Outcome of Childhood Acute Promyelocytic Leukemia With All-Trans-Retinoic Acid and Chemotherapy

2004 ◽  
Vol 22 (8) ◽  
pp. 1404-1412 ◽  
Author(s):  
S. de Botton ◽  
V. Coiteux ◽  
S. Chevret ◽  
C. Rayon ◽  
E. Vilmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Survival Rates ◽  
Age Groups ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Results Of Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Purpose To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL). Patients and Methods Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both. Results Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ months, six remained in second CR after 17+ to 66+ months, and three patients had died. The 5-year event-free survival (EFS), relapse, and overall survival rates were 71%, 27%, and 90%, respectively. No difference between adults and children included in the APL93 trial was seen for CR rate, 5-year relapse rate, EFS, and overall survival, but significantly better survival was seen in children after adjustment on WBC counts (P = .02) and incidence of microgranular M3 variant (P = .04). Conclusion ATRA combined with CT for induction and also probably for maintenance provides as favorable results in children with APL as in adults and currently constitutes the reference first-line treatment in both age groups.

scholarly journals All-trans-retinoic acid–induced pseudotumor cerebri in acute promyelocytic leukemia

2014 ◽  
Vol 05 (03) ◽  
pp. 273-275
Author(s):  
T. M. Anoop ◽  
Nidhi Jain ◽  
Sreejith G. Nair ◽  
Geetha Narayanan
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Induction Therapy ◽  
Treatment Strategy ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

ABSTRACTAll-trans-retinoic acid is an integral part in the treatment strategy of acute promyelocytic leukemia (APL). Here we describe a case of pseudotumor cerebri associated with all-trans-retinoic acid (ATRA) during the induction therapy in an adult with acute promyelocytic leukemia (APL).

Expression of the Wilms’ Tumor 1 (WT1) Gene Renders Acute Promyelocytic Leukemia Cells Resistant to All-Trans-Retinoic-Acid-Induced Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4385-4385
Author(s):  
Aschwin L. Menke ◽  
Ruth H.J.N. Knops ◽  
Jurgen A.F. Marteijn ◽  
Willemijn Wissink ◽  
Josie Smeets ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Wilms Tumor ◽  
Promyelocytic Leukemia ◽  
Induced Differentiation ◽  
Expression Levels ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Wilms Tumor 1

Abstract Acute myeloid leukemia is characterized by the uncontrolled proliferation of immature cells that have lost their ability to differentiate. In the case of acute promyelocytic leukemia (AML-M3), the cells can be forced to differentiate by pharmacological dosages of all-trans retinoic acid (ATRA), a phenomenon that is successfully used in the treatment of APL patients. About 70% of the patients, suffering from PML-RARa -positive acute promyelocytic leukemia, can be cured with a combination of ATRA and anthracycline - based chemotherapy. However, relapse remains a major problem. The molecular mechanisms by which the retinoic acid receptors mediate their biological functions have been studied extensively and although various retinoic acid-responsive genes have been identified, the target genes that are crucially involved in leukemogenesis are unknown. The Wilms’ Tumor 1 gene, has been implicated in the development of leukemia. WT1 overexpression can be detected in most acute leukemias and is particularly highly expressed in APL cells. Several groups have found an inverse correlation between the expression levels of WT1 and the overall survival of leukemia patients. The underlying mechanism, however, remains to be elucidated. We have shown that the Wilms’ Tumor 1 (WT1) is strongly downregulated in APL cells, during ATRA-induced differentiation. Using a newly developed realtime RT-PCR method we have found that the expression levels of all four major WT1 isoforms are downregulated. To study the biological activity of each WT1-isoform, we have retrovirally transduced the APL cell line NB4, with the 4 major WT1 isoforms and analyzed the effect on ATRA-induced differentiation. Using flowcytometry and NBT staining, we show that ectopic expression of the different WT1-isoform inhibited ATRA-induced differentiation and subsequently, the apoptosis of APL cells, albeit with different potential. WT1-transduced cells survived pharmacological dosages of ATRA for more than 14 days and in some cases even continued to grow. These data indicate that downregulation of WT1 is essential for ATRA-induced differentiation of APL cells and provide an explanation why AML patients with high WT1 expression levels have worse overall survival in comparison to patients with low WT1 expression levels.

Pseudotumor Cerebri Associated with All-Trans Retinoic Acid Treatment During Induction Therapy for Acute Promyelocytic Leukemia: A Case Report and Literature Review

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4264-4264
Author(s):  
Dylan Holmes ◽  
David M. Aboulafia
Keyword(s):  
Retinoic Acid ◽  
Intracranial Pressure ◽  
Literature Review ◽  
Acute Promyelocytic Leukemia ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Induction Treatment ◽  
Fluid Composition ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 4264 Pseudotumor cerebri (PC) is a rare disorder characterized by elevated intracranial pressure with normal cerebrospinal fluid composition, normal cranial imaging findings, and symptoms and signs of increased intracranial pressure. A number of medications have been linked to PC including vitamin A and its derivative all-trans-retinoic acid (ATRA). Herein, we describe the case of a 38-year-old woman who was diagnosed with PC during standard induction treatment for acute promyelocytic leukemia (APL). Her neurologic complaints of severe headache and diplopia improved slightly after ATRA was discontinued and she was treated with acetazolamide, but symptoms did not abate until fluconazole was held five days later. Through a literature review, we identified 41 case reports of APL patients with ATRA-associated PC, 23 of which provided details of clinical presentation and follow-up. The median age at diagnosis of PC was 27 for females and 16 for males; the female-to-male ratio was 1.3:1. All 23 patients complained of headache; papilledema was present in all 21 instances (100%) where a retinal exam was described. ATRA was held due to PC in 20 cases (87%), and neurologic symptoms resolved without further intervention in 7 of 20 (35%). The remaining 13 patients were treated with diuretics (11 of 13 cases, 85%), high-volume lumbar punctures (5, 38%), corticosteroids (4, 31%), and/or analgesics (3, 23%). Including our index patient, eight patients were rechallenged with ATRA after neurologic improvement, and 5 (63%) required further interventions to resolve recrudescent symptoms. We identified one other patient whose neurologic complaints persisted despite dose reductions in ATRA. This patient improved only after fluconazole was discontinued. Because both ATRA and fluconazole are metabolized by the cytochrome P-450 system, we suggest that if taken concurrently, they may exacerbate the risk of PC. Physicians should be aware of this interaction between ATRA and fluconazole and consider discontinuing both fluconazole and ATRA in APL patients who develop PC. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pseudotumor Cerebri in a Patient with Acute Promyelocytic Leukemia during Treatment with All-Trans Retinoic Acid.

1998 ◽  
Vol 37 (6) ◽  
pp. 546-549 ◽  
Author(s):  
Fumiaki SANO ◽  
Kazue TSUJI ◽  
Norifumi KUNIKA ◽  
Toshio TAKEUCHI ◽  
Ken OYAMA ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

CD56 Expression Is an Indicator of Poor Clinical Outcome in Patients With Acute Promyelocytic Leukemia Treated With Simultaneous All-Trans-Retinoic Acid and Chemotherapy

2000 ◽  
Vol 18 (6) ◽  
pp. 1295-1300 ◽  
Author(s):  
Felicetto Ferrara ◽  
Fortunato Morabito ◽  
Bruno Martino ◽  
Giorgina Specchia ◽  
Vincenzo Liso ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retinoic Acid ◽  
Clinical Outcome ◽  
Acute Promyelocytic Leukemia ◽  
Statistical Significance ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cd56 Expression ◽  
Wbc Count

PURPOSE: Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy. PATIENTS AND METHODS: Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis. RESULTS: Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56+. No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56+ and CD56− populations. Conversely, compared with patients who were CD56−, patients with CD56+ APL had shorter CR duration (P = .04) and overall survival (P = .002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 × 109 cells/L retained statistical significance in overall survival (P = .04 and P = .02, respectively). CONCLUSION: The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.

scholarly journals Pseudotumor Cerebri in the Setting of Differentiation Syndrome in a Patient with Acute Promyelocytic Leukemia Treated with All-trans Retinoic Acid During Induction Therapy

2021 ◽  
Vol 18 (4) ◽  
pp. 54-58
Author(s):  
Barsha Suwal ◽  
Bishesh Sharma Poudyal ◽  
Rabindra Adhikary
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Systemic Infection ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
High Grade Fever ◽  
Acid Therapy ◽  
Ophthalmic Manifestations ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Introduction: Differentiation syndrome, a well-known complication of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APML), can very rarely have ophthalmic manifestations. Pseudotumor cerebri (PC) in the setting of differentiation syndrome (DS) in patients undergoing induction with all-trans retinoic acid has rarely been reported elsewhere. We herein report one such case. Case Presentation: A 28-year-old, non-obese female diagnosed as acute promyelocytic leukemia underwent induction with all- trans retinoic acid and Idarubicin. On day 4 of the treatment, she developed high grade fever (104 – 105 F), dry cough, hypotension, tachycardia, and tinnitus. Chest X ray showed floppy shadows in bilateral lungs. On physical examination, bilateral lower limb edema was noted. She also experienced sudden weight gain of 5 kilogram in 48 hours. After careful exclusion of systemic infection, she was suspected as having DS. She also noticed a reduction in vision in right eye. On eye examination, her best-corrected visual acuity (VA) was 6/60 in the right eye (RE) and 6/6 in the left eye (LE). Fundus evaluation revealed bilateral disc edema with peripapillary hemorrhages along with slight tortuosity of vessels and a yellowish lesion over the fovea in RE. Suspecting DS, she was treated with injection dexamethasone 10 mg twice daily and all- trans retinoic acid was temporarily discontinued. Immediately after its discontinuation, her headache lessened and vision improved gradually. After 2 weeks, her VA was 6/12 in RE and 6/6 in LE which improved to 6/6 in both eyes at 3 months. The patient was also receiving oral voriconazole for fungal prophylaxis and the potentiation effect of all- trans retinoic acid could thus be explained. Conclusion: Pseudotumor cerebri associated with all-trans retinoic acid treatment in acute promyelocytic leukemia, even though frequently reported in pediatric patients, is rare in adults. Ophthalmological evaluation is mandatory in all these patients under all-trans retinoic acid therapy.

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