scholarly journals Omission of Planning CT Reduces Patient Radiation Exposure during CT-Guided Bone Marrow Biopsy and Aspiration

Tomography ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 747-751
Author(s):  
Robert Devita ◽  
Kaushik Chagarlamudi ◽  
Jared Durieux ◽  
David Jordan ◽  
Brian Nguyen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Diagnostic Yield ◽  
Ct Scans ◽  
Procedure Time ◽  
Ct Fluoroscopy ◽  
Bone Marrow Biopsies ◽  
Ct Guided ◽  
Group 2 ◽  
Planning Ct ◽  
Group 1

The purpose of this study is to evaluate the impact of eliminating a preprocedural planning computed tomography during CT-guided bone marrow biopsy on the technical aspects of the procedure, including patient dose, sample quality, procedure time, and CT fluoroscopy usage. Retrospective analysis of 109 patients between 1 June 2018 and 1 January 2021 was performed. Patients were grouped based on whether they received a planning CT scan. Relative radiation exposure was measured using dose-length product (DLP). Secondary metrics included number of CT fluoroscopic acquisitions until target localization, total number of CT fluoroscopic acquisitions, biopsy diagnostic yield, and procedure time. A total of 43 bone marrow biopsies with planning CT scans (Group 1) and 66 bone marrow biopsies without planning CT scans (Group 2) were performed. The average total DLP for Group 1 and Group 2 was 268.73 mGy*cm and 50.92 mGy*cm, respectively. The mean radiation dose reduction between the groups was 81% (p < 0.0001). Significantly more CT fluoroscopy acquisitions were needed for needle localization in Group 2 than Group 1 (p < 0.0001). Total number of CT fluoroscopy acquisitions was four for Group 1 and eight for Group 2 (p = 0.0002). There was no significant difference between the groups in procedure time or diagnostic yield. Patients without a planning CT scan received more fluoroscopic CT acquisitions but overall were exposed to significantly less radiation without an increase in procedure time.

Incidence of Autoimmunity in Patients (pts) with Low-Risk (LR) Myelodysplastic Syndrome (MDS): 10 Years Follow-up

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4931-4931
Author(s):  
Ahmed Elkhanany ◽  
Curtis A. Hanson ◽  
Mrinal Patnaik ◽  
Michelle Elliott ◽  
Mark Litzow ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Autoimmune Diseases ◽  
Who Classification ◽  
Conflicts Of Interest ◽  
World Health ◽  
Treatment Modalities ◽  
Bone Marrow Biopsies ◽  
Group 2 ◽  
Group 1

Abstract Abstract 4931 Background: Autoimmunity, evidenced by positive serology or autoimmune diseases, has been noted to co-exist in pts with MDS. Autoimmune dysfunction has been found in some pts with a variant of MDS called hypocellular MDS, where immune suppressant medications have role in treatment. Clinical implications of AI on survival are not well described. Aim: To study clinical influence of autoimmunity on pts with LR-MDS. Methods: All adult pts diagnosed with LR (RCUD, RARS, and RCMD) MDS at the Mayo Clinic between 1996 to 2000 were studied. Retrospective data collection included pts' demographics, laboratory tests, bone marrow biopsies, treatment modalities and survival information. Autoimmunity (AI) was considered present if pts had evidence of positive serological testing (such as rheumatoid factor (RF), anti-nuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA)) and/or were diagnosed with autoimmune diseases (such as rheumatoid arthritis, vasculitis, autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP)). IRB approval was obtained in accordance with Helsinki Declaration. Chi-Square, t-test and Anova were used for comparatives between groups, and Kaplan-Meier test was applied for survival estimates using JMP 9. 0 software. Results: A total of 134 adult pts were found to have LR-MDS at the time of their diagnosis. Sixty-six percent (89) were males, 13% (17) had antecedent hematological disease (AHD), and only 7% (9) had prior radio- or chemotherapy. Thirty-nine (29%) had evidence of AI. At the time of diagnosis, pts' median Hgb was 9. 3 g/dL, white blood cells (WBC) 4. 1×109/L, and platelets 151×109/L. On comparison, there was no difference between pts with AI (group 1) to the rest of the sample (group 2) (p = 0. 12, 0. 85 and 0. 23, respectively). Bone marrow cytogenetics were abnormal in 42% (56) pts, with 44 pts have one cytological anomaly, and only 2 have four anomalies. Twenty-four pts (18%) had RCUD, 60 (44%) RARS and 50 (37%) RCMD, as defined by World Health Organization (WHO) classification (Vardiman et al, 2008). Karyotype anomalies within the three WHO classes were found in 12/19 pts (63%), 15/52 pts (29%), and in 29/42 pts (70%), respectively. Of note, among those with karyotype anomalies, the mean number of cytogenetic abnormalities was significantly different across the three categories (F=6. 89, p=. 0014), with means of 0. 5, 0. 3, and 0. 9 respectively. Seven pts (5%) progressed into acute myeloid leukemia. Seventy percent of pts (94) remained as stable disease. Of the 134 pts studied, 39 (29%) were found to have evidence of AI, with 24/48 (50%) had abnormal serological tests, and 29/134 (21%) had an autoimmune disease. When tested, positive RF was found in 7/25 (28%), ANA in 14/42 (33%), anti dsDNA in 1/11 (9%), anti SS-A/-B in 2/3 (66%), ANCA in 1/12 (8%), anti-smooth muscle in 1/2 (50%), and anti-histone in 1 pt. As per autoimmune diseases, rheumatoid arthritis was identified in 6 pts (4%), vasculitides in 9 (7%), AIHA in 4 pts (3%), Sjögren syndrome in 3 (2%), myositis in 2 (1. 4%), ITP in 2 pts (1. 4%). There was no difference in AI frequency based on WHO classification (p 0. 17) or based on cytogenetic grouping (p 0. 37). Overall survival in pts with LR-MDS was found to be lower in group 1 as compared to group 2 but did not reach statistical significance (p=0. 109), with median survival of 40 months and 81 months, respectively. Conclusion: AI is a frequent finding in pts with LR-MDS, seen in up to 29% of pts. On comparison there was no difference in hematological parameters of both groups with or without AI (CBC, cytogenetics, and WHO classification). There was no survival difference in LR-MDS pts with AI compared to pts without AI. Larger size studies are needed to confirm our findings. Disclosures: No relevant conflicts of interest to declare.

The Certainty of a Post-Bone Marrow Diagnosis: A Study of the Yield of Bone Marrow Biopsies in a Community Hospital Setting

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-35
Author(s):  
Manasi M. Godbole ◽  
Peter A. Kouides
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Fever Of Unknown Origin ◽  
Conflicts Of Interest ◽  
Diagnostic Yield ◽  
Hospital Setting ◽  
Unknown Origin ◽  
Nutritional Deficiencies ◽  
Bone Marrow Biopsies

Introduction: Most studies on the diagnostic yield of bone marrow biopsy including the one by Hot et al. have focused on the yield of bone marrow biopsies in diagnosing the source of fever of unknown origin. However, there have not been any studies performed to our knowledge looking at overall practice patterns and yield of bone marrow biopsies for diagnoses other than fever of unknown origin. We aim to determine the most common indications for performing bone marrow biopsies in a community-based teaching hospital as well as the yield of the biopsies in patients with specified and unspecified pre-test indications to estimate the rate of uncertain post-test diagnoses. Methods: We performed a retrospective data collection study at Rochester General Hospital, NY. A comprehensive search was conducted in our electronic medical data to identify all patients who underwent bone marrow biopsies over a 5 year period from January 2011 - December 2016 for indications other than fever of unknown origin. Patient data including demographics, pre-bone marrow biopsy diagnosis and post-bone marrow diagnosis was obtained. All patients above the age of 18 who underwent bone marrow biopsy for indications other than fever of unknown origin or follow up treatment of a hematological malignancy were included. Results: A total of 223 biopsies were performed. The median age was 59 years (age range- 23-95). One hundred and sixteen patients were male and 107 were female. The most common indications for performing bone marrow biopsy were evaluation of the following possible conditions: multiple myeloma (n=54), myelodysplastic syndrome [MDS] (n=47), lymphoma (n=28) and leukemia (n=18) as well as non-specific indications such as pancytopenia (n=40), anemia (n=22) and thrombocytopenia (n=11). The proportion of cases confirmed by bone marrow biopsy was 45/54 (83%) with the pre-marrow diagnosis of multiple myeloma, 34/47 cases (72%) with the pre-marrow diagnosis of MDS, 15/18 (83%) with the pre-marrow diagnosis of leukemia and 13/28 (46%) in those with the pre-marrow diagnosis of rule out lymphoma. Thirteen cases (18%) with possible MDS had post-bone marrow diagnoses of leukemia, anemia of chronic disease, myelofibrosis or medication-related changes. Five out of twenty two cases (23%) for anemia and 3/11 cases (27%) for thrombocytopenia without otherwise specified pre-bone marrow etiology had uncertain diagnosis after bone marrow biopsy. Conclusion: In about a fifth of patients necessitating a bone marrow, the diagnosis is discordant and can be surprising. It is also worth reporting that in these discordant results, non-hematological causes such as medications, anemia due to chronic diseases or conditions such as cirrhosis or splenomegaly from other etiologies were among the final diagnoses. Interestingly, 20% of the patients with unspecified pre-bone marrow diagnoses such as anemia or thrombocytopenia in our study had an unclear post-bone marrow diagnosis despite undergoing bone marrow biopsy. Our findings are a reminder that the bone marrow exam does not always lead to a definitive diagnosis and the need by exclusion to include in the differential non-hematological etiologies such as nutritional deficiencies, chronic kidney disease or autoimmune disorders. Disclosures No relevant conflicts of interest to declare.

Frameless ROSA® Robot-Assisted Lead Implantation for Deep Brain Stimulation: Technique and Accuracy

2019 ◽  
Vol 19 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Lannie Liu ◽  
Sarah Giulia Mariani ◽  
Emmanuel De Schlichting ◽  
Sylvie Grand ◽  
Michel Lefranc ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Ct Scans ◽  
X Rays ◽  
Robot Assisted ◽  
Lead Position ◽  
The Mean ◽  
Group 2 ◽  
Deep Brain ◽  
Group 1

Abstract BACKGROUND Frameless robotic-assisted surgery is an innovative technique for deep brain stimulation (DBS) that has not been assessed in a large cohort of patients. OBJECTIVE To evaluate accuracy of DBS lead placement using the ROSA® robot (Zimmer Biomet) and a frameless registration. METHODS All patients undergoing DBS surgery in our institution between 2012 and 2016 were prospectively included in an open label single-center study. Accuracy was evaluated by measuring the radial error (RE) of the first stylet implanted on each side and the RE of the final lead position at the target level. RE was measured on intraoperative telemetric X-rays (group 1), on intraoperative O-Arm® (Medtronic) computed tomography (CT) scans (group 2), and on postoperative CT scans or magnetic resonance imaging (MRI) in both groups. RESULTS Of 144 consecutive patients, 119 were eligible for final analysis (123 DBS; 186 stylets; 192 leads). In group 1 (76 patients), the mean RE of the stylet was 0.57 ± 0.02 mm, 0.72 ± 0.03 mm for DBS lead measured intraoperatively, and 0.88 ± 0.04 mm for DBS lead measured postoperatively on CT scans. In group 2 (43 patients), the mean RE of the stylet was 0.68 ± 0.05 mm, 0.75 ± 0.04 mm for DBS lead measured intraoperatively; 0.86 ± 0.05 mm and 1.10 ± 0.08 mm for lead measured postoperatively on CT scans and on MRI, respectively No statistical difference regarding the RE of the final lead position was found between the different intraoperative imaging modalities and postoperative CT scans in both groups. CONCLUSION Frameless ROSA® robot-assisted technique for DBS reached submillimeter accuracy. Intraoperative CT scans appeared to be reliable and sufficient to evaluate the final lead position.

scholarly journals Intracoronary Injection of CD133-Positive Enriched Bone Marrow Progenitor Cells Promotes Cardiac Recovery After Recent Myocardial Infarction

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Jozef Bartunek ◽  
Marc Vanderheyden ◽  
Bart Vandekerckhove ◽  
Samer Mansour ◽  
Bernard De Bruyne ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Left Ventricular ◽  
Recent Myocardial Infarction ◽  
Stent Restenosis ◽  
Intracoronary Administration ◽  
Group 2 ◽  
In Stent Restenosis ◽  
Group 1

Background— Bone marrow CD133-postive (CD133 + ) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133 + progenitor cells after intracoronary administration in patients with recent myocardial infarction. Methods and Results— Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133 + progenitor cells (12.6±2.2×10 6 cells) 11.6±1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0±2.6% to 52.1±3.5%, P <0.05), but only tended to increase in case-matched group 2 patients (from 44.3±3.1% to 48.6±3.6%, P =NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5±1.0% to 16.1±1.3%, P <0.05) but remained unchanged in group 2 patients (from 11.1±1.1% to 12.7±1.3%, P =NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0±4.1% to 22.5±4.1%, P <0.05) and no change in group 2 (from 25.0±3.0% to 22.6±4.1%, P =NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with 18 fluorodeoxyglucose in the infarct-related territory increased from 51.2±2.6% to 57.5±3.5% ( P <0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months. Conclusion— In patients with recent myocardial infarction, intracoronary administration of enriched CD133 + cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.

scholarly journals P338 The road to zero-fluoroscopy catheter ablation in recurrent paroxysmal atrial fibrillation using ICE: training, learning, getting closer

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
I A Minciuna ◽  
M Puiu ◽  
G Cismaru ◽  
S Istratoaie ◽  
G Simu ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Radiation Exposure ◽  
Radiofrequency Catheter Ablation ◽  
Procedure Time ◽  
Total Procedure Time ◽  
The Mean ◽  
Group 2 ◽  
Total Procedure ◽  
Zero Fluoroscopy ◽  
Group 1

Abstract INTRODUCTION Catheter ablation is the treatment of choice for patients with recurrent paroxysmal atrial fibrillation (AF) in which antiarrhythmic drug therapy has failed to maintain sinus rhythm. Since its first introduction, intracardiac echocardiography (ICE) has proved to increase the efficacy and reduce complications in AF catheter ablation. One of the main advantages of ICE in the electrophysiology laboratory is the reduction of radiation exposure, for both the patient and the physician. Multiple recent studies have shown the feasibility and safety of zero or near-zero fluoroscopy AF ablation, including transseptal puncture, and outlined the importance of using ICE under the support of 3D mapping systems in reducing radiation exposure. PURPOSE The aim of this study was to show whether the use of ICE reduced the radiation exposure and total procedure time in recurrent paroxysmal AF patients undergoing radiofrequency catheter ablation. METHODS Forty patients that undergone radiofrequency catheter ablation for recurrent paroxysmal AF between January 2018 and May 2019 were included. They were divided in two groups: Group 1 – 20 patients in which ICE was performed and Group 2 – 20 patients in which ablation was performed without ICE guidance. We compared the total ablation time and fluoroscopy dose and time between the two groups. The total ablation time was defined as the time from the groin puncture until the withdrawal of all catheters. RESULTS Among the 40 patients included, 28 were men (70%) and the mean age was 57 years old. The mean procedure time was similar between the two groups (175 ± 52.0 for group 1 and 193 ± 49.9 for group 2, p = 0.33). The difference between the two groups was observed in fluoroscopy dose (9914.13 ± 5018.14 vs. 14561.43 ± 7446.1, p = 0.02) and time (26.04 ± 12.5 vs. 40.52 ± 12.6, p = 0.001). We found that in both groups higher fluoroscopy dose was correlated with higher fluoroscopy time (R = 0.74, p = 0.0001 vs. R = 0.57, p = 0.008) and higher total procedure time (R = 0.63, p = 0.002 vs. R = 0.46, p = 0.03). Furthermore, there was also a correlation between higher fluoroscopy dose and time (R = 0.59, p = 0.005 vs. R = 0.58, p = 0.006). No severe procedure-related complications were recorded. CONCLUSIONS This study shows that the use of ICE for recurrent paroxysmal AF catheter ablation reduces radiation exposure by lowering the fluoroscopy dose and the time of exposure. As a result, by increasing the training and learning curve in low-experienced centers it may finally get us closer to the ideal zero or near-zero fluoroscopy ablation. Abstract P338 Figure. ICE-guided transseptal puncture

Short-term endocrine consequences of total body irradiation and bone marrow transplantation in children treated for leukemia

1993 ◽  
Vol 136 (2) ◽  
pp. 331-338 ◽  
Author(s):  
M. Ryalls ◽  
H. A. Spoudeas ◽  
P. C. Hindmarsh ◽  
D. R. Matthews ◽  
D. M. Tait ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Cranial Irradiation ◽  
Peak Serum ◽  
Gh Secretion ◽  
Igf I ◽  
Group 2 ◽  
Total Body ◽  
Serum Gh ◽  
Group 1

ABSTRACT We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation (group 1) and fourteen of whom had not (group 2), before and 6–12 months after total body irradiation (TBI) for bone marrow transplantation in leukaemia. Fourier transformation demonstrated that group 1 children had a faster periodicity of GH secretion before TBI than group 2 children (160 vs 200 min) but the amplitude of their GH peaks was similar. There were no differences between the groups in circadian cortisol rhythm, serum concentrations of insulin-like growth factor-I (IGF-I), sex steroids and basal thyroxine (T4). The peak serum GH concentrations observed after insulin-induced hypoglycaemia were similar between the two groups but the majority of patients had blunted responses. TBI increased the periodicity of GH secretion in both groups (group 1 vs group 2; 140 vs 180 min), but the tendency to attenuation of amplitude was not significant. There were no significant changes in the peak serum GH concentration response to insulin-induced hypoglycaemia which remained blunted. Serum IGF-I, sex steroid, cortisol or T4 concentrations were unchanged. Low-dose cranial irradiation has an effect on GH secretion affecting predominantly frequency modulation leading to fast frequency, normal amplitude GH pulsatility. This change is accentuated by TBI. In patients with leukemia, there is a marked discordance between the peak serum GH response to insulin-induced hypoglycaemia compared with the release of GH during 24-h studies, irrespective of the therapeutic regimen used. Pharmacological assessment of GH reserve needs to be interpreted with caution in such situations. Journal of Endocrinology (1993) 136, 331–338

Mobilization of Stem Cells from the Bone Marrow Is Required for Neovascularization of Ischemic Limbs in Mice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4233-4233
Author(s):  
Jeong-A Kim ◽  
Chang -Hoon Lee ◽  
Jin-A. Yoon ◽  
Woo-Sung Min ◽  
Chun-Choo Kim
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Hind Limb Ischemia ◽  
Ischemic Limb ◽  
Group 3 ◽  
Group 2 ◽  
Surgically Induced ◽  
Group 1

Abstract We examined whether the injection of bone marrow mononuclear cells (BM-MNCs) or mesenchymal stem cells (MSCs) might augment angiogenesis and collateral vessel formation in a mouse model of hind limb ischemia. C57BL/6 BM-MNCs were isolated by centrifugation through a Histopaque density gradient and MSCs were obtained from C57BL/6 bone marrow and cultured in low-glucose DMEM media. Unilateral hind limb ischemia was surgically induced in C57BL/6 mice (control; n=4), and autologous BM-MNCs (Group 1; n=4, 1.8±0.2 x107/animal) or MSCs (Group 2; n=4, 1.0±0.14 x106/animal) or BM-MNCs and MSCs (Group 3; n=4, 2.3±0.1 x107 and 1.1±0.21 x106/animal) were transplanted into the ischemic tissue. Six weeks after transplantation, the group 1, group 2 and group 3 had a higher capillary/muscle ratio (0.82±0.12 vs 0.85±0.08 vs 0.97 ±0.03) than control (0.46±0.12, p&lt;0.05) (Fig. 1). This result suggested that direct local transplantation of autologous BM-MNCs or MSCs seems to be a useful strategy for therapeutic neovascularization in ischemic tissues. Next, we evaluated whether bone marrow derived stem cells were participated in the process of local injected stem cells forming new vessels. In general, mobilizing stem cells from bone marrow to local site, MMP-9 has been known as an important molecule. So we used the MMP-9 deficient KO mice and wild type, 129SvEv mice were used in the experiments. Autologous BM-MNCs and MSCs were transplanted into the ischemic limb in MMP-9 (−/−) (n=4) after unilateral hind limb ischemia was surgically induced and then the same experiments was done in MMP-9 (+/+) mice (n=4). The number of the injected BM-MNCs and MSCs was 2.2±0.05 x107 and 0.87±0.17 x106/animal in MMP-9 (−/−). And the number of the injected BM-MNCs and MSCs was 2.1±0.17 x107 and 0.98±0.09 x106/animal in MMP-9 (+/+). No difference was seen in the BM-MNCs and MSCs were injected or not (0.52±0.07 vs 0.49±0.03,) in MMP-9 (−/−). But, in the case that BM-MNCs and MSCs were injected, the higher capillary/muscle ratio was seen in MMP-9 (+/+) compared to control (0.86 ±0.09 vs 0.49±0.03, P&lt;0.05) (Fig 2). This data indicated that the mobilization of bone marrow derived stem cells would have an important role in the neovasculrization although the stem cells were injected directly into the muscle of ischemic limb. Figure Figure Figure Figure

Dasatinib Has Activity in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL/SLL), a Phase II Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3162-3162 ◽  
Author(s):  
Philip C. Amrein ◽  
Eyal Attar ◽  
Tak Takvorian ◽  
Ephraim Hochberg ◽  
Karen K. Ballen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Performance Status ◽  
Lymphocytic Leukemia ◽  
Ct Scans ◽  
Fish Analysis ◽  
Ecog Performance Status ◽  
Bone Marrow Biopsies ◽  
Lyn Kinase ◽  
Grade 3

Abstract Background: Preclinical studies have shown that CLL cells overexpress lyn kinase protein, and in vitro inhibition of lyn kinase leads to apoptosis of the CLL cells (Contri, J Clin Invest 2005). Because dasatinib has been shown to inhibit lyn kinase in CML cells at concentrations easily achievable in patients, we undertook this phase II study in patients with previously treated CLL/SLL. Methods: Patients were required to be over 18 years of age, have a diagnosis of CLL/SLL by flow cytometry or immunohistochemistry, and have failed either 1 course of treatment with a fludarabine-containing regimen or 2 non-fludarabine containing regimens. The starting dose of dasatinib was 140 mg daily by mouth. This dose could be reduced to 100 mg or 80 mg daily for toxicity. At baseline all patients had bone marrow biopsies and CT scans, and these were repeated at 2 months. Sequential blood and bone marrow samples were tested for lyn kinase activity. Results: Among the 15 patients enrolled there were 10 male and 5 female subjects with a median age of 59 years (40–78 years). ECOG performance status was 0 in 9 subjects, 1 in 3, and 2 in 3 subjects. All patients had previously received fludarabine, and 5 patients required treatment within 6 months of their last regimen. The median number of prior treatments was 3 (range: 1 to 7). By cytogenetic/FISH analysis there were 5 patients with del(17p) and 6 patients with del(11q). All patients required treatment by NCI–WG criteria. The major toxicity encountered was myelosuppression: grade 3 + 4 neutropenia in 10 subjects, grade 3 + 4 thrombocytopenia in 4 subjects. Gastrointestinal toxicity was minor with only 1 subject experiencing grade 3 diarrhea. Other toxicities: 1 patient had a grade 2 pleural effusion, 1 patient had a transient serum K=9.9 (likely an artifact of high white count and without clinical sequelae), and 1 patient had a transiently prolonged QTc of 516 ms. There were no fatal events, and all toxicities were reversible. The median duration on study was 10 weeks, but 5 responding or stable patients have remained on treatment for over 9 months. Partial responses (PR) by NCI-WG criteria were achieved in 2 of the 15 patients (13% with 90% CI 2%–36%). An additional 2 patients would have qualified for PR (lasting &gt;2 months) except for myelosuppression. Among the remaining 11 patients, 6 had nodal responses (2 CR and 4 PR) by physical exam (PE) without a 50% reduction in lymphocytosis. CT scans confirmed nodal responses in 3 of the 10 patients with nodal responses by PE. The relationship between clinical response and lyn kinase, bcl-2, and mcl-1 expression will be presented at the meeting. Conclusions: Dasatinib has modest activity in CLL, and combinations with standard agents, perhaps in an intermittent schedule, should be considered in subsequent trials.

Comprehensive Workup of Myelodysplastic Syndromes: Comparing Targeted DNA Sequencing, Oligo/SNP Microarray and Higher Dimensional Flow Cytometry.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2519-2519
Author(s):  
Marilyn L Slovak ◽  
Ya-Hsuan Hsu ◽  
Hseuh-Hua Chen ◽  
Yongbao Wang ◽  
Philip N Mowrey ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Myelodysplastic Syndromes ◽  
Marker Panel ◽  
Snp Microarray ◽  
Dimensional Flow ◽  
Higher Dimensional ◽  
Cd56 Expression ◽  
Group 2 ◽  
Group 1

Abstract Abstract 2519 The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic diseases characterized by ineffective hematopoiesis, cytopenias, and dysplasia in the erythroid, myeloid or megakaryocytic lineages. However, MDS can be difficult to recognize when blasts are not increased. Subtle phenotypic shifts in early MDS can be detected using higher-dimensional flow cytometry, by DNA mutation profiling, or by detection of a range of large and small genomic abnormalities by genome-wide SNP microarray. We compared the diagnostic potential of these 3 modalities in a group of 33 patients >50 years old referred for workup of cytopenia (17 blood, 16 bone marrow aspirate samples). Platforms compared were an oligo/SNP 2.6 million-probe microarray (Cytoscan HD, Affymetrix), a 161-amplicon targeted exome sequencing assay that includes TET2, ASXL1, EZH2, IDH1, IDH2, JAK2, KRAS, and NRAS (Ion Torrent protocol with PCR/product harvesting using Fluidigm Access Array), and flow cytometry using a 6-color, 22-marker panel and an 8-color, 26-marker panel (BD FACS Canto II). Nine patients had increased myeloblasts consistent with MDS (up to 20% in blood or 5%–20% in bone marrow)(Group 1), 23 had cytopenia(s) without increase in blasts (Group 2); an additional patient had a B-cell lymphoma. Group 1 patients all had aberrations detected by at least 1 of the 3 modalities (Table). In Group 2, 1 patient had unequivocal alterations by all 3 methods, 8 by 2 assays, and 6 by 1 assay; the other 9 patients had no unequivocal aberrations (Table). Copy-neutral loss of homozygosity (CN-LOH) of >10 Mb was the sole genomic aberration observed in 3 cases of cytopenia without an increase in blasts (affecting 5q, 7q and 20q), whereas others had losses/gains at chromosomal sites characteristic of MDS [i.e., partial 1q trisomy, del(5q), del(7q), +8, del(13q) and del(20q)]. Genes with mutations detected by sequencing Submicroscopic gene deletions or CN-LOH detected by array Flow cytometry abnormality Group 1: Cytopenia(s) with increased blasts (n=9) ASXL1 (2)
 TET2 (1)
 KRAS (1)
 EZH2 (1)
 JAK2 (1) BRAF (3)
 EZH2 (3)
 FLT3 (2)
 TP53 (2)
 RPS14 (2)
 EPO (2)
 ASXL1 (1)
 ETV6 (1) Myeloid maturation (9/9)
 CD56 expression (5/9) Group 2: Cytopenia(s) without increased blasts (n=24) TET2 (4)
 ASXL1 (2)
 KRAS (2)
 IDH2 (1) BRAF (2)
 EZH2 (2)
 TET2 (2)
 ASXL1 (1)
 ETV6 (1)
 RPS14 (1)
 EPO (1)
 TP53 (1) Myeloid maturation (9/24)
 CD56 expression (1/24) Among older MDS patients with cytopenias(s) but no increase in blasts, phenotypic and genomic profiling can frequently identify aberrations similar to those seen in higher-grade MDS. Locations of some submicroscopic deletions included loci commonly implicated in MDS pathogenesis. Detection of these aberrations in peripheral blood should facilitate the diagnosis of early MDS. Disclosures: No relevant conflicts of interest to declare.

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