Durable Molecular Remission in Two Acute Promyelocytic Leukemia (APL) Patients Treated with Arsenic Trioxide at First Molecular Relapse.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1847-1847 ◽  
Author(s):  
Dan Douer ◽  
Laleh Ramezani ◽  
Kristy Watkins ◽  
Robert Louie ◽  
Martin S. Tallman
Keyword(s):  
Arsenic Trioxide ◽  
Liver Toxicity ◽  
Single Agent ◽  
Disease Free Survival ◽  
Rest Period ◽  
Clinical Relapse ◽  
Rt Pcr ◽  
History Of ◽  
Optimal Approach ◽  
Grade Iii

Abstract Background: The recurrent detection of the PML- RARα transcripts in APL patients in complete remission (CR) is predictive of clinical relapse. Intervention at the time of molecular relapse rather than at the time of overt clinical relapse may minimize the risks associated with the disease as well as treatment-related complications. Previous studies have shown that patients treated at molecular relapse had improved overall survival compared to patients treated at clinical relapse; however, the optimal approach to the treatment of molecular relapse has not yet been established. Arsenic trioxide is active as a single agent in APL patients who developed overt clinical relapse after treatment with ATRA and anthracycline chemotherapy. We evaluated the use of single agent arsenic trioxide in APL patients who are still in first hematological CR but have become RT-PCR positive. Methods: So far, 2 patients were studied, both females with the long form of RAR RARα (bcr1), aged 29 and 39 years. These patients had normal bone marrow morphology but were found to be RT-PCR positive twice in an interval of at least 2 months, while in first CR at 12 and 36 months, respectively. Arsenic trioxide, 0.15 mg/kg/dose, was administered intravenously for 5 days per week for 5 weeks (total of 25 doses) with a 3 to 6 week rest period between cycles up to a maximum of 4 cycles. Results: Both patients became PCR negative after the first cycle of arsenic trioxide. One patient completed four cycles of therapy. The second patient had a history of diabetes mellitus, received only 20 doses of the first cycle and was removed from the study because of grade III sensory neurotoxicity. The only other side effects were grade II headache in both patients and self-limited grade III liver toxicity in one patient. Both patients remain RT-PCR negative at 30 and 28 months after enrollment, respectively, without further therapy. Conclusions: Without treatment, these patients could be expected to have developed a clinical relapse within 4–10 months. Arsenic trioxide induced a durable second molecular relapse, extending disease-free survival and obviating the need for more intensive treatment, such as chemotherapy and stem cell transplantation.

First-line treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7073-7073
Author(s):  
A. Ghavamzadeh ◽  
K. Alimoghaddam ◽  
S. Ghaffari ◽  
S. Rostami ◽  
M. Jahani ◽  
...  
Keyword(s):  
Complete Remission ◽  
Arsenic Trioxide ◽  
Single Agent ◽  
Disease Free Survival ◽  
Early Mortality ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
One Year ◽  
First Line Treatment

7073 Background: Standard treatment of APL is ATRA plus chemotherapy but Arsenic Trioxide (ATO) is most potent single agent against APL cells. Role of ATO in first line therapy of APL needs to clarify. Methods: Between may 2000 and September 2006,we treated 141 new cases of APL(Median age 28±12.8 y/o min=11,max=71) by 2 hours iv infusion of 0.15mg/kg ATO until complete remission. Trial approved by IRB and consent form obtained. Diagnosis was by clinical and morphologic characteristics and confirmed by cytogenetic and RT-PCR for detection of t(15,17) and presence of PML-RARa. After complete remission patients received consolidation by 28 days infusion of ATO for one or four courses.(one consolidation one month after CR and for some patients second, third and forth consolidations one month after first one and two another , one year and two year after CR) Results: : complete remission observed in 121 cases(85.8%) and early mortality rate was14.9%(most common cause of early mortality was APL syndrome,61.9%).Median follow up was 28 months. For patients who achieve to complete remission,one, two and three year disease free survival were 95.6%± 2%, 76.9±4% and 57± 6%,respectively. Many relapsed patients salvaged again with ATO alone so, two and three years overall survival for this cohort was 95.6%±2% and 83.7%±4%. Increasing number of consolidation from one to four couldn’t increase DFS or OS in one and two years after CR. Conclusions: ATO is effective in treatment of new cases of APL. Introduction of ATO in first line treatment of APL(with or without ATRA plus chemotherapy) needs a multi center randomized clinical trial. No significant financial relationships to disclose.

New Cases of Acute Promyelocytic Leukemia Treatment by Arsenic Trioxide Alone and Their Long Term Follow up

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 506-506 ◽  
Author(s):  
Ardeshir Ghavamzadeh ◽  
Kamran Alimoghaddam ◽  
Shahrbano Rostami ◽  
Seyed Hamidolah Ghaffari ◽  
Mohamad Jahani ◽  
...  
Keyword(s):  
Complete Remission ◽  
Arsenic Trioxide ◽  
Conflicts Of Interest ◽  
Promising Result ◽  
Single Agent ◽  
Disease Free Survival ◽  
Long Term Follow Up ◽  
Wbc Count

Abstract Abstract 506 Long term follow-up of APL patients treated by ATRA and chemotherapy is available and shows promising results of DFS and OS. Although several studies show acceptable efficacy of Arsenic Trioxide in new cases of APL, its long term result needs better clarification. Materials and methods: one hundred ninety seven, new cases of APL treated by Arsenic trioxide (0.15 mg/kg daily i.v infusion till complete remission). After achieving to CR patients received 4 more courses of Arsenic trioxide as consolidation. Then patients followed by CBC and RT-PCR on peripheral blood for detection of MRD every three months or till relapse or death. Results: Morphologic complete remission rate was 85.8% and most common cause of remission failure was early death due to hemorrhage of APL differentiation syndrome.(14.7%) Most important prognostic factor for early mortality is high WBC count at presentation. Disease free survival was 90%+/−2%, 72.7%+/−3% and 66.7%+/−4% for 2, 3 and 5 years respectively. Relapse for patients who remained in CR after 5 years was very uncommon. Overall survival for patients after diagnosis by intention to treat analysis was 80.2%+/−3%, 75.9%+/−3% and 64.4%+/− 4% for 2, 3 and 5 years. Also OS and DFS were the same between patients with high and low WBC count. Conclusion: Long term follow up of newly diagnosed cases of APL, treated with single agent Arsenic Trioxide shows promising result. Arsenic trioxide potentially eliminates the adverse effect of prognostic factors of APL treatment such as high WBC count. We suggest that it is time to integrate Arsenic trioxide in treatment of new cases of APL. Disclosures: No relevant conflicts of interest to declare.

Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3413-3419 ◽  
Author(s):  
Ezhilarasi Chendamarai ◽  
Poonkuzhali Balasubramanian ◽  
Biju George ◽  
Auro Viswabandya ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Minimal Residual Disease ◽  
Acute Promyelocytic Leukemia ◽  
Residual Disease ◽  
Single Agent ◽  
High Risk Group ◽  
Promyelocytic Leukemia ◽  
Rt Pcr ◽  
Increased Risk ◽  
Minimal Residual

Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR–based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy.

Phase II Study of Single-Agent Arsenic Trioxide for the Front-Line Therapy of Acute Promyelocytic Leukemia

2011 ◽  
Vol 29 (20) ◽  
pp. 2753-2757 ◽  
Author(s):  
Ardeshir Ghavamzadeh ◽  
Kamran Alimoghaddam ◽  
Shahrbano Rostami ◽  
Seyed Hamidolah Ghaffari ◽  
Mohamad Jahani ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Residual Disease ◽  
Single Agent ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Long Term Follow Up

Purpose The long-term follow-up results of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy show high cure rates. Several studies have shown high efficacy of single-agent arsenic trioxide in newly diagnosed APL. However, long-term follow-up results are needed. Patients and Methods One hundred ninety-seven patients with newly diagnosed APL were treated with arsenic trioxide 0.15 mg/kg daily intravenous infusion until complete remission (CR). After achieving CR, the patients received one to four more courses of therapy with arsenic trioxide as consolidation and were observed with reverse-transcriptase polymerase chain reaction studies from peripheral blood (to detect of minimal residual disease) every 3 months or until relapse or death. Results The morphologic CR rate was 85.8%. The most common cause of remission failure was early death owing to APL differentiation syndrome (13.2%). The most important prognostic factor for early mortality was a high WBC count at presentation. The 5-year disease-free survival (DFS) rate was 66.7% ± 4% (SE). Relapse after 5 years in CR was rare. The 5-year overall survival (OS) rate by intention-to-treat analysis was 64.4% ± 4%. In patients who achieved CR, OS and DFS were identical. Conclusion The long-term follow-up of newly diagnosed patients with APL treated with single-agent arsenic trioxide shows high rates of DFS and OS.

Validation of weekly-dose cisplatin combined with radiation therapy in locally advanced head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6076-6076
Author(s):  
B. C. Boulmay ◽  
C. E. Riggs ◽  
M. Lawson ◽  
C. Morris ◽  
W. M. Mendenhall
Keyword(s):  
Radiation Therapy ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Definitive Treatment ◽  
Weekly Dose ◽  
Grade Iii

6076 Background: Impressive outcomes have been achieved using multiagent neoadjuvant and concomitant chemotherapy combined with radiation in definitive treatment of head and neck cancer; these are associated with significant toxicities. The purpose of this study was to determine the efficacy and toxicities of single-agent weekly (CDDP) during curative-intent radiation therapy. Methods: 36 patients with AJCC Stage II (3%), Stage III (14%), Stage IV (83%) squamous cell carcinoma of the larynx, hypopharynx, oropharynx and oral cavity treated from 6/2000 to 11/2003 were retrospectively reviewed. Subjects received 72 Gy irradiation given either by hyperfractionation or IMRT technique with CDDP 30 mg/m2/wk throughout the radiation course. Cisplatin was held for Grade III/IV toxicities. The endpoints were best response, percentage of Grade III/IV toxicities, disease-free survival (DFS), overall survival (OS). Results: The median number of cycles of CDDP administered was 6. Grade III/IV toxicities: 11% of patients had anemia, 6% thrombocytopenia, 33% leukopenia, 0% renal failure, and 25% developed Grade III/IV mucositis; 1 patient (3%) died due to complications directly related to therapy. Responses to therapy included 72% CR, 17% PR, and 5% SD. Median follow-up for all patients was 19 months (34.5 months for living patients), DFS at 3 years (yrs.) was 59%, and OS at 3 yrs, was 40%. Nine patients died of disease up to 2.6 (median, 0.7) yrs. after treatment, while 11 died of intercurrent diseases up to 5.1 (median, 1.8) yrs. later. Fifteen are alive (2 with recurrence) at median 2.7 yrs. after treatment. Conclusion: Concomitant weekly CDDP with full-course radiation is feasible, tolerable, highly active, and comparable to more complex, costly and toxic regimens. Intercurrent disease was a significant contributor to mortality in our population. Our regimen is an attractive alternative to sequential chemoradiotherapy programs. No significant financial relationships to disclose.

Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 443-449 ◽  
Author(s):  
Silvia Buonamici ◽  
Emanuela Ottaviani ◽  
Nicoletta Testoni ◽  
Vittorio Montefusco ◽  
Giuseppe Visani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Real Time ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Good Prognosis ◽  
Clinical Relapse ◽  
Rt Pcr ◽  
Molecular Monitoring ◽  
Acute Myeloid

Abstract The inv(16) cytogenetic subtype of acute myeloid leukemia (AML) has a relatively good prognosis. Many patients achieve complete remission (CR). The prognostic uncertainty of negative qualitative reverse transcription–polymerase chain reaction (RT-PCR) assays suggests the need to identify prognostically significant critical thresholds by real-time RT-PCR. A reliable and sensitive (10−5) real-time RT-PCR assay was set up for the evaluation of relevant CBFβ-MYH11/ABL transcript ratios and was applied to the 21 patients with inv(16) AML routinely referred for cytogenetic and molecular monitoring in Seràgnoli Institute (Bologna, Italy) since 1990. Among the 18 patients who underwent ablative chemotherapy, all achieved CR with a 3-year disease-free survival probability of 63% (95% CI, 40%-87%) and no recorded events after 26 months. Five patients had relapses; 2 died of disease and 3 entered second CR. Analysis of the 125 bone marrow (or peripheral blood) samples studied by real-time RT-PCR showed that transcript ratios of samples taken during CR at any time before a relapse were always greater than 0.12%, whereas those of samples taken during first or second CR from patients who did not subsequently have relapses were always less than 0.25%. This suggests that transcript ratios greater than 0.25% may correspond to high risk for relapse, whereas ratios below 0.12% might indicate the patient is in a curable state. If confirmed, such thresholds could open the way to a new phase in post-CR therapeutic decision making for patients with inv(16) AML.

scholarly journals “Old wine in a new bottle” - post COVID-19 infection, central serous chorioretinopathy and the steroids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Srinivasan Sanjay ◽  
Poornachandra B. Gowda ◽  
Bhimasena Rao ◽  
Deepashri Mutalik ◽  
Padmamalini Mahendradas ◽  
...  
Keyword(s):  
Virus Disease ◽  
Anterior Segment ◽  
Central Serous Retinopathy ◽  
Oral Antibiotics ◽  
Rt Pcr ◽  
Case Presentation ◽  
Ocular Manifestations ◽  
Corrected Distance Visual Acuity ◽  
History Of ◽  
The Right

Abstract Introduction Corona virus disease (COVID-19) pandemic can cause myriad of ocular manifestations. We report a case of unilateral multi focal central serous retinopathy, post COVID-19 infection in an Asian Indian female. Case presentation A 42-year-old female presented to us with unilateral blurring, in the right eye (OD), 12 days after COVID-19 infection. She had fever, chills, shortness of breath and cough with tiredness and was COVID- RT PCR positive. She was administered intravenous and oral antibiotics with injection heparin/remdesivir, during her 7 day stay at the hospital. She was also on steroid inhalers. She had no systemic history of note. On ocular evaluation, her corrected distance visual acuity was 20/40 in OD and 20/20 in left eye (OS). Anterior segment was normal. Anterior vitreous was clear. Fundus examination of the OD showed central serous retinopathy (CSCR) with OS being normal. Conclusion CSCR can occur post COVID-19 due to steroid administration and physicians administering it should be aware of this and refer the patients to an ophthalmologist earlier.

Association of combined phase I/II study of a novel bicyclic peptide and MMAE conjugate BT8009 in patients with advanced malignancies with Nectin-4 expression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS2668-TPS2668
Author(s):  
Meredith McKean ◽  
Gerald Steven Falchook ◽  
Johanna C. Bendell ◽  
Babar Bashir ◽  
Neil Palmisiano ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Single Agent ◽  
Pancreatic Head ◽  
Uncontrolled Hypertension ◽  
Clinical Activity ◽  
Highly Active ◽  
History Of ◽  
Cyp3a4 Inhibitors ◽  
Critical Organ ◽  
Peptide Targeting

TPS2668 Background: BT8009 is a Bicycle Toxin Conjugate (BTC), a novel class of chemically synthesized molecules, comprising a bicyclic peptide targeting Nectin-4 tumor antigen, linked to cytotoxin (monomethyl auristatin E [MMAE]) via a valine-citrulline (val-cit) cleavable linker. Nectins (Nectin-1, -2, -3, and -4) and nectin-like molecules (Necl) are Ca2+ independent immunoglobulin-like cell adhesion molecules. Recent studies have shown the importance of Nectin-4 in several human cancers, including lung, ovarian, breast and bladder cancer; however, the precise roles and clinical relevance of Nectin-4 in tumors remain largely unknown. The Nectin-4 targeted enfortumab vedotin, linked to MMAE via a val-cit linker, is highly active in late-stage bladder cancer and demonstrates notable additional clinical activity as a single agent and in combination with pembrolizumab1. Skin toxicities, bone marrow suppression, peripheral neuropathy and diabetes have been associated with enfortumab, with some of these toxicities already noted with MMAE-bearing antibody therapies. We anticipate a similar toxicity profile for BT8009 in clinical studies. BT8009 exhibited a favorable preclinical profile and was effective in a range of cell-derived xenograph tumor models. Methods: Study BT8009-100 (NCT04561362) will evaluate safety and tolerability of weekly and every other week BT8009 administration, alone and in combination with q4w nivolumab. Determination of both a realistic phase 2 dose and a sequence will also be key to further exploration of safety and efficacy signals, along with an early examination of the role of baseline immunohistochemistry-ascertained levels of tumor Nectin-4. Patients will be recruited with advanced solid tumors associated with Nectin-4 expression after exhausting SOC options (i.e., bladder, breast, pancreatic, head and neck, gastric, esophageal and ovarian). Patients must have available tumor tissue, acceptable hematologic and other critical organ function and be willing to participate. Appropriate ethical and regulatory approvals and advice will be in place and adhered to. Exclusion criteria include uncontrolled brain metastases, uncontrolled hypertension, concomitant CYP3A4 inhibitors and significant history of autoimmune disease for the nivolumab cohorts. PK serial collections will be taken on D1 through D15. Radiologic tumor assessments for response per RECIST will be taken every two months. 1. Enfortumab Vedotin. FDA_data. 761137Orig1s000MultiDiscliplineR.pdf (fda.gov). Clinical trial information: NCT04561362.

Phase Ib trial of vactosertib in combination with pomalidomide in relapsed multiple myeloma: A corticosteroid-free approach by targeting TGF-β signaling pathway.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8039-8039
Author(s):  
Ehsan Malek ◽  
Sunjin Hwang ◽  
Paolo Fabrizio Caimi ◽  
Leland L. Metheny ◽  
Benjamin Kent Tomlinson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Immune System ◽  
Transforming Growth Factor ◽  
Single Agent ◽  
Cell Activity ◽  
Type I ◽  
Phase Ib ◽  
Progression Of Disease ◽  
Grade Iii

8039 Background: Immunosuppression and osteoclast activation are two hallmarks of the bone marrow environment in Multiple Myeloma (MM). Corticosteroids have been used historically as part of anti-myeloma regimens due to their anti-plasma cell activity, however they potentially could suppress immune system and activate osteoclast further; therefore there is an unmet need for corticosteroid-free approaches in the era of emerging anti-cancer immunotherapy modalities. There is an abundance of Transforming Growth Factor-beta (TGF-β), a crucial cytokine in suppression of immune system as well as catabolic bone remodeling, in the MM microenvironment. Vactosertib (Vacto) is a small molecule TGF-β type I receptor inhibitor that has shown single agent activity against myeloma in the syngeneic 5T33MM murine mouse model. Here, we report the phase Ib trial of Vacto in combination with pomalidomide (Pom) without any corticosteroids (NCT03143985). Methods: pts with relapsed MM with at least two lines of therapies enrolled on a 3 + 3 dose escalation design and received Vacto, 60 mg/d, 120 mg/d, 100 mg BID and 200 mg BID in combination with standard dose of Pom (4mg) without corticosteroids. The primary objectives of the study was to assess safety and recommended phase 2 dose. Vacto tablets, taken once or twice daily for 5 days followed by 2 days without treatment, is administered in 28-day cycles, until progression of disease or intolerable toxicity. Results: 15 pts were enrolled on the study (Table). The most common non-hematologic adverse event (AE) was grade II fatigue and pain in one pt, one episode of grade III renal failure that took less than 7 days to get back to baseline on another patient, sinus bradycardia that reversed to sinus rythem and an Afib that was rate controlled with beta blocerks. No grade IV non-hematologic AE was observed. Three pts had grade III hematologic AE, no grade IV hematologic AE. Three out of 15 pts experienced progression of disease (PFS-6: 80%). Conclusions: The phase Ib data shows safety of this agent in combination with Pom. The efficacy assessment (PFS-6: 80%) is higher than the historical control (PFS-6: 20% in randomized Phase II study by Richardson et al. Blood. 2014) with Pom only (PFS-6: 20%) or Pom with corticosteroids (PFS-6: 40%). Further advancement of this agent in clinical trial pipelines for MM is planned. Clinical trial information: NCT03143985. [Table: see text]

Molecular and Cultures based Diagnosis of Infectious Bursal Disease Virus (IBDV) in Vaccinated and Non Vaccinated Poultry Flocks 

2021 ◽  
Author(s):  
Ritesh S. Shinde ◽  
Harshad C. Chauhan ◽  
Sandip S. Patel ◽  
Kishan Kumar Sharma ◽  
Arun C. Patel ◽  
...  
Keyword(s):  
Embryo Culture ◽  
Infectious Bursal Disease ◽  
Fibroblast Cells ◽  
Culture Result ◽  
Rt Pcr ◽  
Culture Methods ◽  
Bursal Disease ◽  
History Of ◽  
Chicken Fibroblast ◽  
Pooled Sample

Background: In recent years, Infectious bursal disease is continuously occurring even after vaccination in India and requires an inclusive diagnosis. Therefore, the present study was undertaken to diagnose IBD through molecular and culture methods. Methods: One pooled sample, from each of 54 flocks having birds with IBD like symptoms, was collected. History of bird type, age and vaccination was recorded. Samples were subjected to RT-PCR, egg embryo culture and chicken fibroblast cells culture. Result: A total of 49669 out of 517900 (9.59 %) of birds, aging 3-6 weeks, were displaying the signs similar to IBD.In RT-PCR, 21 (38.88%) samples were found positive which belonged to11 (52.38%) vaccinated and 10 (47.62%) unvaccinated flocks.The RT-PCR positive samples were successfully cultivated for the virus through egg embryo and cell culture. The CEF culture was found least sensitive compared to egg embryo culture and RT-PCR. 

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