An experimental study on the early diagnosis of traumatic brain injury in rabbits based on a noncontact and portable system

Closed cerebral hemorrhage (CCH) is a common symptom in traumatic brain injury (TBI) patients who suffer intracranial hemorrhage with the dura mater remaining intact. The diagnosis of CCH patients prior to hospitalization and in the early stage of the disease can help patients get earlier treatments that improve outcomes. In this study, a noncontact, portable system for early TBI-induced CCH detection was constructed that measures the magnetic induction phase shift (MIPS), which is associated with the mean brain conductivity caused by the ratio between the liquid (blood/CSF and the intracranial tissues) change. To evaluate the performance of this system, a rabbit CCH model with two severity levels was established based on the horizontal biological impactor BIM-II, whose feasibility was verified by computed tomography images of three sections and three serial slices. There were two groups involved in the experiments (group 1 with 10 TBI rabbits were simulated by hammer hit with air pressure of 600 kPa by BIM-II and group 2 with 10 TBI rabbits were simulated with 650 kPa). The MIPS values of the two groups were obtained within 30 min before and after injury. In group 1, the MIPS values showed a constant downward trend with a minimum value of −11.17 ± 2.91° at the 30th min after 600 kPa impact by BIM-II. After the 650 kPa impact, the MIPS values in group 2 showed a constant downward trend until the 25th min, with a minimum value of −16.81 ± 2.10°. Unlike group 1, the MIPS values showed an upward trend after that point. Before the injury, the MIPS values in both group 1 and group 2 did not obviously change within the 30 min measurement. Using a support vector machine at the same time point after injury, the classification accuracy of the two types of severity was shown to be beyond 90%. Combined with CCH pathological mechanisms, this system can not only achieve the detection of early functional changes in CCH but can also distinguish different severities of CCH.

Download Full-text

Cerebral oxygenation, vascular reactivity, and neurochemistry following decompressive craniectomy for severe traumatic brain injury

Journal of Neurosurgery ◽

10.3171/jns/2008/108/5/0943 ◽

2008 ◽

Vol 108 (5) ◽

pp. 943-949 ◽

Cited By ~ 66

Author(s):

Chi Long Ho ◽

Chee Meng Wang ◽

Kah Keow Lee ◽

Ivan Ng ◽

Beng Ti Ang

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Decompressive Craniectomy ◽

Severe Traumatic Brain Injury ◽

Reactivity Index ◽

Outcome Group ◽

The Mean ◽

Group 2 ◽

Biochemical Indices ◽

Group 1

Object This study addresses the changes in brain oxygenation, cerebrovascular reactivity, and cerebral neurochemistry in patients following decompressive craniectomy for the control of elevated intracranial pressure (ICP) after severe traumatic brain injury (TBI). Methods Sixteen consecutive patients with isolated TBI and elevated ICP, who were refractory to maximal medical therapy, underwent decompressive craniectomy over a 1-year period. Thirteen patients were male and 3 were female. The mean age of the patients was 38 years and the median Glasgow Coma Scale score on admission was 5. Results Six months following TBI, 11 patients had a poor outcome (Group 1, Glasgow Outcome Scale [GOS] Score 1–3), whereas the remaining 5 patients had a favorable outcome (Group 2, GOS Score 4 or 5). Decompressive craniectomy resulted in a significant reduction (p < 0.001) in the mean ICP and cerebrovascular pressure reactivity index to autoregulatory values (< 0.3) in both groups of patients. There was a significant improvement in brain tissue oxygenation (PbtO2) in Group 2 patients from 3 to 17 mm Hg and an 85% reduction in episodes of cerebral ischemia. In addition, the durations of abnormal PbtO2 and biochemical indices were significantly reduced in Group 2 patients after decompressive craniectomy, but there was no improvement in the biochemical indices in Group 1 patients despite surgery. Conclusions Decompressive craniectomy, when used appropriately in protocol-driven intensive care regimens for the treatment of recalcitrant elevated ICP, is associated with a return of abnormal metabolic parameters to normal values in patients with eventually favorable outcomes.

Download Full-text

Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension

Journal of Neurosurgery Pediatrics ◽

10.3171/2009.1.peds08319 ◽

2009 ◽

Vol 4 (1) ◽

pp. 40-46 ◽

Cited By ~ 124

Author(s):

Gad Bar-Joseph ◽

Yoav Guilburd ◽

Ada Tamir ◽

Joseph N. Guilburd

Keyword(s):

Blood Pressure ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Pressure ◽

Intracranial Hypertension ◽

Repeated Measures ◽

Intervention Group ◽

Decrease Blood Pressure ◽

Group 2 ◽

Group 1

Object Deepening sedation is often needed in patients with intracranial hypertension. All widely used sedative and anesthetic agents (opioids, benzodiazepines, propofol, and barbiturates) decrease blood pressure and may therefore decrease cerebral perfusion pressure (CPP). Ketamine is a potent, safe, rapid-onset anesthetic agent that does not decrease blood pressure. However, ketamine's use in patients with traumatic brain injury and intracranial hypertension is precluded because it is widely stated that it increases intracranial pressure (ICP). Based on anecdotal clinical experience, the authors hypothesized that ketamine does not increase—but may rather decrease—ICP. Methods The authors conducted a prospective, controlled, clinical trial of data obtained in a pediatric intensive care unit of a regional trauma center. All patients were sedated and mechanically ventilated prior to inclusion in the study. Children with sustained, elevated ICP (> 18 mm Hg) resistant to first-tier therapies received a single ketamine dose (1–1.5 mg/kg) either to prevent further ICP increase during a potentially distressing intervention (Group 1) or as an additional measure to lower ICP (Group 2). Hemodynamic, ICP, and CPP values were recorded before ketamine administration, and repeated-measures analysis of variance was used to compare these values with those recorded every minute for 10 minutes following ketamine administration. Results The results of 82 ketamine administrations in 30 patients were analyzed. Overall, following ketamine administration, ICP decreased by 30% (from 25.8 ± 8.4 to 18.0 ± 8.5 mm Hg) (p < 0.001) and CPP increased from 54.4 ± 11.7 to 58.3 ± 13.4 mm Hg (p < 0.005). In Group 1, ICP decreased significantly following ketamine administration and increased by > 2 mm Hg during the distressing intervention in only 1 of 17 events. In Group 2, when ketamine was administered to lower persistent intracranial hypertension, ICP decreased by 33% (from 26.0 ± 9.1 to 17.5 ± 9.1 mm Hg) (p < 0.0001) following ketamine administration. Conclusions In ventilation-treated patients with intracranial hypertension, ketamine effectively decreased ICP and prevented untoward ICP elevations during potentially distressing interventions, without lowering blood pressure and CPP. These results refute the notion that ketamine increases ICP. Ketamine is a safe and effective drug for patients with traumatic brain injury and intracranial hypertension, and it can possibly be used safely in trauma emergency situations.

Download Full-text

Role of Cisternal Drainage in Patients with Traumatic Brain Injury Undergoing Decompressive Craniectomy

Nepal Journal of Neuroscience ◽

10.3126/njn.v15i3.23271 ◽

2019 ◽

Vol 15 (3) ◽

pp. 14-20

Author(s):

Amit Thapa ◽

Rupendra Bahadur Adhikari ◽

Bidur KC ◽

Bikram Shakya

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Functional Outcome ◽

Decompressive Craniectomy ◽

Brain Injuries ◽

Injury Severity ◽

Absolute Risk ◽

Group 2 ◽

Cisternal Drainage ◽

Group 1

The effect of decompressive craniectomy (DC) on survival and functional outcome in traumatic brain injuries (TBI) is far from satisfactory. Additional modalities including cisternal drainage (CD) that provides good control of refractory intracranial pressure (ICP) intraoperatively need careful scrutiny. Two centre retrospective superiority study with one centre offering only standard decompressive craniectomy (DC) i.e. Group 1 and the other centre supplementing cisternal drainage (CD) to standard DC i.e. Group 2 was conducted. Consecutive patients with traumatic brain injury with signs of brain herniation or CT scan showing mass lesion or diffuse brain edema or midline shift or with GCS less than 9 or rapid fall in GCS over 2 points with persistently raised ICP of 25 mmHg over 15 minutes between August 2012 and July 2017 were included. The primary outcome was rating on Glasgow Outcome Scale (GOS) at 6 months post operatively, with GOS (1-3) categorized as ‘Unfavorable’ and GOS (4,5) as ‘Favorable’. Patients either received DC alone (Group 1=73 patients, 48.7%) or DC with CD (Group 2=77 patients, 51.3%). 107 (71.3%) severe, 36 (24%) moderate, and 7 (4.7%) mild head injuries cases received 72 unilateral and 78 bilateral DC. GOS 1 was observed in 32 DC only group (43.8%) and 22 DC plus CD group (28.6%) (p=0.052), an absolute risk reduction of 15.2% was found. Outcome (favorable sun favorable) against all strata of head injury severity, predominant radiological feature, laterality of surgery, and patient characteristics across the two groups were statistically not significant, however the groups were statistically significantly different on age and GCS at presentation (p=0.016 & 0.034 consecutively). Distinct survival benefit in patients with traumatic brain injury receiving cisternal drainage during decompressive craniectomy did not translate to better functional outcome.

Download Full-text

Cerebrovascular reactivity in patients with cerebral contusion and its possible pharmacological correction

Kazan medical journal ◽

10.17750/kmj2016-903 ◽

2016 ◽

Vol 97 (6) ◽

pp. 903-908

Author(s):

R F Garifullin ◽

V I Danilov ◽

R H Karimov

Keyword(s):

Traumatic Brain Injury ◽

Blood Flow ◽

Brain Injury ◽

Cerebrovascular Reactivity ◽

Comprehensive Treatment ◽

Cerebral Contusion ◽

Comprehensive Therapy ◽

Acute Traumatic Brain Injury ◽

Group 2 ◽

Group 1

Aim. Evaluation of dimephosphone as a medication for correction of cerebrovascular reactivity damage in patients with acute traumatic brain injury of mild to moderate severity.Methods. The study included 40 patients with acute traumatic brain injury admitted to the Department of Neurosurgery of Kazan City Clinical Hospital №7. All patients were divided into 2 groups: patients who did not receive dimephosphone were included in group 1, in group 2 patients received drug therapy identical to that in group 1 but with additional 15% solution of dimephosphone 15 ml 3 times a day for 12 days. Evaluation of cerebral blood flow was conducted by transcranial Doppler with the use of analyzer of blood flow velocity «Sonomed 300M». Patients underwent daily functional tests (compression test, hypercapnic test, hypocapnic test) during the days 1 to 12 of hospital stay.Results. The conducted study confirms disorders of cerebrovascular reactivity in patients with acute traumatic brain injury. Also it was found that patients treated with dimephosphone as part of comprehensive therapy at a dose of 15 ml of 15% solution 3 times a day, cerebrovascular reactivity indices (index of vasomotor reactivity, overshoot coefficient) recovered significantly faster.Conclusion. All patients in the acute period of traumatic brain injury with cerebral contusion have disorders of cerebrovascular reactivity; recovery of cerebrovascular reactivity in patients with traumatic brain injury is accelerated by inclusion of dimephosphone in comprehensive treatment.

Download Full-text

DYNAMICS OF THE CONTENT OF WATER-ELECTROLYTE EXCHANGE IN PATIENTS WITH TRAUMATIC BRAIN INJURY DURING PERIOPERATIVE PERIOD

Journal of the Grodno State Medical University ◽

10.25298/2221-8785-2020-18-5-575-583 ◽

2020 ◽

Vol 18 (5) ◽

pp. 575-583

Author(s):

D. P. Markevich ◽

◽

A. V. Marochkov ◽

V. A. Livinskaya ◽

◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Adverse Outcome ◽

Perioperative Period ◽

Sodium Potassium ◽

Initial Stage ◽

Calcium Phosphorus ◽

Group 2 ◽

Electrolyte Exchange ◽

Group 1

Objective. To study the dynamics of the content of sodium, potassium, chloride, magnesium, calcium, phosphorus and iron of the serum and determine the possibility of their use as prognostic criteria for the outcome of treatment of patients with traumatic brain injury (TBI).Material and methods. Two groups were formed of 76 patients with TBI. Group 1 - 46 patients with a favorable outcome of treatment, group 2-30 patients with an adverse outcome. Serum electrolytes between groups were compared during the first 10 days after craniotomy at 7 stages of the study.Results. Between groups of patients differences in the content of K+ at the initial stage of the study (1-2 hours before surgery); Na+ and Cl- at stage 2 of the study (11 (6; 17) hours after surgery) and iron at 5-7 stages of the study (at the 5th, 7th and 10th day after the operation) were revealed. At all stages of the study when comparing groups of patients by the content of phosphorus, magnesium and calcium in the blood serum no significant differences were revealed.Conclusion. The best predictor of an adverse TBI outcome was serum iron on the 5th day after surgery – 2.5 (1.9; 5.2) mmol/l, AUC=0.73, Se=68.8, Sp=60%; on the 7th day after the operation - 3.7 (2.6; 4.3) mmol/l, AUC=0.73,Se=64.7%, Sp=72%; on the 10th day after the operation, 3.6 (1.9; 5.7) μmol/l, AUC=0.69, Se=73.7%, Sp=52.4%.

Download Full-text

Predictive value of positive high-sensitivity troponin T in intubated traumatic brain injury patients

Journal of Neurosurgery ◽

10.3171/2017.7.jns17675 ◽

2018 ◽

Vol 129 (6) ◽

pp. 1541-1549 ◽

Cited By ~ 3

Author(s):

Ayman El-Menyar ◽

Mohammad Asim ◽

Rifat Latifi ◽

Shrikant I. Bangdiwala ◽

Hassan Al-Thani

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Predictive Value ◽

Troponin T ◽

National Level ◽

High Sensitivity ◽

High Sensitivity Troponin ◽

Group 2 ◽

High Sensitivity Troponin T ◽

Group 1

OBJECTIVEThe clinical relevance of high-sensitivity troponin T (HsTnT) in trauma patients is not well explored. In this study, the authors aimed to study the predictive value of serum HsTnT in intubated patients who had sustained traumatic brain injury (TBI).METHODSA retrospective analysis was conducted for all intubated TBI patients between 2010 and 2014 at a national level 1 trauma center. Data were analyzed and compared based on the HsTnT status on admission (group 1, negative results; and group 2, positive results). Receiver operating characteristic curves were used to determine sensitivity, specificity, and cutoff level of HsTnT to predict mortality. Time to earlier discharge from hospital or death was modeled using Cox proportional hazard models to describe the relationship between HsTnT and in-hospital mortality.RESULTSOf the 826 intubated TBI patients, 490 underwent HsTnT testing; 65.7% had positive HsTnT results. Patients in group 2 had a higher Injury Severity Score (p = 0.001) and head Abbreviated Injury Scale (AIS) score (p = 0.004) than those in group 1. In addition, group 2 patients were more likely to have lower Glasgow Coma Scale scores (p = 0.001) and more likely to experience intraventricular hemorrhage, brain edema, pneumonia, and sepsis (p = 0.001). HsTnT values positively correlated with head AIS score (r = 0.19, p = 0.001) and varied by the type of lesion and time to death. Ventilator days and length of hospital stay were more prolonged in group 2 patients (p = 0.001). Area under the curve (AUC) analysis showed that HsTnT ≥ 26.5 ng/L predicted all-cause mortality (AUC 0.75, 95% CI 0.699–0.801) with 80% sensitivity. Positive HsTnT was an independent predictor of mortality in multivariate models (adjusted OR 3.10, 95% CI 1.308–7.351) even after excluding chest injury (adjusted OR 4.18, 95% CI 1.320–13.231).CONCLUSIONSPositive HsTnT results are associated with poor outcomes in intubated patients with TBI. In this subset of patients, measuring serum HsTnT on admission is a useful tool for early risk stratification and expedited care; however, further prospective studies are warranted.

Download Full-text

Protective Effects of Propolis Extract in a Rat Model of Traumatic Brain Injury via Hsp70 Induction

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.736 ◽

2019 ◽

Vol 7 (17) ◽

pp. 2763-2766 ◽

Cited By ~ 1

Author(s):

Steven Tandean ◽

Iskandar Japardi ◽

Michael Lumintang Loe ◽

Wibi Riawan ◽

Julius July

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Caspase 3 ◽

Brain Cell ◽

Hsp70 Expression ◽

Propolis Extract ◽

Significant Difference ◽

Group 3 ◽

Group 2 ◽

Group 1

BACKGROUND: Traumatic brain injury (TBI) is one of the major global health problems. Secondary brain injury is a complex inflammation cascades process that causes brain cell apoptosis. Propolis is a natural product that has neuroprotective property. AIM: This study aimed to investigate the effect of propolis toward Hsp70 expression with apoptosis marker in brain tissue after TBI. METHODS: Thirty-three Sprague Dawley rats were randomised into three treatments group, i.e. sham-operated controls, closed head injury (CHI), and CHI with propolis extract (treatment group). In the treatment group, propolis was given 200 mg/kg per oral for 7 days then harvested brain tissues after sacrificed by cervical dislocation at day 8. We investigated Hsp70, Caspase 3, apoptosis-inducing factor (AIF), and TUNEL assay expression using immunohistochemistry staining. Statistical test using one-way ANOVA test and Tukey HSD as post hoc test. RESULTS: Mean of positive Hsp70 stained cells in group 1 was 6.82 ± 2.14, group 2 was 3.91 ± 2.26, and group 3 was 9.64 ± 3.53 with a significant difference of Hsp70 expression distribution within groups (p = 0.0001). Mean of positive caspase 3 stained cells in group 1 was 5.45 ± 2.30, group 2 was 13.82 ± 2.44, and group 3 was 7.03 ± 1.54 with a significant difference of caspase3 expression distribution within groups (p=0.0001). Mean of positive AIF stained cells in group 1 was 5.36 ± 2.11, group 2 was 12.82 ± 1.40, and group 3 was 8.09 ± 1.81 with a significant difference of AIF expression distribution within groups (p = 0.0001). Mean of positive TUNEL assay stained cells in group 1 was 4.82 ± 2.04, group 2 was 11.55 ± 1.51, and group 3 was 7.64 ± 1.96 with a significant difference of TUNEL test expression distribution within groups (p = 0.0001). CONCLUSION: Propolis may protect brain cell from apoptosis after injury by maintaining Hsp70 expression in addition to antioxidant and anti-inflammatory.

Download Full-text

Serum S100B Determination in the Management of Pediatric Mild Traumatic Brain Injury

Clinical Chemistry ◽

10.1373/clinchem.2011.180828 ◽

2012 ◽

Vol 58 (7) ◽

pp. 1116-1122 ◽

Cited By ~ 41

Author(s):

Damien Bouvier ◽

Mathilde Fournier ◽

Jean-Benoît Dauphin ◽

Flore Amat ◽

Sylvie Ughetto ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Reference Interval ◽

Pediatric Emergency ◽

Cranial Computed Tomography ◽

Serum S100b ◽

Significant Difference ◽

Hospitalization Costs ◽

Group 2

Abstract BACKGROUND The place of serum S100B measurement in mild traumatic brain injury (mTBI) management is still controversial. Our prospective study aimed to evaluate its utility in the largest child cohort described to date. METHODS Children younger than 16 years presenting at a pediatric emergency department within 3 h after TBI were enrolled prospectively for blood sampling to determine serum S100B concentrations. The following information was collected: TBI severity determined by using the Masters classification [1: minimal or Glasgow Coma Scale (GCS) 15, 2: mild or GCS 13–15, and 3: severe or GCS <13]; whether hospitalized or not; good or bad clinical evolution (CE); whether cranial computed tomography (CCT) was prescribed; and related presence (CCT+) or absence (CCT−) of lesions. RESULTS For the 446 children enrolled, the median concentrations of S100B were 0.21, 0.31, and 0.44 μg/L in Masters groups 1, 2, and 3, respectively, with a statistically significant difference between these groups (P < 0.05). In Masters group 2, 65 CCT scans were carried out. Measurement of S100B identified patients as CCT+ with 100% (95% CI 85–100) sensitivity and 33% (95% CI 20–50) specificity. Of the 424 children scored Masters 1 or 2, 21 presented “bad CE.” S100B identified bad CE patients with 100% (95% CI 84–100) sensitivity and 36% (95% CI 31–41) specificity. Of the 242 children hospitalized, 81 presented an S100B concentration within the reference interval. CONCLUSIONS Serum S100B determination during the first 3 h of management of children with mTBI has the potential to reduce the number of CCT scans, thereby avoiding unnecessary irradiation, and to save hospitalization costs.

Download Full-text

NIMG-04. PREDICTING THE BRAF MUTATIONAL STATUS IN PATIENTS WITH MELANOMA BRAIN METASTASES USING RADIOMICS - A BICENTRIC STUDY

Neuro-Oncology ◽

10.1093/neuonc/noab196.504 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi127-vi128

Author(s):

Anna-Katharina Meissner ◽

Robin Gutsche ◽

Norbert Galldiks ◽

Martin Kocher ◽

Stephanie T Juenger ◽

...

Keyword(s):

Brain Metastases ◽

Test Data ◽

Targeted Therapies ◽

Braf V600e Mutation ◽

Braf V600e ◽

Support Vector ◽

Mutational Status ◽

Melanoma Brain Metastases ◽

Group 2 ◽

Group 1

Abstract BACKGROUND The BRAF V600E mutation is present in approximately 50% of patients with melanoma and is an important prerequisite for a response to targeted therapies such as BRAF inhibitors. In the majority of patients, the BRAF mutational status is based on the analysis of tissue samples from the extracranial primary tumor only. Since the extracranial and intracranial BRAF mutational status may be discrepant, the additional information on the BRAF mutational status of melanoma brain metastases would be of clinical value, e.g., for the prediction of response to targeted therapies. Here, we evaluated the potential of MRI radiomics for the determination of the intracranial BRAF mutational status in patients with melanoma brain metastases. PATIENTS AND METHODS Fifty-nine patients with melanoma brain metastases from two university hospitals (group 1, 45 patients; group 2, 14 patients) were operated with subsequent genetic analysis of the intracranial BRAF mutational status. All patients underwent structural MRI preoperatively. Areas of contrast enhancement were manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After image preprocessing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. RESULTS Twenty-two patients (49%) in group 1, and 6 patients (43%) in group 2 had an intrametastatic BRAF V600E mutation. Using the best performing six parameter radiomics signature, a linear support vector machine classifier yielded an area under the ROC curve (AUC) of 0.92 (sensitivity, 83%; specificity, 88%) in the test data. CONCLUSION The developed radiomics classifier allows a non-invasive prediction of the intracranial BRAF V600E mutational status in patients with melanoma brain metastases and may be of value for treatment decisions.

Download Full-text

Treatment of Adult T-ALL with a Pediatric Asparaginase-Intensive Protocol Results in Survival Benefit When Compared to Other Adult Based Protocols

Blood ◽

10.1182/blood.v112.11.3956.3956 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3956-3956

Author(s):

Murtadha K. Al-Khabori ◽

Mark Minden ◽

Vikas Gupta ◽

Aaron D. Schimmer ◽

Andre C. Schuh ◽

...

Keyword(s):

Multivariate Analysis ◽

Treatment Regimen ◽

Lymphoblastic Leukemia ◽

Remission Induction ◽

Entire Group ◽

Induction Phase ◽

Newly Diagnosed ◽

Significant Difference ◽

Group 2 ◽

Group 1

Abstract T cell acute lymphoblastic leukemia (T-ALL) accounts for 14–22% of adult ALL. No prospective comparisons between different chemotherapy protocols have been done. Since 2000 a modified DFCI protocol (Silverman et al, Blood2001;97:121–1218) has been used as standard treatment for all newly diagnosed patients with T-ALL at Princess Margaret Hospital (PMH). This protocol includes a remission induction phase, a CNS prophylaxis phase with intrathecal chemotherapy and 12 Gy cranial irradiation, a 30-week intensification phase including weekly asparaginase, and a 72-week maintenance phase. We compared outcomes using this regimen to previous results for all newly diagnosed T-ALL from 1990 – 2000 at PMH using the standard institutional protocol in use at the time. Between 1990–2000, 44 patients (Group 1) were treated with a variety of protocols, including 9203ALL PMH protocol (11 patients), L10 (2 pts), Protocol C (7 pts), HyperCVAD (15 pts) and ECOG E2993 (9 pts). From 2000–2007, 33 T-ALL patients were treated with modified DFCI protocol (Group 2). The median age for all patients was 31 years (range 14–69 years). There was no significant difference between the two groups with respect to age at diagnosis, presenting WBC (median or percent > 100 ×109/L), CSF positivity, or cytogenetics. More patients from Group 1 underwent allogeneic stem cell transplantation (BMT) in CR-1 (54%) as compared to those in Group 2 (54% vs. 14%, P = 0.001), primarily due to a change in BMT policy in 2002. The median follow up was 23 months (range 1–161 months) for the entire group and 53 months (range 14–161 months) for the surviving patients. Sixty-nine patients (90%) achieved complete remission, and 37 patients have relapsed. The CR rates were not significantly different between the two groups. The 3-year failure-free survival (FFS) was significantly higher in Group 2 (DFCI protocol) as compared with Group 1 (other protocols) (89% vs. 27%, P = 0.0001). Multivariate analysis using Cox proportional hazard model showed only the treatment regimen received (DFCI vs. others) to have a statistically significant impact on FFS (P = 0.0001). The 3-year overall survival (OS) was significantly higher in the DFCI group compared to the group receiving the other protocols (81% vs. 45%, P = 0.0006). On multivariate analysis, only the treatment regimen received (P=0.001) and the CSF status (P=0.014) had a significant impact on OS; BMT did not have a significant impact on OS. When patients were censored at the time of transplant, the FFS and OS analyses still showed statistically significant benefit for patients treated on DFCI protocol (P = 0.0001 and 0.03, respectively). In summary, treatment outcomes have markedly improved from 2000 onward as compared to the previous decade. Although improvements in supportive care and reduced use of allogeneic BMT may have been factors, it is likely that the institution of the DFCI pediatric protocol was the primary factor in the improved outcome. These results support the use of such pediatric asparaginase-intensive pediatric protocols for adult T-ALL.

Download Full-text