 207-212 ◽  
Author(s):  
V. Kohl ◽  
C. Müller ◽  
O. A. Cornely ◽  
K. Abduljalil ◽  
U. Fuhr ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Body Height ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Cell Transplant ◽  
Mixed Effect ◽  
Hematopoietic Stem ◽  
Factors Influencing

ABSTRACT The objectives of the present study were to elucidate the factors influencing the pharmacokinetics of prophylactically administered posaconazole in allogeneic hematopoietic stem cell transplant (SCT) recipients. Between May 2007 and November 2008, clinical data were obtained from all SCT recipients at the University Hospital of Cologne undergoing therapeutic drug monitoring (TDM) of serum prophylactic posaconazole concentrations. The posaconazole concentrations were determined by high-performance liquid chromatography. We developed a population pharmacokinetic model using nonlinear mixed-effect modeling (NONMEM). The list of covariates tested included age; body weight; body height; gender; posaconazole dose; race; coadministration of antineoplastic chemotherapy; day of stem cell transplantation; concomitant ranitidine, pantoprazole, cyclosporine, or tacrolimus administration; coincident fever; diarrhea; and plasma gamma-glutamyltransferase activity. A total of 149 serum posaconazole concentrations from 32 patients were obtained. A one-compartment model with first-order absorption and elimination as the basic structural model appropriately described the data, with the apparent clearance being 75.8 liters/h (95% confidence interval [CI], 65.2 to 86.4 liters/h) and the apparent volume being distribution of 835 liters (95% CI, 559 to 1,111 liters). Among the covariates tested, significant effects were found for age (decrease in the volume of distribution of 123 liters per year of age) and the presence of diarrhea (59% loss of bioavailability). A basis for prediction of the mean posaconazole concentrations in allogeneic SCT recipients with hematological malignancies is provided for a given dose. Corresponding adjustments of the starting dose according to the presence of diarrhea and according to age appear to be justified before TDM results are available.

scholarly journals Tandem Autologous Hematopoietic Stem Cell Transplantation in Very Young Patients with Multiple Myeloma

2020 ◽  
Vol 09 (04) ◽  
pp. 233-235
Author(s):  
Rahul Naithani ◽  
Nitin Dayal ◽  
Reeta Rai
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Young Patients ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Platelet Recovery

Abstract Introduction Multiple myeloma (MM) in very young patients is uncommon, and no treatment guidelines exist for these patients. Patients and Methods We performed a retrospective analysis of five very young myeloma patients who underwent tandem autologous hematopoietic stem cell transplantation (HSCT). Results The median age was 37 years (range = 34–40 years). A median of two leukapheresis was performed (range = 1–4). The median number of hematopoietic stem cells collected was 5.4 × 106/kg (4.4–8.2 × 106/kg). During first transplant, four patients received melphalan of 200 mg/m2 and one patient received melphalan of 140 mg/m2 (due to renal failure) as conditioning regimen. Second transplant conditioning was melphalan of 200 mg/m2 for one patient and melphalan of 140 mg/m2 for remaining four patients. Two patients were in complete remission, and two were in very good partial remission and one patient progressed to active disease at the time of tandem autologous bone marrow transplant. All patients developed significant mucositis. Neutrophil and platelet recovery was longer in tandem autologous hematopoietic stem cell transplant. More viral infections were seen in tandem transplant. Day 30 and day 100 mortality was nil. Conclusion We present data on tandem autologous HSCTs in very young patients with MM in India. Responses continued to improve in this small series.

scholarly journals A review on recipients of hematopoietic stem cell transplantation patients with COVID-19 infection

2021 ◽  
Vol 8 ◽  
pp. 204993612110132
Author(s):  
Kamal Kant Sahu ◽  
Ahmad Daniyal Siddiqui
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Real World Data ◽  
Hematopoietic Stem ◽  
Geographical Regions

For the last few months, various geographical regions and health sectors have been facing challenges posed by the current COVID-19 pandemic. COVID-19 has led to significant disruption in the normal functioning of potentially life-saving therapies of hematopoietic cell transplant and chimeric antigen receptor therapy. As transplant physicians are gaining more information and experience regarding the undertaking of these complex procedures during the ongoing COVID-19 pandemic, we believe it is important to discuss the challenges faced, prognostic risk factors, and outcomes of COVID-19 in post-hematopoietic stem cell transplantation patients based on the available real-world data.

A novel drug interaction between busulfan and blinatumomab

2017 ◽  
Vol 25 (1) ◽  
pp. 226-228 ◽  
Author(s):  
Karen Sweiss ◽  
John G Quigley ◽  
Annie Oh ◽  
Jonathan Lee ◽  
Rosa Ye ◽  
...  
Keyword(s):  
Stem Cell ◽  
Drug Interaction ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Drug Disposition ◽  
Therapeutic Drug ◽  
Hematopoietic Stem

Busulfan is an alkylating agent used in pre-transplant conditioning for patients undergoing hematopoietic stem cell transplantation. Several factors contribute to variations in busulfan drug disposition including bioavailability, age, liver function, genetic polymorphisms, and concurrent administration of other drugs. Busulfan is metabolized by hepatic oxidation via the cytochrome P450 3A4 system as well as through conjugation with glutathione. Interactions with drugs such as phenytoin, itraconazole, and metronidazole have been reported to alter busulfan clearance and result in sub- or supra-therapeutic concentrations. We report a case of a clinically significant drug interaction between intravenous busulfan and the bifunctional T-cell engager, blinatumomab, observed through busulfan therapeutic drug monitoring. We found that busulfan clearance was reduced resulting in a higher area under the concentration-time curve when it was administered 48 h after blinatumomab. Repeat busulfan pharmacokinetic testing two weeks later demonstrated increased clearance of the drug and a 31% higher dose recommendation. Similar to other protein therapeutics, cytokine elevations during blinatumomab treatment can lead to cytochrome 3A4 suppression. We hypothesize that the increased busulfan levels observed could be related to a cytokine-mediated CYP3A4 suppression. This represents a unique pharmacologic consideration in hematopoietic stem cell transplantation which would impact several drugs that undergo CYP3A4 metabolism, including calcineurin inhibitors, cyclophosphamide, sirolimus, and triazole antifungals. Additionally, this mechanism of CYP3A4 suppression may be relevant in treatments and disease states where cytokine levels are elevated such as haploidentical stem cell transplantation, graft-versus-host disease, and use of chimeric antigen receptor T-cell therapy.

scholarly journals BK virus-associated hemorrhagıc cystitis in patients wıth allogeneıc hematopoıetıc cell transplantation: report of three cases

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Duygu Mert ◽  
Hikmetullah Batgi ◽  
Alparslan Merdin ◽  
Sabahat Çeken ◽  
Mehmet Sinan Dal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hemorrhagic Cystitis ◽  
Immunosuppressive Treatment ◽  
Active Agent ◽  
Bk Virus ◽  
Cell Transplant ◽  
Hematopoietic Stem

BK virus is a human polyoma virus. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine. The reduction of immunosuppression is effective in the treatment of BK virus infection. There are also several agents with anti-BK virus activity. Cidofovir is an active agent against a variety of DNA viruses including poliomyoma viruses and it is a cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three cases of allogeneic stem cell transplantation due to acute myeloid leukemia (AML). BK virus were detected as the cause of hemorrhagic cystitis in these patients. Irrigation of the bladder was performed. Then levofloxacin 1×750 mg intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased. In the first case, treatment with leflunomide was started, but patient died due to refractory AML and severe graft-versus-host disease after 4th day of leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of immunosuppressive treatment decreased the BK virus load and resulted symptomatic improvement in the second case. Initiation of cidofovir was planned in the third case. Administration of cidofovir together with the reduction of immunosuppression in the treatment of hemorrhagic cystitis associated with BK virus in allogeneic stem cell transplant recipients could be a good option.

scholarly journals The Evolution of Intracardiac Hemodynamics Post Autologous Stem Cell Transplant in a Case of Multiple Myeloma Associated with Severe Tricuspid and Mitral Valve Insufficiency

2017 ◽  
Vol 2 (s4) ◽  
pp. 45-47
Author(s):  
Cezara-Iuliana Tudor ◽  
Erzsébet Lázár ◽  
Marius-Vasile Găzdac ◽  
Annamária Pakucs ◽  
Eszter Mild ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Heart Function ◽  
Cell Transplant ◽  
Severe Condition ◽  
Hematopoietic Stem

AbstractStem cells are undifferentiated cells that can divide and become differentiated. Hematopoietic stem cells cannot transform into new stem cells such as cardiomyocytes or new heart valves, but they act through paracrine effects, by secreting cytokines and growth factors that lead to an increase in contractility and overall improved function. In this case report, we present how autologous stem cell transplantation can bring two major benefits: the first refers to hematological malignancy and the second is about the improvement of the heart condition. We present the case of a 60-year-old patient diagnosed with multiple myeloma suffering from a bi-valve severe condition in which autologous stem cell transplantation led to the remission of the patient’s malignant disease and also improved the heart function.

scholarly journals Acute Kidney Injury and CKD Associated with Hematopoietic Stem Cell Transplantation

2019 ◽  
Vol 15 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Amanda DeMauro Renaghan ◽  
Edgar A. Jaimes ◽  
Jolanta Malyszko ◽  
Mark A. Perazella ◽  
Ben Sprangers ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Thrombotic Microangiopathy ◽  
Kidney Injury ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Wide Range

Hematopoietic stem cell transplantation is a life-saving therapy for many patients with cancer, as well as patients with some nonmalignant hematologic disorders, such as aplastic anemia, sickle cell disease, and certain congenital immune deficiencies. Kidney injury directly associated with stem cell transplantation includes a wide range of structural and functional abnormalities, which may be vascular (hypertension, thrombotic microangiopathy), glomerular (albuminuria, nephrotic glomerulopathies), and/or tubulointerstitial. AKI occurs commonly after stem cell transplant, affecting 10%–73% of patients. The cause is often multifactorial and can include sepsis, nephrotoxic medications, marrow infusion syndrome, hepatic sinusoidal obstruction syndrome, thrombotic microangiopathy, infections, and graft versus host disease. The risk of post-transplant kidney injury varies depending on patient characteristics, type of transplant (allogeneic versus autologous), and choice of chemotherapeutic conditioning regimen (myeloablative versus nonmyeloablative). Importantly, AKI is associated with substantial morbidity, including the need for KRT in approximately 5% of patients and the development of CKD in up to 60% of transplant recipients. AKI has been associated universally with higher all-cause and nonrelapse mortality regardless of transplant type, and studies have consistently shown extremely high (>80%) mortality rates in those patients requiring acute dialysis. Accordingly, prevention, early recognition, and prompt treatment of kidney injury are essential to improving kidney and patient outcomes after hematopoietic stem cell transplantation, and for realizing the full potential of this therapy.

scholarly journals Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

2019 ◽  
Vol 14 (5) ◽  
pp. 719-727 ◽  
Author(s):  
Xianghua Huang ◽  
Wencui Chen ◽  
Guisheng Ren ◽  
Liang Zhao ◽  
Jinzhou Guo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Lupus Nephritis ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem

Background and objectivesOur study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis.Design, setting, participants, & measurementsFrom July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment.ResultsTwenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33–71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7–9) and 9 (6–10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60–80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%.ConclusionsAutologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.

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