Therapy-Related Acute Promyelocytic Leukemia

2003 ◽  
Vol 21 (11) ◽  
pp. 2123-2137 ◽  
Author(s):  
M. Beaumont ◽  
M. Sanz ◽  
P.M. Carli ◽  
F. Maloisel ◽  
X. Thomas ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Acute Promyelocytic Leukemia ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Promyelocytic Leukemia ◽  
Actuarial Survival ◽  
All Trans Retinoic Acid ◽  
Primary Disorder ◽  
Primary Neoplasm ◽  
Median Interval

Purpose: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. Patients and Methods: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. Results: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin’s lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine–based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. Conclusion: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II–targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.

Preliminary Results of a Consolidation Therapy Consisting Single Anthracycline Agent and Alternative All-Trans Retinoic Acid in Acute Promyelocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4284-4284
Author(s):  
Zhang Jie ◽  
Xiaojian Meng ◽  
Zhen Cai ◽  
Xiujin Ye ◽  
He Huang
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Treatment Strategies ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Preliminary Results ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 4284 Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with distinctive biologic and clinical features that is now highly curable. However, there are complicated issues in treatment strategies for induction, consolidation and maintenance that remain to be studied. The optimal regimen and the duration of consolidation is one of the above controversies. Patients and methods: Six patients (4 males, 2 females) were enrolled in this observation with a median age of 28 years (18–36). All were diagnosed de novo APL with demonstration of the abnormal increased promyelocytes of 53–90% accompanied with detection of t(15;17) or PML/RARα rearrangements. At diagnosis, WBC counts were 0.9–4.6×109/L and platelet counts were 13–84×109/L. Induction therapy was composed of all-trans retinoic acid (ATRA) with or without anthracycline or homoharritonine. After achieving complete remission (CR) following the above regimens, consolidation therapy was given monthly consisting single anthracycline agent of idarubincin (8–10 mg/m2/d, day 1–3) or aclarubicin (8–12 mg/m2/d, day 1–7) and alternative ATRA (25 mg/m2/d, day 1–15). After 12–18 months of consolidation, patients received maintenance therapy including methotrexate (12 mg/m2/d, per week) plus 6 mercaptopurine (30 mg/m2/d, qod ×12 days) and alternative ATRA (25 mg/m2/d, day 1–15) for one year. Results and conclusions: At present, all of the six patients are in continuous CR status, four of whom ceased treatment and are undergoing regular monitoring. Preliminary results from our experience demonstrates that single anthracycline and alternative ATRA can act as a valid option with limited toxicity for APL and might be used as a consolidation strategy, particularly for low and intermediate-risk patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Acute Promyelocytic Leukemia: 37 Years Long Ongoing Survival in a de novo Patient with Metal-Based Ayurvedic Treatment

2020 ◽  
Vol 06 (03) ◽  
pp. 147-148
Author(s):  
Balendu Prakash ◽  
Shikha Prakash ◽  
Sneha Tiwari
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
De Novo ◽  
Fusion Gene ◽  
Bone Marrow Aspiration ◽  
Promyelocytic Leukemia ◽  
New Delhi ◽  
Medical Centers ◽  
All Trans Retinoic Acid ◽  
Established Line ◽  
Ayurvedic Treatment

AbstractAcute promyelocytic leukemia (APML) is a subtype of acute myeloid leukemia. The condition is clinically marked by anemia, fatigue, weakness, frequent infections, and fever associated with easy bleeding and coagulopathy. The diagnosis is made through bone marrow aspiration exhibiting increased promyelocytes and test for PML-RARα fusion gene. There has been remarkable progress in the treatment of APML in the past few decades with the induction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). This has also brought down mortality and relapse rates considerably. Similarly, nearly 90% patients are able to live disease free for about 10 years. However, there are certain hindrances to these treatments majorly due to side effects, relapses, and limited periods of remission associated with ATRA and ATO. Here, a freshly diagnosed case of APML is being reported. The patient was diagnosed in leading medical centers of Aligarh and New Delhi and only treated with blood transfusions in the absence of an established line of treatment in 1982. The patient has completed 37 years long survival without any sign of the disease and any adverse effect. This approach could be considered as an add-on medical therapy for APML.

scholarly journals New frontiers of target therapy in oncology: acute promyelocytic leukemia

2014 ◽  
Vol 31 (1) ◽  
pp. 17-28
Author(s):  
Ivan Petković ◽  
Ivica Pejčić ◽  
Svetislav Vrbić
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Target Therapy ◽  
Promyelocytic Leukemia ◽  
Hematopoietic Stem ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Optimal Drug ◽  
Risk Patients

SUMMARY By introduction of all-trans retinoic acid (ATRA) in de novo acute promyelocytic leukemia (APL) an revolution in therapy of this disease has been made. The rate of molecular complete remissions (CR) have been doubled compared to conventional chemotherapy with anthracyclines ranging from 90% to 95%. Consolidation therapy is required in order to reduce the risk of early relapse. Maintenance therapy is recommended as it further reduces the risk of relapse, especially in high-risk patients. The relapse rate in APL is relatively high, about 30% and is the most common within three years of starting the treatment. Another agent, arsenic trioxide (ATO) is the optimal drug that achieves high CR rate in relapsed, approximately 80% and hematopoietic stem cell transplantation (HSCT) may prolong the overall survival in patients with APL. ATRA and ATO have become a paradigm of targeted therapy, and APL is a paradigm of curable disease, at least in comparison to other forms of acute myeloid leukemia (AML).

scholarly journals Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3383-3390 ◽  
Author(s):  
Syed Khizer Hasan ◽  
Ashley N. Mays ◽  
Tiziana Ottone ◽  
Antonio Ledda ◽  
Giorgio La Nasa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multiple Sclerosis ◽  
Acute Promyelocytic Leukemia ◽  
Dna Cleavage ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Promyelocytic Leukemia ◽  
Chromosome 15 ◽  
Topoisomerase Iiα ◽  
Intron 2

Abstract Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17) translocation is a well-recognized complication of cancer treatment with agents targeting topoisomerase II. However, cases are emerging after mitoxantrone therapy for multiple sclerosis (MS). Analysis of 12 cases of mitoxantrone-related t-APL in MS patients revealed an altered distribution of chromosome 15 breakpoints versus de novo APL, biased toward disruption within PML intron 6 (11 of 12, 92% vs 622 of 1022, 61%: P = .035). Despite this intron spanning approximately 1 kb, breakpoints in 5 mitoxantrone-treated patients fell within an 8-bp region (1482-9) corresponding to the “hotspot” previously reported in t-APL, complicating mitoxantrone-containing breast cancer therapy. Another shared breakpoint was identified within the approximately 17-kb RARA intron 2 involving 2 t-APL cases arising after mitoxantrone treatment for MS and breast cancer, respectively. Analysis of PML and RARA genomic breakpoints in functional assays in 4 cases, including the shared RARA intron 2 breakpoint at 14 446-49, confirmed each to be preferential sites of topoisomerase IIα-mediated DNA cleavage in the presence of mitoxantrone. This study further supports the presence of preferential sites of DNA damage induced by mitoxantrone in PML and RARA genes that may underlie the propensity to develop this subtype of leukemia after exposure to this agent.

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.

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