Epidural Clonidine or Bupivacaine as the Sole Analgesic Agent during and after Abdominal Surgery 

1999 ◽  
Vol 90 (5) ◽  
pp. 1354-1362 ◽  
Author(s):  
Marc De Kock ◽  
Philippe Gautier ◽  
Athanassia Pavlopoulou ◽  
Marc Jonniaux ◽  
Patricia Lavand'homme
Keyword(s):  
High Dose ◽  
General Anesthetics ◽  
Visual Analogue Pain ◽  
Pain Scores ◽  
Arterial Blood ◽  
Sedation Scores ◽  
Group 3 ◽  
Group 2 ◽  
High Doses ◽  
Group 1

Background The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. Methods Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. Results During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. Conclusion Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.

High-dose enoxaparin in the treatment of abdominal angiostrongyliasis in Swiss mice

2017 ◽  
Vol 92 (6) ◽  
pp. 662-667 ◽  
Author(s):  
A.S.S. Sandri ◽  
R. Rodriguez ◽  
M.M. Costa ◽  
S.M. Porto ◽  
D. Schwingel ◽  
...  
Keyword(s):  
Survival Rates ◽  
Mesenteric Arteries ◽  
High Dose ◽  
Control Groups ◽  
Intestinal Infarction ◽  
Intestinal Lesions ◽  
Group 2 ◽  
High Doses ◽  
And Control ◽  
Group 1

AbstractAbdominal angiostrongyliasis (AA) is caused by Angiostrongylus costaricensis, which inhabits mesenteric arteries. There is no drug treatment for AA, and since intestinal infarction due to thrombi is one of the main complications of the disease, the use of anticoagulants may be a treatment option. Thus, we aimed to assess the effect of high doses of enoxaparin on the prevention of ischaemic intestinal lesions and on the survival of mice infected with A. costaricensis. Twenty-four mice were infected with L3 of A. costaricensis and divided equally into two groups: Group 1, control treated with placebo, and Group 2, treated daily with enoxaparin (2.5 mg/kg) for 50 days. All mice were subjected to necropsy and histological analysis. The results from gross and microscopic assessments showed no variation in the prevalence of lesions between the groups. An analysis was also performed among survivors and non-survivors, showing that animals that died often presented lesions, such as granulation tissue in the serosa, and intestinal infarction and adhesion. The mortality rate did not vary between the enoxaparin-treated and control groups. Thus, we showed that high doses of enoxaparin have no protective effect against AA, as the survival rates and lesions of mice did not vary between the treated and control groups. Considering that the use of prophylactic doses was also shown to be ineffective in a previous study, we do not recommend the use of enoxaparin for AA treatment.

scholarly journals Glycopenia - induced sympathoadrenal activation in diabetes mellitus and uncontrolled arterial hypertension: an observational study

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Abimbola Abobarin-Adeagbo ◽  
Andreas Wienke ◽  
Matthias Girndt ◽  
Rainer U. Pliquett
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Insulin Dose ◽  
Hypertensive Crisis ◽  
Plasma Norepinephrine ◽  
Arterial Blood ◽  
Group 3 ◽  
Group 2 ◽  
Group 1 ◽  
Diabetes Patients

Abstract Background Aim of this study is to investigate a possible association of hypoglycemic episodes and arterial hypertension. We hypothesize that hospitalized insulin-treated diabetes patients with hypertensive crisis have more hypoglycemic episodes than their counterparts without hypertensive crisis on admission. Methods In a prospective, observational cohort study, 65 insulin-treated diabetes patients (type 1, type 2, type 3c) were included in Group 1, when a hypertensive crisis was present, as control patients in Group 2 without hypertensive crisis or hypoglycemia, in Group 3, when a symptomatic hypoglycemia was present on admission. All patients were subjected to open-label continuous glucose monitoring, 24-h blood-pressure- and Holter electrocardiogram recordings, and to laboratory tests including plasma catecholamines. Results 53 patients, thereof 19 Group-1, 19 Group-2, 15 Group-3 patients, completed this study. Group-1 patients had the highest maximum systolic blood pressure, a higher daily cumulative insulin dose at admission, a higher body-mass index, and a higher plasma norepinephrine than control patients of Group 2. Group-3 patients had more documented hypoglycemic episodes (0.8 ± 0.5 per 24 h) than Group-2 patients (0.2 ± 0.3 per 24 h), however, they were not different to the ones in Group-1 patients (0.4 ± 0.4 per 24 h). Plasma norepinephrine and mean arterial blood pressure were higher Group-1 and Group-3 patients than in control patients of Group 2. At discharge, the daily cumulative insulin dose was reduced in Group-1 (− 18.4 ± 24.9 units) and in Group-3 patients (− 18.6 ± 22.7 units), but remained unchanged in Group-2 control patients (− 2.9 ± 15.6 units). Conclusions An association between hypoglycemic events and uncontrolled hypertension was found in this study.

scholarly journals Interpleural Administration of Bupivacaine after Cholecystectomy: A Comparison with Intercostal Nerve Block

1989 ◽  
Vol 17 (3) ◽  
pp. 269-274 ◽  
Author(s):  
D. W. Blake ◽  
G. Donnan ◽  
J. Novella
Keyword(s):  
Local Anaesthetic ◽  
Intercostal Nerve ◽  
Intercostal Nerve Block ◽  
Nerve Blocks ◽  
Pain Scores ◽  
Lower Pain ◽  
Chest X Ray ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Pethidine requirements and verbal pain scores were recorded in 36 patients after cholecystectomy via subcostal incision. All patients also received 20 ml 0.5% bupivacaine with adrenaline 1/200,000. Group 1 (12 patients) received unilateral intercostal nerve blocks. Interpleural catheters were inserted through the 8th intercostal space in the remaining patients; 12 received local anaesthetic via the catheter immediately after surgery (Group 2) and 12 were given local anaesthetic at three hours (Group 3). Small asymptomatic pneumothoraces were noted on chest X-ray in six of the 24 patients with interpleural catheters. Both types of local anaesthesia produced lower pain scores than pethidine alone (P < 0.05) with 25% of intercostal nerve blocks and 63% of interpleural catheters requiring no pethidine in the following three hours. The provision of catheter ‘top-ups’ between six and 18 hours after surgery also resulted in lower pain scores and a reduction in pethidine requirements (P < 0.05).

High-dose lidocaine does not affect defibrillation efficacy: implications for defibrillation mechanisms

1998 ◽  
Vol 274 (4) ◽  
pp. H1113-H1120 ◽  
Author(s):  
Michael R. Ujhelyi ◽  
J. Jason Sims ◽  
Allison Winecoff Miller
Keyword(s):  
Ventricular Fibrillation ◽  
Cycle Length ◽  
Low Dose ◽  
High Dose ◽  
Channel Blockade ◽  
Group 3 ◽  
Baseline Values ◽  
Group 2 ◽  
Very High ◽  
Group 1

This study assessed the effect of low (10 mg ⋅ kg−1 ⋅ h−1) and very high (18 mg ⋅ kg−1 ⋅ h−1) doses of lidocaine on defibrillation energy requirements (DER) to relate changes in indexes of sodium-channel blockade with changes in DER values using a dose-response study design. In group 1 (control; n = 6 pigs), DER values were determined at baseline and during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 ( n = 7), DER values were determined at baseline and during treatment with low-dose lidocaine followed by high-dose lidocaine. In group 3 ( n = 3), DER values were determined at baseline and high-dose lidocaine. Group 3 controlled for the order of lidocaine treatment with the addition of high-dose lidocaine after baseline. DER values in group 1 did not change during D5W. In group 2, low-dose lidocaine increased DER values by 51% ( P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of baseline values ( P = 0.02, low dose vs. high dose). DER values during high-dose lidocaine in group 3 also remained near baseline values (16.2 ± 2.7 to 12.9 ± 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidocaine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the lidocaine dose increased. However, the greatest increase in DER occurred when ventricular fibrillation cycle length was minimally affected, demonstrating a negative correlation ( P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-response curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refractoriness during ventricular fibrillation may be the electrophysiological mechanism by which high-dose lidocaine limits the adverse effects that low-dose lidocaine has on DER values. However, there is a possibility that an unidentified action of lidocaine is responsible for these effects.

Evaluation of the Impact of Three Different Pre-Transplant Strategies On the Outcome of Myeloma Patients Candidates to High-Dose Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1223-1223
Author(s):  
Alessandro Corso ◽  
Silvia Mangiacavalli ◽  
Luciana Barbarano ◽  
Annalisa Citro ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Patient Flow ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Oral Dexamethasone ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p<0.00001). The number of responsive pts progressively increased from 87% after Vel-Dex (CR 31%), to 96% after transplant (CR 38%). Response rates of group 1 and 2 patients were not significantly different either after induction (p=0.6), after DCEP (p=0.5), and after Tx (p=0.65). On intention to treat basis, vel-dex induction produced a better, although not significant, PFS (34.6 months vs 29 in group 1 and 26.8 in group 2, p=0.56). OS were not statistically different among the three groups, event though the different follow-up could affect the analysis (median OS 110 in group 1, 66 months in group 2, and not reached in group 3, p=0.37). In multivariate analysis PFS was improved only by the achievement of CR (p=0.001). No significant difference was observed between VGPR or PR (p=0.43). Conclusion In this study, only CR not VGPR impacts on the outcome. Vel-Dex producing a significant high CR rate after TX (38%), seems to improve survival of MM patients candidate to high-dose therapy with respect to conventional pre-transplant strategies. Disclosures Morra: Roche:.

scholarly journals High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte-macrophage colony-stimulating factor on the autograft

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 610-616 ◽  
Author(s):  
MR Bishop ◽  
JR Anderson ◽  
JD Jackson ◽  
PJ Bierman ◽  
EC Reed ◽  
...  
Keyword(s):  
High Dose Chemotherapy ◽  
High Dose ◽  
Continuous Intravenous Infusion ◽  
Colony Stimulating Factor ◽  
Group 3 ◽  
Macrophage Colony Stimulating Factor ◽  
Group 2 ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Group 1

Between June 1989 and June 1992, 144 patients participated in sequential clinical trials using peripheral blood progenitor cells (PBC) as their sole source of hematopoietic rescue following high-dose chemotherapy. All patients had received prior extensive combination chemotherapy and had marrow defects that precluded autologous bone marrow transplantation (ABMT). PBC were collected according to a single apheresis protocol. The initial 86 patients (group 1) had PBC collected without mobilization. Beginning in April 1991, PBC were mobilized solely with recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Thirty-four patients (group 2) received rHuGM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion, and 24 patients (group 3) received rHuGM-CSF at a dose of 250 micrograms/m2/d by continuous intravenous infusion. Patients underwent at least six aphereses and had a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg collected. Cytokines were not routinely administered immediately after transplantation. A median of nine aphereses were required to collect PBC in group 1 and seven aphereses for groups 2 and 3 (P = .03). The time required to recover 0.5 x 10(9)/L granulocytes after transplant was significantly shorter (P = .0004) for the mobilized groups; the median time to recovery was 26 days for group 1, 23 days for group 2, and 18 days for group 3. Transplantation of PBC mobilized with rHuGM-CSF resulted in a shorter time to platelet (P = .04) and red blood cell (P = .01) transfusion independence. Mobilization with rHuGM-CSF alone resulted in efficient collection of PBC, that provided rapid and sustained restoration of hematopoietic function following high-dose chemotherapy. Mobilization of PBC with rHuGM-CSF alone is an effective method for patients who have received prior chemotherapy and have bone marrow abnormalities.

scholarly journals Glycopenia-Induced Sympathoadrenal Activation in Diabetes Mellitus And Uncontrolled Arterial Hypertension: An Observational Study.

2020 ◽  
Author(s):  
Abimbola Abobarin-Adeagbo ◽  
Andreas Wienke ◽  
Matthias Girndt ◽  
Rainer U. Pliquett
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Insulin Dose ◽  
Hypertensive Crisis ◽  
Plasma Norepinephrine ◽  
Arterial Blood ◽  
Group 3 ◽  
Group 2 ◽  
Group 1 ◽  
Diabetes Patients

Abstract Background: Aim of this study is to investigate a possible association of hypoglycemic episodes and arterial hypertension. We hypothesize that hospitalized insulin-treated diabetes patients with hypertensive crisis have more hypoglycemic episodes than their counterparts without hypertensive crisis on admission.Methods: In a prospective, observational cohort study, 65 insulin-treated diabetes patients (type 1, type 2, type 3c) were included in Group 1, when a hypertensive crisis was present, as control patients in Group 2 without hypertensive crisis or hypoglycemia, in Group 3, when a symptomatic hypoglycemia was present on admission. All patients were subjected to open-label continuous flash glucose monitoring, to 24-hour blood-pressure and Holter electrocardiogram recordings, and to laboratory tests including plasma catecholamines. Results: 53 patients, thereof 19 Group-1, 19 Group-2, 15 Group-3 patients, completed this study. Group-1 patients had the highest maximum systolic blood pressure, a higher daily cumulative insulin dose at admission, a higher body-mass index, and a higher plasma norepinephrine than control patients of Group 2. Group-3 patients had more documented hypoglycemic episodes (0.8 ± 0.5 per 24 hours) than Group-2 patients (0.2 ± 0.3 per 24 hours), however, they were not different to the ones in Group-1 patients (0.4 ± 0.4 per 24 hours). Plasma norepinephrine and mean arterial blood pressure were not different between Group-1 and Group-3 patients, though higher than in Group-2 patients. At discharge, the daily cumulative insulin dose was reduced in Group-1 (-18.4 ± 24.9 units) and Group-3 patients (-18.6 ± 22.7 units), but remained unchanged in Group-2 patients (-2.9 ± 15.6 units).Conclusions: An association between hypoglycemic events and uncontrolled hypertension was found in this study.

scholarly journals Effects of Aqueous Colocasia esculenta Extracts on Selected Biochemical Parameters in Phenyl Hydrazine Induced Male Anemic Albino Rats

2020 ◽  
pp. 13-23
Author(s):  
Adekunle Abiodun Ayoade ◽  
Adedayo Emmanuel Ogunware ◽  
Ifeoluwa Israel Odekunle ◽  
Pelumi Abimbola Adedigba
Keyword(s):  
Plant Extract ◽  
Total Protein ◽  
Low Dose ◽  
Colocasia Esculenta ◽  
High Dose ◽  
Phenyl Hydrazine ◽  
Group 3 ◽  
Group 2 ◽  
Protein Serum ◽  
Group 1

Aims: In this study, the effect of Colocasia esculenta a hematinic plant on biochemical parameters levels (Direct, Total and unconjugated bilirubin, creatinine, total protein, serum albumin and urea) was assessed to determine if the plant extract can reverse the abnormality in the values of these parameter. Methodology: The experimental animals were divided into four groups as follows; group 1(non-anemic control), group 2 (anemic untreated), group 3 (anemic treated with low dose of plant extract 100 mg/ml), group 4 (anemic treated with high dose of plant extract 500 mg/ml). Anemia was induced in group 1, group 2 and group 3 with 60 mg/kg of phenyl hydrazine for 2 days. After induction of anemia group 2 and group 3 was treated with 100 mg/kg and 500 mg/kg of plant extract for 7 days. After 7-day blood sample was collected through heart puncture and centrifuged for serum. Then, Bilirubin, creatinine, total protein, serum albumin and urea test were carried out. Results: The anemic untreated group had the highest bilirubin, creatinine and urea value of 1.3 mg/dl, 3.97 mg/dl and 71.78 g/l respectively compared to the non-anemic control (bilirubin-0.4 mg/dl, creatinine-3.13 mg/dl and urea 60.35 mg/dl), anemic treated with low dose (bilirubin-0.37 mg/dl,creatinine-1.40 mg/dl and urea-41.82), and anemic treated with high dose (bilirubin-0.25 mg/dl, creatinine-0.86 mg/dl, and urea-48.66 mg/dl) with significant increase in phenyl hydrazine value at p<0.05 .The anemic nontreated group experienced a reduced value of total protein and albumin of 49.78 g/l and 24.46 g/l respectively compared to the non-anemic control (total protein-66.2 g/l and albumin-37.67 g/l) ,anemic treated with low dose (total protein-67.5 g/l and albumin-19.2 g/l), and anemic treated with high dose (total protein-21.9 g/l and albumin-81.6 g/l). Conclusion: The obtained results from this study revealed the anti-anemia potentials of aqueous extracts of Colocasia esculenta.

scholarly journals Atelocollagen Injection Improves Tendon Integrity in Partial-Thickness Rotator Cuff Tears: A Prospective Comparative Study

2020 ◽  
Vol 8 (2) ◽  
pp. 232596712090401
Author(s):  
Jong-Ho Kim ◽  
Dong-Jin Kim ◽  
Hyo-Jin Lee ◽  
Baek-Kyu Kim ◽  
Yang-Soo Kim
Keyword(s):  
Rotator Cuff ◽  
Rotator Cuff Tears ◽  
Type I ◽  
Pain Scores ◽  
Partial Thickness ◽  
Functional Scores ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Ongoing controversy surrounds the best treatment modality for partial-thickness rotator cuff tears. Purpose: To investigate the effects of atelocollagen injection in patients with small, symptomatic, intratendinous rotator cuff tears. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: From January 2014 to December 2017, 94 patients who had small, symptomatic, intratendinous rotator cuff tears were enrolled and randomly allocated to 1 of 3 groups: intratendinous injection with 0.5 mL of type I atelocollagen (group 1, n = 32), intratendinous injection with 1 mL of type I atelocollagen (group 2, n = 30), and no injection of type I atelocollagen (group 3, n = 32). American Shoulder and Elbow Surgeons score, Constant Shoulder Score, visual analog scale pain score, and range of motion were evaluated before injection; at 3, 6, and 12 months after injection; and at final follow-up. Magnetic resonance imaging (MRI) was performed at least 6 months after injection to evaluate rotator cuff integrity. Results: Demographic data did not differ significantly among the 3 groups before injection ( P > .05). The mean follow-up period was 24.7 months. The functional and pain scores in groups 1 and 2 were significantly improved at final follow-up ( P < .05). No significant improvement was seen in functional or pain scores at final follow-up in group 3 ( P > .05). Groups 1 and 2 had significantly better functional scores compared with group 3 at final follow-up ( P < .05). The proportion of patients with a decrease in size of the torn tendon on follow-up MRI at least 6 months after atelocollagen injection was significantly higher in group 1 (28.1%; P = .02) and group 2 (36.7%; P = .003) compared with group 3 (6.3%). Conclusion: Atelocollagen injection can improve the functional outcome and integrity of the tendon in intratendinous rotator cuff tears.

WT1 Levels At Diagnosis and POST-Induction Provide Prognostic Information in Adult De Novo AML. Results From the Spanish Cetlam Group.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2524-2524
Author(s):  
Josep F Nomdedeu ◽  
Montserrat Hoyos ◽  
Maite Carricondo ◽  
Elena Bussaglia ◽  
Camino Estivill ◽  
...  
Keyword(s):  
Bone Marrow ◽  
De Novo ◽  
High Dose ◽  
Prognostic Impact ◽  
Post Induction ◽  
Group 3 ◽  
Group 2 ◽  
De Novo Aml ◽  
Intermediate Dose ◽  
Group 1

Abstract Abstract 2524 WT1 monitoring is an almost universal target to follow de novo AML. Its exppression in myeloid malignancies is upregulated in parallel to the blast percentage. Recently, WT1 determination has been standardized as result of an European Leukemia Net initiative. Early reports have demonstrated that the best results are obtained when peripheral blood is used to establish clinical predictions. Pediatric studies in AML have shown that raised WT1 levels after induction associate with unfavourable outcome. Despite all the mentioned, WT1 quantitation has not yet gained widespread use, in part because some AML show normal WT1 levels at diagnosis. To investigate the prognostic impact of the normalized bone marrow WT1 levels at diagnosis and post-induction in a consecutive series of de novo AML patients enrolled in the CETLAM group trials. Available bone marrow samples at diagnosis (586 cases) and post induction (367 cases) were obtained in each participating center and sent to the CETLAM repository center at the Hospital de la Santa Creu i Sant Pau for complete immunophenotype and molecular analyses. One μg of RNA was reverse transcribed to cDNA in a total reaction volume of 20μl containing Cl2Mg 5mM, 10× Buffer, DTT 10mM, dNTP's 10mM each, random hexamers 15μM, RNAsin 20 units (Promega) and 200 units of MMLV enzyme. WT1 expression levels were determined by real-time quantitative polymerase chain reaction (RQ-PCR) in an ABI PRISM 7700® Genetic Analyzer (Applied Biosystems, Foster City, CA) using the primers and conditions described by the ELN group (Cilloni et al J. Clin. Oncol 2009;27:5195-201). For WT1 copy number titration, the IPSOGEN® (Marseille, France) plasmid was employed. Results were expressed as copies and four normal bone marrow samples were used as test controls. Patients were treated between 2004 and 2011 according to the CETLAM03 protocol. Adults up to 70 years of age received induction chemotherapy with idarubicin, intermediate-dose cytarabine and etoposide, followed by consolidation with mitoxantrone and intermediate-dose ara-C. Subsequently, patients with favourable cytogenetics at diagnosis received one cycle of high-dose cytarabine.G-CSF priming during induction and consolidation was used. Patients with favorable cytogenetics and high leukocyte counts at diagnosis were treated with autologous transplantation instead of high-dose cytarabine. Furthermore, patients with a normal karyotype but an adverse molecular profile (FLT3 mutations or MLL rearrangements) were allocated to the treatment for unfavorable cases; this included allogeneic transplantation from an HLA-identical donor. Overall survival (OS) was measured from the date of enrolment until the date of death. Leukemia-free survival (LFS) for patients who achieved a CR was calculated from the date of CR to relapse or death. OS and LFS were plotted by the Kaplan-Meier method; differences between curves were analyzed by the log-rank test. The probability of relapse was calculated using cumulative incidence estimates and taking into account the competing risk of death in remission. A WT1 cut-off value of 5065.2 copies at diagnosis was obtained. Two hundred and four samples had WT1 levels greater than this value, whereas 382 samples showed levels below this cut-off. These groups had statistically different OS 55±3 vs 33±5 p<0.001, LFS 52±3 vs 30±6 p:0.004 and CIR 34±3 vs 56±6 p<0.001. As regards the post-induction results, four groups were established: Group 0 (135 patients) with WT1 levels between 0 and 17.5 copies, Group 1 (107 patients) with WT1 values ranging from 17.6 to 76 copies, Group 2 (54 patients) with WT1 between 76.1 and 170.5 copies and Group 3 (71 patients) with WT1 levels after induction greater than>170.6 copies. These groups showed statistically significant differences(p<0.001) in terms of OS: Group 0 59±4 months, Group 1 50±5 months, Group 2 45±7 months and Group 3 23±6 months. LFS was also statiscally different: Group 0: 58±4, Group 1: 46±5, Group 2: 39±8 and Group 3:19±8 (all p<0.001). Lastlly, CIR was markedly different between the four groups: Group 0:25±4, Group 1: 44±5, Group 2: 46±8 and Group 3: 68±8(p<0.001) . WT1 quantitation at diagnosis and post-induction provide a simple and well standardized measurement of the prognostic risk of adult AML patiens. Larger series need to be analyzed to ascertain whether this determination could be incorporated to initial AML risk stratification. Disclosures: No relevant conflicts of interest to declare.

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