scholarly journals Long Term Follow up from the NCRI AML17 Trial of Attenuated Arsenic Trioxide and ATRA Therapy for Newly Diagnosed and Relapsed Acute Promyelocytic Leukaemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 897-897
Author(s):  
Nigel H Russell ◽  
Alan K. Burnett ◽  
Robert K Hills ◽  
Sophie Betteridge ◽  
Michael Dennis ◽  
...  
Keyword(s):  
High Risk ◽  
Low Risk ◽  
Newly Diagnosed ◽  
Molecular Monitoring ◽  
Term Survival ◽  
Cns Disease ◽  
Significant Difference ◽  
Risk Of Relapse

Abstract Background: Two randomized studies have reported comparison of the "chemo-free" combination of ATO+ATRA with Anthracycline/ ATRA (AIDA) in APL. The GIMEMA-AMLSG-SAL trial, using a daily schedule improved both survival and relapse risk in patients with newly diagnosed, low or intermediate-risk APL. (Lo Coco et al., NEJM 2013; 369: 111-21). The NCRI AML17 trial using an attenuated dosing schedule in all risk groups resulted in a very low risk of relapse, significantly better EFS but no significant survival advantage Aims: The NCRI AML17 Trial compared AIDA vs the chemo-free combination of ATO (in an attenuated schedule) + ATRA. Here we present long term survival results for randomized patients and for 24 patients who received the same chemo-free schedule of ATO + ATRA after relapsing from the AIDA arm of the trial. Methods: From May 2009 to October 2013, 235 patients aged >16 who entered the AML17 trial with molecularly confirmed APL were randomized to either ATRA+ATO (8 week induction 0.3mg/kg d1-5 w1, 0.25mg/kgx2/w w2-8, followed by 4 consolidation courses of 0.3mg/kgx2 w1, 0.25mg/kgx2/ w2-4 (63 ATO doses) OR AIDA schedule: Idarubicin (Ida)12mg/m2 d2,4,6,8 + ATRA to d60) (induction) then Ida 5mg/m2 d1-4 + ATRA d1-15 (Course 2); Mitox. 10mg/m2 d1-4 + ATRA d1-15 (course 3); Ida 12mg/m2 d1 + ATRA d1-15 (Course 4). ATRA was 45mg/m2/d. Maintenance was not given. High risk patients could receive Gemtuzumab Ozogamicin (d1,6mg/m2). Another 70 patients were treated in AML17 with AIDA after closure of the randomization. 25/189 patients relapsed post AIDA and 24 were treated with a median of 4 cycles (range 1-5) of ATRA + ATO, 11/24 were later transplanted. Follow-up is complete to 1 January 2016. Results: The median age was 47y (16-77); 57 had WBC>10x109/L (27 AIDA, 30 ATRA+ATO) and 49 (24 AIDA, 25 ATRA+ATO) were >60y. The early results of the randomization for newly diagnosed patients have been reported (Burnett et al. Lancet Oncol. 2015, 16 (13):1295). 91% entered morphological CR with no significant difference in CR rate between the arms (Chemo-free 94%, Chemo 89%; OR 0.54 (0.21-1.34), p= 0.18). The OS at 4 years was 93% (Chemo-free) vs 89% (Chemo), HR 0.60 (0.26-1.42) p= 0.2, but EFS was significantly superior with ATRA+ATO (91% vs 70%, HR 0.35 (0.18-0.68) p=0.002). With a longer median follow-up of 53.4 months 5-year survival is now 93% (chemo-free) v 87% (chemo) (HR 0.61 (0.27-1.35) p=0.2). A significant reduction in relapse (2% vs 16% at 5 years, HR 0.19 (0.09-0.45) p=0.0005) translates to continuing significant RFS benefit for the chemo-free approach (96% vs 82%; HR 0.30 (0.13-0.67) p=0.004). This is seen both in low risk (95% vs 86% HR 0.45 (0.17-1.20) p=0.11) and high risk disease (100% vs 69% HR 0.10 (0.02-0.46) p=0.003), p=0.11 for heterogeneity. 25 patients relapsed following AIDA therapy, of whom 1 died in frank relapse before treatment could be initiated and 24 (5 with concomitant CNS involvement) were treated with the attenuated ATO + ATRA schedule. Of these 16 were treated at molecular relapse, reflecting the value of centralised MRD monitoring as part of the trial protocol. All 24 patients achieved molecular CR post ATO +ATRA. Eleven patients were transplanted (8 autograft, 3 allograft) including 4 of the 5 patients with CNS disease. 3 patients have had a second molecular relapse after ATO + ATRA salvage (1 transplanted and 2 not transplanted). The 3-year overall survival post-relapse is 96% with the only other death occurring post-transplant after 37 months. Summary/Conclusion: The combination of ATO + ATRA continues to show a very low risk of relapse irrespective of risk group resulting in significantly better RFS compared to AIDA and excellent survival but no survival benefit has emerged primarily because of effective salvage interventions for AIDA-treated patients with most patients treated at molecular relapse. Molecular monitoring for t(15;17) is therefore essential to optimize therapy with AIDA. For patients treated with frontline ATO+ATRA molecular monitoring is of questionable value once achievement of molecular CR has been documented, but molecular surveillance remains important in those with relapsed disease. The attenuated AML17 ATO dosing approach is effective both upfront and in patients relapsing post AIDA and these results question the role of transplantation as consolidation in patients achieving molecular CR2 with ATO + ATRA who do not have CNS disease at relapse. Disclosures Burnett: CTI Life Sciences, London: Employment. Hills:TEVA: Honoraria. Grimwade:TEVA: Research Funding.

Should adult medulloblastoma patients at low risk receive adjuvant chemotherapy? Long-term results of a prospective study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2018-2018
Author(s):  
E. Franceschi ◽  
A. Tosoni ◽  
M. Ermani ◽  
V. Blatt ◽  
P. Amistà ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Survival Rates ◽  
Low Risk ◽  
Long Term Results ◽  
High Risk Patients ◽  
Significant Difference ◽  
Risk Patients

2018 Background: Due to the rarity of medulloblastoma (MB) in adults, the few studies available on this condition are retrospective, and the follow-up tends to be short. Furthermore, the different therapeutic strategies used in these patients makes it difficult to assess survival rates and prognostic factors. Methods: Between January 1989 and February 2001, a prospective phase II trial was performed to evaluate the efficacy of treatment for adults with medulloblastoma. Patients were completely staged with a neuroradiological examination of the brain and neuraxis and by CSF cytology, according to Chang’s staging system. Low risk patients received radiotherapy alone, while high risk patients were given 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The results of the preliminary analysis of this study at a median follow-up of 3.7 years are reported elsewhere. The present papers reports on the long- term results of the same trial. Results: After a median follow up of 7.6 years, among a total of 36 enrolled adults with medulloblastoma, overall progression free survival (PFS) and overall survival (OS) at 5 years were 72% (range 59% to 84%) and 75% (62% to 91%), respectively. No difference was found between low and high risk patients in terms of PFS and OS at 5 years: in low-risk patients the 5-year PFS was 80% (range, 59–100%) and the 5-year OS, 80% (range, 58 - 100%); in high-risk patients the 5-year PFS was 69% (range, 54 -89%) and the 5-year OS, 73% (range, 58 - 92%). Conclusions: A long-term follow-up is essential to evaluate the real impact of treatments in adult patients with MB. Since there is no significant difference between low-risk and high-risk patients for PFS and OS, the use of chemotherapy is also questionable in low-risk patients. No significant financial relationships to disclose.

scholarly journals The Impact of EUTOS Long-Term Survival (ELTS) Score on Predicting Progression and Survival Among Turkish Patients with Chronic Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4600-4600
Author(s):  
Mert Bektaş ◽  
Tuğrul Elverdi ◽  
Ayşe Salihoğlu ◽  
Muhlis Cem Ar ◽  
Şeniz Öngören ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Roc Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Term Survival ◽  
Hazard Ratios ◽  
Sokal Score

Abstract Introduction and Objectives: For patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP), four baseline prognostic scores are commonly used including the Sokal score and the most recently introduced EUTOS long-term survival (ELTS) score. The ELTS score was shown to be superior to the Sokal score for predicting survival. The aim of the study is to evaluate the value of ELTS score on predicting disease progression and survival in Turkish pts with CML-CP. Material and Method: Demographic, laboratory and clinical features, disease responses to tyrosine kinase inhibitor (TKI) therapy and survival of CML-CP pts, who received upfront imatinib (IM) between 2003 and 2018 were analyzed retrospectively. Treatment responses were reevaluated according to European LeukemiaNet 2013 recommendations. Risk groups analysis, discrimination and hazard ratios (HRs) were evaluated with Cox regression and Kaplan-Meier survival analysis. Receiver operating characteristic (ROC) analysis was performed to examine the effects of scores on predicting overall survival (OS) and progression-free survival (PFS). Results: A total of 185 pts were included, of which 103 (55.7%) were male and median age was 47 years (range, 16 - 81 years) (Table 1). The percentages of pts with low-, intermediate-, and high-risk ELTS scores were 60.5%, 25.9%, and 13.5%, respectively. For the Sokal score, these percentages were 37.3%, 40.5%, and 22.2% respectively. For Sokal high-risk pts, only 46.3% were classified as high-risk according to the ELTS score. Similarly, 44% of pts with intermediate Sokal risk had low-risk ELTS score (Fig. 1). Seventy-seven pts (41.6%) had at least one comorbidity, and the most common comorbidities were hypertension (21.6%), diabetes mellitus (13%), and ischemic heart disease (12.4%) (Table 1). The median durations of IM therapy and follow-up were 2728 (range, 14 - 6320 days) and 3473 (range, 71 - 6320 days) days, respectively. Complete hematologic and early molecular (BCR-ABL1 IS <10% at 3 months) responses at 3 months were 95.6% and 75.9%, respectively. Complete cytogenetic and major molecular response rates at 6 and 12 months were 72.3% and 86.1% and 45.4% and 54%, respectively. Thirty-five pts (18.9%) switched to second-generation TKI therapy and 6 pts (3.2%) progressed to advanced-phase disease during the follow-up (Table 1). For PFS, with reference to the low-risk Sokal score, the HR of high-risk groups was 9.301 (95% CI: 1.086-79.656, p=0.042) (Fig. 2A). Similarly, with reference to the low-risk ELTS score, the HR of intermediate- and high-risk groups were 4.744 (95% CI: 0.43-52.314, p=0.204) and 14.642 (95% CI: 1.523-140.791, p=0.020) (Fig. 2B). Regarding OS, with reference to the low-risk Sokal score, the HR of the intermediate- and high-risk groups were 1.835 (95% CI: 0.564-5.964, p=0.313) and 6.412 (95% CI: 2.11-19.489, p=0.001), respectively (Fig. 2C). With reference to the low-risk ELTS score, the HR of the intermediate- and high-risk groups were, 3.263 (95% CI: 1.242-8.576, p=0.016) and 7.258 (95% CI: 2.762-19.074, p<0.001) respectively (Fig. 2D). In the ROC analysis, the ELTS score was superior than the Sokal risk score for both predicting PFS (AUC=0.820 vs. AUC=0.818) and OS (AUC=0.762 vs. AUC=0.744). During the follow-up, 27 (14.6%) pts died, of which 6 died due to CML progression and causes of death were unrelated to CML in 21. Conclusion: In our study, we showed that the ELTS score could successfully predict high-risk pts compatible with the literature. With higher hazard ratios and better risk group stratifications, the ELTS score outperformed the Sokal score. The ELTS score can help clinicians to better discriminate poor prognostic pts and can promote optimal treatment strategies for these pts with potentially worse prognosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract 15741: Long Term Survival Following Transcatheter Aortic Valve Replacement: Results From a Single US High Volume Center

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ricardo O Escarcega ◽  
Rebecca Torguson ◽  
Marco A Magalhaes ◽  
Nevin C Baker ◽  
Sa’ar Minha ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Transcatheter Aortic Valve Replacement ◽  
Term Survival ◽  
Transcatheter Aortic Valve ◽  
Significant Difference ◽  
Long Term Mortality

Introduction: Mortality following Transcatheter aortic valve replacement (TAVR) has been reported up to 5 years. However, mortality after 5 years remains unclear. Hypothesis: We aim to determine the mortality in patients undergoing TAVR >5 years follow up. Methods: From our institution’s prospectively collected TAVR database we analyzed all patients undergoing TAVR to a maximum follow up of 8 years. We divided our population into transapical TAVR (TA-TAVR) and transfemoral TAVR (TF-TAVR) groups. A Kaplan-Meier survival analysis was conducted. Results: A total of 511 patients who underwent TAVR were included in the analysis. Patients undergoing TA-TAVR had higher rates of peripheral vascular disease compared with TF-TAVR (56% vs 29%, p<0.001) and Society of Thoracic Surgeons Score (10.9 ± 4 vs 9.2 ± 4, p<0.001). TA-TAVR was associated with higher mortality at 1 year (32% vs 21%, p=0.01). However, there was no significant difference in very-long term mortality of patients undergoing TA-TAVR vs TF-TAVR (Figure). Conclusions: Long-term mortality following TAVR surpasses 50%. While in the first 2 years TA-TAVR is associated with higher mortality rates after three years the survival rates are similar in both approaches.

scholarly journals ACTR-38. A SINGLE CENTER STUDY: LONG-TERM OUTCOMES OF COMBINED CHEMORADIATION THERAPY WITH TEMOZOLOMIDE FOR NEWLY DIAGNOSED GLIOBLASTOMA IN KOREAN PATIENT

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi21-vi21
Author(s):  
Kyeong-O Go ◽  
Ha Young Yang ◽  
Kihwan Hwang ◽  
Jung Ho Han ◽  
Hyoung Soo Choi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Adjuvant Treatment ◽  
Genetic Factors ◽  
Newly Diagnosed ◽  
Factors Affecting ◽  
Korean Patients ◽  
Significant Difference ◽  
Newly Diagnosed Glioblastoma

Abstract In newly diagnosed glioblastoma (GBM), Temozolomide (TMZ) during and after radiation therapy has become standard treatment. This study describes the long-term use and follow-up results of this therapy for GBM. From 2004 to 2013 in a single institute, 112 Korean patients with newly diagnosed GBM were analyzed retrospectively. The Kaplan-Meier method, the two-sided log-rank test and Cox’s regression analysis was used to determine survival and its affecting factors. The toxicities of TMZ were evaluated using CTCAE v5.0. During the median follow-up period of 18.8 months, median PFS and OS were 9.2 and 20.3 months, respectively. This better survival outcome than the Stupp’s original study might be probably a large treatment effect of a single institution, ethnicity, and associated genetic factors. The TMZ during radiation therapy was completed in 108 patients (96.4%) and TMZ after radiation therapy in 59 patients (52.7%). Eight patients presented with grade 3 or 4 hematologic toxic effects during the protocol. Sixty-six patients (58.9%) received salvage treatment because of the poor response to adjuvant treatment or progression of the disease who achieved completion of adjuvant treatment was shown significantly longer median OS (p= 0.007) and PFS (p< 0.001). Age (< 60 years), preoperative KPS score (≥ 90), the extent of resection (≥ 78% by volumetric measurement, gross total resection), and completion of the Stupp’s protocol were significant factors affecting better survival. Between the sexes, and ages over 65 years did not show any significant difference among their groups. With marginal significances, the mutated IDH-1 and the methylated MGMT promoter showed longer median PFS(p= 0.075 and 0.777, respectively) and OS (p= 0.085 and 0.131, respectively). TMZ during and after radiation therapy might be effective and safe for newly diagnosed Korean patients with GBM. Further studies about various clinical and genetic factors affecting better survival are mandatory.

Pre-irradiation chemotherapy for infants and children with medulloblastoma: a preliminary report

1989 ◽  
Vol 71 (6) ◽  
pp. 820-826 ◽  
Author(s):  
Cynthia S. Kretschmar ◽  
Nancy J. Tarbell ◽  
William Kupsky ◽  
Beverly L. Lavally ◽  
Jay S. Loeffler ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Complete Response ◽  
Drug Regimen ◽  
Direct Evaluation ◽  
Term Survival ◽  
Content Type ◽  
Disease Free

✓ From March, 1984, through June, 1987, 21 newly diagnosed children with high-risk medulloblastoma (Chang Stage T3 to T4) were treated on a 9-week postoperative, pre-irradiation chemotherapy regimen consisting of vincristine and cisplatin. The children over 2 years old then received radiation therapy. Six infants (aged 6 to 18 months) were maintained on chemotherapy consisting of MOP (nitrogen mustard, vincristine, and procarbazine) until the age of 2 years, at which time they were referred for irradiation. Of 13 children with measurable disease following surgery, five showed a definite response on computerized tomography scans to vincristine and cisplatin (one complete response and four partial responses) and five others showed clear marginal responses. Four of the six infants were disease-free at 19, 32, 35, and 57 months from diagnosis. One infant developed progressive disease at the completion of the vincristine and cisplatin course, and a second infant had progression during MOP administration. Three of the 21 children developed hearing loss within the speech frequencies during cisplatin treatments, but there were no other major toxicities. Fifteen children remained disease-free with a median follow-up period of 35 months (range 19 to 57 months). Chemotherapy given between surgery and radiotherapy may allow for the direct evaluation of a specific drug regimen and permit the postponement of radiation therapy in infants. Pre-irradiation vincristine and cisplatin was well tolerated and effective in shrinking the tumor in most children with medulloblastoma. Such chemotherapy regimens have the potential for extending long-term survival in high-risk children.

scholarly journals High Levels of Wilms' Tumor Gene (wt1) mRNA in Acute Myeloid Leukemias Are Associated With a Worse Long-Term Outcome

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1217-1225 ◽  
Author(s):  
Lothar Bergmann ◽  
Cornelius Miething ◽  
Ulrich Maurer ◽  
Jürgen Brieger ◽  
Tunca Karakas ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Wilms Tumor ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Myeloid Leukemias ◽  
First Relapse ◽  
Tumor Gene ◽  
Acute Myeloid

Abstract The tumor suppressor gene wt1 (Wilms' tumor gene) encodes for a zinc finger DNA-binding protein with predominantly transcription repressing properties. Because wt1 has been shown to be expressed in the vast majority of patients with acute myeloid leukemias (AML), we investigated the relevance of wt-1 mRNA expression regarding prognosis and possible prediction of relapse during follow-up. Totally bone marrow-derived blasts of 139 AML patients (129 newly diagnosed AML patients, 22 AML patients again in first relapse, and 10 AML patients analyzed primarily in first relapse) were studied for wt1 mRNA expression. Seventy-seven patients were analyzed for wt1 mRNA expression during follow-up. wt1-specific reverse transcription-polymerase chain reaction (RT-PCR) was performed and the amplification product was visually classified as not, weakly, moderately, or strongly amplified, as described previously. PCR products were quantitated by competitive PCR using a shortened homologous wt1 construct standard in representative cases. The expression of wt1 transcripts was correlated to age, French-American-British (FAB) subtype, phenotype, karyotype, and long-term survival. wt1 mRNA was detectable in 124 of 161 (77%) samples at diagnosis and in first relapse. wt1 expression was independent from age, antecedent myelodysplastic syndrome or FAB subtype, with the exception of a significant difference in M5 leukemias showing wt1 transcripts in only 40% (P = .0025). There was no correlation between the level of wt1 mRNA and response to treatment or the prognostic groups defined by the karyotype. Concerning long-term survival, patients with high levels of wt1 had a significantly worse overall survival (OS) than those with not detectable or low levels. The 3-year OS for all newly diagnosed AMLs was 13% and 38% (P = .038), respectively, and 12% and 43% (P = .014) for de novo AMLs. The difference was more distinct in patients less than 60 years of age. During follow-up, all patients achieving complete remission became wt1 negative. Reoccurrence of wt1 transcripts predicted relapse. The data indicate that high expression of wt1 mRNA is associated with a worse long-term prognosis.

Long-Term Outcome of Iron-Induced Cardiac Disease in Patients with Thalassemia Major Treated with Combined DFP/DFO or DFO Alone.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1764-1764
Author(s):  
Maria Eliana Lai ◽  
Stefania Vacquer ◽  
Alessia Pepe ◽  
Aurelio Maggio ◽  
Maria P. Carta ◽  
...  
Keyword(s):  
High Risk ◽  
Cardiac Disease ◽  
Risk Group ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Low Risk ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract We conducted a 4-yr prospective trial to evaluate the long-term effects of combined deferiprone (DFP)/deferoxamine (DFO) on reversal of cardiac complications in thalassemia major compared to those of DFO alone. Twenty-eight patients (pts) with cardiac disease requiring medication were stratified according to their risk for cardiac death. Fourteen pts were high risk, serum ferritin (SF) > 2500 ug/L on two-thirds of occasions since the onset of cardiac disease. Of those with a SF < 2500 ug/L (low risk), six had progressive decrements of left ventricular ejection fraction (LVEF). Nine high-risk pts and six low-risk pts were placed on DFP/DFO (DFP, 75 mg/kg/d divided t.i.d.; DFO, 40 – 50 mg/kg over 8 – 12 h at night 5 – 7 d/wk. The others infused DFO alone. If SF fell below 500 ug/L, DFO infusions were reduced to 2 d/wk. Cardiac follow-up (including blood work and ECG) was done at 4-m intervals. M-mode and two-dimensional echocardiograms were done at 4- to 6-m intervals. Cardiac T2* was not available at the beginning of the study. All but eight patients (3 death, 1 refusal, 2 claustrophobic, 2 pacemaker) subsequently had at least one T2* assessment. Routine lab tests were done at 1- to 6-m intervals. Blood counts were done at 7- to 10-d intervals for those taking DFP. Mean follow-up was approximately 40 m. Compliance with DFO was significantly better among low-risk pts in both treatment groups (DFP/DFO, 82% vs 61%; DFO alone, 83% vs 52%) as was that with DFP (94% vs 76%). At baseline, no statistically significant differences were observed between the SF levels, LVEFs or left ventricular shortening fractions (LVSFs) of pts on DFP/DFO or DFO alone in either risk group except for the LVEFs of the low-risk group (DFP/DFO, 56.5% +/− 5.5%; DFO alone, 65.4% +/− 5.0%; p = 0.032). In the high-risk group, four cardiac events (3 deaths, 1 worsening of CHF) occurred in the group getting DFO alone vs none in the DFP/DFO-treated group. The latter pts showed a decrease in SF and an increase in both LVEF and LVSF at the end of study (EOS). The three pts who died (at 17 to 35 m) had increased SFs. These pts were not rescued by IV DFO (98 +/− 12 mg/kg/d). The two DFO-treated pts who survived had marginally improved T2*s (1.5 to 3.0 ms and 7.6 to 8.8 ms) over the year prior to EOS. Only one of the seven evaluable pts on DFP/DFO had a T2* < 10 ms, the others averaging 19.4 +/− 6.7 ms. Among the low-risk pts, those on DFP/DFO showed a reduction in SF and an improvement in both LVEF and LVSF. Those on DFO alone had increased SF but essentially no change in LVEFs or LVSFs. Five pts on DFP/DFO had T2* evaluations. In two pts, T2* rose from 9.0 to 37 ms (38 m) and from 9.3 to 11.8 ms (17 m). The remaining three had T2* values > 20 ms at EOS. Similar results were seen in low-risk pts on DFO alone. These finding clearly support the notion that DFP/DFO has a beneficial effect upon the heart, even in well established disease. Moreover, our finding of low T2* values associated with low SF levels indicates the importance of tailoring treatment to each individual.

Long-Term Follow-Up Confirms the Benefit of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (As2O3) as Front Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 565-565 ◽  
Author(s):  
Yuan-Fang Liu ◽  
Yong-Mei Zhu ◽  
Zhan-Zhong Shi ◽  
Jun-Min Li ◽  
Li Wang ◽  
...  
Keyword(s):  
Remission Induction ◽  
Newly Diagnosed ◽  
Front Line ◽  
Current Group ◽  
Historical Cohort ◽  
Term Survival ◽  
Long Term Survival ◽  
Historical Group

Abstract PURPOSE: To further confirm the benifit of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL), we observed the long-term survival of the current group (median follow-up: 48 months) and compared it with our historical control. PATIENTS AND METHODS: There were two groups of patients with newly diagnosed APL enrolled in this analysis. The current cohort of patients includes 60 patients since April 2001. The historical cohort of patients included 56 patients from May 1998 to March 2001. No statistically significant differences were found between these two groups in terms of clinical characteristics including sex and age distribution or hematological data before treatment. For the current cohort of patients, all patients received 25mg/m2 ATRA orally and 0.16mg/kg As2O3 intravenously per day till CR. Once CR achieved, they were given 3 courses of consolidation chemotherapy and then 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. For the historical group, ATRA was given either 25mg/m2 daily till CR, chemotherapy was added in case of leukocytosis. The post-remission therapy consists of chemotherapy with or without ATRA. Quantitative real-time reverse transcription-polymerase chain reaction (RQ-RT-PCR) measurements of PML-RARa mRNA were retrospectively assessed before treatment, after CR, after consolidation, after maintenance and during follow-up period. The efficacy of these two protocol in terms of remission induction, molecular response and long-term survival were compared with our historical control. RESULT: In the current group, 56 (93.3%) patients achieved CR, and the median time to CR was 27 days. Compared with the historical group, the combined therapy induced an early hematological response. Till the last follow-up at April 2006, two patients underwent extramedullary relapse, one of them also relapsed in marrow thereafter, one patient died from CNS leukemia, and all the other patients were alive and remained in hematological remission. With a median follow-up of 48 months (25 to 60 months), the 4-year OS and EFS was estimated 98.1%±1.8% and 94.2%±3.3%. For the historical group, after a median follow-up of 56 months (12 to 79 months), the 4-year OS and EFS was estimated 83.4%±5.4% (P=0.012) and 45.6%±7.6% (P<0.00001). For the current group, PML-RARa normalized dose was more significantly decreased after remission induction and after consolidation as compared with the historical cohort. In the last follow-up, all of the available event-free patients of the current group remain in molecular remission (PML-RARa DoseN undetectable). CONCLUSION: These 4-year data of follow-up demonstated a benefit of front-line combination of ATRA and As2O3 regarding long-term survival (OS or EFS) of patients with newly diagnosed APL. With prolonged follow-up, we might be able to find a better chance of curing the disease.

Long Term Follow up of Patients with CML in Chronic Phase Treated with First-Line Imatinib Suggests That Earlier Achievement of a Major Molecular Response Leads to Greater Stability of Response.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2113-2113 ◽  
Author(s):  
Susan Branford ◽  
Rebecca Lawrence ◽  
Andrew Grigg ◽  
John Francis Seymour ◽  
Anthony Schwarer ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Low Risk ◽  
Initial Slope ◽  
Molecular Response ◽  
Average Dose ◽  
Major Molecular Response ◽  
First Line ◽  
Significant Difference

Abstract A major molecular response (MMR) by 12 or 18 months (m) of standard dose imatinib for patients (pts) with newly diagnosed chronic phase CML is associated with a low risk of progression to accelerated phase or blast crisis. Phase II/III trials suggest that MMR may be achieved earlier with higher doses of imatinib. We determined whether the timing of MMR affects the long term stability of response with regard to the acquisition of BCR-ABL mutations and/or loss of MMR (collectively defined as an “event”) for pts with up to 8 years of follow up since commencing first-line imatinib. All pts treated with 400 to 600mg of first-line imatinib who were monitored regularly at our institution for BCR-ABL levels by real-time quantitative PCR and mutation analysis by direct sequencing were evaluated: 181 pts were followed for a median of 45m (range (r) 3–96m). The event rate was compared for pts dependent on the time to MMR (≤0.1% IS (international scale)) in 6m intervals to 18m of imatinib. The events for pts with undetectable BCR-ABL (complete molecular response, CMR) were also determined. Strict sensitivity criteria were used for CMR: undetectable BCR-ABL where the sensitivity of analysis indicated BCR-ABL was &lt;0.003% IS, (equivalent to at least 4.5 log below the standardized baseline) which was confirmed on a subsequent analysis. Loss of MMR was defined as a confirmed &gt;2 fold rise from nadir to a level &gt;0.1% IS in pts who maintained imatinib dose. 144/181 pts (80%) achieved MMR at a median of 12m (r 3–53m). Consistent with other studies, maintaining a higher dose of imatinib in the first 6m of therapy was associated with a significantly higher frequency of pts achieving MMR by 6m. 118 pts received an average dose of &lt;600mg in the first 6m and 18/118 (15%) achieved MMR by 6m, whereas 63 pts received an average dose of 600mg in the first 6m and 23/63 (37%) achieved MMR by 6m, P=0.002. Mutations were detected in 14/181 pts (8%) at a median of 9m (r 3–42m). An event occurred in 8 pts with MMR at a median of 36m (r12–57m) after commencing imatinib, including one patient who had achieved CMR. Mutations were found in 4 pts and 3/4 lost MMR. The remaining 4 lost MMR without a mutation. The one patient with a mutation who did not lose MMR had a 3-fold rise in BCR-ABL at the time of mutation detection and responded to a higher imatinib dose. The other pts with mutations had therapeutic intervention upon cytogenetic relapse (2) or loss of MMR (1). The 4 pts with loss of MMR and no mutation had accelerated phase (1), cytogenetic relapse (2) and one maintained CCR with 3m of follow up. The median fold rise in BCR-ABL upon loss of MMR was 26 (r 4–220). The probability of an event if MMR was achieved by a) 6m was 0% (n=41 evaluable pts), b) &gt;6 to 12m was 12% (n=40) and c) 12 to 18m was 19% (n=33). The median follow up since MMR was achieved was not significantly different for the groups: 49m (r 3–87m), 38m (r 6–87m), 40m (r 9–78m), respectively, P=0.5. The risk of an event for pts with MMR achieved by 6m was significantly lower than in pts with MMR achieved by &gt;6 to 18m, P=0.04. CMR occurred in 55 pts who were followed for a median of 24m (r 3–55m) after its attainment. Only 1 event occurred in these 55 pts, which was at 6m after CMR was achieved and 57m after commencing imatinib. This patient had maintained MMR for 45m but loss of a major cytogenetic response occurred 6m after loss of MMR. There was a significant difference in the probability of CMR by 60m of imatinib dependent on the time to MMR, P&lt;0.0001 (Figure). All pts failed to achieve CMR by 60m if not in MMR at 18m whereas the actuarial rate of CMR at 60m was 93% in those with MMR by 6m. The initial slope of BCR-ABL decline correlated strongly with the decline over the longer term. The mean time to CMR after attainment of MMR was significantly faster for pts with MMR by 6m compared to those with MMR at &gt;6 to 12m and &gt;12 to 18m: 24m vs 37m vs 42m, respectively, P=0.001. This suggests the rate of BCR-ABL reduction below the level of MMR was faster in pts with MMR by 6m, which may be clinically beneficial as none of these pts had a subsequent event. Based on these findings we propose that inducing earlier molecular responses with higher dose imatinib or more potent kinase inhibitors may lead to more durable and deeper responses. It remains possible however, that early molecular response reflects a more biologically favourable disease rather than being the direct cause of more durable response. Finally, CMR was associated with an extremely low risk of events, making it an appropriate next target of therapy after MMR is achieved. Figure Figure

Sign in / Sign up

Export Citation Format

Share Document