scholarly journals Pilot Study on the Safety of Intravenous Arsenic Trioxide and Oral Realgar-Indigo Naturalis Formula Administrated in Children with Acute Promyelocytic Leukemia: A Single-Center Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2611-2611
Author(s):  
Linya Wang ◽  
Yuanyuan Zhang ◽  
Ruidong Zhang ◽  
Jiaole Yu ◽  
Ying Wu ◽  
...  
Keyword(s):  
Risk Group ◽  
White Cell Count ◽  
Arsenic Concentration ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Arsenic Level ◽  
Indigo Naturalis ◽  
Postremission Therapy ◽  
Arsenic Retention

Objective Intravenous arsenic trioxide (ATO) and all-trans retinoic acid have become the front-line treatments for patients with acute promyelocytic leukemia (APL). Realgar-Indigo naturalis formula (RIF), an oral arsenic drug, not only shows a clinical efficacy comparable to ATO but also promotes incorporating an outpatient postremission therapy model into clinical practice for both low-risk and high-risk APL patients in China. However, the safety of ATO/RIF used in children with APL is unknown. To assess the safety of arsenic (ATO/RIF) administrated in children with APL, we designed the study. Methods Children with newly diagnosed APL treated with CCLG-APL2016 protocol (ChiCTR-OIN-17011227) in Beijing Children's Hospital from July 2016 to December 2018 were eligible for the study. The arsenic concentrations in different tissues, including plasma, urine, hair and nail, were measured at 10 time points: before ATO/RIF(D0), on the 7th, 14th and 28th day of ATO/RIF administration(D7, D14, D28), on the end of consolidation therapy (Con), during the 10 weeks of maintenance therapy (W10), on the cessation of therapy, after six months, one year and 1.5 years without arsenic administration. Adverse reactions were observed to evaluate the safety of arsenic received in children with APL. Results Nineteen patients with newly diagnosed APL were enrolled, including 9 boys and 7 girls with an onset average age of (10.9±3.7) years. There were 14 patients in low-risk group (white cell count <10,000/ul) and 5 patients in high-risk group (white cell count≥10,000/ul). All of them got hematologic complete remission (HCR) and molecular complete remission (MCR). The time to get HCR and MCR were 31 days (range, 27~74days) and (72.2±16.4) days, respectively. Besides, there were 13 patients getting ATO and 6 patients getting RIF in induction phase, and all patients receiving RIF as an outpatient postremission therapy. It showed that plasma and urine arsenic levels were significantly elevated after ATO/RIF administration. The median plasma arsenic ranged from 38.4 ng/ml to 76.10 ng/ml on D7, D14, D28, Con and W10 while the median urine arsenic retention ranged from 1562.80ng/ml to 3791.00ng/ml on D7, D14, D28, Con and W10. Plasma arsenic level rapidly decreased to 1.01 ng/ml after six months without RIF administration, which was slightly higher than D0 (1.01ng/ml vs 0.60ng/ml, P=0.043) and decreased to normal after 1 year without arsenic administration compared with D0 (0.55 ng/ml vs 0.60ng/ml, P=0.655). Urine arsenic level decreased to normal within 0~6 months off therapy (25.80ng/ml vs 13.74ng/ml, P=0.866). Hair arsenic (6480.95ng/g, range 2616.20-14683.70ng/g) and nail arsenic levels (17896.85ng/g, range 400.00-30334.00ng/g) peaked at the time of cessation of therapy. Hair arsenic level decreased to normal within half a year off arsenic (156.50 ng/g vs 103.45 ng/g, P=0.345) while nail arsenic retention decreased to normal after 1 year off arsenic (P=0.655). In addition, Spearman rank correlation analysis showed that plasma arsenic concentration was positively correlated with urine (r=0.825, P<0.001), hair (r=0.595, P<0.001) and nail (r=0.584, P<0.001) arsenic. Urine arsenic were also positively correlated with hair (r=0.624, P<0.001), and nail (r=0.575, P<0.001). And arsenic concentration in hair was positively correlated with nail (r=0.805, P<0.001), too. Conclusions Through the detection of arsenic concentration in different periods and different tissues, it was found that the plasma arsenic concentration could be maintained within the effective concentration range in each treatment stage, and the arsenic concentration in plasma and hair gradually decreased to normal after six months off arsenic. Urine and nail arsenic went down to normal after 1 year off arsenic. Up to now, with a longest follow-up period of 34.7 months and the mean follow-up time of 19.6 months, the short-term response of arsenic disappeared after symptomatic therapy or arsenic reduction, and no chronic side effects of arsenic were observed. Therefore, the use of ATO/RIF in children with APL is safe, but it still needs long-term follow-up. Disclosures No relevant conflicts of interest to declare.

Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long-Term Follow-Up Data

2010 ◽  
Vol 28 (24) ◽  
pp. 3866-3871 ◽  
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Ezhilarasi Chendamarai ◽  
Kavitha M. Lakshmi ◽  
Salamun Desire ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Single Agent ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Long Term Follow Up

Purpose We previously reported our results with a single-agent arsenic trioxide (ATO) –based regimen in newly diagnosed cases of acute promyelocytic leukemia (APL). The concern remained about the long-term outcome of this well-tolerated regimen. We report our long-term follow-up data on the same cohort. Patients and Methods From January 1998 to December 2004, 72 patients with PML/RARα+ APL were enrolled. All patients were treated with a single-agent ATO regimen. Results Overall 62 (86.1%) achieved a hematologic remission (complete remission). After the initial report, an additional seven patients have relapsed for a total of 13 relapses. There were no additional toxicities to report on follow-up. At a median follow-up 60 months, the 5-year Kaplan-Meier estimate (± SE) of event-free survival, disease-free survival, and overall survival (OS) was 69% ± 5.5%, 80% ± 5.2%, and 74.2% ± 5.2%, respectively. The OS in the good risk group as defined by us remains 100% over this period. Conclusion Single-agent ATO as used in this study in the management of newly diagnosed cases of APL is safe and is associated with durable responses. Results in the low-risk group are comparable to that reported with conventional therapy while additional interventions would probably be required in high-risk cases.

scholarly journals The simpler, the better: oral arsenic for acute promyelocytic leukemia

Blood ◽  
2019 ◽  
Vol 134 (7) ◽  
pp. 597-605 ◽  
Author(s):  
Hong-Hu Zhu ◽  
Jiong Hu ◽  
Francesco Lo-Coco ◽  
Jie Jin
Keyword(s):  
Quality Of Life ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Special Focus ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Therapy Model ◽  
Indigo Naturalis ◽  
Postremission Therapy

Abstract Arsenic trioxide and all-trans retinoic acid have become the frontline treatments for patients with acute promyelocytic leukemia (APL). Despite the long wait for an oral arsenic drug, a commercially available agent, realgar–indigo naturalis formula (RIF), was not launched in China until 2009. Since then, over 5000 APL patients have been treated with oral RIF in China. Oral arsenic not only shows a clinical efficacy comparable to that of IV formulations but also displays a better safety profile, improved quality of life, and lower medical costs for patients. The promising results promote incorporating an outpatient postremission therapy model into clinical practice for both low-risk and high-risk APL patients in China. In this review, we discuss the evolution of oral arsenic RIF in the treatment of APL, with a special focus on how to address the related complications during induction therapy.

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.

Single Agent Arsenic Trioxide Regimen for the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Initial Results of a Multicenter Randomized Controlled Study From India to Study the Optimal Duration of Arsenic Trioxide Maintenance Therapy (IAPLSG04).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2082-2082 ◽  
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Farah Jijina ◽  
Cecil Ross ◽  
Reena Nair ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Single Agent ◽  
Promyelocytic Leukemia ◽  
Controlled Study ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Short Period

Abstract Abstract 2082 Poster Board II-59 Single agent arsenic trioxide (ATO) has proven efficacy in the management of newly diagnosed cases of acute promyelocytic leukemia (APL). To validate findings of an initial single center experience (Blood 2006:107; 2627) with this low cost, well tolerated, effective regimen, a multicenter study was undertaken in a resource constrained environment. Additionally, in an effort to improve on the earlier experience and study the role of duration of maintenance on reducing late relapses, patients were randomized to 6 vs. 12 months of ATO maintenance (ClinicalTrials.gov Identifier:NCT00517712). From July, 2004 to December, 2008, 182 patients were initially screened and enrolled based on morphological diagnosis of APL from 7 centers in India. Diagnosis was subsequently confirmed by molecular methods. Twenty seven cases were excluded from analysis (6 RT-PCR negative, 4 IC bleed at diagnosis, 5 septic/pneumonia at diagnosis, 9 withdrew consent prior to randomization and some were treated with other protocols, 1 withdrawn by investigator prior to randomization). Patients were treated with single agent ATO at standard doses (10mg/day for adults and 0.15mg/kg/day for pediatric patients) for up to 60 days in induction; this was followed by a 28 day consolidation after a 4 week break. Four weeks after completion of consolidation patients who were in molecular remission were randomized to 6 vs. 12 months of maintenance therapy with ATO administered for 10 days/month. Hydroxyurea was permitted for control of leucocytosis. Anthracyclines were permitted in induction for patients presenting with or WBC count rising >20×109/L in the first week, >50×109/L in the second week and for those who developed a differentiation syndrome. Of the 155 patients who could be evaluated 136 (87.7%) achieved hematological remission (CHR). One patient had primary induction failure and was removed from the study while the other 18 were induction deaths at a median of 17 days (range: 4 – 69). During induction, 52 (33.5%) patients received an anthracycline and 116 (75%) received hydroxyurea. A differentiation syndrome was documented in 25 (16%) cases and was fatal in one. Grade III/IV non hematological toxicity was seen in 26 (16.7%), which resolved in the majority after discontinuing ATO for a short period. One hundred and thirty six patients were randomized, 64 (47%) and 72 (53%) into a 6 and 12 month maintenance regimen respectively. A protocol change after randomization was done in 3 cases for persistent toxicity. Five (3.6%) patients did not complete the scheduled maintenance regimen due to poor compliance or was discontinued by the investigator. At a median follow up of 24 months, the 3-year Kaplan-Meir estimate of overall survival (OS), event free survival (EFS) and disease free survival (DFS) of the entire cohort was 76.87±4.33%, 71.57±4.64% and 80.69±4.77% respectively. Fourteen patients relapsed, the median time to relapse was 19.3 months (range: 9-51). The baseline characteristics of the two groups (6vs12 months) were not significantly different. Post randomization, the two groups were analyzed on an intention to treat basis. The OS, EFS and DFS of the two groups were not statistically significantly different. There was also no evidence that the group that received 12 months of maintenance had any increased incidence of toxicity. Single agent ATO based regimen as reported previously is well tolerated and results in durable remissions. Longer follow up is required to see if 12 months of maintenance therapy reduces risk of late relapses. Disclosures: No relevant conflicts of interest to declare.

Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long Term Follow-up Data.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 846-846
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Kavitha M Lakshmi ◽  
Auro Viswabandya ◽  
Ezhilarasi Chendamarai ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Single Agent ◽  
High Risk Group ◽  
Reproductive Age ◽  
Newly Diagnosed ◽  
Long Term Follow Up ◽  
Good Risk

Abstract Abstract 846 We had previously reported a well tolerated regimen using single agent arsenic trioxide (ATO) (Blood 2006:107; 2627) leading to durable remissions in patients with newly diagnosed acute promyelocytic leukemia (APL). Briefly, the regimen consisted of ATO (10mg/day for adults and 0.15mg/kg/day for pediatric patients) for up to 60 days in induction; this was followed by a 28 day consolidation after a 4 week break. Four weeks after completion of consolidation, patients received ATO for 10 days/month for 6 months. A concern with the previous report was the relatively short duration of follow up. Here we report the long term follow-up data of the same cohort. As previously reported, 72 newly diagnosed cases of APL were enrolled. 62 patients (86.1%) achieved hematological remission. The remaining died prior to achieving remission. There were no primary induction failures. Twenty two (30.6%) of these patients were considered good risk group (WBC count at diagnosis <5×109/L and a platelet count >20×109/L), the rest were considered high risk. Since publication of the last report an additional 7 patients have relapsed to give a total of 13 relapses, 2 were in the good risk group and the remaining 11 in the high risk group. The relapses in the good risk group were salvaged with an autologous SCT and have durable continued second remissions. The median time to relapse was 1.5 years. Five (38.52%) of these relapses occurred beyond 2 years and included both relapses in the good risk group. At a median follow-up of 58 months the 5-year Kaplan-Meier overall survival (OS), event free survival (EFS) and disease free survival (DFS) of the entire cohort was 74.22±5.26%, 68.93±5.52% and 80.00±5.17% respectively. The 5-year OS and EFS of the good risk and high risk group was 100±00% vs. 63.30±6.9% and 90.00±6.71% vs. 59.66±6.99% respectively. Beyond induction, all deaths followed relapse of disease. There were no second malignancies reported. Besides the previously reported toxicities, which were mild and transient in most cases, there were no new toxicities that were reported on continued follow up of these cases. Since completion of therapy, in spite of counseling and advising against pregnancy, 3 males and 4 females in the reproductive age group have had 8 normal children. No abortions, still births or fetal defects were reported among patients in the reproductive age group in this cohort. Hair and nail samples from 5 cases that had completed maintenance therapy more than 24 months earlier have been collected for analysis, the results of which are awaited. At our center the cost of administering this regimen is a quarter of that of a conventional ATRA plus anthracycline based regimen. Additionally, after the initial induction therapy the rest of the treatment did not require hospital admission nor did it result in any Grade III/IV hematological toxicity. Single agent ATO based regimen as reported previously is well tolerated, results in durable remissions and does not have any significant late side effects. In the good risk group it is associated with excellent clinical outcomes while in the high risk group additional interventions are probably required to reduce the risk of late relapses. In a resource constrained environment it is probably the best option. Disclosures: No relevant conflicts of interest to declare.

Transfusion Needs In 28 Cases Of Acute Promyelocytic Leukemia: A Single Institutional Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4827-4827
Author(s):  
Fleur M. Aung ◽  
Jordan Myint ◽  
Erin T Roughneen ◽  
Benjamin Lichtiger
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Response To Therapy ◽  
Red Cells ◽  
Bleeding Complications ◽  
Induction Phase ◽  
Newly Diagnosed ◽  
Molecular Remission ◽  
Severe Coagulopathy

Introduction Acute Promyelocytic Leukemia (APL), a distinct subtype of acute myeloid leukemia is a relatively rare disease, characterized by a severe coagulopathy which is often present at the time of diagnosis. Mortality due to bleeding complications during induction is more common in this subtype than in other FAB classifications. The number of newly diagnosed cases in the US is estimated to be 600 to 800 cases a year. The introduction of all-trans retinoic acid (ATRA) into the therapy of APL has completely revolutionized the management and outcome of this disease. The treatment and cure of patients with APL depend not only on the effective use of combination therapy but also involves critical supportive care measures. Aim The aim of this study was to analyze the number of red cells, platelets, plasma and cryoprecipitate transfused during the induction phase of treatment until time to response. Method Patient and transfusion data was retrospectively collected from the Leukemia Department files and Blood bank records at the UT MD Anderson Cancer Center from 2010 to 2011. Results There were 28 newly diagnosed APL patients ([16F: 12 M]; 2 AA/6 Hispanic/20 White), median age 49 (21-84) and included patients who did not go on to clinical trials due to early complications. Karyotyping was obtained on 26 (93%) patients. Confirmation of the PML-RARα short or long transcripts was obtained in 25 (89%) patients by quantitative RT-PCR all of whom showed the PML-RARα fusion transcript. Induction therapy was started on day -1 to day 0 from the date of diagnosis in 5 (18%) patients, Day 1 in 13 (46%), Day 2 in 1 (3%), Day 3 in 3 (11%), Day 4 in 2 (7%), Day 6 in 3 (11%) and Day 7 in 1 (3%) patient. 24 (86%) patientsreceived Arsenic + ATRA, 3 (11%) received Arsenic + ATRA + Idarubicinand 1 (3%)received Arsenic + ATRA + Gemtuzumab Ozogamicin. 4 (14%) patients died early from complications of severe coagulopathy. Response to therapy was noted in 24 (86%) patients, median 25 (range 19-63) days from start of treatment. Red cells were transfused to 25 (89%) patients, median 6 (range 1-29) units, platelets to 23 (82%) patients, median 5 (1-47) units, plasma to 11 (39%) patients, median 8 (2-38) units and cryoprecipitate to 14 (50%) patients, median 10 (2-20) units. There was 1 (3%) patient who did not require blood or blood products, 3 (11%) did not require red cell transfusions, 5 (18%) platelet transfusions, 17 (61%) plasma transfusions and 14 (50%) did not require cryoprecipitate. Of the 24 patients who responded to therapy, 22 (79%) patients are alive. One patient has been lost to follow up. The remaining 21 (75%) patients are in molecular remission with a median follow-up of 714 (256-1110) days from the date of response. Two (7%) patients died in molecular remission from unrelated non-hematologic causes (204, 283 days from their date of response). Table 1 The results of the laboratory studies at the time of diagnosis/ time of response are as follows; WBC median 1.2 K (0.5-17.9)/median 3.3 K/UL (1.0-5.5), Hgb median 8.39 G/Dl (5.9-12.1/median 10.3 G/Dl (8.1-12.1), platelet count median 31 K/UL (3-87)/median 180 K/UL (49-1335), BM blast median 1% (0-64), median 1% (0-4), BM progranulocytes median 59% (0-93)/median 1% (0-7), BM normoblast median 9% (1-35)/median 28% (0-72%), PT median 16.2 secs (14.7-21.0)/ median 14.3 sec (13.1-15.5), INR median 1.29 (1.12-1.76)/median 1.10 (0.97-1.20), aPTT median 29.9 secs (26.0-41.0)/ median 32.2 secs (24.1-47.4), D -Dimer median 19.83 mcg/ml (3.71->20.00)/median 0.96 mcg/ml (0.39-6.09), Fibrinogen median 172 MG/DL (77-461)/ median 399 MG/DL (164-856) and LDH median 883 IU/L (374-2561)/median 591 IU/L (444-1084). Conclusion In conclusion, our review found that the majority of cases required red cells and platelet transfusion but only 50% of the patients required plasma or cryoprecipitate transfusion support for their coagulopathy. Disclosures: No relevant conflicts of interest to declare.

Prognostic Value Of GELF Criteria and FLIPI2 For Newly Diagnosed Follicular Lymphoma Receiving R-CHOP Chemotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4368-4368
Author(s):  
Satsuki Murakami ◽  
Harumi Kato ◽  
Kazuhito Yamamoto ◽  
Hirofumi Taji ◽  
Daiki Hirano ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Cross Validation ◽  
Risk Group ◽  
Clinical Stage ◽  
Tumor Burden ◽  
Stage Ii ◽  
Treatment Modalities ◽  
Newly Diagnosed ◽  
Combined Model

Abstract Follicular lymphoma (FL) is the most frequent low-grade lymphoma and survival duration is heterogeneous. Follicular lymphoma international prognostic index 2 (FLIPI2) is a useful prognostic tool for the identification of patients with FL at different risk in the rituximab era. On the other hand, Groupe d’Etude des Lymphomas Folliculaires (GELF) criteria is defined for patients in whom immediate therapy is necessary. In this study, we determined the value of FLIPI2 and GELF criteria as prognostic tools for follicular lymphoma. Among 181 consecutive FL patients newly diagnosed in our institute from 2000 to 2011, data of FLIPI2 and GELF criteria were available for 147 patients. Of the 147 patients, a total of 102 patients were diagnosed as clinical stage II to IV and received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) based chemotherapy. The remaining 45 patients were treated with CHOP like regimens or other treatment modalities. Of the 102 patients who had rituximab usage, 2 patients (2%) received rituximab maintenance therapy. Detailed patients characteristics were shown in Table 1. Survival analysis was carried out using the Kaplan–Meier product-limit method.Table 1Baseline patients’ characteristics (stage ≥II, received R-CHOP)ALL (n=102)Cross-validation cohort (n=65)n (%)n (%)Sex (Male)45 (44)33 (51)Median age (range)58.5 (39-84)58 (39-79)Age (>60)38 (37)24 (37)ECOG PS (>1)2 (2)1 (2)Stage ≥III85 (83)52 (80)Bulky (≥7 cm)19 (19)13 (20)Serum LDH level (>normal)29 (28)19(28)Histology (Grade1/2/3)15/74/1110/46/8FLIPI2Low17 (17)14 (22)Intermediate58 (57)38 (58)High27 (26)13 (20)GELF criteria (High)56 (55)32 (49)Rituximab maintenance2(2)1(2) First, we performed analysis using 102 patients who were diagnosed as clinical stage II to IV and received R-CHOP based chemotherapy. With a median follow-up of 6.3 years (range: 0.7-14.0 years), the 6-year overall (OS) and progression-free survival rates (PFS) of the 102 patients were 89% (95%CI: 78 to 98) and 62% (95%CI: 51 to 71), respectively. According to FLIPI2, three risk groups (low risk, intermediate risk and poor risk) were separated in OS analysis. Estimated 6-year OS rates in patients with high and low tumor burden defined by GELF were 82% and 98%, respectively (P=0.02, Log-rank). PFS rates of patients with high tumor burden defined by GELF criteria were worse compared to those with low tumor burden (53% vs. 72%, p=0.02, Log-rank). When we divided patients into two group using both FLIPI2 and GELF criteria (FLIPI2-GELF combined model), patients, who had high tumor burden defined by GELF criteria and who were classified intermediate risk or poor risk group defined by FLIPI2 (FLIPI2-GELF high) showed worse OS rates compared to the remaining (FLIPI2-GELF low) patients (83% vs. 95%, p=0.03, Log-rank). Patients with FLIPI2-GELF high also represented worse PFS rates compared to FLIPI2-GELF low patients (51% vs. 72%, p<0.01, Log-rank). The results suggested that FLIPI2-GELF combined model could more precisely separate patients into each risk group. For validation, we next performed cross-validation analysis using 65 patients who were diagnosed as clinical stage II to IV and received R-CHOP based chemotherapy. The patients were selected from the first cohort of 102 cases (Table 1). With a median follow-up of 6.2 years (range: 0.7-14.0 years), estimated 6-year OS rates in patients with high and low tumor burden defined by GELF were 80% and 97%, respectively (P=0.03, Log-rank). Estimated 6-year PFS rates in patients with high and low tumor burden defined by GELF were 51% and 66%, respectively (P=0.12, Log-rank). Using FLIPI2-GELF combined model, estimated 6-year OS rates in patients with FLIPI2-GELF high and low were 78% and 97%, respectively (P=0.02, Log-rank). Estimated 6-year PFS rates in patients with FLIPI2-GELF high and low were 47% and 68%, respectively (P=0.04, Log-rank). In 147 cases treated with R-CHOP, CHOP based regimens,or other treatment modalities, FLIPI2-GELF combined model also could divide the two group in OS (p=0.01) and PFS (p<0.01) analyses. In conclusion, we confirmed GELF criteria could be used for reproducible prognostic tool for newly diagnosed follicular lymphoma receiving R-CHOP based chemotherapy. GELF criteria combined with FLIPI2 might be a more precise and repeatable prognostic indicator for survival after first-line therapy in patients with follicular lymphoma. Disclosures: No relevant conflicts of interest to declare.

Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type: long-term follow-up in acute promyelocytic leukemia

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2651-2656 ◽  
Author(s):  
Joseph G. Jurcic ◽  
Stephen D. Nimer ◽  
David A. Scheinberg ◽  
Tony DeBlasio ◽  
Raymond P. Warrell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Promyelocytic Leukemia ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Pcr Assays

Abstract The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PML/RAR-α fusion messenger RNA species that can be detected by reverse transcription–polymerase chain reaction (RT-PCR) amplification. Breakpoints within intron 3 of PML produce a short PML/RAR-α isoform, whereas breakpoints within intron 6 result in a longer form. Using RT-PCR, serial evaluations were performed on the bone marrow of 82 patients with APL (median follow-up, > 63 months) who received retinoic acid (RA) induction followed by postremission treatment with chemotherapy, RA, and biologic agents. Sixty-four patients attained a clinical complete remission and had at least 2 RT-PCR assays performed after completing therapy. Forty of 47 patients (85%) with newly diagnosed APL who were induced using RA had residual disease detectable by RT-PCR before additional therapy. After 3 cycles of consolidation therapy, residual disease was found in only 4 of 40 evaluable patients (10%). Among newly diagnosed patients who had 2 or more negative RT-PCR assays, only 3 of 41 (7%) had a relapse, whereas all 4 patients (100%) who had 2 or more positive results had a relapse. Among 63 newly diagnosed patients, those who expressed the short isoform appeared to have shorter disease-free and overall survival durations than patients who expressed the long isoform. These data indicate that 2 or more negative RT-PCR assays on bone marrow, performed at least 1 month apart after completing therapy, are strongly associated with long-term remissions. Conversely, a confirmed positive test is highly predictive of relapse.

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