scholarly journals Pharmacokinetics of mycophenolic acid after haplo-hematopoietic stem cell transplantation in Japanese recipients

2020 ◽  
pp. 107815522098081
Author(s):  
Kazuki Uchiyama ◽  
Yoshitaka Saito ◽  
Yoh Takekuma ◽  
Junichi Sugita ◽  
Takanori Teshima ◽  
...  

Purpose Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) prodrug, is used to prevent graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). Although previous studies have reported that enterohepatic circulation (EHC) of MPA, which is usually observed in MMF-treated patients, does not occur in HSCT patients, it is unclear what happens in haploidentical–HSCT (haplo-HSCT) patients, who are using post-transplant cyclophosphamide. This study was conducted to investigate MPA pharmacokinetics in haplo-HSCT patients. Methods Seventeen haplo-HSCT patients, who received MMF for GVHD prophylaxis, were enrolled in this study. We collected blood samples on days 14 and 28, and plasma MPA concentrations were measured by high-performance liquid chromatography; pharmacokinetic parameters such as area under the curve (AUC), mean residence time (MRT), and apparent oral clearance (CL/F) were measured with moment analysis. We also evaluated EHC as AUC6-12h/AUC0-12h. Results There was no significant difference in MPA pharmacokinetic parameters between days 14 and 28. There was also no difference between the pharmacokinetic parameter changes and diarrhea. Additionally, varying plasma MPA concentrations suggested that MPA EHC did not occur. Conclusion In this study, we revealed the pharmacokinetics of MMF in Japanese haplo-HSCT recipients. Additionally, our study demonstrated that MPA EHC might not occur in Japanese haplo-HSCT recipients.

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2644-2650 ◽  
Author(s):  
Georg Mann ◽  
Andishe Attarbaschi ◽  
Martin Schrappe ◽  
Paola De Lorenzo ◽  
Christina Peters ◽  
...  

AbstractTo define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL+), we compared the outcome of MLL+ patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL+. Among the 277 of 297 MLL+ patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g/L. Ninety-seven of 297 MLL+ patients (33%) had such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL+ acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487.


JBMTCT ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. p94
Author(s):  
Patricia Elkiki dos Santos

Abstract Objective: The success of autologus hematopoietic stem cell transplantation relies on CD34+ cells' availability in peripheral blood (PB),  which is affected by several factors as age, sex, type of the disease, treatments, and others. In that regard, this prospective study aimed to evaluate the influence of these factors, correlating them with the pre-apheresis CD34+ cell count. Method: Before autologous hematopoietic stem cell transplantation, CD34+ cells were quantified in the pre-apheresis PB and the final product. Then, after the determination of minimum CD34+ value, clinical and laboratory parameters were compared between patients with higher and lower CD34+ cells count. Results: Out of the 34 patients, 29 presented more than 20,000 leukocytes/μl. Patients who failed in the mobilization presented <20,000 leukocytes/μl. There was a significant difference between the groups with different pre-apheresis CD34+ cells status regarding age (p=0.025), leukocyte count (p<0.001) and mononuclear cells (p=0.001) in PB. In addition, the pre-apheresis CD34+ ≥14 cells/μl group was related to a better yield of these cells in the final product and with the requirement of a single collection to obtain the minimum yield, of 2x106 CD34+/kg. Conclusion: This study demonstrates age and leukocyte count relate to CD34+ count in PB, and that CD34+ cells yield in the collection, can be predicted by  CD34+ cells frequency in PB.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5211-5211
Author(s):  
De Pei Wu ◽  
Junjie Cao ◽  
Caixia Li ◽  
Xiaojin Wu

Abstract Objective: To compare the dendritic cells reconstitution after different allogeneic hematopoietic stem cell transplantation in early time Methods: From June 2004 to March 2005, Twenty-eight patients undergoing allo-HSCT were enrolled in this study. There were 16 patients who undergone normal HSCT, 8 patients who undergone Haploidentical HSCT and 4 patients who undergone Nonmyeloablative HSCT. Three-colour flow cytometry was applied to study the alteration of the percentage and number in circulating peripheral blood dendritic cells subsets on day 14,day 30,day 60 after transplantation among three distinct type HSCT. Results: The dendritic cells subsets number of myeloablative HSCT patients were very low. No difference was observed in the kinetics of DC1 (Lin−HLA-DR+CD11c+)and DC2 (Lin−HLA-DR+CD123+) reconstitution between the normal HSCT group and Haploidentical HSCT group patients(p&lt;0.05). There was significant difference between myeloablative HSCT group and normal healthy individuals(p&lt;0.01). There was significantly different between the non-myeloablative HSCT group and the myeloablative HSCT group in the kinetics of DC1 and DC2 reconstitution(p&lt;0.05). Conclusion: The early reconstitution of dendritic cells in Nonmyeloablative HSCT patients is earlier than the patients who undergone myeloablative HSCT. The early reconstitution of dendritic cells in normal HSCT and Haploidentical HSCT patients were later than others.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4376-4376
Author(s):  
Xiaojin Wu ◽  
Wu Depei ◽  
Aining Sun ◽  
Xiaowen Tang ◽  
Zhengzheng Fu ◽  
...  

Abstract Objective: To investigate the incidence, risk factor and management of CMV reactivation in patients revived hematopoietic stem cell transplantation(HSCT). Methods: 374 patients including 275 consecutive allogeneic and 99 autologous patients after bone marrow/stem cell transplantation from May 2001 to December 2007 were studied at our institution with nest-PCR and pp65 antigen assay. Anticoagulant blood samples were obtained from the recipients once weekly after days 14. After three months the CMV monitoring was performed every one month or every three months. If the patients catch CMV again after three year, the CMV monitoring was performed again. Results: The incidence of CMV positive in autologous patients was 3.03% and was 54.91% in allogeneic patients with a median onset of 48 days post transplants during 1 to 81 months. The difference between them is significant; The infection rate in the nonmyeloablative allogeneic peripheral stem cell transplantation (NST) group was 61.76%, in the group of HLA—identical sibling donor HSCT(sib-HSCT) was 47.10%, in haploidentical hematopoietic stem cell transplantation (Hi-HSCT) group was 75.00% and in the group of unrelated bone marrow transplantation (UR-BMT) was 57.45%. The infection rate of CMV in the Hi-HSCT group was higher than that in the group of sib-HSCT with significant difference (P&lt;0.05); The incidence rate of CMV infection in patients with regimen including ATG was higher than that without ATG ((65%&47.1%, P&lt;0.05); The incidence rate of CMV infection in patients with III–IV grade aGVHD and patients without III–IV aGVHD had not significant difference (P&gt;0.05). There was not significant difference in the occurance of aGVHD between the patients with and without CMV infection (P&gt;0.05).5.87.8% patients are effective on antiviral therapy, incidence of CMV disease is very low, 0.65% patients catch CMV more than once. Conclusion FCMV infection is common in our study, Minoriting CMV for long time is necessary, which benefit to antiviral therapy and judging of prognosis.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4293-4293
Author(s):  
Jacques-Olivier Bay ◽  
Aurelie Cabrespine-Faugeras ◽  
Reza Tabrizi ◽  
Pierre Bordigoni ◽  
Karin Bilger ◽  
...  

Abstract Purpose: Objective was to assess indication, feasibility and efficacy of double allograft with reduced intensity conditioning. Patients and Methods: All double allogeneic hematopoietic stem cell transplantation (AHSCT) after reduced intensity regimen reported to Promise database were retrospectively studied. Because of the initial lack of clinical and biological data in the Registry, all centers were contacted to improve the database. Results: 66 double mini-allografts were realized in 25 french transplant centers. At this time, 35 mini-allografts presented complete informations corresponding to 14 transplant centers. Diagnosis was LAM (n=15), aplasic anemia (n=5), MDS and/or MPS (n=5), LAL (n=2), Myeloma (n=2), ovarian cancer (n=1), LNH (n=2), LLC (n=1), LMC (n=1) and Hodgkin lymphoma (n=1). Median age at first transplantation was 49.3 years [12.75–64.9] with a median time from diagnosis to first transplant of 22.9 months [3.6–163.7]. Disease status before transplant was progression (n=5), partial response (n=3), complete response (n=18), induction failure (n=2) and chronic phase (n=2). The 5 aplasic anemias were not evaluable for this status. Most patients received fludarabine (n=31), SAL (n=22), busulfan (n=15) based regimen. Graft source was PBSC in 74% of grafts. Median age of donor was 42 years [4–68]. HLA relation of donor with patient was identical sibling (n=22), match unrelated (n=10) or mismatch unrelated (n=3). Second allograft indication was relapse (n=22), lost of graft (n=7), no engraftment (n=5) or residual disease (n=1). Eihgty percents of patients underwent a different conditioning. It was similar for only 7 patients (same n=1, increase SAL dose n=1, SAL addition n=2, dose reduction n=1). Median time between the two allografts was of 7.6 month [1.1–61.0]. Source of stem cells and donor were changed in 13.6% and 37% of allograft respectively. The median time to reach an absolute neutrophil count of 0.5 × 109/l and platelet count of 50 × 109/l was shorter after second allograft (21.4 days [12.4–759.5] versus 16.8 days [6.2–105.4] and 16.3 days [9.3– 71.3] versus 14.26 [3.1–83.7]) with no significant difference. Overall incidence of acute GvH was similar after the two allografts (34% versus 43%). However, acute GvH grade III–IV proportion seems to be higher after second allograft (8% versus 40%). Similarly, proportion of chronic GvH was 23% versus 27% with an increase of extensive GvH after second allograft (50% versus 66%). Response was improved by second allograft in five patients (15%) and allowed to engraftment in 3 patients (7%). To date, 8 patients are still alive. 14 patients died from progression and 11 of TRM (3 multiple organ failure, 5 respiratory failure, 2 fungal infection and 1 rejection) giving a TRM proportion of 31%. With a median follow-up of 57.1 months [21.9–128.8], the median overall survival (OS) was of 24 months [2–71]. Delay greater than 7.7 months and same source of stem cell between two mini-allografts improved OS (50 months versus 9 months, p = 0.0085 and 28 months versus 14 months, p=0.11). Conclusions: Our preliminary results suggests response improvement after double AHSCT with reduced conditioning. However, TRM proportion was high.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4695-4695
Author(s):  
Xiao-hui Zhang ◽  
Haixia Fu ◽  
Lan-Ping Xu ◽  
Dai-Hong Liu ◽  
Kaiyan Liu ◽  
...  

Abstract Abstract 4695 Prolonged thrombocytopenia is a frequent complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its pathogenesis has remained obscure. In present study, by using a flow cytometry technique, we determined the frequency of bone marrow megakaryocytes (MKs) and MKs ploidy distributions in allo-HSCT recipients with or without prolonged thrombocytopenia (n=32 and 27, respectively) and in 13 healthy volunteers. Along with that, the expression of c-Mpl in MKs was measured. The result showed a significant difference in MKs ploidy distributions between the 3 groups. Both the allo-HSCT patients with or without prolonged thrombocytopenia showed a significant shift to low ploidy cells (left shift) with 55.63±18.62% and 44.63±19.38% of their MKs in ploidy classes 2N to 8N, respectively. In contrast, the healthy volunteers had only 25.97±10.70% of their MKs in ploidy classes 2N to 8N. And the patients with prolonged thrombocytopenia showed a marked increase in cells ≤8N, a significant decrease in the 16N and ≥32N cells comparing to patients without prolonged thombocytopenia, which told us there were more less mature MKs in the allo-HSCT recipients with prolonged thrombocytopenia. We concluded that prolonged thrombocytopenia and slow platelet engraftment after allo-HSCT may be related to reduced ploidy and immaturation of MKs. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4900-4900
Author(s):  
Ana Carolina Oliver ◽  
Federico Superchi ◽  
Roberto Superchi ◽  
Matilde Canabal ◽  
Jubin Silvana ◽  
...  

Abstract Introduction: Cardiovascular disease is the leading cause of death, in Uruguay it corresponds to 30%. To the known risk factors, the use of QT and RT are added. The improvement in response and overall survival of hematologic patients allow a longer time to develop cardiovascular complications. Cardiotoxicity has been extensively studied in the context of breast cancer and the use of anthracyclines; however, there are very few data on hematopoietic stem cell transplantation (HSCT). Objective: Assess subclinical myocardial damage by measuring biomarkers and echocardiography and identify patients at high risk of developing cardiotoxicity after HSCT. Methods: This is a prospective, single-center study between April 2017 and November 2020. Population: adult patients admitted in the British Hospital Transplant Unit, Montevideo Uruguay to receive either an autologous or allogeneic HSCT. Measurement: cardiac biomarkers (pro-BNP, Troponin T, Troponin I and CPK) at admission, D1, D14 and D30. Echocardiograms were performed on admission and at D30 by the same team of 3 echocardiographers with the same machine. It was repeated at D100 if some alteration was seen. Results: We included 158 transplants: 148 autologous and 10 allogeneic. The characteristics of the population and results are shown in Table 1. 126 raised some biomarker during the first 100 days (79.7%). Pro-BNP is the biomarker that most frequently rises after admission until day 100: 125/158 (79.1%). The kinetics of the biomarkers are shown in Figure 1. Regarding echocardiograms, there were no patients with a cardiotoxicity criterion defined by: a decrease in LVEF of more than 10% to a value less than 53%. Regarding myocardial deformability, there was a reduction in strain between the initial echocardiogram and D30 in 76 patients of 116 patients with both determinations (65.5%). A reduction of 15% or more was evidenced in 18 (11.3%). Of them, 13 (72.2%) had elevated biomarkers in the first 100 days. Of the patients who did not have strain changes, 78.6% had elevated biomarkers. No statistically significant relationship was found between strain reduction and the presence or absence of elevated biomarkers in the first 100 days. With a median follow-up of 23.3 months (0.89-48.62), 11 (7%) developed clinical cardiotoxicity: hypertension 6, arrhythmia 4, pulmonary embolism 1, sudden death 1. We have strain data of 6/11 patients, and there was no reduction of 15%. Of the 11, 90.9% raised some biomarker during the 100 days. Median development time of cardiotoxicity: 10.3 months (0.03-36.6). 133 had one year follow up so, the incidence of clinical cardiotoxicity at 1 year is 4.5%. There were no differences in elevated biomarkers in the first 100 days and use of Melphalan (p = 0.096) however, there was a difference with BEAM versus other plans, p = 0.035. The reduction in strain at day 30 was not influenced by Melphalan or BEAM. Patients with subclinical myocardial damage were older than those without it: mean age: 56.7 +/- 11.2 versus 44.1 +/- 13.1, p = 0.0001. There was no statistically significant difference between patients who had elevated biomarkers in the first 100 days versus those who did not in relation to a history of diabetes, hypertension, dyslipidemia, heart disease or previous use of anthracyclines. Either in patients with a 15% reduction in strain versus those without. This is one of the first studies worldwide that comprehensively evaluates cardiovascular function during HSCT. Given the small number of observed cardiac complications, greater follow-up of this subpopulation with elements of subclinical cardiotoxicity is required to determine if they are indeed predictive parameters of cardiovascular complications in the future in the transplant setting. Conclusions: Subclinical cardiotoxicity is common in transplantation: Pro-BNP is the biomarker that most frequently rises after admission until day 100: 79.1%. Strain reduction of 15% or more occurs in 11,3%. Subclinical myocardial damage parameters were not associated with type of conditioning, previous use of anthracyclines, comorbidities and clinical cardiotoxicity at 1 year. Clinical cardiotoxicity post HSCT is low, 4,5% at 1 year. We must do a longer-term follow-up in order to evaluate whether the combination of pro-BNP associated with strain reduction can be predictive factors of clinical cardiotoxicity. Figure 1 Figure 1. Disclosures Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees .


Sign in / Sign up

Export Citation Format

Share Document