scholarly journals Clinical Profile, Complications and Outcomes of Patients with Acute Promyelocytic Leukemia: Indian Perspective

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4385-4385
Author(s):  
Tejasvini Vaid ◽  
Mukul Aggarwal ◽  
Pradeep Kumar ◽  
Rishi Dhawan ◽  
Jasmita Dass ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
High Risk Group ◽  
Promyelocytic Leukemia ◽  
Low Risk ◽  
P Value

Abstract Background: The introduction of all-trans-retinoic-acid (ATRA) and arsenic trioxide (ATO) has changed acute promyelocytic leukaemia (APL) from a highly fatal malignancy to a major success in the sphere of haemato-oncology, with long-term survival exceeding 90% in some studies [1]. While literature from the developed world boasts of outstanding outcomes of patients with APL, there is a paucity of data on management strategies, complications and outcomes from the developing world in general and India in particular [2]. With a large population residing in rural areas, high infection rates and limited access to healthcare, we aim to delineate the challenges faced in curing APL in the developing world. Methods: We retrospective collected data from medical records of all patients diagnosed with APL between January 2016 to December 2020 in the department of Hematology. A presumptive diagnosis of APL was made based on the presence of abnormal promyelocytes in peripheral blood or bone marrow and flow cytometry (CD13, CD33 positive, HLADR, CD34 negative). The diagnosis was confirmed by the presence of PML-RARα fusion gene by RT-PCR. Data on baseline characteristics, therapy, complications and outcome was collected. Overall survival (OS) was defined from the date of diagnosis to death or date of last follow up. Disease free survival (DFS) was defined from the date of first remission to date of first relapse, death or date of last follow up. Results: 64 patients were treated during the study period. Baseline characteristics, therapy administered and induction outcomes are mentioned in Table 1. Complications: 56.25% patients developed differentiation syndrome (DS). The incidence was higher in Sanz high-risk group as compared to Sanz-low risk group (68.8% vs 43.2%, p value 0.044). The incidence of infection at presentation was similar in Sanz high-risk and low-risk groups (55.2% vs 59.4%, p value 0.7). The incidence of new episode of febrile neutropenia during therapy was 62.5% and was higher in Sanz high-risk group as compared to low-risk group (75% vs 50%, p value 0.039). On multivariate analysis, development of infection during induction was a significant predictor of death or relapse (p value 0.02 HR:0.3; 95% CI 0.12-0.84). 17.2% patients developed pseudotumor cerebri. All of them were treated with acetazolamide, 6 patients' symptoms persisted despite acetazolamide and the dose of ATRA was lowered to 25mg/m2. 3 patients developed thrombosis. One patient had superior sagittal sinus thrombosis at presentation and two patients developed central line related thrombosis during therapy. 15.6% patients developed hepatotoxicity of which 3 had an underlying chronic liver disease. The remaining had a normal liver echotexture on ultrasonography and viral markers were normal; the liver dysfunction was attributed to drug induced liver injury. One patient who received AIDA protocol developed PSVT and improved with adenosine. Another patient who received ATRA+ATO+Daunorubicin developed accelerated hypertension and was managed symptomatically. Outcomes 75% patients attained complete remission after induction. 9 patients died from infection, 6 from bleeding and one from DS. At a median follow up of 26 months, 2 patients belonging to high-risk group had relapsed. They received reinduction with ATRA and ATO; one succumbed to pancreatitis during induction, the other attained CR2 and is on maintenance therapy. The 4-year DFS and OS was 71.25% (95% CI 59.9 to 82.5) and 73.13% (95% CI 62.2 to 84.1) respectively. Patients in Sanz low risk group had a better 4-year DFS (84.9% vs 58.3%, p value 0.026) and OS (84.9% vs 62.5%, p value 0.044) as compared to the Sanz high-risk group. There was a trend towards improved outcomes in high-risk patients with the use of ATRA+ATO+Daunorubicin. Conclusion: APL patients in India have a higher incidence of DS, pseudotumor cerebri, hepatotoxicity, baseline infections & new infections during induction complicating therapy. CR rate, DFS, OS were comparable to other population-based studies. ATRA, ATO and daunorubicin combination is the preferred protocol for treating high-risk patients. REFERENCES: 1. Iland HJ et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012;120(8):1570-80 2. Lo-Coco F et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111-21. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effective Treatment of Acute Promyelocytic Leukemia With All-Trans-Retinoic Acid, Arsenic Trioxide, and Gemtuzumab Ozogamicin

2009 ◽  
Vol 27 (4) ◽  
pp. 504-510 ◽  
Author(s):  
Farhad Ravandi ◽  
Eli Estey ◽  
Dan Jones ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Promyelocytic Leukemia ◽  
Platelet Recovery ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Purpose We examined the outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) with or without gemtuzumab ozogamicin (GO) but without traditional cytotoxic chemotherapy. Patients and Methods From February 2002 to March 2008, 82 patients with APL were treated with a combination of ATRA plus ATO. The first cohort of 65 patients received ATRA and ATO (beginning on day 10 of ATRA). High-risk patients (WBCs ≥ 10 × 109/L) received GO on the first day. From July 2007, the second cohort of 17 patients received ATRA and ATO concomitantly on day 1. They also received GO on day 1, if high risk, and if their WBC increased to more than 30 × 109/L during induction. Monitoring for PML-RARA fusion gene was conducted after induction and throughout consolidation and follow-up. Results Overall, 74 patients achieved complete remission (CR) and one achieved CR without full platelet recovery after the induction, for a response rate of 92%. Seven patients died at a median of 4 days (range, 1 to 24 days) after inclusion in the study from disease-related complications. The median follow-up is 99 weeks (range, 2 to 282 weeks). Among the responding patients, three experienced relapse at 39, 52, and 53 weeks. Three patients died after being in CR for 14, 21, and 71 weeks, all from a second malignancy. The estimated 3-year survival rate is 85%. Conclusion The combination of ATRA and ATO (with or without GO) as initial therapy for APL was effective and safe and can substitute chemotherapy-containing regimens.

Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3469-3473 ◽  
Author(s):  
Elihu Estey ◽  
Guillermo Garcia-Manero ◽  
Alessandra Ferrajoli ◽  
Stefan Faderl ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Promyelocytic Leukemia ◽  
Low Risk ◽  
High Risk Patients ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Risk Patients

We examined whether combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) might be an alternative to ATRA plus chemotherapy in untreated acute promyelocytic leukemia (APL). Twenty-five low-risk patients (white blood cell [WBC] count less than 10 × 109/L [10 000/μL]) received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily, beginning day 10 of ATRA), and in complete remission (CR) received ATO plus ATRA, without chemotherapy, unless they were reverse transcriptase–polymerase chain reaction (RT-PCR)–positive 3 months from CR date or had molecular relapse. Nineteen high-risk patients were treated identically, but received chemotherapy, generally 9 mg/m2 gemtuzumab ozogamycin (GO) on day 1 of induction. The CR rate was 39 of 44 (24 of 25 in low-risk, 15 of 19 in high-risk). Disease recurred at 9, 9, and 15 months, respectively, in 3 high-risk patients. The median follow-up time from CR date in the 36 patients alive in first CR is 16 months (15 months in low-risk, 20 months in high-risk), with 9 patients followed for at least 24 months. Each of the 36 patients was PCR-negative at last follow-up. Thus, none of the low-risk patients has received chemotherapy, and only 3 high-risk patients (the 3 with relapsed disease) have received chemotherapy past induction. ATRA plus ATO may serve as an alternative to chemotherapy in low-risk untreated APL (eg, in older patients) and, when combined with GO, may improve outcome in high-risk patients.

Abstract 19763: Role of HAS-BLED Score on Major Bleeding in Atrial Fibrillation Undergoing Percutaneous Coronary Intervention With Drug-eluting Stents

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yoshitaka Ito ◽  
Kazuhiro Naito ◽  
Katsuhisa Waseda ◽  
Hiroaki Takashima ◽  
Akiyoshi Kurita ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Stent Implantation ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk

Background: While anticoagulant therapy is standard management for atrial fibrillation (Af), dual antiplatelet therapy (DAPT) is needed after stent implantation for coronary artery disease. HAS-BLED score estimates risk of major bleeding for patients on anticoagulation to assess risk-benefit in Af care. However, it is little known about usefulness of HAS-BLED score in Af patient treated with coronary stents requiring DAPT or DAPT plus warfarin (triple therapy: TT). The aim of this study was to evaluate the role of HAS-BLED score on major bleeding in Af patients undergoing DAPT or TT. Methods: A total of 837 consecutive patients were received PCI in our hospital from Jan. 2007 to Dec. 2010, and 66 patients had Af or paroxysmal Af at the time of PCI. Clinical events including major bleeding (cerebral or gastrointestinal bleeding) were investigated up to 3 years. Patients were divided into 2 groups based on HAS-BLED score (High-risk group: HAS-BLED score≥4, n=19 and Low-risk group: HAS-BLED score<4, n=47). DAPT therapy was required for a minimum 12 months after stent implantation and warfarin was prescribed based on physicians’ discretion. Management/change of antiplatelet and anticoagulant therapy during follow-up periods were also up to physicians’ discretion. Results: Baseline characteristics were not different between High-risk and Low-risk group except for age. Overall incidence of major bleeding was observed in 8 cases (12.1%) at 3 years follow-up. Major bleeding event was significantly higher in High-risk group compared with Low-risk group (31.6% vs. 4.3%, p=0.002). However, management of DAPT and TT was not different between the 2 groups. Among component of HAS-BLED score, renal dysfunction and bleeding contributed with increased number of the score. Conclusion: High-risk group was more frequently observed major bleeding events compared with Low-risk group in patients with Af following DES implantation regardless of antiplatelet/anticoagulant therapy.

Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 534-534
Author(s):  
Natasha Catherine Edwin ◽  
Jesse Keller ◽  
Suhong Luo ◽  
Kenneth R Carson ◽  
Brian F. Gage ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Discriminative Ability ◽  
Blood Institute ◽  
C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long-Term Follow-Up Data

2010 ◽  
Vol 28 (24) ◽  
pp. 3866-3871 ◽  
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Ezhilarasi Chendamarai ◽  
Kavitha M. Lakshmi ◽  
Salamun Desire ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Single Agent ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Long Term Follow Up

Purpose We previously reported our results with a single-agent arsenic trioxide (ATO) –based regimen in newly diagnosed cases of acute promyelocytic leukemia (APL). The concern remained about the long-term outcome of this well-tolerated regimen. We report our long-term follow-up data on the same cohort. Patients and Methods From January 1998 to December 2004, 72 patients with PML/RARα+ APL were enrolled. All patients were treated with a single-agent ATO regimen. Results Overall 62 (86.1%) achieved a hematologic remission (complete remission). After the initial report, an additional seven patients have relapsed for a total of 13 relapses. There were no additional toxicities to report on follow-up. At a median follow-up 60 months, the 5-year Kaplan-Meier estimate (± SE) of event-free survival, disease-free survival, and overall survival (OS) was 69% ± 5.5%, 80% ± 5.2%, and 74.2% ± 5.2%, respectively. The OS in the good risk group as defined by us remains 100% over this period. Conclusion Single-agent ATO as used in this study in the management of newly diagnosed cases of APL is safe and is associated with durable responses. Results in the low-risk group are comparable to that reported with conventional therapy while additional interventions would probably be required in high-risk cases.

scholarly journals The predictive role of Ki-67 protein in determining the aggressiveness of primary malignant bone tumors. A retrospective study

2019 ◽  
Vol 2 (2) ◽  
pp. 91-95
Author(s):  
Ioan-Mihai Japie ◽  
Dragoș Rădulescu ◽  
Adrian Bădilă ◽  
Alexandru Papuc ◽  
Traian Ciobanu ◽  
...  
Keyword(s):  
High Risk ◽  
Ewing Sarcoma ◽  
Bone Tumors ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
The Other ◽  
Malignant Bone Tumors ◽  
Ki 67

AbstractIntroduction: In order to diagnose and stage malignant bone tumors, the pathologic examination of harvested pieces with immunohistochemistry test is necessary; they also provide information regarding the prognosis on a medium to long term. Among tissular biomarkers with potential predictive value, a raised Ki-67 protein level is used to determine the risk of local recurrence or metastasis.Material and method: This study was performed on 50 patients with primary malignant bone tumors admitted in the Traumatology and Orthopedy Department of University Emergency Hospital, Bucharest. Patients repartition according to diagnosis was the following: 21 patients with osteosarcoma, 18 patients with chondrosarcoma, 6 patients with Ewing sarcoma, 3 patients with malignant fibrous histiocytoma, and 2 with fibrosarcoma. The follow-up period was between 12 and 72 months with a mean of 26 months.Results: Patients were aged between 18 and 77 years old, with a mean age of 41,36. There were 22 women and 28 men. No sex or age difference was notable for the tumor outcome. After calculating the Ki-67 LI, 36 patients were included in the high-risk group (Ki-67 LI > 25%), while 14 had a low risk for metastasis and local relapse (Ki-67 < 25%). The low-risk patients had chondrosarcoma (8 patients), osteosarcoma (5 patients), and fibrosarcoma (1 patient). During the follow-up, 8 patients, all belonging to the high risk group, developed metastasis, while 5 patients developed local recurrences; 4 patients who relapsed belonged to the high risk group and 1 to the low risk group. Metastases developed in 3 patients with osteosarcoma, 2 with Ewing sarcoma, 2 with chondrosarcoma and 1 patient with fibrosarcoma. Most metastases occurred within one year after surgery. The other fibrosarcoma patient developed local recurrence after 6 months, while the other local recurrences occurred in osteosarcoma patients (2 cases) and 1 in a Ewing sarcoma patient and chondrosarcoma patient.Conclusions: Our study concluded that while Ki-67 LI values are useful in determining the aggressivity of primary malignant bone tumors, it should always be used in conjunction with the clinical, imaging and anatomopathological diagnosis methods in order to accurately predict the patients’ outcome.

scholarly journals Validation of Clinical Prognostic Models and Integration of Genetic Biomarkers of Drug Resistance in CLL Patients Treated with Ibrutinib

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 186-186 ◽  
Author(s):  
Inhye E. Ahn ◽  
Xin Tian ◽  
Maher Albitar ◽  
Sarah E. M. Herman ◽  
Erika M. Cook ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Prognostic Models ◽  
Discovery Cohort ◽  
Treatment Naïve ◽  
Equity Ownership

Abstract Introduction: We previously reported a prognostic scoring system in CLL using pre-treatment factors in patients treated with ibrutinib [Ahn et al, 2016 ASH Annual Meeting]. Here we present long-term follow-up results and validation of the prognostic models in a large independent cohort of patients. We also determine the incidence of resistance-conferring mutations in BTK and PLCG2 genes in different clinical risk groups. Methods and Patients: The discovery cohort comprised 84 CLL patients on a phase II study with either TP53 aberration (deletion 17p or TP53 mutation) or age ≥65 years (NCT01500733). The validation cohort comprised 607 patients pooled from four phase II and III studies for ibrutinib in treatment-naïve or relapsed/refractory CLL (NCT01105247; NCT01578707; NCT01722487; NCT01744691). All patients received single-agent ibrutinib 420mg once daily. We used Cox regression models to identify independent predictors of PFS, Kaplan-Meier method to estimate probabilities of PFS, log-rank test to compare PFS, and Cochran-Armitage trend test to compare the incidence of mutation among subgroups. We used R version 3.5.0 or SAS® version 9.3 for statistical analyses. For biomarker correlation, we tested cellular DNA or cell-free DNA collected from patients in the discovery cohort with the targeted sequencing of BTK and PLCG2 genes. Result: At a median follow-up of 5.2 years, 28 (33.3%) of 84 patients in the discovery cohort progressed or died. 52 (61.9%) patients had treatment-naïve CLL. Independent factors of PFS on univariate analysis were; TP53 aberration, prior treatment, and β-2 microglobulin (B2M) >4mg/L (P<0.05 for all tests). Unmutated IGHV and advanced Rai stage (III/IV) showed a trend toward inferior outcome without reaching statistical significance. Because higher levels of B2M were associated with relapsed/refractory CLL, we performed two multivariate Cox regression models to assess B2M and prior treatment status separately. Risk groups were determined by the presence of TP53 aberration, advanced Rai stage, and B2M >4mg/L for Model 1, and TP53 aberration, advanced Rai stage, and relapsed/refractory CLL for Model 2 (Table 1). The high-risk group had all three adverse risk factors; the intermediate-risk group had two risk factors; and the low-risk group, none or one. The median PFS of the high-risk group was 38.9 months for Model 1 and 38.4 months for Model 2, and was significantly shorter than those of intermediate and low-risk groups. In the validation cohort, 254 (41.8%) of 607 patients progressed or died at a median follow-up of 4.2 years. 167 (27.5%) patients had treatment-naïve CLL. Both models showed statistically significant differences in PFS by risk groups (Table 1). For the high-risk group, 4-year PFS was 30.2% in Model 1 and 30.5% in Model 2, which were inferior to those of intermediate (53.4 and 52.4%) and low-risk groups (68.7 and 73.7%). Model 1 classified 20% of patients and Model 2 classified 28% of patients to the high-risk group. BTK and PLCG2 mutations are common genetic drivers of ibrutinib resistance in CLL. To determine whether the incidence of these mutations correlates with prognostic risk groups, we performed targeted sequencing of BTK and PLCG2 of samples collected from patients in the discovery cohort. We used cell-free DNA for patients who received long-term ibrutinib (≥3 years) and had low circulating tumor burden, and cellular DNA, for samples collected within 3 years on ibrutinib or at progression. Of 84 patients, 69 (82.1%) were tested at least once, and 37 (44.0%) were tested at least twice. The frequency of testing was similar across the risk groups by two models (P>0.05). The cumulative incidences of mutations at 5 years in the low-, intermediate-, and high-risk groups were: 21.4%, 44.8% and 50%, respectively, by Model 1 (P=0.02); and 22.6%, 41.4% and 66.7%, respectively, by Model 2 (P=0.01). Conclusion: We developed and validated prognostic models to predict the risk of disease progression or death in CLL patients treated with ibrutinib. Risk groups classified by three commonly available pre-treatment factors showed statistically significant differences in PFS. The clinically-defined high-risk disease was linked to higher propensity to develop clonal evolution with BTK and/or PLCG2 mutations, which heralded ibrutinib resistance. Disclosures Albitar: Neogenomics Laboratories: Employment. Ma:Neogenomics Laboratories: Employment. Ipe:Pharmacyclics, an AbbVie Company: Employment, Other: Travel; AbbVie: Equity Ownership. Tsao:Pharmacyclics LLC, an AbbVie Company: Employment. Cheng:Pharmacyclics LLC, an AbbVie Company: Employment. Dean:CTI BioPharma Corp.: Employment, Equity Ownership; Pharmacyclics LLC, an AbbVie Company: Employment, Equity Ownership. Wiestner:Pharmacyclics LLC, an AbbVie Company: Research Funding.

scholarly journals Walking a Tightrope: Dosage Modifications and Treatment Outcomes of All-Trans-Retinoic Acid, Arsenic Trioxide, and Daunorubicin for High-Risk Acute Promyelocytic Leukemia

2020 ◽  
pp. 1749-1756
Author(s):  
Madhav Danthala ◽  
Krishna Reddy Golamari ◽  
Arun Seshachalam ◽  
Anupama Mikkilineni ◽  
Sitalata Chappidi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Tertiary Care ◽  
Standard Of Care ◽  
Drug Dosage ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

PURPOSE The use of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) in the treatment of low- and intermediate-risk acute promyelocytic leukemia (APL) is the standard of care. We report the combined use of ATRA, ATO, and daunorubicin (DNR) in patients newly diagnosed with high-risk APL. The primary focus was to describe the drug dosage modifications made in the real-world scenario. METHODS In this descriptive study, we included 16 out of 28 patients with high-risk APL from two tertiary care centers in South India (Vijayawada and Trichy) between January 2015 and December 2018. A unique approach of initiating ATRA at a dose of 25 mg/m2 on day 1 and escalation to 45 mg/m2 after cytoreduction with DNR and hydroxyurea was followed in all patients to avert differentiation syndrome, in the setting of hyperleukocytosis at presentation. RESULTS All patients who survived the first 3 days of admission achieved complete remission after a median duration of 29 days. There were no deaths during induction or consolidation, and the regimen was well tolerated; two patients developed grade 3/4 peripheral neuropathy requiring treatment modification. After a median follow-up duration of 1.9 years, there were no hematologic or molecular relapses. CONCLUSION The study sheds light on the modifications made to recommended dosages of ATRA, ATO, and DNR to optimize outcomes in high-risk APL and reaffirms the importance of ATO use in the front-line setting to achieve durable responses with minimal toxicity.

Procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer (version 3)

2007 ◽  
Vol 46 (05) ◽  
pp. 206-212 ◽  
Author(s):  
J. Dressler ◽  
W. Eschner ◽  
F. Grünwald ◽  
M. Lassmann ◽  
B. Leisner ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Risk Group ◽  
Standard Procedure ◽  
High Risk Group ◽  
Low Risk ◽  
Whole Body ◽  
Thyroglobulin Antibodies ◽  
Follow Up Care

SummaryVersion 3 of the procedure guideline for 131I whole-body scintigraphy (WBS) is the counterpart to the procedure guideline for radioiodine therapy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. 131I WBS 3–6 months after 131I ablation remains a standard procedure in an endemic area for thyroid nodules and the high frequency of subtotal surgical procedures. Follow-up without 131I WBS is only justified if the following preconditions are fulfilled: low-risk group pT1–2, pN0 M0 with histopathologically confirmed pN0, 131I uptake <2%, 131I WBS during ablation without any suspicious lesion, stimulated thyroglobulin (Tg)-level 3–6 months after ablation <2 ng/mL, and absence of anti-thyroglobulin- antibodies with normal recovery-testing. If patients from the low-risk group show normal 131I WBS 3–6 months after ablation and stimulated Tg is of <2 ng/mL, there will be no need for additional routine 131I WBS. If patients from the high-risk group show normal 131I WBS and stimulated Tg-level of <2 ng/mL 3–6 months after ablation, the follow- up care should include repeated stimulated Tgmeasurements. If the Tg-level remains below 2 ng/mL, an additional 131I WBS will be not necessary. The recommended intervals for stimulated Tg-testing are adapted to the prior intervals for 131I WBS-testing in the high-risk group. Increased anti-thyroglobulin-antibodies or incomplete recovery-testing make an individual strategy of follow- up care necessary, which include 131I WBS.

Incidence of Secondary Neoplasms In Patients with Acute Promyelocytic Leukemia Treated with All-Trans-Retinoic Acid (ATRA) with Chemotherapy or with Arsenic Trioxide (ATO).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1085-1085
Author(s):  
Alireza Eghtedar ◽  
Stefan Faderl ◽  
Hagop Kantarjian ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Secondary Neoplasms ◽  
Secondary Cancers ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 1085 Background: Progress in the treatment of patients (pts) with acute promyelocytic leukemia (APL) with the use of modern all-trans retinoic acid (ATRA)-containing regimens has resulted in the majority of pts achieving long-term disease-free survival. There is little data on the incidence and patterns of secondary neoplasms in pts treated with these regimens. Objective: To compare the incidence of secondary neoplasms in pts with APL treated with two different ATRA-containing regimens. Methods: We retrospectively examined the charts of 160 pts with APL treated with ATRA plus chemotherapy (n=54) or ATRA plus arsenic trioxide (ATO)(n=106) as their initial induction regimen at the University of Texas – M. D. Anderson Cancer Center from 1991 to 2009. Twenty seven (17%) pts had a remote history of a prior unrelated cancer. Pt characteristics and the incidence of secondary cancers per unit time of follow-up were compared. Results: The median age at diagnosis of the entire population was 44 years (range, 13 – 81) and the median age for the chemotherapy plus ATRA group was 38 years (range, 13–67) vs. 46 years (range, 14 – 81) for the pts treated with ATO plus ATRA (p= 0.001). Thirty (55%) and 54 (50.9%) in each cohort were women (p=0.52) and 2 (3.7%) and 26 (24.5%) were older than 60 years of age, respectively (p= 0.001). Twenty (37%) and 30 (28.3%) had high risk disease (WBC > 10 × 109/l)(p= 0.3), and 34 (62.9%) and 76 (71.6%) had low risk disease (WBC ≤ 10 × 109/l), respectively. Fifty one (94.4%) and 105 (99%) pts treated using the two regimens achieved a CR. The median follow-up time for the two cohorts was 136 and 29 months [ranges, (5 to 193) and (1 to 93), respectively]. Nine and 2 pts in the two groups developed secondary cancers including 2 breast cancers, 3 MDS/AML, 1 vulvar cancer, 1 prostate cancer, 1 colon cancer and 1 soft tissue sarcoma in the chemotherapy group vs. 1 melanoma and 1 pancreatic cancer in ATO group. The cumulative incidence of secondary cancers in the two cohorts is shown in figure 1. Conclusion: Treatment of pts with APL using the non-chemotherapy regimen of ATRA plus ATO is not associated with a higher incidence of secondary cancers (p=0.29) adjusted for unit time exposure. Disclosures: Off Label Use: Use of arsenic trioxide in frontline therapy of APL. Ravandi:Cephalon: Honoraria, Research Funding, Speakers Bureau.

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