scholarly journals Once-Daily Intravenous Busulfan with Therapeutic Drug Monitoring Compared to Conventional Oral Busulfan Improves Survival and Engraftment in Children Undergoing Allogeneic Stem Cell Transplantation

2008 ◽  
Vol 14 (1) ◽  
pp. 88-98 ◽  
Author(s):  
Imke H. Bartelink ◽  
Robbert G.M. Bredius ◽  
Tessa T. Ververs ◽  
Martine F. Raphael ◽  
Charlotte van Kesteren ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Drug Monitoring ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Once Daily

The Useful Individualized Assessment of Immunosuppressive Therapy with Cyclosporine A (CsA) after Allogeneic Stem Cell Transplantation by Simultaneous Analyses of Cytokine Production among CD4+ T Cells and Blood CsA Levels.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5076-5076
Author(s):  
Nobuhiro Tsukada ◽  
Tatsuo Furukawa ◽  
Hiromi Ito ◽  
Noriko Izumi ◽  
Akihito Momoi ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Therapeutic Drug Monitoring ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cytokine Production ◽  
Therapeutic Drug ◽  
Ifn Γ ◽  
Cd4 Lymphocytes

Abstract Cyclosporin A (CsA) is the most common immunosuppressive agent used for recipients undergoing allogeneic stem cell transplantation (SCT). CsA require therapeutic drug monitoring (TDM) for both its effectiveness and toxicity, but the schedule of administration and optimal blood levels vary among institutions. To establish better assessment of CsA effect on individual immune responsiveness, we analyzed the proportion of IFN-γ+ or IL-2+ cells among CD4+ lymphocytes using 3-color flow cytometric analysis before and after CsA administration. CsA is administered as 3-hour infusion or oral medication twice daily in equally divided doses. 83 peripheral blood samples from 8 allogeneic BMT recipients are analyzed. Cells were cultured in the presence of phorbol 12-myristate 13-acetate, ionomycin, and brefeldin A at 37°C for 4hrs and then stained for surface markers and intracytoplasmic IFN-γ and IL-2. Blood CsA levels were simultaneously measured. We found that the proportion of IFN-γ+CD4+ or IL-2+CD4+ lymphocytes were inversely proportional to blood CsA levels (Figure 1). To achieve profound inhibition of IL-2 production, high concentration of CsA is required (e.g. 600–800 ng/ml for less that 5 % IL-2+CD4+ cells). In vitro experiments were also conducted using lymphocytes from healthy donors with or without activation with CD3 and CD28 to show how the sensitivity to CsA is different in between activated and resting T cells. We found that higher CsA concentration is required for inhibiting IL-2 production from CD4+ lymphocytes activated with CD3 and CD28 than from resting CD4+ lymphocytes (Figure 2). In this regard, our 3 hour intravenous CsA infusion can be superior to continuous intravenous infusion in inhibiting activated T cells. Further analyses are required, but the simultaneous assessment of cytokine production among CD4+ T cells and blood CsA levels may be a useful index to estimate the degree of immunosuppression afforded by CsA and may enable us individualized therapeutic drug monitoring of this agent. Since more and more patients are undergoing cord blood transplantation (CBT) or reduced-intensity stem cell transplantation (RIST), this assessment may also be useful for the establishment of immunosuppressive therapy for those patients.

scholarly journals Rhino-Orbital-Cerebral Mucormycosis after Allogeneic Hematopoietic Stem Cell Transplantation and Isavuconazole Therapeutic Drug Monitoring during Intestinal Graft versus Host Disease

2019 ◽  
Vol 11 (1) ◽  
pp. e2019061 ◽  
Author(s):  
Giacomo Andreani ◽  
Gianluca Fadda ◽  
Dario Gned ◽  
Matteo Dragani ◽  
Giovanni Cavallo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Drug Monitoring ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Drug Monitoring ◽  
Sinus Surgery ◽  
Therapeutic Drug ◽  
Hematopoietic Stem

  A  diagnosis of rhino-orbital-cerebral mucormycosis was made in a 59-year-old man with a secondary acute myeloid leukemia a few days after hematopoietic stem cell transplantation. Prompt treatment with combined antifungal therapy (liposomal amphotericin B and isavuconazole) followed by a procedure of endoscopic sinus surgery resulted in the resolution of the infection. Therapeutic drug monitoring of isavuconazole was performed during the year of treatment showing an increment of plasma concentrations in correspondence with the improvement of intestinal GvHD, thus suggesting that in this or similar conditions TDM for isavuconazole can be of value. A literature review of cases of rhino-orbital-cerebral and rhino-cerebral mucormycosis in allogeneic hematopoietic stem cell transplant recipients was performed.

scholarly journals Highly Variable Plasma Concentrations of Voriconazole in Pediatric Hematopoietic Stem Cell Transplantation Patients

2012 ◽  
Vol 57 (1) ◽  
pp. 235-240 ◽  
Author(s):  
Imke H. Bartelink ◽  
Tom Wolfs ◽  
Martine Jonker ◽  
Marjolein de Waal ◽  
Toine C. G. Egberts ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Drug Monitoring ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Hematopoietic Stem ◽  
Intrapatient Variability

ABSTRACTInvasive fungal infections are of great concern in pediatric hematopoietic stem cell transplantation (HSCT) recipients. Voriconazole is usually the drug of first choice for treating or preventing invasive aspergillosis. Optimum trough levels (Ctroughs) are between 1 and 5 mg/liter. It is unclear whether these levels are reached with currently advised pediatric dosing schedules. Between 2007 and 2011, 11 patients <2 years of age, 31 between 2 and 12 years, and 20 between 12 and 20 years were (prophylactically or therapeutically) treated with voriconazole in the HSCT unit of UMC Utrecht. For children <2 years of age, the dosage recommended for 2 to 12 years was used. In 34% of children who started with the recommended dose, an adequateCtroughwas reached irrespective of age or administration route. After therapeutic drug monitoring (TDM)-based dose adjustments, adequateCtroughs were reached in 80% of the patients at median doses of 31.5 (age, <2 years), 16 (age, 2 to 12 years), and 9.4 mg/kg of body weight/day (age, >12 years) (P= 0.034). The intrapatient variability inCtroughranged between 1 and 238%. Voriconazole was discontinued in six patients due to toxicity. These patients had a medianCtroughof 0.5 mg/liter at the initial dose (ranging from 0.5 to 2.6 mg/liter), and a medium maximal concentration of 4 mg/liter was reached. Inter- and intrapatient variability is a major concern in voriconazole treatment and necessitates therapeutic drug monitoring of dosing, especially in young children.

Lenalidomide as Salvage Therapy after Allogeneic Stem′Cell Transplantation in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3704-3704
Author(s):  
Friederike Lehmann ◽  
Jean El-Cheikh ◽  
Tatjana Zabelina ◽  
Francis Ayuk ◽  
Christine Wolschke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Dose Reduction ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Optimal Dose ◽  
Hematological Toxicity ◽  
Once Daily ◽  
Grade 3

Abstract Lenalidomide is an immunmodulatory drug, orally administered once daily, which is effective in relapsed multiple myeloma (MM). Here, we evaluated the efficacy and toxicity of lenalidomide in 24 MM patients with relapsed disease after allogeneic stem cell transplantation (allo-SCT). Median age was 59 (range, 37–70) years. The series included 8 females and 16 males. Prior to allo-SCT, all patients were heavily pretreated with a median of 6 chemotherapy cycles including autologous and allo-SCT in all patients. Also, prior to lenalidomide, salvage treatment included donor lymphocyte infusions (DLI) in 18 pts,, thalidomide in 11 pts and bortezomib in 13 pts. Lenalidomide was given at 15mg (n=4) or 25 mg (n=20) orally once daily on day 1–21 every 28 days and in 20 patients in combination with dexamethason.. No prophylactic anticoagulation was used. The median number of completed cycles was 5 (range 2–17). Myelotoxicity according NCI criteria was the primarily and major encountered side effect (leukopenia: 4% grade 4, 21% grade 3, 17% grade 2, thrombopenia: 17% grade 3, 29% grade 2) and led to dose reduction in 54% of the patients. Infectious complications were observed in 50%. Non-hematological toxicity consisted of cramps (n=9), fatique (n=5) and constipation (n=2). Thrombembolic complications (cerebral infarction) were observed in one patient, who received concomitant corticosteroid treatment for acute graft-vs.-host disease (GvHD), but neurological symptoms resolved completely. GvHD of the skin under lenalidomide treatment was seen in 3 patients (one grade 2, and 2 grade 1), with one case occurring shortly after an additional DLI.. Objective remission was achieved in 66% of the patients (CR: 8%, VGPR: 8%, PR: 50%) and stable disease (SD) in 13% of the patients, while in 21% progressive disease was noted. Prior treatment with thalidomide or with bortezomib did not influenced the rate of CR/PR. Surprisingly, patients with del 13q14 achieved a higher CR/PR rate than those without del 13q14 (p=0.02). The median time to progression was 9.7 months (95% CI: 7.5–11.9) and the median overall survival was 19.9 months (95% CI: 17.3–22.5). Lenalidomide is effective in relapsed patients with MM after allo-SCT. Major toxicity is myelotoxicity, which required dose reduction in the majority of patients. The optimal dose of lenalidomide after allo-SCT has to be investigated.

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