scholarly journals A Refined Regimen for Maximally Eliminating Early Life-Threatening Complications for Patients with High-Risk Acute Promyelocytic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3994-3994
Author(s):  
Sanbin Wang ◽  
Lihui Peng ◽  
Lin Liu ◽  
Le Luo ◽  
Stephen Liang
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Low Dose ◽  
Intrathecal Injection ◽  
Promyelocytic Leukemia ◽  
Severe Bleeding ◽  
Life Threatening ◽  
Wbc Count

Abstract Life-threatening complications, such as severe bleeding and/or differentiation syndrome at admission and/or along with induction treatment, among high-risk patients with acute promyelocytic leukemia (APL) are a worldwide puzzle towards the cure of the disease. Taking the rationale that high WBC count, at least in part, may cause cytokine storm related symptoms, we designed this refined regimen with low dose mitoxantrone and ATRA plus arsenic trioxide to determine the safety and efficiency of this WBC reduction, prevention of differentiation syndrome, and supportive care centered approach. In total there were 50 patients with high risk APL (WBC>10x109) from 2003-2017 were enrolled with a medium follow-up of 39 months (15-72 months). Our treatment strategy and detailed protocol are: 1) WBC reduction: it started with ATRA (25mg/m2/day) and arsenic trioxide (0.15mg/kg/day) based double induction. The advantage of decreased dose of ATRA can help to lower the happening of leukocytosis which will trigger the cytokine releasing related syndrome. Low dose mitoxantrone (3mg/m2) was added from day 2-5 plus hydroxyurea (1.5g, p.o. q6h) started from day 1. The criteria for withdrawal hydroxyurea is once both of the following standard are met: i) the WBC count has continuously decreased for three days after reached the peak value; ii) WBC < 10x109/L. 2) Prevention of Differentiation Syndrome (DS): Dexamethasone (5mg/day) was added once the diagnosis was confirmed at day 1. The criteria to taper dexamethasone are the same as to stop hydroxyurea. We require to withdraw dexamethasone within one week once start the taper process. In general, our goal is to prevent the occurrence of both leukopenia and leukocytosis and maintain the WBC count between 2-20x109. 3) Supportive care: We maintain the PLT count between 20-30x109 and fibrinogen >1.5g/L which helped to decrease the occurrence of myelo-suppression, DS and severe bleeding. 4) CNS Prophylaxis: The Intrathecal injection was given after the CR was achieved. Unless there was evidence of CNS infiltration, we gave intrathecal injection after correcting the coagulation abnormality. The consolidation began at four weeks after the end of induction. It contained four weeks of an on and off schedule of arsenic trioxide (0.15mg/kg/day), in total four cycles, and two weeks of an on and off schedule of ATRA (25mg/m2/day), in total seven cycles. A total of eight intrathecal injections were given on the first and last day of arsenic trioxide. Two death was observed through our strategy during the induction. All patients reached hCR by the end of induction. Relapse occurred in four out of 50 patients, and there was no treatment-related mortality. All the relapsed patients entered CR again after using the same protocol. Grade 3-4 adverse events were observed among 12% of all the cases. Three-year probability of overall survival (pOS) was found to be 92%. Our strategy focus of reducing WBC count sheds new light on maximally eliminating early mortality of high-risk APL patients. Disclosures No relevant conflicts of interest to declare.

Treatment of Acute Promyelocytic Leukemia (APL) At Tawam Hospital UAE

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4347-4347
Author(s):  
Arif Alam ◽  
Harimohan Narayanan ◽  
Shanaaz Sonday ◽  
Sabir Hussain ◽  
Amar Lal ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Supportive Care ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Published Data ◽  
Female Ratio

Abstract Abstract 4347 Acute Promyelocytic Leukemia (APL) is a unique sub-type of Acute Myeloid leukemia associated with a balanced reciprocal translocation between chromosomes 15 and 17 and 80% of the cases present with bleeding diathesis caused by severe coagulopathy. The translocation generates a fusion transcript joining the PML(promyelocyte) and RAR-α (retinoic acid receptor-α) genes. The therapy of APL has been revolutionized by the introduction of differentiating agents All Trans Retinoic Acid (ATRA) and Arsenic Trioxide. All patients were treated as per Pethema protocol. Initially LPA99 (Sanz MA. Blood. 1999 Nov 1;94(9):3015-21) and since January 2012 a risk adapted therapy based on LPA2005 (Sanz MA et al. Blood June 24, 2010 vol. 115 no. 25 5137–5146). Treatment included induction followed by 3 cycles of consolidation and two years of maintenance. Nineteen patients were diagnosed with APL between January 2009 and June 2012. Three patients are excluded from the analysis as karyotyping and/or PCR did not confirm the diagnosis. The median age was 35 years (range 22–53 years). Male to female ratio was 4:1. Nine (56%) patients were stratified as high risk (WBC ≥ 10 ×109/l) while, seven (44%) as intermediate risk and low risk (WBC < 10 ×109/l). Three (19%) patients had early death despite treatment and supportive care. The cause of death was intracranial hemorrhage (1) pulmonary hemorrhage (1) and multi-organ failure (1). Thirteen patients achieved a complete morphological and molecular remission (80%). There has been only 1 case of treatment failure (high risk at presentation). This patient was successfully re-induced with arsenic trioxide and achieved second molecular complete remission. Unfortunately he relapsed a second time and is currently alive in third morphological remission but remains PCR positive for PML/RARα 33 months after diagnosis. Our limited experience shows favorable outcome (CR 80%) for the treatment of APL using the Pethema protocol compared to published data (Tallman MS. Blood 2002;99(3):759–767). Early death rate remains high despite intensive supportive care. The only variable is the availability and initiation of ATRA at the clinical suspicion of diagnosis both at the referring hospitals and treatment center. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Remission in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide (varitrinox) As the First Line in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Gustavo Milone ◽  
Samuel Sarmiento Doncel ◽  
Carol Agudelo Rico ◽  
Fabiola Vizcarra Reyes ◽  
Gina Alejandra Diaz Mosquera ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
First Line ◽  
Risk Patients

Acute promyelocytic leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) in which a chromosomal translocation t (15; 17) (q22; q12) is generated by fusing produces a hybrid PML / RARα gene, generating an altered signal . The combination of transretinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of newly diagnosed standard risk patients with acute promyelocytic leukemia (APL) in several countries. The objective of the present study is to describe the frequency of remission in patients with acute promyelocytic leukemia who were administered as a first line Arsenic Trioxide (varitrinox) during the period from November 2017 to June 2020 in Colombian patients. Methods: Retrospective observational and descriptive study of 12 patients diagnosed with acute promyelocytic leukemia treated with ATO Arsenic trioxide (Varitrinox) as first line, the source of information was provided by the treating hematologists (medical records) by filling out the technical concept format. Active pharmacovigilance scientist in Colombia, this format keeps the identification information of the patient anonymized and the confidentiality of the data is guaranteed as well as compliance with the rules of good clinical practice. Results: Twelve patients with age range between 22 and 69 years with a median age of 34.0 were analyzed. It was found in the analysis that 100% had induction hematologic remission with a median of 45 days. 75% of patients received ATO + ATRA and were at low and intermediate risk, the remaining 25% received ATRA + ATO + Chemotherapy and were at high risk, and intermediate risk. 91.7% of molecular remission in consolidation was obtained and it was measured in cycle 3 by means of PCR (undetectable), 8.3% (n = 1) was positive 3% and is finishing consolidation. Regarding the most frequent adverse events, intravascular coagulation (n = 9), neutropenia (n = 6) and thrombocytopenia (n = 6) were observed. 75% of patients are disease-free, 16.7% are on maintenance (they received ATO + ATRA + Induction chemotherapy) and 8.3% are on consolidation. So far, none of the patients under study have died. Conclusions: Our results support the use of ATO (Varitrinox) in newly diagnosed APL patients (as first line), as a care strategy for low, intermediate and high risk patients. The role of ATRA-ATO is guaranteed in other studies where they manage patients of different risks. Key words: Arsenic trioxide, leukemia promyelocytic acute, leukemia myeloid acute, remission induction, tretinoin. Disclosures No relevant conflicts of interest to declare.

Studies on Treatment of Acute Promyelocytic Leukemia With Arsenic Trioxide: Remission Induction, Follow-Up, and Molecular Monitoring in 11 Newly Diagnosed and 47 Relapsed Acute Promyelocytic Leukemia Patients

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3315-3324 ◽  
Author(s):  
Chao Niu ◽  
Hua Yan ◽  
Ting Yu ◽  
Hui-Ping Sun ◽  
Jian-Xiang Liu ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Pcr Analysis ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
First Choice ◽  
Wbc Count

Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RAR fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RAR expression and therapeutic response. In a follow-up of 33 relapsed cases over 7 to 48 months, the estimated disease-free survival (DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 × 109/L at relapse had better survival than those with WBC count over 10 × 109/L (P = .038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P = .01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.

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.

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.

scholarly journals Arsenic trioxide and low-dose cytarabine in older patients with untreated acute myeloid leukemia, excluding acute promyelocytic leukemia

Cancer ◽  
2008 ◽  
Vol 113 (9) ◽  
pp. 2504-2511 ◽  
Author(s):  
Gail J. Roboz ◽  
Ellen K. Ritchie ◽  
Tania Curcio ◽  
Juliette Provenzano ◽  
Rebecca Carlin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Promyelocytic Leukemia ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

scholarly journals Acute Promyelocytic Leukemia: Simplifying Treatment in a Resource Poor Setting

2021 ◽  
Vol 6 (4) ◽  
pp. 383-387
Author(s):  
Rohan Bhise ◽  
Imtiaz Ahmed ◽  
Sapna Imtiaz
Keyword(s):  
Retinoic Acid ◽  
Supportive Care ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Resource Poor

Introduction: Acute promyelocytic leukemia (APL) is a distinct leukemia which can be treated with differentiating agents alone.Treatment without chemotherapy decreases the cost of treatment and the need for supportive care. Here we present analysis of APL patients treated with arsenic trioxide (ATO)-all trans retinoic acid (ATRA) without chemotherapy in our hospital.Patients and Methods: Forty three patients with newly diagnosed APL were treated with arsenic trioxide(ATO ) and All trans retinoic acid (ATRA) during induction treatment. For consolidation ATRA 45 mg /m2 for two weeks every four weeks was administered for twenty eight weeks. ATO was administered for four cycles, with a cycle length of eight weeks. The drug was administered at 0.15 mg/kg/d for five days per week for four weeks during each cycle.Patients were followed up with once in three month hemogram and once in six month reverse-transcriptase polymerase chain reaction (RT-PCR) for two years and yearly thereafter. Results: The morphologic complete remission (CR) rate was 86.04%.The most common cause of remission failure was early death due to bleeding. None of the low risk patients died during induction therapy. The most important prognostic factor for early mortality was a high white blood cell (WBC) count at presentation. The median overall survival (OS) has not been reached.The two year OS was 83.4% and the three year OS was 74.8%.The estimated five year survival was 74.8%. At a median follow up of 42.6 months the estimated five year survival in the low-intermediate risk group was 93.3% and 59.1% in the high risk group Conclusion: ATO –ATRA can be considered as a treatment option for frontline treatment of all risk APL patients in resource poor settings.The results can be better with better supportive care to prevent early mortality and by salvaging patients who relapse.

Clinical Features and Outcome of 148 Patients with Acute Promyelocytic Leukemia in Brazil.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3326-3326 ◽  
Author(s):  
Rafael H. Jácomo ◽  
Raul Melo ◽  
Fernanda Souto ◽  
Éderson Mattos ◽  
Claudia Oliveira ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Risk Groups ◽  
Developed Countries ◽  
International Committee ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Life Threatening ◽  
American Society ◽  
Low Dose Chemotherapy

Abstract Acute Promyelocytic Leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) which has a high prevalence in Latinos as well as a different distribution of PML breakpoints with a higher incidence of bcr1 isoform. We describe here the characteristics and outcome of 148 consecutive patients, from 11 centers in Brazil. Induction consisted of ATRA and anthracyclines (ida or daunorubicin). All centers used anthracyclines in consolidation but association with AraC was variable. Maintenance was based on low dose chemotherapy, except in 2 centers, which were excluded from survival analysis. The incidence of APL among AML was 28.2%. According to the risk stratification from PETHEMA/GIMEMA groups, 58 (39.2%) patients were classified as high risk (HR), 63(42.6%) as intermediate (IR) and 27 (18.2%) as low risk (LR), a higher frequency of HR patients than the reported by Sanz et al analyzing 217 APL patients (p=0.003). A relatively high frequency of early complications was observed, with 26 (17.6%) and 68 (45,9%) patients presenting with life threatening hemorrhage and disseminated intravascular coagulation (DIC), respectively. Early mortality (death in the first 14 days of diagnosis) was higher than the described in developed countries - 42 (28.4%) patients; bleeding (37 patients) was the leading cause. Both early mortality and bleeding were more frequent in the HR group (p=0.002 and <0.001 respectively). From 106 patients alive at D+15, 88 patients survived induction and 73 were alive and in remission after consolidation. One patient relapsed before finishing consolidation and six were still in induction. There was no difference among risk groups in mortality after day 14 of induction. Mean overall survival (OS) for the 133 patients available for analysis was 614 days (CI95% 515–712). Excluding early mortality, mean OS was 844 days (CI95% 741–948). Mean OS was different among the risk groups - 928(785–1071), 748(598–898) and 313(187–439) days for LR, IR AND HR, respectively (p<0.001). Our data suggest that risk classification, besides identification of relapse probability, can identify patients with higher incidence of bleeding, laboratorial DIC and also those that are predisposed to death secondary to hemorrhage and this may alert to the necessity of a more intensive supportive care in induction for this group. Despite the fact that ATRA and anthracyclines are available in Brazil hospitals, these results show that Brazilian patients have a worse outcome than the reported by the latest trials. It is possible that late referral partially accounts for an increased number of high-risk APL among these Brazilian patients. Hence, in addition of specific drugs availability, prompt access to care and initiation of specific therapy is necessary to improve outcome. In this regard, the International Consortium in APL (IC APL), created in 2005 by the International Committee of the American Society of Hematology, aims to implement a network to allow the exchange of experiences among hematologists in developing countries and international specialists as well as to offer real time discussion of newly-diagnosed patients with APL and ongoing complications.

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