Several studies have reported that oral antibacterials, including ciprofloxacin, administered during mycophenolate mofetil therapy may reduce mycophenolic acid (the active drug moiety) exposure. To ...our knowledge, however, this effect has never been described with antibiotics administered by the parenteral route. We describe a 17‐year‐old female who received intravenous mycophenolate mofetil after bone marrow transplantation, with therapeutic drug monitoring performed during therapy. On day 2 of mycophenolate mofetil therapy, the mycophenolic acid area under the plasma concentration‐time curve was 30.3 mg•hour/L. On day 8, although her mycophenolate mofetil dosage had remained unchanged, the mycophenolic acid area under the plasma concentration‐time curve was unexpectedly lower at 10.7 mg•hour/L. A drug interaction was suspected. Three intravenous antiinfective drugs had been introduced after initial therapeutic drug monitoring had been performed—ciprofloxacin, trimethoprim‐sulfamethoxazole, and caspofungin. The patient subsequently developed severe graft‐versus‐host disease during mycophenolate mofetil therapy and died. Use of the Horn drug interaction probability scale indicated a probable interaction between intravenous mycophenolate mofetil and intravenous ciprofloxacin in this patient. The available literature does not support the role of either trimethoprim‐sulfamethoxazole or caspofungin in a drug interaction with mycophenolate mofetil. Published studies have shown that ciprofloxacin is partially excreted by transintestinal elimination after intravenous administration and that it may greatly reduce the levels of enterobacteria of gastrointestinal flora, which are responsible for mycophenolic acid enterohepatic recirculation. Clinicians should be aware that ciprofloxacin, even administered intravenously, may modify the pharmacokinetics of mycophenolate mofetil. Ciprofloxacin should be used with caution in patients receiving mycophenolate mofetil; if this antiinfective must be used, therapeutic drug monitoring should be performed to guide dosage adjustments.
The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a ...strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 10
TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7-90.7) and 79.3% (72.6-86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5-35.1) and 34.3% (27.0-43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts.
Although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with Fanconi anemia (FA), published series mostly refer to single-center experience ...with limited numbers of patients. We analyzed results in 795 patients with FA who underwent first HSCT between May 1972 and January 2010. With a 6-year median follow-up, overall survival was 49% at 20 years (95% confidence interval, 38-65 years). Better outcome was observed for patients transplanted before the age of 10 years, before clonal evolution (ie, myelodysplastic syndrome or acute myeloid leukemia), from a matched family donor, after a conditioning regimen without irradiation, the latter including fludarabine. Chronic graft-versus-host disease and secondary malignancy were deleterious when considered as time-dependent covariates. Age more than 10 years at time of HSCT, clonal evolution as an indication for transplantation, peripheral blood as source of stem cells, and chronic graft-versus-host disease were found to be independently associated with the risk for secondary malignancy. Changes in transplant protocols have significantly improved the outcome of patients with FA, who should be transplanted at a young age, with bone marrow as the source of stem cells.
Key Points
Bone marrow has been shown to be superior to peripheral blood, as a stem cell source, in young patients (<20 years of age) with acquired aplastic anemia undergoing a matched sibling transplant. The ...aim of this study was to test whether this currently also holds true for older patients with acquired aplastic anemia.
We analyzed 1886 patients with acquired aplastic anemia who received a first transplant from a human leukocyte antigen identical sibling between 1999 and 2009, with either bone marrow (n=1163) or peripheral blood (n=723) as the source of stem cells.
In multivariate Cox analysis negative predictors for survival were: patient's age over 20 years (RR 2.0, P<0.0001), an interval between diagnosis and transplantation of more than 114 days (RR 1.3, P=0.006), no anti-thymocyte globulin in the conditioning (RR 1.6, P=0.0001), a conditioning regimen other than cyclophosphamide (RR=1.3, P=0.008) and the use of peripheral blood as the source of stem cells (RR 1.6, P<0.00001). The survival advantage for recipients of bone marrow rather than peripheral blood was statistically significant in patients aged 1-19 years (90% versus 76% P<0.00001) as well as in patients aged over 20 years (74% versus 64%, P=0.001). The advantage for recipients of bone marrow over peripheral blood was maintained above the age of 50 years (69% versus 39%, P=0.01). Acute and chronic graft-versus-host disease were more frequent in peripheral blood transplants. Major causes of death were graft-versus-host disease (2% versus 6% in bone marrow and peripheral blood recipients, respectively), infections (6% versus 13%), and graft rejection (1.5% versus 2.5%).
This study shows that bone marrow should be the preferred stem cell source for matched sibling transplants in acquired aplastic anemia, in patients of all age groups.
Studies of second malignant neoplasms (SMNs) in childhood are generally conducted in old cohorts. The aim of this study was to determine the actual incidence of all SMNs in a recent cohort. The ...authors studied a cohort of 2907 children included in the population-based Childhood Cancer Registry of the Rhône-Alpes Region for a first cancer diagnosed between 1987 and 2004. Total follow-up was 22,722 person-years, with a median follow-up of 9.8 years (range, 00.0-22.8 years). Fifty-four SMNs were reported in 52 patients. Overall median latency was 5.9 years. Cumulative incidence rates were 2.2% at 10 years and 3.9% at 15, with an overall standardized incidence ratio (SIR) of 13.9 (95% confidence interval CI, 10.4-18.3) and absolute excess risk of 2.2. The SMNs were 12 thyroid carcinomas (SIR 57.1); 9 bone tumors (SIR 32.0); 8 leukemias (SIR 11.9); 5 lymphomas, all related to Epstein-Barr virus following allograft, (SIR 6.7); 5 CNS tumors (SIR 10.5); 4 soft tissue sarcomas (SIR 17.4); 4 carcinomas (no breast cancer); and 7 other cancers. Twelve SMNs appeared after total body irradiation, 16 after focal radiotherapy, and 8 leukemias after chemotherapy. The risk of secondary cancer was highest after retinoblastomas (SIR 41.8), Hodgkin lymphomas (SIR 20.8), leukemias (SIR 18.4), soft tissue sarcomas, CNS tumors, and bone tumors. These recent cohort findings show, on one hand, a high incidence of SMNs but do not capture breast cancers because of the relatively short follow-up and, on the other hand, a different distribution of first and second cancers.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Indirubin-3′-monoxime (IO) is a derivative of indirubin, an active compound of a traditional Chinese medicinal recipe used to treat various inflammatory and malignant diseases. The main in vitro ...targets of IO (i.e. cyclin dependent kinases, glycogen synthase kinase-3β, Stat 3 and Aryl hydrocarbon receptor) are regulators of lymphocyte activation. We investigated the interest of IO and its derivative 6-bromo-indirubin-3′oxime (6BIO) for inhibiting the growth of malignant lymphoid cells. IO (1-20 μM) induced cell cycle inhibition and cell death in malignant B- (IM9, Reh6) and T- (Jurkat, CEM-T) lymphoid cell lines depending to cell type, doses, and duration of treatment. IO and 6BIO (10 μM) treatment for 24 and 48 h were compared: 6BIO treatment resulted in a stronger cytotoxicity and more profound inhibition of cell proliferation. Taken together, these results showed that IO and, moreover, its derivative 6BIO may be potent antiproliferative agents in malignant lymphoid cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction Despite all the therapeutic progress made in multiple myeloma (MM), the standard of care for eligible patients remains an intensive induction therapy followed by high dose melphalan and ...autologous stem cell transplantation (ASCT). Material and methods This present retrospective study included MM patients treated in Lyon between 1997 and 2020. All patients received induction chemotherapy followed by intensive chemotherapy and ASCT, with or without consolidation and maintenance therapy. Number and type of therapeutic lines administered for relapse after ASCT were analyzed. All data were reported in the European blood and marrow transplantation (EBMT) PROMISE registry. Statistical analysis Descriptive analyses were used for demographic variables, biological parameters, and treatment characteristics. Overall survival (OS) and progression-free survival (PFS) were presented using the Kaplan-Meier method and log-rank tests were performed to compare survival curves. Univariate and multivariate analyses were computed using Cox regressions and the multivariate analyses considered the variables for which the univariate ANOVA p-value was≤ 10%. Statistical analyses and graphics were computed with R v4.1.2, with the help of ‘survival’ and ‘ggplot2‘ packages. Results Before ASCT A total of 342 patients were included in the study (median 60 years (range: 28-73), 58% were male, 89.4% were diagnosed with a type III myeloma according to the Salmon and Durie classification. No genetic analysis was performed at that time. Most patients (92.5%) had a performance status (PS) of 0 or 1. The type of myeloma was heavy chain and light chain myeloma for 75.7% patients (68.9% of IgG kappa) and light chain myeloma in 23.1%. The median delay between diagnosis and ASCT was 4.8 months. Before ASCT, patients received an induction therapy with VTD in 54.1% of cases, VD in 30.1%, and more recently VRD in 16.1%. Disease status before ASCT was complete remission (CR) for 17.5% of the patients, partial remission (PR) and very good partial remission (VGPR) for 79.2% of patients and progressive disease or relapse for 3.0% of them. After ASCT The median duration of aplasia was 11 days. At day 100, the response was CR in 166 patients (50.5%), 182 patients (54.7%) received a consolidation treatment and 71 patients (20.8%) a maintenance therapy (Revlimid® for 90% of them). Overall, 227 (66.4%) patients relapsed. The median delay between ASCT and relapse was 22.5 months (0.89-229.13) and the median follow-up duration was 46.7 months (0.33-287.97). Among the 227 patients who relapsed, 6 patients were not treated, 79 patients (23.1%) received one chemotherapy line, 32 patients (9.4%) received two lines, 38 (11.1%) received 3 and 72 (21.1%) received at least 4 lines and up to 8. Overall survival and progression free survival The median OS was 132 95% CI 110.6; NR months from diagnosis and 122.8 100.9; NR months from ASCT. The median PFS was 39.35 36.25; 43.37 months from diagnosis and 31.07 28.42; 35.91 months from ASCT (Figure 1 A, B). In multivariate analysis on OS, the shorter aplasia duration (p<0.001) and consolidation and maintenance (p<0.001) were significantly associated with a significant better OS. The median OS was not reached from ASCT for patients who have received both consolidation and maintenance treatments and no death was reported. (Figure 1 C). For patients receiving chemotherapy lines for relapses after ASCT (Figure 1D) regardless of the number of lines the median OS was102.4 months and the 10-year OS probability was 45.6%. The OS of patients who received 3 lines of treatment was identical to that of patients who received one or 2 lines after ASCT. The median OS after 1 to 2 lines of chemotherapy after ASCT was not reached and was 127.15 months 70.6-NR for those receiving 3 lines (Figure 4B). The OS of patients who received more than 4 chemotherapy lines after ASCT was significantly lower compared to the OS (p=0.0096) with a median 95%CI OS of 85.5 months 65.61-106.15. In conclusion this study showed the significant positive impact on OS of the association consolidation and maintenance. We have also studied the impact of number of chemotherapy lines and the impact on OS and PFS of kind of treatment will be discussed.
To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had ...developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% ± 1% at 1 year and 6.6% ± 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n = 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs.
•Autoimmune diseases do occur after CBT in approximately 5% of patients.•Of these, AIHA or ITP were observed the most often and were treated with prednisone, CSA, and RTX.
Due to a severe impairment of cellular immunity, human cytomegalovirus (HCMV) infection is a common complication occurring after haematopoietic stem cell transplantation (HSCT) procedures (Castagnola ...et al., 2004).
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