A humanized unconjugated antibody targeting CD33 (SGN-33; huM195) is active in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16500-16500
Author(s):  
A. Raza ◽  
N. Galili ◽  
J. G. Jurcic ◽  
G. J. Roboz ◽  
B. L. Wood ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Monocytic Cells ◽  
Complement Dependent Cytotoxicity ◽  
The Mean ◽  
Higher Doses ◽  
Dose Limiting Toxicity ◽  
Bone Marrow Blasts

16500 Background: CD33 is a sialoglycan protein expressed on normal myeloid and monocytic cells as well as the vast majority of myeloid malignancies. A humanized antibody has been developed that recognizes CD33 and induces antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In prior clinical testing, this antibody led to significant reductions in blasts in patients with relapsed and refractory AML. Methods: A phase I single-arm dose escalation trial was initiated at multiple sites to assess the safety, immunogenicity, pharmacokinetics, and activity of SGN-33 at higher doses than previously tested. Cohorts of 3–6 patients with advanced MDS or AML will receive intravenous SGN-33 at weekly doses of 1.5 to 8 mg/kg over 5 weeks. Clinical response will be determined by bone marrow morphology and hematologic improvement. Responding patients will be eligible for 4 additional infusions. Results: Treatment of 6 patients at 1.5 mg/kg/wk has been well-tolerated, with no dose-limiting toxicity or related adverse events > grade 2. The median age is 79.5 years (range 52–88), and all patients were previously untreated. One patient discontinued treatment because of refractory thrombocytopenia, unrelated to SGN-33. CD33 saturation of the bone marrow blasts after 2 infusions ranged from 27% to 84% with an average of 55%. The mean change in bone marrow blasts by flow cytometry after 2 weeks was −9% (range −68% to +44%; N = 5), and the marrow monocytes changed by −39% (range −90% to +86%; N = 5). Two patients have completed re-staging after cycle 1. Blasts decreased from 29% to 12% in an 88 year-old woman with AML and from 11% to 9% in a 79 year-old man with RAEB. Conclusions: SGN-33 is well tolerated at 1.5 mg/kg/wk, and dose escalation is ongoing. Antitumor activity was seen in elderly patients with previously untreated AML and MDS. Incomplete saturation of the CD33 on bone marrow blasts suggests that higher doses may improve efficacy. SGN-33 holds promise for the treatment of patients with myeloid malignancy who are ineligible for aggressive therapy. [Table: see text]

Phase I Trial of Radiosurgery Dose Escalation Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma

Neurosurgery ◽  
2017 ◽  
Vol 83 (3) ◽  
pp. 385-392 ◽  
Author(s):  
Mahmoud Abbassy ◽  
Symeon Missios ◽  
Gene H Barnett ◽  
Cathy Brewer ◽  
David M Peereboom ◽  
...  
Keyword(s):  
Single Dose ◽  
Dose Escalation ◽  
Prospective Trial ◽  
Recurrent Glioblastoma ◽  
Acute Side Effect ◽  
Bevacizumab Treatment ◽  
Prescription Dose ◽  
The Mean ◽  
Higher Doses ◽  
Dose Limiting Toxicity

Abstract BACKGROUND The effectiveness of stereotactic radiosurgery (SRS) for recurrent glioblastoma (rGBM) remains uncertain. SRS has been associated with a high risk of radionecrosis in gliomas. OBJECTIVE To determine the safety of dose escalation of single-fraction radiosurgery for rGBM in the setting of bevacizumab therapy. METHODS We conducted a prospective trial to determine the safety and synergistic benefit of higher doses of SRS administered with bevacizumab for rGBM. A single dose of bevacizumab was given prior to SRS and continued until progression. Dose-limiting toxicity was evaluated in successive cohorts of 3 patients. RESULTS Seven males and 2 females entered the study. The maximum linear diameter of the enhancing tumor was 2.58 cm (2.04-3.09). Prescription dose was escalated from 18 to 22 Gy. The radiosurgery target was chosen before the first dose of bevacizumab, about 1 wk prior to SRS treatment. Pre-SRS bevacizumab treatment was associated with a reduction of the mean volume of the enhancing lesion from 4.7 to 2.86 cm3 on the day of SRS (P = .103). No patient developed an acute side effect related to SRS treatment. The combination of SRS and bevacizumab resulted in a partial response in 3 patients and stable disease in 6 patients. Median progression-free and overall survival were 7.5 and 13 mo, respectively. CONCLUSION A single dose of bevacizumab prior to SRS permitted safe prescription dose escalation up to 22 Gy for rGBM. Further evaluation of the efficacy of SRS for rGBM should be performed in the setting of bevacizumab treatment.

scholarly journals AB0370 SAFETY OF CS20AT04, A HAPLOIDENTICAL ALLOGENEIC BONE MARROW-DERIVED MESENCHYMAL STEM CELLS, IN A PHASE 1 STUDY IN LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1485.2-1485
Author(s):  
C. B. Choi ◽  
T. Y. Lee ◽  
K. S. Kim ◽  
S. C. Bae
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Lupus Nephritis ◽  
Dose Escalation ◽  
Phase 1 ◽  
Allogeneic Bone Marrow ◽  
Additional Patient ◽  
Allogeneic Bone ◽  
Dose Limiting Toxicity

Background:Mesenchymal stem cells are known to have immunomodulatory properties and may potentially have therapeutic effect in lupus nephritis. Mesenchymal stem cells form a haploidentical donor are an attractive cell sourceObjectives:CS20AT04, a haploidentical allogeneic bone marrow-derived mesenchymal stem cell, was evaluated in patients with lupus nephritis for safety and tolerability.Methods:This was a single-arm phase 1 dose-escalation trial of CS20AT04 in adult patients with lupus nephritis (NCT03174587). A 3 + 3 design was used for dose escalation. The starting dose was 2.0 x 106 cells/kg and was escalated to 3.0 x 106 cells/kg if there no dose-limiting toxicity. The primary objective was to determine the maximum tolerated dose and evaluate the safety and tolerability at 28 days after the infusion.Results:Seven patients were enrolled in the study. Patients received CS20AT04 through intravenous infusion. The initial dose of 2.0 x 106 cells/kg was administered for the first 3 patients without any dose limiting toxicity. There was 1 patient who were not administered the full 2.0 x 106 cells/kg dose due to technical error during infusion. The patient did not show dose limiting toxicity, but 1 additional patient was enrolled to have 3 patients who received the full 2.0 x 106 cells/kg dose before escalating to the next level dose. The dose of 3.0 x 106 cells/kg was administered for the next 3 patients without any dose limiting toxicity. Three adverse events were reported (1 diarrhea, 1 toothache, and 1 arthralgia) and they were all NCI-CTC grade I events.Conclusion:CS20AT04 was well tolerated in single dose up to 3.0 x 106 cells/kg in patients with lupus nephritis.Acknowledgments:This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0778).Disclosure of Interests:Chan-Bum Choi: None declared, Tae Yong Lee Shareholder of: Corestem Inc, Employee of: Corestem Inc, Kyung Suk Kim Shareholder of: Corestem Inc, Employee of: Corestem Inc, Sang-Cheol Bae: None declared

scholarly journals Kinetics of bone marrow blasts during induction and achievement of complete remission in acute myeloid leukemia

Haematologica ◽  
2008 ◽  
Vol 93 (8) ◽  
pp. 1263-1265 ◽  
Author(s):  
M. Yanada ◽  
G. Borthakur ◽  
F. Ravandi ◽  
C. Bueso-Ramos ◽  
H. Kantarjian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Kinetics Of ◽  
Bone Marrow Blasts ◽  
Acute Myeloid

Phase II Evaluation of the Tyrosine Kinase Inhibitor MLN518 in Patients with Acute Myeloid Leukemia (AML) Bearing a FLT3 Internal Tandem Duplication (ITD) Mutation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1792-1792 ◽  
Author(s):  
Daniel J. De Angelo ◽  
Richard M. Stone ◽  
Mark L. Heaney ◽  
Stephen D. Nimer ◽  
Ronald Paquette ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Phase Ii ◽  
Plasma Concentrations ◽  
Remission Induction ◽  
Western Blots ◽  
Adequate Treatment ◽  
The Mean ◽  
Trough Plasma ◽  
Bone Marrow Blasts

Abstract MLN518 is a small molecule inhibitor of FLT3, PDGFR and c-Kit that is currently being evaluated as a therapy for AML. Previous phase I evaluation of MLN518 showed that it inhibits the phosphorylation of both wild-type and ITD-mutated FLT3 in patients’ leukemic blasts with an IC90 in the range of 100–175 ng/mL. Anti-leukemic activity was also observed, with decreases in both peripheral and bone marrow blasts. Dose-limiting toxicity, consisting of reversible general muscular weakness and/or fatigue was associated with trough plasma MLN518 concentrations > 1000 ng/mL. We are now conducting a phase II study of MLN518 in patients with relapsed or refractory AML and in untreated patients with AML considered unfit for standard AML therapies. Eligibility requires demonstration of the FLT3 ITD mutation in the patient’s blasts. All patients are treated with MLN518 at an initial dose of 525 mg po bid, with provision for dose reduction if MLN518-associated weakness occurs. Twenty patients have been treated with MLN518 in this study, eighteen of whom are currently evaluable (2 patients have recently started therapy). Toxicities associated with MLN518 therapy have included weakness/fatigue, QTc prolongation (relationship to MLN518 uncertain), and nausea and vomiting. MLN518 plasma concentration-time data for the first fourteen patients demonstrates that all patients achieved steady-state trough plasma concentrations > 150 ng/mL. Both inter- and intra-subject variability (%CV) in trough steady-state concentrations were < 30%. Assessment of total and phosphorylated FLT3 in leukemic blasts isolated from peripheral blood was possible in 4 patients. Western blots from blasts obtained before and after MLN518 dosing demonstrated either partial or complete inhibition of FLT3 phosphorylation with MLN518 plasma concentrations > 130 ng/mL. Of the eighteen evaluable patients, response could not be assessed in three because intercurrent illness and/or MLN518-associated toxicity precluded adequate treatment with MLN518 (≥ 14 days). Seven patients experienced progressive AML without evidence of any anti-leukemic effect. Two patients had stable disease for ≥ 50 days and subsequently underwent bone marrow transplantation. Although no complete or partial remissions have been observed, 6 patients have demonstrated evidence of an anti-leukemic effect with decreases in both peripheral and bone marrow blasts of 1-3 months duration. In these 6 patients the mean decrease in the absolute peripheral blast count was 92%, with a range of 85–100%. The mean decrease in the bone marrow blast percentage was 62%, with a range of 44–94%. We conclude that MLN518 has anti-leukemic activity in FLT3 ITD-mutated AML and should be further evaluated as a component of remission-induction and/or maintenance therapy in this disease.

Consistency Of RQ-PCR Analysis Results In Peripheral Blood and Bone Marrow Samples In Chronic Myeloid Leukemia Patients: Relevance From The Practical and Logistic Point Of View

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2592-2592
Author(s):  
Giovanna Rege-Cambrin ◽  
Carmen Fava ◽  
Enrico Gottardi ◽  
Filomena Daraio ◽  
Emilia Giugliano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Wilcoxon Test ◽  
Molecular Response ◽  
Two Samples ◽  
The Mean

Abstract Background Consensus has been achieved that standardized molecular quantitative analysis (RQ-PCR) on peripheral blood (PB) is a suitable method for monitoring residual disease in chronic myeloid leukemia (CML). However, BM is still obtained at specific timepoints, and in a number of cases, only bone marrow (BM) sample collected for cytogenetic analysis is available. Being one of the laboratory involved in the standardization process of molecular monitoring for CML patients, we decided to perform a comparative analysis of BM and PB samples in order to evaluate the consistency of the results. Methods Between March 2009 and January 2013, 230 consecutive RQ-PCR tests to assess BCR-ABL transcript levels from simultaneously collected PB and BM samples were performed (for a total of 460 analysis) on 77 patients affected by Ph+ CML in chronic phase treated in our center. All samples were analyzed in the same laboratory following international guidelines (Cross N, Leukemia 2012) and results were expressed according to the International Scale; ABL1 was used as control gene. Time from blood-drawn to processing was within 3-4 hours. Results Among the 230 pairs, 3 were considered as not evaluable because of inadequate material; for the purpose of this study, the remaining 227 pairs were considered as “evaluable”. 204 pairs were classified as “fit” when both BM and PB ABL amplification resulted in more than 10.000 copies; 23 pairs were considered unfit for ABL1 <10.000 in either one of the two samples (21) or both (2). The mean number of ABL1 copies in all evaluable samples was 35.639 for BM (SD 21.465) and 30.958 for PB samples (SD 18.696). Correlation analysis was performed on the whole population and in 4 subgroups: No Complete Cytogenetic Response (CCyR, 22%), CCyR without Major Molecular Response (MMR), (21.6%), CCyR with MMR (excluding patients with MR4 or better,19.8%), and CCyR with MR4 – MR4.5 (32,6%). Cytogenetic response was not available in 9 BM samples (4%), not included in the subgroup analysis. Spearman correlation of BCR/ABL ratio values between PB versus BM paired samples resulted in a statistically significant correlation in all groups, both for evaluable and fit pairs. Correlation was stronger in samples that were not in MMR or better (table 1 and figure 1). The Wilcoxon test showed that the mean difference of BCR/ABL values between paired PB and BM samples was not significantly different from zero (in evaluable and fit pairs by considering the whole population). Concordance was further analyzed by the K test which resulted in a coefficient equal to 0.627, corresponding to a notable degree of concordance. For patients in CCyR, agreement on classification of response (MMR, MR4, MR4.5) between paired PB and BM samples was observed in 125/168 evaluable pairs; 22 out of the 43 evaluable cases of disagreement were due to technical failures (in 10 BM and 12 PB samples). In 14 of the remaining 21 cases, PB was more sensitive. Conclusions In a single center experience of molecular analysis, BCR/ABL ratio was highly consistent in BM and PB samples. In less than 10% of the cases a single test did not reach the required sensitivity of 10.000 ABL copies and the double testing allowed to obtain a valid result. This may be especially valuable in evaluating an early response (i.e. at 3 months), when the amount of disease has prognostic relevance. The analysis will be expanded to include samples coming from different centers to evaluate a possible role of timing and transport on data consistency. Disclosures: Saglio: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

Detection of Clonal Hematopoiesis in Cytopenic Patients Using Targeted Sequencing

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1654-1654
Author(s):  
Eric J. Duncavage ◽  
Jennifer O'Brien ◽  
Kiran R. Vij ◽  
Chris A Miller ◽  
Jin Shao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Diagnosis ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
World Health ◽  
Low Grade ◽  
Clonal Hematopoiesis ◽  
The Mean ◽  
Normal Cytogenetics ◽  
Bone Marrow Blasts

Abstract Introduction: The clinical diagnosis of myelodysplastic syndrome (MDS) relies on the presence of persistent cytopenias, not otherwise explained, and evidence of morphologic dysplasia in the bone marrow. Low grade MDS (bone marrow blasts <5%) is defined by the presence of morphologic dysplasia in at least 10% of cells in one or more cell lineage. Low grade MDS is particularly challenging to diagnose, as morphologic dysplasia may be subtle and is subject to high inter-observer variability. The ability to diagnose low grade MDS can be improved by incorporating cytogenetic evaluation of the bone marrow, especially in the setting of equivocal morphologic dysplasia. However, many MDS cases (up to 60%) lack cytogenetic abnormalities, limiting the overall utility of cytogenetics. Multiple recent studies have demonstrated that the majority of MDS patients (over 80% in some studies) harbor recurrent somatic mutations in a core group of genes. We sought to determine if targeted DNA sequencing of genes recurrently mutated in MDS and AML could be useful in the evaluation of cytopenic patients with a normal karyotype being evaluated for the possible diagnosis of MDS. Methods: We screened patients who presented for evaluation of MDS between 2002 and 2014 that had consented for sequencing studies and had banked samples. Patients were selected based on 1) World Health Organization defined cytopenia (WBC <1,800/µL, hemoglobin <10g/dL, platelets <100k/µL) in at least one lineage, 2) bone marrow blasts <5%, 3) WBC <14k/uL, 4) normal cytogenetics, and 5) absence of prior therapy for MDS. Bone marrow specimens were independently re-reviewed by two board certified hematopathologists. DNA was extracted from cryopreserved bone marrow and skin (to serve as a source of normal DNA) and enriched for a panel of 285 commonly mutated myeloid genes. Captured DNA libraries were sequenced on a HiSeq 2500 instrument with 2x101bp reads. The resulting data was analyzed for single nucleotide variants (SNVs) and insertions/deletions (indels) using VarScan2 in paired normal mode. Results: Thirty-eight patients met the selection criteria, and 30 of these had bone marrow aspirates available for morphologic review and were included in the study. A mean unique coverage depth of 913x was achieved for targeted genes and all reported variants had >50x coverage, variant allele fractions (VAFs) >3%, and minor allele frequencies (MAFs) < 1% in any population. Of the 30 sequenced cases, 25 had a somatic mutation in at least one gene (mean 3.3 mutations/case, range 1-10 mutations/case). The most commonly mutated gene was TET2 (7 cases), followed by ASXL1 (5 cases), EZH2 (4 cases), SRSF2 (4 cases), and U2AF1 (4 cases). Of the 285 sequenced genes, 44 were mutated in at least one case, and 14 were mutated in 2 or more cases. The mean VAF (variant reads/total reads) of detected mutations was 27% (range 3-98%). Morphologic review demonstrated definitive dysplasia (≥10% of cells in least one lineage) made by two pathologists in 18 of 30 cases (supporting the clinical diagnosis of MDS), no dysplasia in 6 of 30 cases, and equivocal dysplasia (where hematopathologists did not agree that dysplasia was ≥10%) in 6 of 30 cases. Thirteen of 18 cases (72%) with definitive dysplasia had a mutation, 5/6 cases (83%) without dysplasia had mutations, and 6/6 (100%) cases with equivocal dysplasia harbored somatic mutations. The mean VAF of mutations was 17.5% in cases without dysplasia, 29% in cases with equivocal dysplasia, and 28% in cases with definitive dysplasia. All of these groups included mutations in canonical MDS genes such as TET2, DNMT3A, SRSF2, RUNX1, and EZH2. Conclusions: In this cohort of 30 cytopenic patients with normal cytogenetics, 80% harbored a somatic mutation in at least one myeloid-associated gene. Somatic mutations were detected in 5 of 6 cases without definitive dysplasia (<10% dysplasia) and 6 of 6 cases with equivocal dysplasia. Notably, canonical MDS mutations were found even in the absence of dysplasia. These findings suggest that clonal hematopoiesis may be present in the majority of cytopenic patients independent of dysplasia, a finding that requires independent validation. Identification of somatic gene mutations in patients with morphologically equivocal MDS or cytopenic patients without definitive dysplasia provides a means for tracking clonal disease that could be used to monitor patients for subsequent development of definitive MDS. Disclosures Duncavage: DI&P Consulting: Consultancy; Cofactor Genomics: Consultancy. Jacoby:Sunesis: Research Funding; Novo Nordisk: Consultancy.

scholarly journals Phase I Trial of Targeted Alpha-Particle Therapy Using Actinium-225 (225Ac)-Lintuzumab (Anti-CD33) in Combination with Low-Dose Cytarabine (LDAC) for Older Patients with Untreated Acute Myeloid Leukemia (AML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5293-5293 ◽  
Author(s):  
Joseph G Jurcic ◽  
Farhad Ravandi ◽  
John M. Pagel ◽  
Jae H Park ◽  
B. Douglas Smith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Dose Escalation ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Phase I Trial ◽  
Particle Therapy ◽  
Employment Equity ◽  
Molecular Abnormalities ◽  
Equity Ownership

Abstract Background: Lintuzumab, a humanized anti-CD33 monoclonal antibody, targets myeloid leukemia cells but has only modest activity in AML. To increase the antibody’s potency yet avoid nonspecific cytotoxicity of β-emitting isotopes, 225Ac (t½=10 d), a radiometal that yields 4 α-particles, was conjugated to lintuzumab. A phase I trial showed that 225Ac-lintuzumab is safe at doses ≤ 3 µCi/kg and has anti-leukemic activity across all dose levels studied (Jurcic et al. ASH, 2011). We are conducting a multicenter, phase I dose-escalation trial to determine the maximum tolerated dose (MTD), toxicity, and biological activity of fractionated-dose 225Ac-lintuzumab in combination with LDAC. Patients and Methods: Patients ≥ 60 yrs who had untreated AML with poor prognostic factors, e.g., an antecedent hematologic disorder, unfavorable cytogenetic or molecular abnormalities, and significant comorbidities, were eligible. Patients received LDAC 20 mg twice daily for 10 d every 4-6 wks for up to 12 cycles. During Cycle 1, beginning 4-7 days after completion of LDAC, two doses of 225Ac-lintuzumab were given approximately one week apart. To prevent radiation-induced nephrotoxicity, patients were given furosemide while receiving 225Ac-lintuzumab and spironolactone for one year afterward. Results: Nine patients (median age, 76 yrs; range, 73-81 yrs) were treated. Seven patients (78%) had a history of myelodysplastic syndromes (MDS), for which five (56%) received prior therapy with hypomethylating agents (n=4) or allogeneic hematopoietic cell transplantation (n=1). One patient (11%) had chronic myeloid leukemia in a molecularly undetectable state at the time of AML diagnosis. Six patients (67%) had intermediate-risk cytogenetics, and three (33%) had unfavorable cytogenetics. The median CD33 expression was 76% (range, 45-100%). Patients received 225Ac-lintuzumab at doses of 0.5 (n=3) or 1 (n=6) μCi/kg/fraction. Total administered activity ranged from 68-199 μCi. The median number of cycles administered was 2 (range, 1-4). Dose-limiting toxicity was seen in one patient receiving 1 µCi/kg/fraction who had grade 4 thrombocytopenia with bone marrow aplasia persisting > 6 wks after receiving 225Ac-lintuzumab. Hematologic toxicities included grade 4 neutropenia (n=1) and thrombocytopenia (n=3). Grade 3/4 non-hematologic toxicities included febrile neutropenia (n=6), pneumonia (n=2), bacteremia (n=1), cellulitis (n=1), transient increase in creatinine (n=1), hypokalemia (n=1), and generalized weakness (n=1). Bone marrow blast reductions were seen in 5 of 7 patients (71%) evaluated after Cycle 1. Mean blast reduction was 61% (range, 34-100%). Three of the 7 patients (43%) had marrow blast reductions of ≥ 50%; however, no remissions were observed. Median progression-free survival (PFS) was 2.5 mos (range, 1.7-15.7+ mos). Median overall survival (OS) from study entry was 5.4 mos (range, 2.2-24 mos). For the 7 patients with prior MDS, median OS was 9.1 mos (range 2.3-24 mos). Conclusions: Fractionated-dose 225Ac-linutuzmab in combination with LDAC is feasible, safe, and has anti-leukemic activity. Dose escalation continues to define the MTD, with planned doses up to 2 µCi/kg/fraction. Additional patients will be treated at the MTD in the phase II portion of this trial to determine response rate, PFS, and OS. Disclosures Ravandi: Actinium Pharmaceuticals, Inc.: Research Funding. Pagel:Actinium Pharmaceuticals, Inc.: Equity Ownership, Research Funding. Park:Actinium Pharmaceuticals, Inc.: Research Funding. Wahl:Actinium Pharmaceuticals, Inc.: Research Funding. Earle:Actinium Pharmaceuticals, Inc.: Employment, Equity Ownership. Cicic:Actinium Pharmaceuticals, Inc.: Employment, Equity Ownership. Scheinberg:Actinium Pharmaceuticals, Inc.: Equity Ownership, Research Funding.

Author response for "Increased S100A8 expression in bone marrow plasma by monocytic cells from acute myeloid leukemia patients"

2019 ◽  
Author(s):  
Julie Mondet ◽  
David Laurin ◽  
Caroline Lo Presti ◽  
Marie‐Christine Jacob ◽  
Mathieu Meunier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Author Response ◽  
Monocytic Cells ◽  
Bone Marrow Plasma ◽  
Acute Myeloid
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