ACUTE PROMYELOCYTIC LEUKEMIA (APL) IN PATIENTS AGED > 70 Years.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4160-4160
Author(s):  
Paola Finsinger ◽  
Massimo Breccia ◽  
Clara Minotti ◽  
Ida Carmosino ◽  
Laura Cannella ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Promyelocytic Leukemia ◽  
Very Elderly ◽  
Free Survival ◽  
All Trans Retinoic Acid ◽  
Lost To Follow Up

Abstract Abstract 4160 Acute Promyelocytic Leukemia (APL) is a rare subtype of Acute Myeloid Leukemia (AML) more common in younger adults, with a median age of 45 – 50 years at onset. The use of All-trans Retinoic Acid (ATRA) as tailored treatment has made APL a very curable disease also in patients aged > 60 years; however, there are only few case reports in very elderly APL patients. To address this issue, we revised clinical data and treatment results in 12 patients aged > 70 years with newly diagnosed APL followed at our Institution from 1/91 to 12/2008. Clinical characteristics at onset were as follows: M/F 7/5, median age 74.7 years (range 70.0 – 80.8), M3/M3v 11/1, median WBC 1.3 × 109/l (range 1.0 – 7.4), median PLTS 53 × 109/l (range 12 – 302), BCR1/BCR3 6/6. According to Sanz risk score, 7 patients were at low-risk and 5 at intermediate-risk; 6/12 patients had arterial hypertension, 4/12 a concomitant cardiologic disease, 3/12 a cerebro-vascular disease and 2/12 a previous neoplasia. Induction therapy consisted of ATRA + Idarubicin in 8 patients (2/8 with reduced Idarubicin dosage) and ATRA alone in 4 patients; in this latter group, however, 2/4 needed to add chemotherapy (CHT) based on Mitoxantrone + AraC due to hyperleukocytosis during ATRA treatment. All patients achieved both morphological and molecular Complete Remission (CR) after a median time of 50 (range 29 – 65) and 105 (range 51 – 239) days, respectively. Infective complications were observed in 10/12 patients (4 episodes of FUO, 6 sepsis, 2 cystitis and 1 oral abscess) while ATRA syndrome occurred in 2/12 patients; in addition, there were 3 episodes of cardiac ischemia and 3 episodes of paroxystic atrial fibrillation. All but one patient received consolidation therapy (based on CHT alone in 7 patients, CHT + ATRA in 3 patients and ATRA alone in 1 patient), followed by maintenance treatment in 8 patients. Four patients had a relapse (hematological in 3 cases and molecular in 1 case) after 8, 11, 35 and 56 months respectively. At present, 6 patients are still alive, 4 died due to disease progression (3) or senectus while in CR (1) and 2 were lost to follow-up while in CR: mean event-free survival and overall survival were 89.2 months (95%CI 52.6 – 125.8) and 99.9 months (95%CI 65.0 – 134.7), respectively. In conclusion, ATRA-based treatment of APL is safe and effective also in very elderly patients, with long-lasting disease-free and overall survival. Disclosures: No relevant conflicts of interest to declare.

Treatment of newly diagnosed acute promyelocytic leukemia without cytarabine.

1997 ◽  
Vol 15 (2) ◽  
pp. 483-490 ◽  
Author(s):  
E Estey ◽  
P F Thall ◽  
S Pierce ◽  
H Kantarjian ◽  
M Keating
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Current Treatment ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Current Group ◽  
Free Survival ◽  
All Trans Retinoic Acid

PURPOSE To determine the effect of omission of cytarabine (ara-C) from treatment of newly diagnosed acute promyelocytic leukemia (APL), which allows administration of more anthracycline. PATIENTS AND METHODS Induction consisted of all-trans retinoic acid (ATRA) 45 mg/m2 daily until complete remission (CR) and idarubicin 12 mg/m2 daily for 4 days beginning on day 5 of ATRA. Patients in CR received two courses of idarubicin 12 mg/m2 daily for 3 days and then, until 2 years post-CR date, alternated three cycles of mercaptopurine, vincristine, methotrexate, and prednisone (POMP) with one cycle of idarubicin 12 mg/m2 daily for 2 days. Results in the 43 patients treated (41 with t(15;17) on standard or Southern analysis) were compared with those in 57 historic newly diagnosed APL patients given ara-C with either doxorubicin, amsacrine (AMSA), or daunorubicin without ATRA, using logistic and Cox regression to assess effects of non-treatment-related covariates on patient outcomes. RESULTS The CR rate in the current group was 77% (95% confidence interval [CI], 62% to 88%) and was not significantly different from the historic rate. In contrast, disease-free survival (DFS) in CR is superior in the current group (probability at 1 year 0.87; 95% CI, 0.73 to 1.0). This has translated into superior overall DFS for the current group (P = .03 adjusting for the predictive covariates initial WBC and platelet count; 1-year DFS probability 0.67; 95% CI, 0.52 to 0.82; median follow-up 102 weeks). The current treatment appears better both in patients with and without t(15; 17) on standard cytogenetic analysis. CONCLUSION Given the difficulties inherent in comparing sequential studies and recognizing the multiple differences in treatment between current and historic groups, our results suggest that a large randomized trial incorporating use of ATRA should assess the utility of omitting ara-C from treatment of newly diagnosed APL, thus allowing delivery of more anthracycline.

Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia

2021 ◽  
pp. 107815522110247
Author(s):  
Kyle Zacholski ◽  
Bryan Hambley ◽  
Erin Hickey ◽  
Sarah Kashanian ◽  
Andrew Li ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
All Trans Retinoic Acid ◽  
Grade 3 ◽  
Disease Free

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

scholarly journals Oral arsenic trioxide–based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6535-6543 ◽  
Author(s):  
Wing-Yan Au ◽  
Cyrus R. Kumana ◽  
Harold K. K. Lee ◽  
Shek-Ying Lin ◽  
Herman Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Chemotherapeutic Agents ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Wbc Count ◽  
First Complete Remission

Abstract Seventy-six patients with acute promyelocytic leukemia (APL) in first complete remission after induction and consolidation by daunorubicin and cytosine arabinoside received oral arsenic trioxide (As2O3)-based maintenance. Three regimens were used: oral As2O3 (10 mg/day, regimen A, n = 20), oral As2O3 plus all-trans retinoic acid (ATRA, 45 mg/m2 per day, regimen AA, n = 19), and oral As2O3 plus ATRA plus ascorbic acid (1000 mg/day, regimen AAA, n = 37), each given for 2 weeks every 2 months for 2 years. Patients receiving A, AA, and AAA maintenance did not differ significantly in clinicopathologic features and risk factors. Headache, dyspepsia, reversible liver function derangement, and herpes zoster reactivation were adverse effects observed during maintenance. QTc prolongation and arrhythmias were not encountered. At a median follow-up of 24 months (range, 1-115 months), there were 8 relapses. The 3-year leukemia-free-survival, event-free-survival, and overall-survival were 87.7%, 83.7%, and 90.6%, respectively. Adverse prognostic factors included male gender for leukemia-free-survival, and unrelated cancers for overall survival. Age, presentation WBC count and platelet count, and the type of oral As2O3 maintenance regimens had no impact on survivals. Prolonged oral As2O3 maintenance was feasible and safe and resulted in favorable outcomes when used with a simple induction and consolidation regimen compared with other protocols composed of multiple chemotherapeutic agents.

scholarly journals Does microgranular variant morphology of acute promyelocytic leukemia independently predict a less favorable outcome compared with classical M3 APL? A joint study of the North American Intergroup and the PETHEMA Group

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5650-5659 ◽  
Author(s):  
Martin S. Tallman ◽  
Haesook T. Kim ◽  
Pau Montesinos ◽  
Frederick R. Appelbaum ◽  
Javier de la Serna ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retinoic Acid ◽  
Cumulative Incidence ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Disease Free

Abstract Few studies have examined the outcome of large numbers of patients with the microgranular variant (M3V) of acute promyelocytic leukemia (APL) in the all-trans retinoic acid era. Here, the outcome of 155 patients treated with all-trans retinoic acid–based therapy on 3 clinical trials, North American Intergroup protocol I0129 and Programa para el Estudio de la Terapéutica en Hemopatía Maligna protocols LPA96 and LPA99, are reported. The complete remission rate for all 155 patients was 82%, compared with 89% for 748 patients with classical M3 disease. The incidence of the APL differentiation syndrome was 26%, compared with 25% for classical M3 patients, and the early death rate was 13.6% compared with 8.4% for patients with classical M3 morphology. With a median follow-up time among survivors of 7.6 years (range 3.6-14.5), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse for patients with M3V were 70%, 73%, and 24%, respectively. With a median follow-up time among survivors of 7.6 years (range 0.6-14.3), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse among patients with classical M3 morphology were 80% (P = .006 compared with M3V), 81% (P = .07), and 15% (P = .005), respectively. When outcomes were adjusted for the white blood cell count or the relapse risk score, none of these outcomes were significantly different between patients with M3V and classical M3 APL.

scholarly journals Realgar Indigo Formula Plus ATRA As Postremission Treatment in an Rral and Chemo-Free Model for High-Risk Acute Promyelocytic Leukemia Patients: A Prospective, Multicenter, Phase II Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 873-873
Author(s):  
Hong-hu Zhu ◽  
Ya-fang Ma ◽  
Suning Chen ◽  
Ying Lu ◽  
Jiang Huang ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Phase Ii ◽  
Divided Dose ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Free Model

Abstract Background: Low-risk patients with acute promyelocytic leukemia (APL) can be cured using only ATRA and arsenic trioxide (ATO), without chemotherapy(Lo-Coco F, et al. NEJM 2013) .Our group simplified the protocol by replacing iv ATO with oral arsenic, referred to as RIF, allowing for outpatient, oral and chemotherapy-free treatment for an increasing number of APL patients (Zhu HH, et al. NEJM 2014; 371:2239-41;Zhu HH, et al. Lancet Oncol 2018;19:871-879; Zhu HH, et al. Blood 2019;134:597-605). We also reported a promising single-center results using chemo-free postremission treatment for high-risk APL patients (Zhu HH, Blood 2018;131:2987-2989), which need to be confirmed in a well designed multi-center trial. Objective: To evaluate the efficacy of safety Realgar indigo formula plus retinoic acid as postremission treatment in an oral and chemo-free model for high-risk APL patients . Design, setting and participants: a prospective, multicenter, single-arm, phase II clinical trial conducted in the First Affiliated Hospital, Zhejiang University College of Medicine, China. Eligible patients (>18 years old) with newly diagnosed APL and achieved complete remission(CR) were enrolled since May 2019, with final follow-up in July 31,2021. Interventions: The consolidation therapy included realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and4-week-off regimen for 4 cycles and ATRA (25 mg/m 2 daily in anoral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary endpoint was the 2-year DFS. Secondary endpoints included complete molecular remission (CMR) defined as the absence of detectable PML-RARA transcripts., event-free survival (EFS), OS, and safety. Main outcomes and measures: 38 eligible patients were enrolled including 18 males and 20 females and the median age was 41 years old (18-77 years). The median of WBC count is 25.39（10.2-113.9）×109/L[ >50×10 9/L n=10; (20-50)×10 9/L n=14，(10-20)×10 9/L n=14].All the patients achieved CMR during post-remission treatment phase (7 months). Until now, no molecular, hematologic recurrence,and central nervous system leukemia has happened with median follow-up of 13 months. What's more, this chemotherapy-free, completely oral regimen was well tolerated. C onclusions: These exciting results proved that RIF plus retinoic acid as postremission treatment of high-risk APL was effective, safe and convenient. The study is ongoing, and the effective of this regimen need to be evaluated by more patients and longer time. Figure 1. The overall survival(OS) and disease-free survival (DFS) of high-risk APL patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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.

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 Early Detection of t(8;21) Chromosomal Translocations during Treatment of PML-RARA Positive Acute Promyelocytic Leukemia: A Case Study

2010 ◽  
Vol 4 ◽  
pp. CMO.S6446 ◽  
Author(s):  
Walter Kleine Neto ◽  
Mariana Serpa ◽  
Sabri Saeed Sanabani ◽  
Patricia Torres Bueno ◽  
Elvira Deolinda Rodrigues Pereira Velloso ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Genetic Screening ◽  
Treatment Initiation ◽  
Single Case ◽  
Promyelocytic Leukemia ◽  
Chromosomal Translocations ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Here we describe a female patient who developed acute promyelocytic leukemia (APL) characterized by t(l5;17) translocation at diagnosis. The patient began treatment with all-trans retinoic acid (ATRA) + chemotherapy. During follow up, the patient was found to be negative for the t(15;17) transcript after 3 months of therapy which remained undetectable, thereafter. However, the emergence of a small clone with a t(8;21) abnormality was observed in the bone marrow and peripheral blood (PB) cells between 3 and 18 months following treatment initiation. The abnormal translocation observed in PB cells obtained at 3 months was detected after the second cycle of consolidation therapy and reappeared at 15 months during maintenance treatment, a period without ATRA. Although based on a single case, we conclude that genetic screening of multiple translocations in AML patients should be requested to allow early identification of other emerging clones during therapy that may manifest clinically following treatment.

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