scholarly journals Availability of all-trans retinoic acid and support systems for management of acute promyelocytic leukemia in Michigan and Louisiana, USA

2019 ◽  
Vol 11 (2) ◽  
Author(s):  
Sheldon L. Bolds ◽  
Shruthi M.K. Hassan ◽  
Catherine R. Caprara ◽  
Stephanie Debragga ◽  
Kathryn S. Simon ◽  
...  
Keyword(s):  
Supportive Care ◽  
Acute Promyelocytic Leukemia ◽  
Treatment Protocol ◽  
Promyelocytic Leukemia ◽  
Treatment Protocols ◽  
Successful Treatment Outcome ◽  
All Trans Retinoic Acid ◽  
Care Guidelines ◽  
One Year ◽  
Cure Rates

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia with high induction mortality in the general population despite evidence of high cure rates in the clinical trials. Aggressive supportive care is essential for ideal management of these patients. We conducted a survey to collect data on these important issues required for successful treatment/outcome of APL patients from two states (Michigan and Louisiana) due to their low one-year survival rate among the Surveillance, Epidemiology, and End Results registries. All eligible hospitals (253) were obtained from the Data Medicare online directory. Availability of ATRA, formulary process to obtain it, blood back availability and established treatment protocols for the management of APL patients were queried. Since most of the hospitals surveyed do not have a treatment protocol, we believe that outcome could be improved if a standardized and simplified set of treatment and supportive care guidelines are developed for all hospitals treating APL.

Modern Approaches to Treating Acute Promyelocytic Leukemia

2011 ◽  
Vol 29 (5) ◽  
pp. 495-503 ◽  
Author(s):  
Miguel A. Sanz ◽  
Francesco Lo-Coco
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Virtual Absence ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Improved Outcomes ◽  
Experimental Trials ◽  
Cure Rates ◽  
Standard Risk

The advent of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy have contributed in the past 2 decades to optimize the antileukemic efficacy in acute promyelocytic leukemia (APL), leading to complete remission rates greater than 90%, virtual absence of resistance, and cure rates of nearly 80%. Recently reported studies from large cooperative trials have also shown that more rational delivery of treatment and improved outcomes may derive from the use of risk-adapted protocols. In particular, patients at higher risk of relapse (ie, those presenting with WBC > 10 × 109/L) seem to benefit from treatments that include cytarabine in the ATRA-plus-chemotherapy scheme, whereas patients with standard-risk disease can be successfully managed with less-intensive regimens that contain ATRA and anthracycline-based chemotherapy. After the outstanding results with arsenic trioxide (ATO) in the treatment of APL relapse, several experimental trials have been designed to explore the role of ATO in front-line therapy with the aim not only of minimizing the use of chemotherapy but also to reinforce standard ATRA-plus-chemotherapy regimens and additionally improve therapeutic efficacy. In this review article, we discuss most recent advances in the treatment of patients with newly diagnosed and relapsed APL.

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.

scholarly journals ACUTE PROMYELOCYTIC LEUKEMIA (APL): COMPARISON BETWEEN CHILDREN AND ADULTS

2014 ◽  
Vol 6 (1) ◽  
pp. e2014032 ◽  
Author(s):  
Anna Maria Testi ◽  
Francesco Lococo
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Low Dose ◽  
Adult Population ◽  
Promyelocytic Leukemia ◽  
Multicenter Trials ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Adults And Children ◽  
Cure Rates ◽  
Low Dose Chemotherapy

The outcome of adults and children with Acute Promyelocytic Leukemia (APL) has dramatically changed since the introduction of all trans retinoic acid (ATRA) therapy. Based on the results of several multicenter trials, the current recommendations for the treatment of patients with APL include ATRA and anthracycline-based chemotherapy for the induction of remission and for consolidation, and ATRA combined with low-dose chemotherapy for maintenance. This has improved the prognosis of APL by increasing the complete remission (CR) rate, actually > 90%, decreasing the induction deaths and by reducing the relapse rate, leading to cure rates nowadays exceeding  80% considering both adults and children1-9. More recently the combination of ATRA and arsenic trioxide (ATO) as induction and consolidation therapy has been shown to be at least not inferior and possibly superior to ATRA plus chemotherapy in adult patients with APL conventionally defined as non-high risk (Sanz score)10. Childhood APL has customarily been treated on adult protocols. Data from several trials have shown that the overall outcome in pediatric APL appears similar to that reported for the adult population, however some clinical and therapeutic aspects differ in the two cohorts which require some important considerations and treatment adjustments.

scholarly journals Prolonged Myelosuppression due to Progressive Bone Marrow Fibrosis in a Patient with Acute Promyelocytic Leukemia

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yuta Inagawa ◽  
Yukiko Komeno ◽  
Satoshi Saito ◽  
Yuji Maenohara ◽  
Tetsuro Yamagishi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Promyelocytic Leukemia ◽  
Bone Marrow Biopsy ◽  
Gastric Fluid ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Bone Marrow Fibrosis ◽  
All Trans Retinoic Acid ◽  
Phlegmonous Gastritis ◽  
Marrow Fibrosis

A 34-year-old woman was diagnosed with acute promyelocytic leukemia. Chemotherapy was administered following the JALSG APL204 protocol. Induction therapy with all-trans retinoic acid resulted in complete remission on day 49. She developed coccygeal pain from day 18, which spread to the spine and cheekbones and lasted 5 weeks. She had similar bone pain on days 7–10 of the first consolidation therapy and on days 4–12 of the second consolidation therapy. Oral loxoprofen was prescribed for pain relief. On day 33 of the third consolidation, white blood cell and neutrophil counts were 320/μL and 20/μL, respectively. After she developed epigastralgia and hematemesis, she developed septic shock. Gastroendoscopy revealed markedly thickened folds and diffusely damaged mucosa with blood oozing. Computed tomography revealed thickened walls of the antrum and the pylorus. Despite emergency treatments, she died. Bacterial culture of the gastric fluid yielded Enterobacter cloacae and enterococci growth. Collectively, she was diagnosed with phlegmonous gastritis. Retrospective examination of serial bone marrow biopsy specimens demonstrated progressive bone marrow fibrosis, which may have caused prolonged myelosuppression. Thus, evaluation of bone marrow fibrosis by bone marrow biopsy after each treatment cycle might serve as a predictor of persistent myelosuppression induced by chemotherapy.

Hypercalcemia associated with the interaction between all trans retinoic acid and posaconazole in an acute promyelocytic leukemia case

2021 ◽  
pp. 107815522110078
Author(s):  
Hacer Berna Afacan Ozturk ◽  
Murat Albayrak ◽  
Senem Maral ◽  
Merih Reis Aras ◽  
Fatma Yilmaz ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Serum Calcium ◽  
Promyelocytic Leukemia ◽  
Cytochrome P450 Enzymes ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Normal Ranges ◽  
Rare Side Effect ◽  
High Level

Introduction All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. Case Report A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. Management & Outcome Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. Discussion This case highlights the importance of monitoring ATRA’s side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2862-2864 ◽  
Author(s):  
Bruno Cassinat ◽  
Sylvie Chevret ◽  
Fabien Zassadowski ◽  
Nicole Balitrand ◽  
Isabelle Guillemot ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Event Free Survival ◽  
Free Survival ◽  
Acid Sensitivity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.

Hypercalcemia associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia

1993 ◽  
Vol 17 (5) ◽  
pp. 441-443 ◽  
Author(s):  
Masae Sakakibara ◽  
Motoki Ichikawa ◽  
Yoshiro Amano ◽  
Shigeyuki Matsuzawa ◽  
Kazunaga Agematsu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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