Improvement of transfusion practice and reduction in red blood cell utilization in Belgian hospitals: Results of a national survey and benchmarking.

BACKGROUND AND OBJECTIVES: Belgian health authorities launched a national platform in 2011 to improve the quality of transfusion practices and blood use in Belgian hospitals. No data were available about the quality of hospital transfusion practice at the national level. MATERIALS AND METHODS: Three consecutive national surveys (2012, 2014 and 2016) were performed in all 111 Belgian hospitals to assess the degree of implementation of standards in four process domains related to red blood cell (RBC) transfusion: general quality aspects, ordering of RBC, electronic traceability and reporting of adverse events. The surveys were part of a methodology based on informing, feedback and benchmarking. Responses to questions were analysed semi-quantitatively, and hospitals could score 10 points on each of the domains. RESULTS: The proportion of hospitals scoring below 5 per domain decreased from 16%, 70%, 14% and 11% (2012) to 2%, 17%, 1% and 1% (2016), respectively. Similarly, scores above 7.5 increased from 25%, 1%, 23% and 36% (2012) to 64%, 30%, 68% and 81% (2016), respectively. In 2016, overall quality of transfusion practices, including the four pre-specified domains, improved continuously with an average total score (max = 40) increasing from 24.2 to 30.5 (p = 0.0005). In addition, there was a decrease in the number of distributed and transfused RBC per 1000 population between 2011 and 2019 from 47.0 to 36.5 and 43.5 to 36.1, respectively. CONCLUSION: These data show that the applied methodology was a powerful tool to improve quality of transfusion practices and to optimize utilization of RBC at the national level.

Disease and treatment characteristics of polycythemia vera patients in Belgium: Results from a scientific survey.

OBJECTIVE: The current survey aimed to gather predefined disease parameters and treatment strategies to characterize the polycythemia vera (PV) patient population in Belgium. METHODS: Cross-sectional data from PV patients, seen at least once between May 2014 and May 2015 at 10 sites in Belgium, were collected in aggregated form and analyzed descriptively and quantitatively. RESULTS: Data from 343 PV patients were collected. Of these, 174 (50.7%) were male and 256 (74.6%) were ≥60 years of age. Ninety-two (26.8%) had a prior history of thrombotic events. Considerable proportions of patients had increased hematological parameters (hematocrit > 45% [31.2%], leukocytes > 10 × 109 /L [33.3%], and platelet > 400 × 109 /L [38.2%]). Most patients had non-palpable spleen (284, 87.7%) and no phlebotomies during the past 6 months (197, 57.4%). Low-dose aspirin was given as thrombosis prophylaxis in 249 (72.6%) patients, while 232 (67.6%) received hydroxyurea (HU) as cytoreductive treatment. Forty-one patients (12.0%) were reported as resistant and/or intolerant to HU. Seventeen patients (5.0%) received ruxolitinib in the context of clinical trials. CONCLUSION: This survey provides better insight into the characteristics of Belgian PV patients and currently used treatment strategies. It shows that 232 (67.6%) PV patients continue to receive HU despite being potentially HU-resistant.

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges.

BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2(nd) generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation.

International development of an EORTC questionnaire for assessing health-related quality of life in chronic myeloid leukemia patients: the EORTC QLQ-CML24.

BACKGROUND: Health-related quality of life (HRQOL) is a key aspect for chronic myeloid leukemia (CML) patients. The aim of this study was to develop a disease-specific HRQOL questionnaire for patients with CML to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30. PATIENTS AND METHODS: The process followed a predefined and systematic stepwise iterative process as defined by the EORTC guidelines for questionnaire development. The process was divided into 3 phases: (1) generation of relevant HRQOL issues, (2) operationalization of the HRQOL issues into a set of items, and (3) pretesting the questionnaire for relevance and acceptability. Descriptive statistics and psychometric analyses were also performed. RESULTS: Overall, 655 CML patients were enrolled in 10 countries including the USA and countries in Europe and Asia. Interviews with health-care professionals experienced in CML (n = 59) were also conducted. Results from the interviews, clinical experiences, and statistical analyses were used to develop the EORTC QLQ-CML24. The final module consists of 24 items assessing the following aspects: symptom burden, impact on daily life and on worry/mood, body image problems, and satisfaction with care and with social life. Internal consistency, assessed with Cronbach's alpha coefficients, ranged from 0.73 to 0.83 for the proposed scales. CONCLUSION: The EORTC QLQ-CML24 is an internationally developed HRQOL questionnaire for CML patients, and its implementation in clinical research and practice can provide important information to facilitate clinical decision-making.

High-risk clonal evolution in chronic B-lymphocytic leukemia: single-center interphase fluorescence in situ hybridization study and review of the literature.

BACKGROUND: We studied the relation of clonal evolution (CE) in Chronic B-lymphocytic leukemia (CLL) with prognostic factors and the correlation between CE and disease progression and overall survival. METHODS: With interphase fluorescence in situ hybridization (FISH) analysis, we looked for 11q22 deletion, 17p13 deletion, and trisomy 12. A second FISH was performed approximately 3 yr after the first one or earlier in case of disease progression. RESULTS: High-risk CE, defined as the acquisition of a new 11q or 17p deletion, was observed in 11.5% (11/95) of patients with CLL. The relative risk of CE was not influenced by CD38 and ZAP-70 expression, mutational status of the immunoglobulin heavy chain gene (IgVH), lymphocyte doubling time, and genomic aberrations observed with the first FISH or by treatment given between the sequential genetic analyses. Patients with high-risk CE had a significant shorter survival time (59 months vs. not reached, P = 0.0367). Multivariate analysis identified CE as the strongest independent prognostic marker regarding survival [hazard ratio (HR) 4.1, P = 0.01]. Clonal fluctuation, defined as disappearance of the 11q or 17p deletion, was seen in 11.5% (11/95) of patients. Most patients lost the high-risk clone after treatment despite persistence of a malignant clone. The disappearance of these genomic aberrations did not ameliorate outcome. A few patients have lost spontaneously a small 17p clone. CONCLUSION: This study confirms that CE and clonal fluctuation are common phenomena in CLL. CE was not limited to patients with pre-existing adverse prognostic factors. Acquiring high-risk CE was identified as the strongest independent prognostic factor for impaired survival.

EVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells.

Chromosomal rearrangements involving the MECOM (MDS1 and EVI1 complex) locus are recurrent genetic events in myeloid leukaemia and are associated with poor prognosis. In this study, we assessed the role of MECOM locus protein EVI1 in the transcriptional regulation of microRNAs (miRNAs) involved in the leukaemic phenotype. For this, we profiled expression of 366 miRNAs in 38 MECOM-rearranged patient samples, normal bone marrow controls and MECOM (EVI1) knock down/re-expression models. Cross-comparison of these miRNA expression profiling data showed that MECOM rearranged leukaemias are characterized by down regulation of MIR449A. Reconstitution of MIR449A expression in MECOM-rearranged cell line models induced apoptosis resulting in a strong decrease in cell viability. These effects might be mediated in part by MIR449A regulation of NOTCH1 and BCL2, which are shown here to be bona fide MIR449A targets. Finally, we confirmed that MIR449A repression is mediated through direct promoter occupation of the EVI1 transcriptional repressor. In conclusion, this study reveals MIR449A as a crucial direct target of the MECOM locus protein EVI1 involved in the pathogenesis of MECOM-rearranged leukaemias and unravels NOTCH1 and BCL2 as important novel targets of MIR449A. This EVI1-MIR449A-NOTCH1/BCL2 regulatory axis might open new possibilities for the development of therapeutic strategies in this poor prognostic leukaemia subgroup.

Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study.

Imatinib mesylate (imatinib) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong, patient adherence is critical. The ADAGIO (Adherence Assessment with Glivec: Indicators and Outcomes) study aimed to assess prospectively over a 90-day period the prevalence of imatinib nonadherence in patients with CML; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence; and to examine whether treatment response is associated with adherence levels. A total of 202 patients were recruited from 34 centers in Belgium, of whom 169 were evaluable. One-third of patients were considered to be nonadherent. Only 14.2% of patients were perfectly adherent with 100% of prescribed imatinib taken. On average, patients with suboptimal response had significantly higher mean percentages of imatinib not taken (23.2%, standard deviation [SD] = 23.8) than did those with optimal response (7.3%, SD = 19.3, P = .005; percentages calculated as proportions x 100). Nonadherence is more prevalent than patients, physicians, and family members believe it is, and therefore should be assessed routinely. It is associated with poorer response to imatinib. Several determinants may serve as alert signals, many of which are clinically modifiable.

Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study.

OBJECTIVE: To determine the impact of physiologic changes of pregnancy on pharmacokinetics of chemotherapeutic agents. DESIGN: A preclinical and a clinical case-control trial. SETTING: Institute of Primate Research Nairobi and collaborating hospitals in Belgium, the Netherlands and Czech Republic. POPULATION: Pregnant and nonpregnant women and baboons receiving chemotherapy. METHODS: Chemotherapy pharmacokinetics was compared between the pregnant and nonpregnant state. Standard-dosed chemotherapy regimens were administered in pregnant and nonpregnant baboons/women, followed by serial blood samplings. Drug plasma levels were determined using high performance liquid chromatography and atomic absorption spectrometry. MAIN OUTCOME MEASURES: Area under the curve (AUC), maximal plasma concentration, terminal elimination half-life, clearance and distribution volume of each drug in pregnant and nonpregnant state. RESULTS: Intraindividual comparative pharmacokinetic data were obtained for doxorubicin and paclitaxel/platinum in three and two baboons, respectively. In the clinical trial, two patients were exposed to doxorubicin and one patient was exposed to paclitaxel/platinum during and after pregnancy. Furthermore, a pooled analysis was performed based on 16 cycles of pregnant and 11 cycles of nonpregnant women. Numbers of pregnant/nonpregnant patients were 5/2, 7/5, 4/4 and 2/2 for paclitaxel, doxorubicin, epirubicin and platinum, respectively. For all drugs tested in the preclinical and clinical study, a decreased AUC and maximal plasma concentration and an increased distribution volume and clearance were observed in pregnancy. CONCLUSIONS: Although numbers were too small for statistical significance, pregnancy-associated physiologic alterations appear to lead to a decrease in plasma exposure of chemotherapeutic drugs. The importance of long-term follow-up of women treated with chemotherapy during pregnancy is underscored.

EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22.

Chromosomal translocations involving the EVI1 locus are a recurrent finding in myeloid leukemia and are associated with poor prognosis. In this study, we performed a detailed molecular characterization of the recurrent translocation t(3;17)(q26;q22) in 13 hematologic malignancies. The EVI1 gene locus was rearranged in all 13 patients and was associated with EVI1 overexpression. In 9 out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band 17q22 encompassing the MSI2 (musashi homologue 2) gene. Expression analyses failed to demonstrate ectopic MSI2 expression or the presence of an MSI2/EVI1 fusion gene. In conclusion, we show for the first time that the t(3;17) is indeed a recurrent chromosomal aberration in myeloid malignancies. In keeping with findings in other recurrent 3q26 rearrangements, overexpression of the EVI1 gene appears to be the major contributor to leukemogenesis in patients with a t(3;17).

Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic shock patients with hematological malignancies.

OBJECTIVE: To compare the characteristics and outcome of patients with hematological malignancies referred to the ICU with severe sepsis and septic shock who had or had not received recent intravenous chemotherapy, defined as within 3 weeks prior to ICU admission. DESIGN AND SETTING: Retrospective observational cohort study on prospectively collected data in a medical ICU of a university hospital. PATIENTS: 186 ICU patients with hematological malignancies with severe sepsis or septic shock (2000-2006). MEASUREMENTS AND RESULTS: There were 77 patients admitted with severe sepsis and 109 with septic shock; 91 (49%) had received recent intravenous chemotherapy. Patients with recent chemotherapy more often had a high-grade malignancy and were more often neutropenic, less often had pulmonary infiltrates, and less often required mechanical ventilation. ICU, 28-day, in-hospital, and 6-month mortality rates were 33% vs. 48.4%, 40.7% vs. 57.4%, 45.1% vs. 58.9%, and 50.5% vs. 63.2% in patients with and without recent chemotherapy, respectively. Logistic regression identified four variables independently associated with 28-day mortality: SOFA score at ICU admission, pulmonary site of infection, and fungal infection were associated with worse outcome whereas previous intravenous chemotherapy was protective at borderline significance. After adjustment with a propensity score for recent chemotherapy, chemotherapy was not associated with outcome. CONCLUSIONS: Patients referred to the ICU with severe sepsis and septic shock complicating active chemotherapeutic treatment have better prognosis than commonly perceived.

Infusion of bone marrow derived multipotent mesenchymal stromal cells for the treatment of steroid-refractory acute graft-versus-host disease: a multicenter prospective study.

The prognosis of steroid-refractory acute graft-versus-host disease (aGVHD) remains poor and better treatments are urgently needed. Multipotent mesenchymal stromal cell (MSC)-based therapy emerged as a promising approach but response rates were highly variable across studies. We conducted a multicenter prospective study assessing the efficacy of 1-2 infusion(s) of cryopreserved, third-party donor bone marrow-derived MSCs for treating grade II-IV steroid-refractory or -dependent aGVHD in a series of 33 patients. MSCs were produced centrally and distributed to 8 hospitals throughout Belgium to be infused in 2 consecutive cohorts of patients receiving 1-2 or 3-4 × 106 MSCs/kg per dose, respectively. All patients received MSCs as the first rescue therapy after corticosteroids, with the exception for one patient who received prior treatment with mycophenolate mofetil (that was still ongoing by the time of MSC therapy). In these conditions, MSC therapy resulted in at least a partial response in 13 patients (40.6%) at day 30 and in 15 patients (46%) within 90 days after first MSC infusion. The corresponding complete response rates were 21.6% (7 patients) and 30% (10 patients), respectively. Only 5 patients achieved a sustained complete response, lasting for at least 1 month. The 1-year overall survival was 18.2% (95% CI: 8.82-37.5%). Higher response and survival rates were observed among patients receiving 3-4 × 106 MSCs/kg for first infusion, as compared with patients receiving 1-2 × 106 MSCs/ kg. Response and survival with MSC therapy for SR/SD-aGVHD remains to be optimized.

Outcome in severely ill patients with hematological malignancies who received intravenous chemotherapy in the intensive care unit.

OBJECTIVE: To assess the outcome in severely ill patients with hematological malignancies who receive intravenous chemotherapy in an intensive care unit (ICU) for a life-threatening malignancy-related complication. DESIGN: Retrospective observational study of prospectively collected data. PATIENTS: All 37 critically ill patients with hematological malignancies who received intravenous chemotherapy in the ICU between January 1997 and March 2005 (mean age 46+/-19 years; mean APACHE II 23+/-7). MEASUREMENTS AND RESULTS: Thirty-seven (69%) patients received chemotherapy because of extensive disease with organ involvement (54%), extensive disease without organ involvement (19%), severe disseminated intravascular coagulation (11%), and other reasons (16%). In 41% there was concomitant infection when chemotherapy was initiated, in 86% a high-grade malignancy, and 30% relapsing disease. Twenty-three (62%) patients received mechanical ventilation at the moment of or soon after initiation of chemotherapy for a median duration of 5 days (1-67), and 24% underwent renal replacement therapy during ICU stay. Only ventilation was associated with in-hospital mortality (odds ratio 9.3). ICU, in-hospital, and 6-month mortality rates in nonventilated vs. ventilated patients were 7% and 48%, 14% and 61%, and 54% and 74%, respectively. CONCLUSIONS: Starting chemotherapy in the ICU for a life-threatening malignancy related complication can be lifesaving even when infection or organ failure is present.

Combined evaluation of conventional MRI, dynamic contrast-enhanced MRI and diffusion weighted imaging for response evaluation of patients with multiple myeloma.

PURPOSE: To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) in multiple myeloma (MM) patients after treatment compared to the international myeloma working group (IMWG) response criteria. MATERIALS AND METHODS: The retrospective study includes 27 newly diagnosed patients, providing 99 MRI-investigations. Patients were categorized according to the IMWG response criteria. Quantitative assessment was based on signal intensities (SI) of T1-weighted, fat-saturated T2-weighted and b1000 images, apparent diffusion coefficients (ADC) and parameters from time-intensity-curves (TIC) derived from L3. Qualitative visual analysis of conventional MRI-images, b1000-images and TICs, providing a "combined skeletal score", was used to create MRI response criteria. RESULTS: The combined skeletal score could significantly differentiate between subgroups based on IMWG response criteria (p=0.016). The gold standard plasmacytosis could significantly differentiate between subgroups based on MRI response criteria (p<0.001), as well as slope (p<0.001) and ADC (p=0.006). There is a good agreement between IMWG and MRI response criteria (Kendall's coefficient=0.761). CONCLUSION: Response evaluation of MM-patients based on the combination of anatomical information from conventional MRI with functional information from DCE-MRI and DWI, is useful for monitoring therapy.

Documented and clinically suspected bacterial infection precipitating intensive care unit admission in patients with hematological malignancies: impact on outcome.

OBJECTIVE: To assess the impact of documented and clinically suspected bacterial infection precipitating ICU admission on in-hospital mortality in patients with hematological malignancies. DESIGN AND SETTING: Prospective observational study in a 14-bed medical ICU at a tertiary university hospital. PATIENTS: A total of 172 consecutive patients with hematological malignancies admitted to the ICU for a life-threatening complication over a 4-year period were categorized into three main groups according to their admission diagnosis (documented bacterial infection, clinically suspected bacterial infection, nonbacterial complications) by an independent panel of three physicians blinded to the patient's outcome and C-reactive protein levels. RESULTS: In-hospital and 6-months mortality rates in documented bacterial infection (n=42), clinically suspected bacterial infection (n=40) vs. nonbacterial complications (n=90) were 50.0% and 42.5% vs. 65.6% (p=0.09 and 0.02) and 56.1% and 48.7% vs. 72.1% (p=0.11 and 0.02), respectively. Median baseline C-reactive protein levels in the first two groups were 23 mg/dl and 21.5 mg/dl vs. 10.7 mg/dl (p<0.001 and p=0.001) respectively. After adjustment for the severity of critical and underlying hematological illness and the duration of hospitalization before admission documented (OR 0.20; 95% CI 0.06-0.62, p=0.006) and clinically suspected bacterial infection (OR 0.18; 95% CI 0.06-0.53, p=0.002) were associated with a more favorable outcome than nonbacterial complications. CONCLUSIONS: Severely ill patients with hematological malignancies admitted to the ICU because of documented or clinically suspected bacterial infection have a better outcome than those admitted with nonbacterial complications. These patients should receive advanced life-supporting therapy for an appropriate period of time.

Validation of High Resolution Melting Analysis (HRM) of the Amplified ITS2 Region for the Detection and Identification of Yeasts from Clinical Samples: Comparison with Culture and MALDI-TOF Based Identification.

AIM: Candida species are known as opportunistic pathogens, and a possible cause of invasive infections. Because of their species-specific antimycotic resistance patterns, reliable techniques for their detection, quantification and identification are needed. We validated a DNA amplification method for direct detection of Candida spp. from clinical samples, namely the ITS2-High Resolution Melting Analysis (direct method), by comparing it with a culture and MALDI-TOF Mass Spectrometry based method (indirect method) to establish the presence of Candida species in three different types of clinical samples. MATERIALS AND METHODS: A total of 347 clinical samples, i.e. throat swabs, rectal swabs and vaginal swabs, were collected from the gynaecology/obstetrics, intensive care and haematology wards at the Ghent University Hospital, Belgium. For the direct method, ITS2-HRM was preceded by NucliSENS easyMAG DNA extraction, directly on the clinical samples. For the indirect method, clinical samples were cultured on Candida ID and individual colonies were identified by MALDI-TOF. RESULTS: For 83.9% of the samples there was complete concordance between both techniques, i.e. the same Candida species were detected in 31.1% of the samples or no Candida species were detected in 52.8% of the samples. In 16.1% of the clinical samples, discrepant results were obtained, of which only 6.01% were considered as major discrepancies. Discrepancies occurred mostly when overall numbers of Candida cells in the samples were low and/or when multiple species were present in the sample. DISCUSSION: Most of the discrepancies could be decided in the advantage of the direct method. This is due to samples in which no yeast could be cultured whereas low amounts could be detected by the direct method and to samples in which high quantities of Candida robusta according to ITS2-HRM were missed by culture on Candida ID agar. It remains to be decided whether the diagnostic advantages of the direct method compensate for its disadvantages.

Donor stem cell infusion after non-myeloablative conditioning for tolerance induction to HLA mismatched adult living-donor liver graft.

BACKGROUND AND AIM OF THE STUDY: The induction of transplantation tolerance, defined as the survival of a functioning allograft in the absence of continuing immunosuppressive therapy, would be a major advance. Clinical and experimental data have shown that transplantation tolerance could be induced by pre-transplant myeloconditioning and infusion of donor hematopoietic cells. We investigated the feasibility and safety of a protocol to induce tolerance to HLA mismatched living-donor liver graft by pre-transplant non-myeloablative conditioning followed by donor stem cells (SC) infusion, in patients with advanced liver cancers. PATIENTS AND METHODS: Two patients with intrahepatic cancers who did not fulfill criteria for cadaver liver transplantation were included in the study. Preparative regimen consisted in cyclophosphamide and anti-thymocyte globulin, followed by infusion of purified donor CD34(+) stem cells. Living-donor liver transplantation (LDLT) using the liver right lobe was performed after hematological reconstitution, respectively 40 and 55 days after donor stem cell infusion. Immunosuppressive therapies were discontinued when liver graft function returned to normal. RESULTS: The procedure could be completed in the two patients. No severe toxicity of the preparative regimen was observed. Neither patient presented graft versus host reaction after donor stem cell infusion. A transient macrochimerism was observed in the first case, while no chimerism could be detected in the second. Immunosuppression was discontinued, respectively 90 and 28 days, after liver transplantation, without subsequent rejection episode. In the two cases, liver function remained normal for the study period. In both patients, the period of immune reconstitution was prolonged, as illustrated by persisting low CD4(+) cell counts. Mixed lymphocyte cultures, performed after immunosuppression withdrawal, demonstrated donor specific hyporesponsiveness in the first case, but in a context of global hyporeactivity in the two patients. The first patient died from tumor recurrence 370 days after liver transplantation. The second patient is alive, 270 days after liver transplantation, but with a suspicion of tumor relapse as indicated by the reappearance of tumor marker in blood. CONCLUSION: In the two cases, acceptance of HLA mismatched living-donor liver graft was obtained after non-myeloablative conditioning and donor stem cell infusion. Improving the rate of immune reconstitution appears as a priority to reduce the risk of tumor recurrence in such patients.

Comparison of two functional flow cytometric assays to assess P-gp activity in acute leukemia.

One of the possible causes of treatment failure in acute leukemia is the emergence of multidrug resistance caused by P-glycoprotein (P-gp) overexpression. We compared a flow cytometric assay using JC-1 with a technique using rhodamine 123 (rho123) to evaluate the P-gp function in acute leukemia. Samples from 50 acute leukemia patients were analyzed by both functional assays. The P-gp expression was assessed by an immunological flow cytometric test and the association between the P-gp status and the clinical outcome was evaluated. Of all samples, 28% showed a reversible JC-1 efflux and 36% scored positive for the rho123 assay. In two cases, the leukemic blasts showed a reversible JC-1 efflux whereas they were negative for rho123. These patients had blast cells with a very low P-gp activity. Six samples scored positive for the rho123 assay but were negative for the JC-1 test. Five of these samples did not express P-glycoprotein and were considered false positive. We found a strong correlation between the JC-1 and the rho123 test (R(s)=0.59, p<0.0001) and the JC-1 and the immunological assay (R(s)=0.29, P=0.05). There was also an association between the JC-1 status and the clinical outcome of adult patients (chi2=6.30, P=0.04). In conclusion, we recommend the JC-1 assay to study the P-gp activity in acute leukemia because it is more specific and less labor intensive than conventional functional flow cytometric tests using rhodamine 123. In addition, the JC-1 assay can be used to identify adult patients with an increased risk for adverse clinical outcome.

Validation of the G8 screening tool in older patients with aggressive haematological malignancies.

BACKGROUND: Incidence rates of haematological malignancies increase with age. In these older cancer patients, important information may be missed without a Comprehensive Geriatric Assessment (CGA). A validated screening instrument is needed to identify those patients for whom a CGA would be beneficial. The G8 has recently been validated as a screening tool for older cancer patients in need of a CGA. OBJECTIVES: To test the performance of the G8 screening tool in older patients with aggressive haematological malignancies to identify those who would benefit from a CGA. METHODS: Cross-sectional study of patients ≥70 years with a recently diagnosed haematological malignancy. G8, CGA (including six questionnaires) and Cumulative Illness Rating Scale for Geriatrics (CIRS-G) were completed in each patient. The CGA was considered abnormal when at least one questionnaire showed an impaired score. RESULTS: Fifty patients with median age of 76 years were included; 88% (N = 44) had an abnormal CGA. ROC curve analyses revealed a G8 score ≤14 obtained a sensitivity of 89% (95% CI 75-96) and a specificity of 100% (95% CI 54-100), suggesting an optimal cut-off point. AUC ± SE was 0.949 ± 0.030. Inclusion of comorbidity in the CGA did not change the performance of the G8 (0.943 ± 0.034; P = 0.895). CONCLUSION: The G8 can be used as a valid screening tool in older patients with aggressive haematological malignancies to identify those patients who would benefit from a CGA. Comorbidity should be assessed routinely and independently of the G8.