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Biomedical subjects

T Flohr

Publications and source records attributed to T Flohr.

At least 19 recordsLinked to original sources
PubMed2003

Safety and feasibility of CHOP/rituximab induction treatment followed by high-dose chemo/radiotherapy and autologous PBSC-transplantation in patients with previously untreated mantle cell or indolent B-cell-non-Hodgkin's lymphoma.

Patients with no prior chemotherapy and with advanced and progressive follicular lymphoma (FCL) or mantle cell lymphoma (MCL) were enrolled into a treatment protocol combining CHOP/rituximab-CHOP therapy with subsequent consolidation high-dose therapy (HDT) to evaluate the safety and feasibility of this treatment. Overall, 15 patients were enrolled and 13 patients completed the entire treatment protocol without major toxicities or increased infectious complications. One patient withdrew consent after achieving complete remission (CR) prior to HDT. One patient was taken off study with signs of disease progression after induction treatment. All patients showed stable engraftment after HDT. Response rates appear to be favorable, indicating an additional effect of rituximab and HDT. Overall, 12 of 13 patients achieved CR/CRu and one patient partial remission. Follow-up of immune reconstitution displayed transient severe combined immunodeficiency with slow normalization of the cellular and humoral compartments without a significant increase of infectious complications. Taken together, high-dose chemotherapy can be safely given following treatment with CHOP+rituximab. Efficacy in this small cohort of patients was encouraging with sustained remissions in both FCL and MCL patients. Upfront HDT should be considered as a therapeutic option especially in young and/or high-risk patients.

Adult↗
PubMed2003

[Quantification of cardiac function with multislice spiral CT using retrospective EKG-gating: comparison with MRI].

PURPOSE: To quantify left ventricular function derived from retrospectively ECG-gated multislice spiral CT (MSCT) data sets in comparison to MRI. MATERIALS AND METHODS: In 16 patients (14 males, 2 females, mean age 56.8 +/- 11.5 years), retrospectively ECG-gated MSCT angiography of the coronary arteries and breath-hold steady state free precession cine MRI were performed. From MSCT data-sets, 20 axial image series were reconstructed every 5 % of the RR interval. Multiplanar images were reformatted in the short axis orientation from axial images. End-systolic and end-diastolic images were selected. From these images end-systolic volume (ESV), end-diastolic volume (EDV) and stroke volume (SV) as well as the ejection fraction (EF) and myocardial mass (MM) were determined using the Simpson's method and compared with MRI. Furthermore, image quality was assessed for both imaging modalities using a four point grading scale. RESULTS: All parameters were found to have an excellent correlation between MSCT and MRI data (Pearson's correlation coefficient 0.95 - 0.99), without clinically relevant differences between both modalities. On average, the difference between both methods was 0.5 ml for ESV, 0.8 ml for EDV, 1.3 ml for SV, 0.9 % for EF and 2.3 g for MM. Image quality was slightly better for MRI (1.5 +/- 0.65) than for MSCT (1.64 +/- 0.74). CONCLUSION: Retrospectively ECG-gated MSCT angiography can not only visualize the coronary arteries but also enables precise quantification of the left ventricular function from the same MSCT data set.

Aged↗
PubMed2002

A retrospectively ECG-gated multislice spiral CT scan and reconstruction technique with suppression of heart pulsation artifacts for cardio-thoracic imaging with extended volume coverage.

A method for cardio-thoracic multislice spiral CT imaging with ECG gating for suppression of heart pulsation artifacts is introduced. The proposed technique offers extended volume coverage compared with standard ECG-gated spiral scan and reconstruction approaches for cardiac applications: Thin-slice data of the entire thorax can be acquired within one breath-hold period using a four-slice CT system. The extended volume coverage is enabled by a modified approach for ECG-gated image reconstruction. For a CT system with 0.5-s gantry rotation time, images are reconstructed with 250-ms image temporal resolution. Instead of selecting scan data acquired in exactly the same phase of the cardiac cycle for each image as in standard ECG-gated reconstruction techniques, the patient's ECG signal is used to omit scan data acquired during the systolic phase of highest cardiac motion. With this approach cardiac pulsation artifacts in CT studies of the aorta, of paracardiac lung segments, and of coronary bypass grafts can be effectively reduced.

Aortic Diseases↗
PubMed2002

Reproducibility of coronary calcium quantification in repeat examinations with retrospectively ECG-gated multisection spiral CT.

High reproducibility is a key requirement for coronary calcium scoring in follow-up examinations. We investigated the inter-examination reproducibility of calcium scoring with retrospectively ECG-gated multisection spiral CT (MSCT). Fifty patients were examined twice with MSCT. Slices were reconstructed with retrospective ECG gating in the diastolic phase with 3-mm slice width and up to 125-ms temporal resolution. We calculated the Agatston score, calcium volume with and without isotropic interpolation, and calcium mass, and derived the mean and median variability. We investigated the change of variability with use of 3-mm non-overlapping and overlapping increments (2, 1.5, 1 mm). Use of overlapping increment results in considerably reduced interscan variability. We observed a minimum mean variability of 12% and a minimum median variability of 9% for the Agatston score. For volume and mass quantification we obtained a minimum mean variability of 7.5% and a minimum median variability of 5%. Multisection spiral CT enables coronary calcium quantification with high reproducibility in follow-up examinations mainly founded on image data with reduced partial-volume errors due to overlapping increment.

Adult↗
PubMed2002

[CT angiography of the coronary arteries with a 16-row spiral tomograph. Effect of spatial resolution on image quality].

PURPOSE: To evaluate image quality of coronary CT angiography with retrospectively ECG-gated 16 multi-slice spiral CT (MSCT), reconstructed with 0.75 mm slice thickness for optimal spatial resolution and with 1.3 mm slice thickness, to produce spatial resolution comparable to a 4-MSCT. MATERIALS AND METHODS: Ten patients underwent coronary CT angiography with a 16-MSCT (Siemens Sensation 16, Forchheim, Germany) with 0.75 mm detector collimation. Raw helical CT data were retrospectively reconstructed using two different settings. Setting A: B20f smooth kernel, axial MPR with 1.3 mm slice thickness and 0.7 mm increment. Setting B: B35f "HeartView" medium-smooth kernel, 0.75 mm slice thickness, 0.5 mm increment. In the axial slices two regions of interest (ROIs) were placed in the area of the aortic root (AR) and more caudal in the area of the left ventricle (LV). Image noise was determined by the standard deviation of the CT numbers.Two readers determined visibility of coronary arteries by standardized maximum intensity projections (MIP) post-processing in left, right anterior and left anterior oblique projection plane from setting A and B. Each projection was rated on a five point rating scale concerning plaque delineation. Points determined for each data set were summed up and used for comparison. RESULTS: No significant difference between the CT-numbers was found for setting A and B (A: 283.0 in AR/295.9 in LV and B: 282,9 in AR/297.2 in LV; p >0.2). However, the image noise was significantly different for setting A and B (A: 4.46 in AR/1.67 in LV and B: 8.16 in AR/7.38 in LV; p <0.01). Better delineation of the coronary arteries and atherosclerotic lesions could be achieved from MIP projections in setting B compared to setting A. CONCLUSION: Higher image noise is present in coronary 16-MSCT with thin-slice reconstruction compared to simulated 4-MSCT. However the MIP-reconstructions benefit most from the higher spatial resolution.

Coronary Angiography↗
PubMed2002

Strategies for cardiac CT imaging.

We review the scanning techniques for cardiac CT imaging with single slice and multislice scanners. Combined with prospective triggering for transaxial scanning and retrospective gating for helical scanning the potential advantages and the basic limitations are discussed. Based on those theoretical considerations, the major conclusion is that high resolution data sets with isotropic spatial resolution can be acquired with quadslice, spiral scanning, only. First clinical results support this conclusion.

Heart↗
PubMed2002

Rituximab in vivo purging is safe and effective in combination with CD34-positive selected autologous stem cell transplantation for salvage therapy in B-NHL.

The purpose of this study was to evaluate feasibility and efficacy of Rituximab included into a sequential salvage protocol for CD20(+) B-NHL in relapse or induction failure. Twenty-seven patients with CD20(+) B-NHL in relapse or induction failure received Rituximab combined with DexaBEAM (R-DexaBEAM) for stem cell mobilization. Additional ex vivo selection of CD34-positive cells was performed using the CliniMacs device. Two doses of Rituximab were included in the high-dose therapy regimen (HDT). R-DexaBEAM was well tolerated and 26 of 27 patients mobilized sufficient numbers of CD34(+) blood stem cells. Application of R-DexaBEAM resulted in significant depletion of peripheral B cells. No treatment-related deaths occurred after HDT and all patients showed stable engraftment of hematopoesis. Combined immunodeficiency was observed post HDT and eight patients developed CMV antigenemia. Remission rate post HDT was 96% (CR, 24/26; PR, 1/26). Overall and progression-free survival (PFS) at 16 months post HDT (range 6-27) is 95% and 77%, respectively. With regard to histology, PFS was 71% in aggressive lymphoma (n = 11), 74% in indolent FCL (n = 10) and 100% in MCL (n = 5). The treatment protocol has proven feasible, with high purging efficiency and encouraging remission rates.

Adult↗
PubMed2002

[Visualization of coronary arteries in CT as assessed by a new 16 slice technology and reduced gantry rotation time: first experiences].

PURPOSE: First evaluation of image quality of a new 16-slice multidetector-row computed tomography (MDCT) for the assessment of coronary artery disease and lesion detection of the coronary arteries. MATERIALS AND METHODS: On a newly developed 16-slice CT scanner (SOMATOM Sensation 16, Siemens, Forchheim, Germany) a calcium score as well as a contrast-enhanced CT angiography (CTA) were performed on 4 patients with retrospective ECG-gating and a gantry rotation time of 420 ms to exclude or follow-up coronary heart disease. CTA was performed after injecting 120 ml contrast media intravenously. After medication with a ss-Blocker, the heart rate was between 55 and 67 bpm. RESULTS: The scan time for calcium score was 12 s, for CTA 18 s (scan range 15 and 12 cm, respectively). Volume score was between 0 and 256.4. In the CT angiography the entire coronary tree could be visualized in all patients up to the very distal subsegmental branches. In two patients a complete occlusion of the RCA and the LAD were depicted, respectively. In one of these patients, a large aneurysm of the left anterior ventricular wall was also delineated. CONCLUSION: Considering our first experiences with the new 16-slice technology, an excellent visualization of the entire coronary tree including the very distal and side branches due to substantially increased spatial resolution seems to be achievable. In these patients the acquired image quality raises the hope for improved, non-invasive cardiac diagnostics. In larger studies, the clinical impact of this new technology needs to be further investigated.

Aged↗
PubMed2002

New technical developments in multislice CT--Part 1: Approaching isotropic resolution with sub-millimeter 16-slice scanning.

The introduction of multislice CT was a breakthrough with regard to increased scan speed, improved axial resolution and better utilization of the tube output. The new generation of multislice CT scanners offering simultaneous acquisition of up to 16 sub-millimeter slices represents an important leap on the way towards true isotropic scanning. We present an evaluation of a state-of-the-art 16-slice CT system (SOMATOM Sensation 16, Siemens AG, Forchheim, Germany). After an introduction to the detector design we discuss dose utilization and finally elaborate on multislice spiral scanning with 16 slices. Due to the increased number of slices dose utilization is improved compared to current 4-slice CT scanners, and sub-millimeter collimation needs no longer be restricted to special applications. For CT systems with 8 or more slices, the cone-beam geometry causes severe artifacts if not corrected for by a so-called cone-correction, which thus becomes mandatory in this case. With the Adaptive Multiple Plane Reconstruction AMPR, cone beam artifacts are effectively suppressed, while the benefits of Adaptive Axial Interpolation are maintained: free selection of the spiral pitch according to the clinical needs of an examination, slice width independent of the pitch, full dose utilization at all pitch values. Clinical practice will have to demonstrate the application spectrum that is opened with the new generation of multislice CT systems.

Artifacts↗
PubMed2002

New technical developments in multislice CT, part 2: sub-millimeter 16-slice scanning and increased gantry rotation speed for cardiac imaging.

Despite all promising advances, some challenges remain for ECG-gated multislice CT examinations of the heart and the coronary arteries with current 4-slice detectors: adequate visualization of stents and severely calcified coronary arteries, examination of patients with higher heart rates and patients, who cannot adequately hold their breath for at least 30 sec. The new generation of multislice CT systems offering simultaneous acquisition of up to 16 sub-millimeter slices and gantry rotation times shorter than 0.5 sec has the potential to overcome these limitations. We describe the technical principles of cardiac scanning with a state-of-the-art 16-slice CT equipment (SOMATOM Sensation 16, Siemens AG, Forchheim, Germany). We discuss an extension of the Adaptive Cardio Volume (ACV) reconstruction approach for ECG-gated multislice spiral CT. We show the impact of reduced gantry rotation time (0.42 sec) on temporal resolution, and we demonstrate the influence of slice width on the visualization of stents and plaques. Deviating from general purpose applications a cone-correction is not required for cardiac scanning with 16-slice CT systems. In addition to the absolute improvement, the temporal resolution shows a different dependence on the patient's heart rate for 0.42 sec rotation time, reaching its optimum (105 msec) at 81 BPM. This has the potential to expand the range of heart rates accessible to routine clinical examinations. Owing to sub-millimeter slice width and optimized in-plane resolution characteristics, visualization of stents and severe calcifications in coronary arteries is significantly improved. Clinical experience will be needed to fully evaluate the potential of 16-slice technology for cardiac imaging.

Artifacts↗
PubMed2002

[CT-angiography of the carotid artery: First results with a novel 16-slice-spiral-CT scanner].

PURPOSE: To evaluate a novel multislice CT system (16-slice-spiral-CT scanner) for the diagnosis of carotid artery stenosis. MATERIAL AND METHODS: Five patients with symptomatic atherosclerotic disease of the carotid arteries were examined with a 16- slice-spiral-CT scanner. Collimation was 16 x 0.75 mm, table speed 36 mm/s (pitch of 1.5), rotation time 0.5 s, tube current was 160 eff.mAs at 120 kV. 60 ml of contrast material were injected with a power injector followed by a saline flush. The start delay was measured with test bolus method (20 ml CM). Interactive multiplanar reformation (iMPR) and thin slab MIP as well as volume rendering were used for image evaluation and presentation. RESULTS: Scan time was 9 s for a range of 300 mm. This allowed imaging the whole length of the carotid artery (aortic arch to circle of Willis) in a true arterial phase. Pulsation artefacts did not impair the evaluation of the vessels at the level of the aortic arch. Overall image quality of both "source images" and 3D-reconstructions was excellent, due to a reduced voxel size of 0.03 mm (3). Image evaluation and postprocessing (iMPR, MIP) was done within 15 min. iMPR was highly accurate for demonstrating plaque morphology and determining the percentage of the stenosis. CONCLUSION: For the first time, true arterial phase images of the entire carotid artery with high spatial resolution could be acquired using a 16-slice-spiral-CT scanner. This method offers the potential to replace catheter angiography in the evaluation of carotid artery stenosis.

Blood Flow Velocity↗
PubMed2002

Rituximab as in vivo purging agent in autologous stem cell transplantation for relapsed B-NHL.

In vivo purging may avoid relapse after high dose therapy (HDT) for relapsed lymphoma. Therefore, we have evaluated feasibility and efficacy of Rituximab as in vivo purging agent included into a sequential salvage protocol for CD20+ B-NHL in chemosensitive relapse or induction failure. Thirty seven patients were treated within this protocol and in 36/37 a stem cell product could be acquired with rare NHL contamination. Overall, due to the intensity of treatment there has been a substantial morbidity, including high rates of viral reactivation. However, only one patient died during treatment due to sepsis. Response rates were favourable with an overall response rate of 97% (with 30/35CR). With a maximum follow up of 3.5 years, 15 patients relapsed. Overall, the treatment protocol has proven feasible with high purging efficiency and encouraging remission rates in this unfavourable patient group.

Antibodies, Monoclonal↗
PubMed2001

Detection and quantification of protein phosphatase inhibitor-1 gene expression in total rat liver and isolated hepatocytes.

The mRNA expression of protein phosphatase inhibitor-1 (inhibitor-1) in rat liver was demonstrated using highly sensitive semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Quantification by real-time RT-PCR (LightCycler technology) yielded the same copy number of inhibitor-1 mRNA in total rat liver and isolated hepatocytes (12 copies per cell). This novel finding shows that rat liver expresses indeed inhibitor-1 mRNA, albeit in low amounts. The low copy number explains why the mRNA had not been detected by Northern blotting so far. For comparison, about 425 copies/cell were detected in brain and 2500 copies/cell in skeletal muscle from rat. The full-length coding sequence of rat liver inhibitor-1 was cloned and sequenced, 100% homology with the muscle cDNA was obtained, indicating the expression of the same gene in liver and muscle. In vitro transcription and translation yielded a protein (Mr approximately 30 kDa) which could be detected with a specific antibody by immunoblotting. This indicates an intact open reading frame of inhibitor-1 in rat liver. Immunoblotting of liver extract yielded a very weak band which comigrated with the inhibitor-1 proteins from muscle and brain. It is concluded that mRNA expression of inhibitor-1 may have implications for the regulation of protein phosphatase-1 (PP1) in rat liver.

Animals↗
PubMed2001

Accuracy and reliability of quantitative measurements in coronary arteries by multi-slice computed tomography: experimental and initial clinical results.

AIM: To evaluate the accuracy of non-invasive measurements within coronary arteries by multi-slice computed tomography (MSCT). We present experimental as well as clinical data. MATERIALS AND METHODS: Silicon tubes simulating coronary arteries (outer diameter 6 mm, lumen diameter within stenotic area 2 mm) were used for experimental studies. Clinical data were derived from 15 patients in whom vessel diameters were assessed by MSCT, intracoronary ultrasound (ICUS) and quantitative coronary angiography (QCA). MSCT were performed in a Somatom Volume Zoom(trade mark)CT system (Siemens, Forchheim, Germany) at 2 collimated slice widths (2.5 mm, 1.0 mm). RESULTS: Outer silicon tube diameters were overestimated by MSCT (6.56 mm +/- 0.32 mm). All measurements revealed significantly better results on 1.0 collimation compared to 2.5 mm collimation (outer diameter: 6.36 mm +/- 0.22 mm vs 6.76 mm +/- 0.27 mm, P < 0.0001; lumen diameters: 1.83 mm +/- 0.14 mm vs 1.51 mm +/- 0.19 mm, P < 0.0001). The comparison of vessel diameters within human coronary arteries revealed comparable results between ICUS and MSCT (4.89 mm +/- 0.67 mm vs 4.91 mm +/- 0.71 mm, P = 0.79, r = 0.79, P < 0.0001). QCA-measurements showed significantly lower results (3.67 +/- 0.71, P < 0.0001, r = 0.62, P < 0.001). CONCLUSIONS: Experimental as well as initial clinical results indicate acceptable reliability and accuracy of quantitative measurements by MSCT, when using thin collimated slice widths. Partial volume effects lead to a systematic overestimation of vessel size. MSCT has the potential to become an important non-invasive diagnostic tool in patients with coronary artery disease.

Coronary Angiography↗
PubMed2001

Individually adapted examination protocols for reduction of radiation exposure in chest CT.

RATIONALE AND OBJECTIVES: To develop a simple directive for the reduction of radiation exposure without loss of diagnostic information in routine chest CT examinations. METHODS: Two hundred fifty adult patients (164 male, 86 female) were entered into a prospective trial. All examinations were performed with a multislice CT technique (Somatom Volume Zoom, Siemens). Four groups of 50 patients each were scanned with patient-related specific parameters: individual mA-s values were derived from the estimated body weight: kilograms + 10, +/- 0, - 10, and - 20 mAs. The results were compared with those of 50 patients who were examined by a standard chest protocol by using the parameters 120 mAs and 140 kV. All other parameters including the tube voltage were kept constant. Subjective image quality was rated on a three-point scale: 1 = excellent, 2 = fair, 3 = nondiagnostic. In addition, objective criteria based on signal-to-noise measurements were assessed by using a region-of-interest methodology. RESULTS: Image quality was sufficient in all cases. Mean subjective gradings of image quality, based on soft-tissue window settings, were 1.1 for the 120-mAs protocol, 1.1 for the (body weight [kg] + 10) mAs protocol, 1.1 for the (body weight [kg] +/- 0) mAs protocol, 1.3 for the (body weight [kg] - 10) mAs protocol, and 1.2 for the (body weight [kg] - 20) mAs protocol. Objective criteria based on noise measurements showed mean +/- standard deviation values of 5.7 +/- 0.8 Hounsfield units (HU) for the 120-mAs protocol. For the reduced-dose protocols, values were calculated as 7.6 +/- 1.2 HU (group + 10), 7.9 +/- 1.3 HU (group +/- 0), 8.7 +/- 1.2 HU (group - 10), and finally 9.1 +/- 1.3 HU (group - 20). The best correlation for an entire subgroup was achieved with the - 10 protocol (body weight [kg] - 10) mAs, with nearly constant noise related to body weight in all patients. CONCLUSIONS: By deriving mAs values from body weight estimation, an individually adapted protocol for chest CT can be recommended and easily employed in a clinical setting. With an adaptation of the tube current-time product based on the estimated body weight of the patient - 10 (body weight [kg] - 10 mAs), a well-balanced examination without significant loss of information, even in soft-tissue window settings, can be performed with this particular scanner. For this adapted mAs protocol, a mean reduction of radiation exposure of 45% was achievable, compared with the standard protocol. A maximum decrease per case down to 31 mAs was obtained, without relevant loss of image quality. Therefore, for other types of CT scanners, analogous protocols may be adapted.

Adult↗
PubMed2001

Association between the 5' UTR variant C178T of the serotonin receptor gene HTR3A and bipolar affective disorder.

Serotonin receptor type 3 is a ligand-gated ion channel implicated in behavioural disorders. Our objective was to identify nucleotide variants in a specific portion of the 5' region of the serotonin receptor gene (HTR3A) containing upstream open reading frames (uORFs) and to investigate their effect on bipolar disease. Mutations in uORFs have been recently shown to cause disease by changing expression on the translational level. We identified one polymorphism, C195T, and one missense mutation, C178T (Pro16Ser) within an upstream open reading frame. No significant association was found between the C195T polymorphism and bipolar affective disorder. A significant association was, however, found between the variant C178T in 156 patients with bipolar disorder compared to 156 healthy controls (P = 0.00016). To investigate the relevance of this variant on gene expression, luciferase reporter constructs containing the C178T (Pro16Ser) allele were established and compared to the C178T plus C195T and wild-type alleles. Reporter constructs containing the C178T (Pro16Ser) allele drove 245% and 138% expression compared to the wild-type allele. These findings show that the C178T(Pro16Ser) variant in HTR3A may represent a functional variant and affect the susceptibility to bipolar disorder.

5' Untranslated Regions↗
PubMed2000

Rapid and reliable quantification of minimal residual disease in acute lymphoblastic leukemia using rearranged immunoglobulin and T-cell receptor loci by LightCycler technology.

The detection of minimal residual disease (MRD) using immunoglobulin and T-cell receptor (TCR) rearrangements as PCR targets provides important prognostic information on the in vivo effectiveness of treatment in acute lymphoblastic leukemia (ALL). Here we report on the real-time quantification of MRD in 25 ALL patients using LightCycler technology. We designed and adapted allele-specific oligonucleotide (ASO)-PCR protocols that enabled the detection of >90% of the IGH, IGK, TCRD, and TCRG rearrangements observed in ALL patients. In all patients, at least two suitable markers could be identified (average, 3.4 markers/patient). We applied ASO-PCR with 35 immunoglobulin and TCR rearrangements (11 IGH, 6 IGK, 12 TCRG, and 6 TCRD) and compared the sensitivity and practicability of the LightCycler strategy with conventional ASO-PCR on a block thermocycler followed by quantification with gel electrophoresis. The LightCycler measured leukemia-specific PCR products at each cycle (real-time) by staining the PCR product with the DNA-binding dye SYBR Green I. LightCycler technology showed a higher sensitivity than the conventional method in eight cases, whereas the sensitivity of the other markers matched exactly. The detection level varied between 10(-4) and 10(-6) leukemic cells. Furthermore, we determined the MRD status of 27 bone marrow follow-up samples from 15 ALL patients by both methods and revealed comparable results. However, the LightCycler also allowed accurate quantification in samples containing relatively high levels (>10(-3)) of residual leukemia cells. The conventional ASO-PCR technique comprises various laborious and time-consuming PCR experiments and post-PCR steps to determine the number of cycles with the optimal linearity and sensitivity of the PCR. Real-time quantification through LightCycler technology obviates these post-PCR steps, provides the highest sensitivity via software analysis, and therefore represents a rapid, reliable, sensitive, and cost-effective technique for the routine monitoring of MRD in ALL patients.

Adult↗