Remission Induction Therapy In Patients Research Articles

Predictive Factors for Efficacy of Oral Tacrolimus Induction Therapy in Moderate to Severe Ulcerative Colitis Patients: Large Multicenter Retrospective Cohort Study.

Tacrolimus (TAC), a calcineurin inhibitor, is used for remission induction therapy in patients with moderate to severe ulcerative colitis (UC), with short-term efficacy and related predictive factors shown in previous cohort studies. However, most studies reported data for only a limited number of patients enrolled from a single center. We performed a large multicenter retrospective cohort study to identify factors related to prediction of clinical remission in UC patients treated with oral TAC. The medical records of patients with moderate to severe UC treated with oral TAC as induction therapy at 7 institutions between April 2009 and March 2017 were retrospectively reviewed. A total of 216 patients who received TAC for induction were analyzed, of whom 123 (56.9%) showed clinical remission at week 12. Logistic regression analysis indicated that previous or current use of antitumor necrosis factor (TNF)-α antibodies (odds ratio [OR], 0.259; P = .006), and concomitant treatment with 5-aminosalicylate (5-ASA) at the baseline (OR, 0.268; P = .005) were independent predictive factors correlated with failure of clinical remission, whereas higher levels of C-reactive protein (OR, 1.124; P = .014) predicted achievement of clinical remission. Results of this multicenter study clearly indicate the efficacy of TAC induction therapy for patients with moderate to severe UC. Notably, previous or current use of anti-TNF-α antibodies was associated with poor achievement of clinical remission by week 12.

ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial

IntroductionBoth rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown...

Lupus low disease activity state within 12 months is associated with favourable outcomes in severely active systemic lupus erythematosus.

To demonstrate the significance of the time to attain lupus low disease activity state (LLDAS) after remission induction therapy in patients with severely active SLE. We enrolled 79 patients starting prednisolone ≥0.4 mg/kg/day for active lupus with a BILAG 2004 index of A ≥ 1 or B ≥ 2, or for severe flare based on the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI). The time to LLDAS attainment was divided into ≤6, 6-12 and >12 months and non-LLDAS; associations between the timing of LLDAS and flares, damage accrual and ≥50% LLDAS attainment were examined. The mean SLEDAI was 17; median starting dose of prednisolone, 0.95 mg/kg/day; and mean observational period, 39.7 months. Six (7.6%) and 41 (51.9%) patients achieved LLDAS within 6 and 12 months. Patients with a shorter time to LLDAS achievement were more likely to spend ≥50% of the time in LLDAS and had a lower cumulative prednisolone dose; no differences were observed in damage accrual. Patients requiring longer than 12 months to achieve LLDAS had a higher prevalence of thrombocytopenia and those with non-LLDAS had lower renal function and a higher starting dose of prednisolone and steroid pulse therapy than those who achieved LLDAS within 12 months. Achieving LLDAS within 12 months of induction therapy may be favourable in patients with severely active SLE. The low frequency of LLDAS attainment in high-risk populations highlights the need for a new strategy for SLE treatment.

The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

Expression Changes of CX3CL1 and Interleukin-6 Genes During Remission Induction Therapy in Patients with Acute Myeloid Leukemia

Background: Acute myeloid leukemia (AML) syndrome is a hematologic malignancy due to the extensive clonal proliferation of leukemic precursor cells and is rapidly fatal unless treated or in response to chemotherapy. Cytogenetic findings have an important role in the prognosis and categorization of AML. This study aimed to investigate the expression changes in CX3CL1 and Interleukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study, 69 patients (36 males, 33 female) with AML were selected from tertiary medical health centers. A quantitative polymerase chain reaction was performed for mRNA expression of CX3CL1 and IL-6 genes before and after induction chemotherapy using the 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 were significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: We showed that chemotherapy significantly increases the expression of CX3CL1 and IL-6, which can be used as a prognostic factor of AML. [GMJ.2021;10:e2288]

Association between mortality and cytomegalovirus reactivation during remission induction therapy in patients with rheumatic diseases.

To elucidate the characteristics of patients with rheumatic diseases with cytomegalovirus (CMV) reactivation. In our study, we consecutively reviewed patients with rheumatic diseases who received remission induction therapy in our institution from January 2012 to March 2016 and enrolled the patients who were evaluated about CMV infection. CMV reactivation was characterised by the detection of polymorphonuclear leukocytes with CMV pp65. The characteristics and clinical courses of the patients with CMV reactivation were compared to those without CMV. We observed CMV reactivation in 71 (39.7%, CMV-positive group) out of 179 patients. Age (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.002-1.044, p=0.03), lymphocyte counts (OR 0.999, 95% CI 0.999-1.000, p=0.03), and initial prednisolone dose (OR 18.596, 95% CI 2.399-144.157, p<0.01) were considered as independent relevant risk factors for CMV reactivation. Patients in the CMV-positive group showed significantly higher incidences of all infections (48%) and severe infections (31%) than those in the CMV-negative group (48% vs .31%, p=0.037; 31% vs. 6%, p<0.001, respectively). Higher mortality was observed in the CMV-positive group than in the CMV-negative group (14.1% vs. 1.9%). The lymphocyte counts were more relevant to CMV infection and mortality than were the serum IgG levels. Our study revealed that CMV reactivation occurred in one third of all patients with rheumatic diseases who were undergoing intensive remission induction therapy, and it was found to be relevant to other severe infections and infection-related deaths.

Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study

BackgroundThe aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN).MethodsIn total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels.ResultsThe mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74).ConclusionAs urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.

Efficacy of mycophenolate mofetil as a remission induction therapy in antineutrophil cytoplasmic antibody: associated vasculitis—a meta-analysis

ObjectivesA few studies on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treatments have shown the therapeutic efficacy of mycophenolate mofetil (MMF). However, the therapeutic efficacy of MMF compared with that of...

Initial high-dose corticosteroids and renal impairment are risk factors for early severe infections in elderly patients with antineutrophil cytoplasmic autoantibody-associated vasculitis

Recent large observational studies of antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) show that severe infection is a major cause of death and that the majority of infections occur during the early phase of initiating remission-induction therapy. Many risk factors for severe infection have been suggested, but these have been inconsistent. Nevertheless, infectious risk factors in elderly patients with AAV have not been adequately investigated in previous studies.In this retrospective observational study, we examined potential predictors of severe infection within 90 days (early severe infections) after remission-induction therapy in patients with AAV aged 65 years or older. We included 167 consecutive elderly patients with AAV admitted to our hospital. Data from medical history and remission-induction therapy were analyzed for predictive risk factors associated with early severe infections. The relationship between initial doses of corticosteroids and cumulative incidence of severe infections was also analyzed. A multivariate analysis of risk factors for early severe infections was performed using logistic regression analysis. The Kaplan-Meier method was used to estimate the overall survival, and the log-rank test was used to evaluate the differences between patients with and without early severe infections. Gray method was used to compare the cumulative incidence of severe infections in patients who did and did not receive initial high-dose corticosteroids.Logistic regression analysis showed that initial high-dose corticosteroid administration (prednisolone ≥0.8 mg/kg/d) (odds ratio [OR] 3.86, P = .030) and serum creatinine levels at diagnosis ≥1.5 mg/dL (OR 5.13, P = .003) were independent predictors of early severe infection although administration of cyclophosphamide or rituximab was not. The cumulative incidence of severe infections was also significantly higher in patients who received initial high-dose corticosteroids (P = .042), and patients with early severe infections exhibited a high mortality rate within 6 months (P < .001).Our findings suggest that initial high-dose corticosteroids and renal impairment at diagnosis are associated with a higher risk of early severe infections and early death in elderly patients with AAV.

Use of corticosteroids for remission induction therapy in patients with new-onset ulcerative colitis in real-world settings

ABSTRACTBackground: Corticosteroids may be temporarily effective for ulcerative colitis (UC), but long-term use increases the risk of adverse drug reactions.Objective: The goal of the study was to examine steroid use in remission induction therapy after diagnosis of UC.Study Design: A retrospective observational study using the Japan Medical Data Center (JMDC) Claims Database from January 2008 to December 2014.Setting: Clinics, university hospitals, and national/public hospitals.Intervention: Initiation of steroids after diagnosis of UC.Main outcome measures: Start time and annual rate of steroid use, and use during the first 6 months of remission induction therapy.Results: The subjects were 399 patients were newly diagnosed with UC in the study period. The rate of steroid use after diagnosis was 58.4% in 2009, and showed a significant decreasing trend yearly after 2010 (p ≤ 0.0001). Regarding the start time, 52.2% of patients began steroids within 60 days after diagnosis of UC. At 6 months after initiation, 23.7% continued to use steroids and 73.9% of these patients used high-dose steroids.Conclusion: In treatment of UC after diagnosis, many patients continue to use steroids for >6 months after initiation. Reduced use of steroids based on clinical practice guidelines for UC should be promoted.

Fatal visceral disseminated varicella zoster infection during initial remission induction therapy in a patient with lupus nephritis and rheumatoid arthritis\u2014possible association with mycophenolate mofetil and high-dose glucocorticoid therapy: a case report

BackgroundVisceral disseminated varicella zoster viral (VZV) infection is a rare but severe complication with a high mortality rate in immunosuppressed individuals, and an increased susceptibility to VZV has been reported in kidney transplant recipients who are treated with mycophenolate mofetil (MMF). In Japan, MMF is currently approved for patients with lupus nephritis (LN) and data to indicate its optimal dosage are still insufficient.Case presentationA 46-year-old Japanese woman with rheumatoid arthritis was diagnosed as having systemic lupus erythematosus (SLE) and LN class III (A/C). Although initial remission-induction therapy with prednisolone and tacrolimus was started, her serum creatinine level and urinary protein excretion were elevated. Methylprednisolone pulse therapy was added, and tacrolimus was switched to MMF. Two months after admission when she was taking 40 mg of PSL and 1500 mg of MMF daily, she suddenly developed upper abdominal pain and multiple skin blisters, and disseminated visceral VZV infection was diagnosed. Laboratory examinations demonstrated rapid exacerbation of severe acute liver failure and coagulation abnormalities despite immediate multidisciplinary treatment, and she died of hemorrhagic shock 7 days after the onset of abdominal pain. A serum sample collected at the time of admission revealed that she had recursive VZV infection.ConclusionsMMF together with high-dose glucocorticoid therapy may increase the risk of VZV infection in Asian patients with SLE. Accumulation of evidence for parameters of safety, such as the area under the blood concentration–time curve of mycophenolic acid, should be urgently considered in order to establish a safer protocol for remission induction therapy in Asian patients with LN.

Adsorptive Depletion of Myeloid Lineage Leucocytes as Remission Induction Therapy in Patients with Ulcerative Colitis after Failure of First-Line Medications: Results from a Three-Year Real World, Clinical Practice

Background/Aims: In patients with active ulcerative colitis (UC), pharmacologics, although initially effective in most patients, are associated with refractoriness, loss of response or unfavourable side effects as additional morbidity factors. Depletion of myeloid lineage leucocytes like the CD14(+)CD16(+) monocyte phenotype, which is a major source of tumour necrosis factor-α, by granulocyte/monocyte apheresis (GMA) if effective, is also known to be free from side effects. Methods: In clinical practice setting, 77 consecutive patients with moderate to severe UC, who failed to respond to first-line medications received GMA with the Adacolumn as remission induction therapy. Patients who achieved remission were followed for 3 years. Results: Among the 77 patients, 46.8% were corticosteroids-naïve, 26% corticosteroid-dependent and 27.3% corticosteroid-refractory. The overall clinical remission rate was 79.2%, and the overall mucosal healing (MH) rate according to the Mayo endoscopic subscore ≤1 was 58.5%. MH rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 70.8, 56.3, and 38.5%, respectively. The 3-year sustained clinical remission rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 83.3, 68.8, and 23.1%, respectively. Conclusion: Corticosteroid-naïve patients appeared to benefit the most from the Adacolumn GMA, and attain a favourable long-term clinical course. Accordingly, GMA should be a first-line therapy in this clinical setting.

Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial

BackgroundRituximab is effective as therapy for induction of remission in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the effect of rituximab is not sustained, and subsequent relapse rates are high, especially in patients with a history of relapse. There is a need to identify whether maintenance therapy with rituximab is superior to the current standard of azathioprine or methotrexate for prevention of relapse following induction with rituximab.Methods/designRITAZAREM is an international, multicenter, open-label, randomized controlled trial designed to demonstrate the superiority of repeated doses of intravenous rituximab compared to daily orally administered azathioprine as a relapse prevention strategy in patients with AAV with relapsing disease who undergo induction of remission with rituximab. Patients with AAV will be recruited at the time of relapse and will receive rituximab and glucocorticoid induction therapy. If the disease is controlled by 4 months, patients will be randomized in a 1:1 ratio to receive rituximab (1000 mg every 4 months for five doses) or azathioprine (2 mg/kg/day) as maintenance therapy. Patients will be followed for a minimum of 36 months. The primary outcome is the time to disease relapse. It is estimated that 190 patients will need to be recruited to ensure that at least 160 are randomized.DiscussionThe RITAZAREM trial will provide the largest trial dataset for the use of rituximab as remission-induction therapy for patients with AAV comparing two remission-maintenance strategies following induction with rituximab, and explore whether prolonged B-cell depletion leads to sustained treatment-free remissions after discontinuation of immunosuppressive therapy.Trial registrationClinicalTrials.gov identifier: NCT01697267. Registered on 31 August 2012.

P315. Remission induction therapy in patients with remitting-relapsing ulcerative colitis dependent and refractory to corticosteroids or intolerant to thiopurines

P315. Remission induction therapy in patients with remitting-relapsing ulcerative colitis dependent and refractory to corticosteroids or intolerant to thiopurines

P503 Effectiveness of infliximab as remission-induction therapy in patients with active ulcerative colitis

P503 Effectiveness of infliximab as remission-induction therapy in patients with active ulcerative colitis

AB0776 Examination of changes in the prognosis and prognostic factors of microscopic polyangitis in japan

ObjectivesWe investigated changes in the prognosis and prognostic factors with respect to remission induction therapy in patients with microscopic polyangitis (MPA).MethodsAmong patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in...

A phase II study of elacytarabine plus idarubicin as second course remission-induction therapy in patients with acute myeloid leukemia.

TPS207 Background: Elacytarabine is a fatty acid derivative (elaidic acid ester) of the antimetabolite cytarabine,which is widely used in the treatment of AML. Preclinical data has shown that the entry of cytarabine into tumour cells is dependent on the expression of specific membrane transporter proteins, particularly of hENT1 (human equilibrative nucleoside transporter 1). Decreased expression of hENT1 is a major factor in cytarabine resistance in childhood AML (Hubeek et al., 2005). For entry into cells elacytarabine is independent from transporters and offers therefore an opportunity for treating patients not likely to benefit from cytarabine. In phase I studies activity of elacytarabine has been observed in patients with refractory/relapsed AML, as monotherapy as well as in combination with idarubicin. Synergy has been observed for the combination elacytarabine and anthracycline in vitro, and in phase I the combination has demonstrated a safety profile similar to cytarabine and idarubicin. Methods: Patients with AML who have failed their first remission-induction course of a cytarabine based combination will be treated with elacytarabine in combination with idarubicin. The study is ongoing and will recruit up to 50 patients at 10 sites in the USA and Europe. As of 28th January, 8 sites are activated and 16 patients have been enrolled. The objective of the study is to determine response rates to the combination treatment and to evaluate by immunohistochemistry the hENT1 status of AML cells. The hENT1 expression level will be analysed at time of diagnosis and/or before elacytarabine treatment. The goal is to explore the relationship between response to cytarabine and to elacytarabine and the AML hENT1 status. Key Inclusion Criteria: Patients with AML who have received one previous cytarabine containing regimen and who have more than 5 % remaining blasts in the bone marrow following the first induction course. Bone marrow sample will be collected for the determination of the hENT1 expression level prior to treatment in the protocol. Patients must be 18 years of age or older and have an ECOG performance status of 0 – 2.

Amonafide L-Malate (AS1413) in Combination with Cytarabine Is Equally Effective in Older and Younger Patients with Secondary Acute Myeloid Leukemia (AML); Final Data From a Phase II Study.

Abstract 1047Poster Board I-69 Background:A major issue in the treatment of AML is the low response rate achieved with standard remission induction therapy in patients with “poor-risk” prognostic factors. One such poor-risk factor is secondary AML (sAML), AML following myelodysplasia or cytotoxic therapy for other malignancies. sAML is strongly associated with multi-drug resistance (MDR) mechanisms: up to 70% of sAML patients show overexpression of P-glycoprotein (Pgp) or other MDR mechanisms. Amonafide L-malate (amonafide, AS1413) is a unique DNA intercalator that is not a substrate for MDR, unlike anthracyclines commonly used in the treatment of AML. This phase II study evaluated amonafide in combination with cytarabine in patients with sAML. Methods:Patients received amonafide 600 mg/m2/day IV on days 1-5 and cytarabine 200 mg/m2/day IV by continuous infusion on days 1-7. Induction was repeated if leukemia persisted on day 14 marrow examination. Consolidation consisted of hematopoietic stem cell transplant (HSCT; n=10) or intermediate-dose (n=13)/high-dose (n=7) cytarabine, depending on age and HSCT donor availability. Bone marrows were centrally reviewed. The primary endpoint was complete remission with (CR) or without (CRi) hematopoietic recovery; secondary endpoints were duration of remission (DOR), survival and safety. Results:88 patients with a median age of 62.5 years (range 23-87) were treated; Of these, 45 (51%) had received prior leukemogenic therapy (tAML) and 43 (49%) had prior MDS; 1 (1%) had favorable, 36 (41%) had intermediate and 42 (48%) had unfavorable cytogenetics. Overall CR + CRi rate was 42% (CRi 3%); median duration of remission (DOR) was 312 days. CR rates and DOR among age <60 and ≥60, 13/33 (39.4%), 312 days and 24/55 (43.6%), 316 days; among tAML and prior MDS, 18/45 (40%), 512 days and 19/43 (44.2%), 186 days; intermediate and unfavorable cytogenetics, 23/36 (61.1%), 282 days and 10/42 (23.8%), 322 days. Median overall survival for the whole population was 200 days and for responders 435 days. Non-hematologic grade ≥ 3 adverse events included febrile neutropenia (35%), hypotension (16%), pneumonia (14%), respiratory failure (11%), and bacteremia (11%). The death rate within 28 days of induction therapy was 20.5%. Median time to hematopoietic recovery of neutrophil count > 500/cmm and platelets of 20,000/cmm was 29 and 28 days, respectively. Conclusions:Amonafide produced a high complete remission rate and durable responses in both older and younger patients with sAML. Efficacy was maintained across several poor-prognosis subgroups frequently characterized by MDR, for which amonafide is not a substrate. A phase III study (ACCEDE) is evaluating amonafide + cytarabine vs. daunorubicin + cytarabine in patients with sAML. Disclosures:Erba:Genzyme: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria; Pharmion: Honoraria; MGI Pharma: Honoraria; Cephalon: Honoraria, Research Funding; Wyeth: Research Funding; Antisoma: Research Funding; Lilly: Research Funding; Gemin-X: Research Funding; Kanisa: Research Funding. O'Donnell:Genzyme: Consultancy; Eisai: Consultancy; Celgene: Consultancy. Allen:Antisoma: Research Funding. Powell:Antisoma: Research Funding. Stone:Celgene: Consultancy, Speakers Bureau; Merck: Consultancy; Genzyme: Consultancy; Eisai: Consultancy. Bennett:Antisoma: Consultancy. Lundberg:Antisoma: Employment. Capizzi:Antisoma: Consultancy. Rizzieri:Antisoma: Research Funding.

Development of a Novel Assay Using Bioluminescent Reporter Bacteria To Determine the Sensitivity of AML Cells to Cytosine Arabinoside.

The nucleoside analogue cytosine arabinoside(Ara-C) has been a cornerstone of remission induction therapy for patients with AML for three decades. Even today, approximately 70% of adults fail to achieve durable complete remission with regimens including Ara-C. This project involves the development of a simple, rapid, economical test to determine Ara-C sensitivity of patient cells to enable clinicians to consider the efficacy of this drug prior to patient treatment.Bacteria expressing lux genes have been successfully used to study real time pharmacodynamics of antimicrobial agents. We have extended this elegant reporter gene technology to determine cellular penetration of Ara-C, into AML cells. AraC has no effect on E. coli since it does not express deoxycytidine kinase (dCK) and has the ability to deaminate AraC into AraU through the activity of cytidine deaminase (cdd). To render E. coli sensitive to AraC, a cdd-deficient strain was used as the host to express the human dCK gene carried on pTrc99-A plasmid under the control of the lac promoter. The expression of dCK, induced by the addition of IPTG, made E. coli sensitive to AraC. E. coli was then made self-bioluminescent by introducing the pAL2 plasmid carrying the lux operon (luxABCDE)AML cell lines were incubated with therapeutic levels of Ara-C (100 μM),washed, and re-suspended in fresh media containing bioluminescent modified E. coli and 0.1% saponin, to lyse the AML cells. Light levels and optical density were monitored using a microtitre plate reader (Fluorstar Optima, BMG Labtec).Cell lines minus drug were used so as to generate control lysates and supernantants.It was possible to detect significant increases in light levels from the lysate and supernatant of an AML cell-line known to be Ara-C sensitive (KG-1a). The lysate from a cell-line (THP-1) known to deaminate Ara-C through the over production of cytidine deaminase showed no increase in light production in the presence of Ara-C. In addition no difference in light levels was observed from the supernatant of these resistant cells. The control supernatant from both cell lines showed no change in light output. These findings indicate that this assay could be used to evaluate the uptake and metabolism of Ara-C by leukaemia cells. With refinement, the assay could be used to specify at which point in Ara-C metabolism AML cells acquire resistance. Furthermore, this technology could be modified to examine the sensitivity of AML cells to other established chemotherapeutic agents such as anthracyclines thus giving a genuinely helpful chemosensitivity profile to clinicians involved in patient care and customising treatment for individual patients.

Clinical Efficacy of Intravenous Immunoglobulin for Patients with MPO-ANCA-Associated Rapidly Progressive Glomerulonephritis

Background: To determinewhether intravenous immunoglobulin (IVIg) cancontrol disease activity in patients with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated rapidly progressive glomerulonephritis (RPGN). Methods: Twelve patients with serologically and histologically confirmed MPO-ANCA-associated RPGN (7 men, 5 women; mean age 71 ± 3 years) received IVIg (400 mg/kg/day) alone for 5 days. The effects of IVIg were evaluated by white blood cell counts, serum C-reactive protein levels, Birmingham Vasculitis Activity Score, rate of change in reciprocal creatinine (1/Cre), and plasma tumor necrosis factor-α levels after IVIg administration. Corticosteroids with or without cyclophosphamide were commenced after IVIg. Results:After IVIg treatment, a significant decrease was observed in white blood cell count (p < 0.05), C-reactive protein values (p < 0.001), and Birmingham Vasculitis Activity Score (p < 0.001) concomitant with the amelioration of systemic symptoms. The rate of change in 1/Cre significantly improved (p < 0.05). Plasma tumor necrosis factor-α levels that were significantly elevated in patients before IVIg compared with normal controls (p < 0.0001), rapidly declined after IVIg with a significant reduction(p < 0.05). Three months post-treatment with IVIg, all patients showed improvement of disease without serious infectious complications. Conclusion: IVIg is a potential component of remission induction therapy for patients with MPO-ANCA-associated RPGN.