[show abstract][hide abstract] ABSTRACT: Posaconazole prescribing information recommends an upfront cyclosporine dose-reduction upon initiation of posaconazole prophylaxis. We examined this recommendation in the early phase of allogeneic transplantation, where cyclosporine levels potentially becoming subtherapeutic following upfront dose-reduction would be deleterious to transplant outcome. Our data show that while posaconazole leads to an increase in cyclosporine levels, subsequent cyclosporine dose-reduction can be safely guided by therapeutic drug monitoring and is not required upfront. Therefore, the current recommendation may be modified.
Antimicrobial Agents and Chemotherapy 10/2012; · 4.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: INTRODUCTION: During routine analysis of chimerism in bone marrow transplant patients pre-transplant genotype of the recipient or the donor might lack. We aimed to develop a new method to analyze DNA results suitable when reference genotypes are not available. METHODS: The method was based on the balance between heterozygotes. It was implemented in a standard computer spreadsheet, and considered the hypothetical donor-recipient genotype combinations. Hypotheses with peak height ratios and allele sharing tendency above a critical threshold were accepted. The results were compared with those obtained with prior knowledge of reference genotypes. RESULTS: The algorithm predicted correctly the proportion of donor/recipient chimerism, even in the absence of reference genotypes. In fact, the predicted values were closely correlated (r(2)>0.98) and free of systematic bias (slope 0.98-1.04), in comparison with the reference values obtained with prior knowledge of the donor and recipient genetic profiles. CONCLUSIONS: This study constitutes a proof-of-concept of the application of the heterozygote balance for the quantitative study of chimerism. The algorithm computes post-transplant chimerism in an easy and time-efficient way, even when the donor and recipient reference genotypes are unavailable. Therefore, it can be a useful tool for laboratories involved in chimerism analysis.
Clinica chimica acta; international journal of clinical chemistry 09/2012; 414C:85-90. · 2.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated a FLAGIDA-lite protocol (fludarabine 40 mg/m(2)/d orally days 1-5, cytarabine 20 mg/m(2)/d subcutaneously days 1-5, G-CSF 300 μg/d subcutaneously days 1-5, and idarrubicin 15 mg/m(2)/d orally days 1-3) in 38 consecutive patients older than 70 years of age with acute myeloid leukemia (32 patients) or refractory anemia with excess blasts-2 (six patients) and no prior therapy. Seventy-nine percent had intermediate/unfavorable karyotype and 79% had a high comorbidity. Overall response was 55% [complete response (CR) 47%] and 37% were refractory. CR rate was 52% in patients between 71 and 79 years of age and 38% in patients 80 years or older. The 4-week induction mortality was 16% (8% in patients between 70 and 79 years of age and 32% in patients 80 years or older). Overall survival (OS) at 3 years was 22% (31.3% in patients between 70 and 79 years and 15.4% in patients 80 years or older). Relapse-free survival (RFS) at 3 years was 15%. A total of 65 cycles (47 as induction and 18 as consolidation) were administered, 46 of them (70%) in an outpatient setting. In summary, this FLAGIDA-lite protocol is an effective and well-tolerated option for patients between the ages of 70 and 79 years with acute myeloid leukemia or refractory anemia with excess blasts-2 and is usually feasible as outpatient treatment, but is not beneficial for most patients 80 years or older.
American Journal of Hematology 01/2012; 87(1):42-4. · 4.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adults with high-risk acute lymphoblastic leukemia (HR-ALL) have a poor outcome with standard chemotherapy and usually undergo unrelated stem cell transplantation (SCT) if a matched sibling donor is not available. We analyzed the outcome of adult patients with unrelated SCT for HR-ALL and studied the possible effect of the hematopoietic stem cell source of the transplant. A total of 149 adult patients (median age, 29 years, range, 15-59 years) with HR-ALL underwent unrelated SCT in 13 Spanish institutions between 2000 and 2007. Patients in first complete remission (CR1) at transplantation had at least one adverse prognostic factor (advanced age, adverse cytogenetics, hyperleukocytosis, or slow response to induction therapy). ALL was in CR1 in 81 patients (54%), in second CR (CR2) in 37 patients (25%), in third CR (CR3) in 11 patients (7%), and with overt disease in 20 patients (13%). The hematopoietic source was unrelated cord blood (UCB) in 62 patients and an unrelated donor (UD) in 87 patients. The patients undergoing UCB-SCT and UD-SCT were comparable in terms of the main clinical and biological features of ALL, except for a higher frequency of patients with more overt disease in the UCB-SCT group. There was no statistically significant difference in overall survival (OS) or disease-free survival (DFS) at 5 years between the 2 groups. Treatment-related mortality (TRM) was significantly lower in the UCB-SCT group (P = .021). The probability of relapse at 1 year was 17% (95% confidence interval [CI], 7%-27%) for the UD-SCT group and 27% (95% CI, 14%-40%) for the UCB-SCT group (P = .088), respectively. Only disease status at transplantation (CR1, 41% [95% CI, 18%-64%] vs CR2, 51% [95% CI, 17%-85%] vs advanced disease, 66% [95% CI, 46%-86%]; P = .001) and the absence of chronic graft-versus-host disease (74% [95% CI, 46%-100%] vs 33% [95% CI, 17%-49%]; P = .034) were significant factors for relapse. All unrelated transplantation modalities were associated with high treatment-related mortality for adult HR-ALL patients without a sibling donor. UCB-SCT and UD-SCT were found to be equivalent options. Disease status at transplantation and chronic GVHD were the main factors influencing relapse in both transplantation modalities.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2010; 16(7):957-66. · 3.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: Scedosporium prolificans is an emerging fungus that causes rapid progressive and disseminated infections in immunodepressed patients. We present a case of a 34-year-old woman with chronic myelogenous leukemia who received a bone marrow transplantation and suffered a sudden respiratory failure in +67 day. Chest radiographies showed growing bilateral patchy condensations. Computed Tomography depicted bilateral nodular condensation of alveolar space. S. prolificans was detected from sputum, but the patient died 72 h later. Imaging findings of lung scedosporiosis are nonspecific, but CT may provide a prompter diagnosis and allow to add newer antifungal treatments. This report presents the first imaging report of lung scedosporiosis.
[show abstract][hide abstract] ABSTRACT: Scedosporium prolificans is an emerging opportunistic fungal agent encountered in severely neutropenic patients. The purpose of this paper is to describe the main cranial CT findings from a retrospective review of six patients (four men and two women, 18-66 years old) afflicted with disseminated infection by S. prolificans with neurological symptoms. They were severely neutropenic and presented with severe respiratory failure and conscience deterioration, with a subsequent 100% mortality. The final diagnosis was established by autopsy (performed in five patients) and blood culture findings. Cranial CT showed multiple low-density lesions in four patients without contrast enhancement located in the basal ganglia and corticomedullary junction. Autopsy findings of these lesions demonstrated necrosis and hyphae proliferation inside brain infarcts. Also, two of the patients had a subarachnoid hemorrhage, but angiography could not be performed. CT and autopsy findings were fairly similar to those encountered in cerebral aspergillosis; however, possibly because of its rapid and fatal evolution, no edema or ring enhancing lesions were encountered. Thus, Scedosporium can be included as a rare but possible cause of invasive fungal disseminated central nervous system infections in severely neutropenic patients.
European Radiology 03/2006; 16(2):496-502. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Combinations of beta-lactams plus aminoglycosides have become standard therapy for suspected infections in patients with profound neutropenia. However, it is not clear whether such combinations are advantageous over therapy with a broad-spectrum antibiotic.
To assess the clinical effectiveness and the cost-effectiveness ratio of empirical therapy of febrile neutropenia with imipenem/cilastatin (I/C) versus piperacillin/tazobactam plus amikacin (P/T+A).
Prospective, multicenter observational study with 2 matched parallel cohorts treated with I/C (500 mg/6 h iv) or P/T+A (P/T: 4 g/6 h iv; A: 20 mg/kg/day iv).
Therapeutic success was defined as the resolution of fever following > or = 7 days of unchanged antibiotic treatment. An economic comparison was conducted focusing on the daily treatment costs, and the management of its toxicity.
There were 343 eligible patients (180 I/C, 163 P/T+A), of whom 290 were evaluable for the primary clinical effectiveness analysis. Follow-up information beyond 7 days of study inclusion was only available for 52% of all evaluable patients. Treatment success was observed in 42% of I/C patients compared with 31% of P/T+A patients (95% CI: -0.01, 21.4). The incidence of drug-related adverse experiences was 13% for I/C and 6% for P/T+A, with no differences in moderate or severe adverse experiences nor in those causing discontinuation of antibiotic therapy. Treatment costs were 189.55 euros (95% CI: 127.46-251.46) lower per episode of febrile neutropenia for patients treated with I/C.
The clinical effectiveness of I/C was similar to that of P/T+A. In both treatment groups toxicity was low and did not limit antibiotic therapy. Resource consumption was lower with I/C.
Current Medical Research and Opinion 06/2005; 21(5):645-55. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Short-tandem repeat (STR) genotyping is widely used for forensic purposes and it is also used to determine the proportions of donor and recipient cells after hematopoietic stem-cell transplantation. New STR multiplexes have recently been developed to analyze the complete CODIS plus D19S433 and D2S1338, such as AmpFℓSTR® Identifiler® Plus PCR Amplification kit (Applied Biosystems) and Investigator™ IDplex® (Qiagen). The objective of this study was to compare the sensitivity of both kits in the analysis of chimerism. The Investigator™ IDplex® allowed quimerism detection only in 10 (67%) of the 15 cases with chimerism detected by using the Identifiler® Plus kit, suggesting that the latter may have higher sensitivity.
Forensic Science International Genetics Supplement Series