scholarly journals Changing the Fate of Children with Acute Lymphoblastic Leukemia (ALL) in a Limited Resources Setting

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5075-5075
Author(s):  
Yajaira Valentine Jimenez-Antolinez ◽  
Julia Esther Colunga Pedraza ◽  
José Eduardo Mares-Gil ◽  
Emma Lizeth Estrada ◽  
Jesus Mauricio Gonzalez-Diaz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Relapse Rate ◽  
Lymphoblastic Leukemia ◽  
Limited Resource ◽  
Outcome Evaluation ◽  
Event Free Survival ◽  
Free Survival ◽  
Early Relapse

Introduction Pediatric acute Lymphoblastic Leukemia (ALL) patients have about 90% overall survival (OS) in developed countries. However, many children in low-middle income countries (LMIC) do not have access to appropriate drugs at optimal doses, a multidisciplinary medical team, laboratory resources for diagnosis and follow-up, and appropriate support therapy for morbidities and treatment-related toxicities. A 50-60% five-year OS has been reported in children with ALL in Mexico, and our center is not the exception. This low survival rate has pushed Mexican centers to develop strategies highlighting collaboration between centers with economic, research and teaching resources ("Mexico en Alianza con St. Jude MAS"), and outpatient treatment. However, each center must adapt their chemotherapy protocol to its own supplies and possibilities. We report the results of a risk adapted therapy protocol in a limited-resource treatment setting. Materials and Methods All pediatric patients with a diagnosis of ALL from January 2017 to December 2018 were classified according to risk as shown in Figure 1. Depending on risk classification, modifications to the induction, consolidation and intermediate maintenance regimens were made. The higher the risk, the higher the intensity of the regimen, as defined by the number of anthracycline doses, the presence or absence of high-dose methotrexate, and the duration of the consolidation and maintenance phases (Table 1). Demographic data is reported using distribution analysis, and the Kaplan-Meier method is used to analyze and predict overall survival, event-free survival (EFS) and relapse. Our results were compared with previous results from our institution. Results There were 35 male and 25 female patients; median age at diagnosis was 5.5. B-cell and T-cell lymphoblastic leukemia was the diagnosis in 57 (95%), and 3 (5%) patients, respectively, with a follow-up of 16 (8-30) months. Twenty-three (38%), 21 (35%), and 16 (26%) children were classified as high, intermediate and low risk ALL, respectively. After one week of corticosteroids 46 (77%) of patients had a good response. At the end of induction 53 patients had an evaluable MRD (88%), out of which 9 were positive (17%). Median follow-up was 16 (0.6-30) months. Mortality at induction was 6 (10%) patients. Very early relapse was observed in 3(5%) of patients. Estimated 2-year relapse rate was 6%, event-free survival was 84.1%, and OS was 85%. A comparison of results obtained with previous regimens (protocols 1 and 2) and the risk-adapted treatment (protocol 3) is observed in Table 2. Conclusions The implementation of a modified chemotherapy regimen based on adjusted stratification risk was associated to improved responses as reflected by MRD. A decrease in very early relapse rate to 5%, without increasing the toxicity and death during induction was observed. Periodic and prospective outcome evaluation in a limited-resource setting is fundamental to adjust and to standardize therapy. Long-term follow-up of this patient group is required to compare OS and EFS at 5 years. This is a preliminary report, but it seems that we are changing the fate of Mexican children with ALL. Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

The Importance of Hypersensitivity in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5242-5242
Author(s):  
Yesim Oymak ◽  
Sultan Aydin Koker ◽  
Tuba Hilkay Karapinar ◽  
Dilek Ince ◽  
Yilmaz Ay ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Dramatic Improvement ◽  
Event Free Survival ◽  
Free Survival ◽  
Erwinia Asparaginase ◽  
Overall Survival Rates

Abstract Background Acute lymphoblastic leukemia (ALL) remains the most common pediatric malignancy in the world. Overall survival rates have increased from 30% in the 1960s to 90% in past 10 years. Enabling this dramatic improvement are the multi-agent chemotherapeutic regimens in which asparaginase is cornerstone. Unfortunately, hypersensitivity to asparaginase has been a commonly-reported adverse event, associated with inferior outcomes in ALL. Methods Between January 1, 2005 and December 31, 2012, 97 patients were enrolled in the study. Selection criteria included those were diagnosed with ALL and given the ALL-BFM-2000 protocol at Dr. Behcet Uz Children's Hospital. Data regarding age at diagnosis, sex, follow-up duration, hypersensitivity of L- asparaginase, status of relapse and outcome were gathered from the patients’ files. The event-free survival (EFS) and the overall survival (OS) of the patients who developed and did not develop hypersensitivity to L- asparaginase were compared. Peg-asparaginase was given to patients who developed L- asparaginase hypersensitivity, and erwinia asparaginase was given if the patients developed peg-asparaginase. The asparaginase activity could not be measured. Kaplan mayer test was used to calculate the EFS and the OS. Results A total of 97 patients were evaluated. Thirty-two were standard risk, 49 were moderate risk, and 15 were high risk. 61 patients were male, and 36 were female. The median age (range) at diagnosis was 5 (1-15) years. Median (range) follow-up duration was 5.1 (0.08-7.3) years. Of the 97 patients, 28 (29.2%) developed L-asparaginase hypersensitivity. The event-free survival was 84.5 ± 4.6%, and 62.6 ± 9.4% for patients who developed and did not develop hypersensitivity, respectively (p=0.01). The overall survival rates were 89.2 ± 3.9 % and 74.6 ± 8.3% for patients who developed and did not develop hypersensitivity, respectively (p=0,07). Figure 1. Event-free survival. The five years EFS±SE for the patients who developed and did not develop native L- asparaginasehypersensitivity were 84.5 ± 4.6% and 62.6 ± 9.4%, respectively (p=0.01). Figure 1. Event-free survival. The five years EFS±SE for the patients who developed and did not develop native L- asparaginasehypersensitivity were 84.5 ± 4.6% and 62.6 ± 9.4%, respectively (p=0.01). Conclusions This study demonstrated that EFS was lower in patients with L-asparaginase hypersensitivity than those without hypersensitivity, although there were no differences in terms of OS. All of the patients with hypersensitivity received a sufficient dose of peg-asparaginase or erwinia asparaginase according to the ALL-BFM-2000 protocol. The lower EFS for patients who were switched to peg-asparaginase because of L- asparaginase may be explained by silent inactivation of peg-asparaginase. If the activity of asparaginase could not be measured, it could be preferable to switch to erwinia asparaginase. Disclosures No relevant conflicts of interest to declare.

scholarly journals Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3122-3133 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
W Hiddemann ◽  
S Sauter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Multicenter Trial ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
To Receive

Abstract In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

scholarly journals Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1112-1115 ◽  
Author(s):  
James B. Nachman ◽  
Nyla A. Heerema ◽  
Harland Sather ◽  
Bruce Camitta ◽  
Erik Forestier ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Study Groups ◽  
Event Free Survival ◽  
Prognostic Implication ◽  
Monosomy 7 ◽  
Free Survival ◽  
Modal Chromosome Number

Abstract One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploidy (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% ± 4.4% and 49.8% ± 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P = .01; 8-year estimate, 52.2% vs 30.1%) and OS (P = .017; 69% vs 37.5%). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse EFS but similar OS. Doubling of the hypodiploid clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33-39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy.

Is It Better to Treat Adolescents with Acute Lymphoblastic Leukemia as Old Children or as Young Adults?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3968-3968 ◽  
Author(s):  
Marta Alves ◽  
Liane Daudt ◽  
Karina L. M. Mazzucco ◽  
Adriano Taniguchi ◽  
Tiago Nava ◽  
...  
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Poor Risk ◽  
Wbc Count

Abstract PURPOSE: To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents. PATIENTS AND METHODS: From January 1997 to December 2007, 34 and 11 adolescents (10 to 20 years of age) were treated according to German pediatric BFM 90 and 95 and adult BFM 84 protocols, respectively. Age, B/T lineage, WBC count, complete remission, cytogenetics, and response to steroids were analyzed. Age, B/T lineage and WBC count were similar. Poor risk-cytogenetics (t (9;22),t(4;11) and hypodiploidy less than 45 chromosomes were present only in BFM 90 and 95 group. Among the different prognostic factors, we retrospectively analyzed the effect of the trial on achieving overall survival (OS) and event-free survival (EFS). RESULTS: OS in 10 years and EFS was, respectively, 68.6% and 68.7% for the pediatric protocol and 31.4% and 21.6% for the adult protocol. CONCLUSION: This study’s findings were similar to others in USA, UK, France, Italy and Holland that clearly demonstrate that current pediatric regimens are more effective for adolescents and may contribute to indicate that adolescents should be included in intensive pediatric protocols. Keywords: leukemia, survival, adolescent.

scholarly journals Intensive chemotherapy in children with acute lymphoblastic leukemia. Interim analysis in a referral center in Colombia.

2016 ◽  
Vol 64 (3) ◽  
pp. 417 ◽  
Author(s):  
Angela Maria Trujillo ◽  
Adriana Linares Ballesteros ◽  
Isabel Cristina Sarmiento
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Developed Countries ◽  
Event Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Treatment Abandonment ◽  
Cancer In Children

Background: Acute lymphoblastic leukemia is the most common cancer in children. In developed countries, overall survival rates are around 80%, while in developing countries, survival rate is much lower due to high rates of relapse, and abandonment and complications arising from the disease treatment.Objectives: To assess induction mortality, relapse and treatment abandonment. To describe the most frequent side effects of chemotherapy. To evaluate survival rates of patients and compare the findings found in this study with the existing literature.Material and methods: A retrospective cohort study was conducted on patients aged 1 to 18 with acute lymphoblastic leukemia, who received treatment under the BFM ALL IC 2009 protocol at Fundación Hospital La Misericordia (HOMI), from November 2012 to December 2014.Results: 119 patients were included. Death occurred in two cases during induction (1.67%) and in nine (7.7%) due to treatment, all of them caused by infection/sepsis and in complete remission. Six patients abandoned treatment (5%), while seven relapses occurred (5.9%). All patients experienced some type of side effect related to chemotherapy, the most frequent being febrile neutropenia (41.2%) and grade 3-4 infections (15.8%). Overall survival and event-free survival rates were 79.9% and 73.3%, respectively.Conclusions: Evaluating complications of treatment and death allows adopting measures and strategies to reduce such complications.

scholarly journals Pediatric-Based Versus Adult Treatment Protocols in Young Adults (18-40 years) with Standard Risk Acute Lymphoblastic Leukemia: The BC Cancer Agency Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3770-3770 ◽  
Author(s):  
David Simon Kliman ◽  
Michael J Barnett ◽  
Raewyn Broady ◽  
Donna L. Forrest ◽  
Alina S. Gerrie ◽  
...  
Keyword(s):  
British Columbia ◽  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Small Cohort ◽  
Standard Risk

Abstract Introduction In recent decades, overall survival rates for children with acute lymphoblastic leukemia (ALL) have improved dramatically. Unfortunately, older patients have not experienced the same benefit. Recent years have seen investigation into the use of pediatric protocols for younger adults with ALL. Increased toxicity has often limited use to patients 40 years or younger. The Leukemia/Bone Marrow Transplant Program of BC is the referral center for adults with ALL in British Columbia. Approximately 20 patients are newly diagnosed with ALL each year. Until 2008, an adult protocol (known as ALL 89-1) was used in patients over 18 years. Since 2008, pediatric-based chemotherapy has been offered to patients 40 years or younger. We analyzed whether this change altered complete remission (CR), relapse and survival rates. We assessed whether the more intense protocol increased toxicity. Methods A retrospective analysis was performed on patients treated for ALL on a pediatric-based protocol. These protocols (ALL 08-01 and ALL 13-01) were modifications of the Donna Farber Cancer Institute 01-175 protocol. The format included induction with high dose methotrexate, followed by central nervous system (CNS) therapy including cranial irradiation. A single cycle of etoposide and high-dose cytarabine was given. Consolidation and continuation cycles included doxorubicin, asparaginase, vincristine and dexamethasone. Patients were included if they were aged 18-40 years and had standard risk, Philadelphia chromosome negative ALL. Between February 2008 and November 2014, 25 eligible patients were identified. These were compared with the 23 consecutive standard risk patients most recently treated with ALL 89-1. They had been diagnosed between February 2003 and July 2008. Exclusion criteria were age greater than 40 and non-standard risk ALL. Demographic and clinical data were collected on all patients from the Leukemia Program databases. Overall survival (OS) was calculated from time of diagnosis until death. Event free survival (EFS) was calculated from diagnosis until death, induction failure or relapse. Estimation of OS and EFS was performed using the Kaplan-Meier method. Patient characteristics were compared using Chi-squared test or Fisher's exact test. Ethics approval was obtained from the University of British Columbia ethics board. Results The median age of the combined patient group was 24.5 years. There were no statistically significant differences pre-treatment between groups. Combined median follow up was 28.7 months All 25 patients receiving a pediatric protocol achieved a CR, compared to 19 of 22 with the adult protocol. Despite the more intense chemotherapy dosing regimen in the pediatric protocol, there was no increase in hospitalizations, invasive fungal infections or deaths from treatment toxicity (Table 1). There was a trend towards increased thrombotic events in the pediatric-treated group, at 32% versus 9%. These included deep vein thrombosis in 4 patients, pulmonary emboli in 2, and cerebral sinus thrombosis in 2. Relapse occurred in 24% of the pediatric-treated patients and 45% of the adult-treated ones (p=0.215). Allogeneic stem cell transplantation was performed in 4 patients in the former group and 7 in the latter. Nine of these were carried out in CR2 or later, with two patients going into transplant with active disease. Overall survival following transplant was 44%. Two year event free survival was significantly improved in the group treated on the pediatric protocol (Figure 1), at 79% versus 36% (p=0.011). There was a trend towards improved overall survival in this small cohort, at 83% versus 49% (Figure 2). Conclusions A pediatric-based ALL treatment protocol was tolerated in patients up to the age of 40 years. In our centre, this is associated with an increase in EFS, and a trend towards increased OS, even considering the small cohort. We await with interest the results of larger studies investigating the ideal upfront therapy for young patients with ALL. Table 1. Results All Patients N=47 Adult N=22 Pediatric N=25 P Number % Number % Number % CR after induction 44 of 47 94 19 of 22 86 25 of 25 100 .095 Severe infection 20 of 47 43 9 of 22 41 11 of 25 44 .831 Thrombosis 10 of 47 21 2 of 22 9 8 of 25 32 .079 Pancreatitis 2 of 47 4 0 of 22 0 2 of 25 8 .491 Toxicity deaths 3 of 47 6 2 of 22 9 1 of 25 4 .593 Relapse 16 of 47 34 10 of 22 45 6 of 25 24 .215 AlloHSCT 11 of 47 23 7 of 22 32 4 of 25 16 .303 Disclosures No relevant conflicts of interest to declare.

scholarly journals Excellent Outcome of Children with Down Syndrome (DS) and Acute Lymphoblastic Leukemia (ALL) Treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols 00-001 and 05-001

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 761-761
Author(s):  
Uma H. Athale ◽  
Maneka Puligandla ◽  
Kristen E. Stevenson ◽  
Barbara L. Asselin ◽  
Luis A. Clavell ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Children With Down Syndrome ◽  
Dana Farber Cancer Institute ◽  
Induction Failure

Abstract Background Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are shown to have increased therapy-related morbidity and mortality. Hence, therapy modifications and/or dose-reductions are common treatment strategies for this patient (pt) population. Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols have used same risk-stratified treatment for children with and without DS and ALL. Aim: To define the toxicity profile and outcome of children with DS and de novo ALL treated on DFCI ALL Consortium therapy protocols 00-001 and 05-001 using therapy identical to non-DS patients. Methods: Demographic, clinical and outcome data of DS and non-DS patients enrolled on the DFCI ALL protocols 00-001 (2000-2004) and 05-001 (2005-2011) were analyzed. Risk categorization and protocol therapy have previously been described (J Clin Oncol 2013; 31:1202-10; Lancet Oncol 2015;16:1677-90). On both protocols, DS ALL pts were treated identically to non-DS pts without any dose reduction or modification, except for the option for DS ALL pts to receive 3 doses of leucovorin after IT methotrexate. Fisher's exact test was used to compare toxicities in the DS and non-DS pts and Gray test was used to compare the cumulative incidence of fracture and osteonecrosis. Overall survival (OS) was defined as time from registration to death. Event-free survival (EFS) was defined as time from registration to first event (defined as induction failure, relapse, second malignant neoplasm (SMN) or death due to any cause). Induction failure and induction death were included as events at time zero. Disease-free survival (DFS) was defined as time from complete remission (CR) to relapse, SMN or death. Pts without an event were censored at the last known follow-up. The Kaplan-Meier method was used for survival estimation and Greenwood's formula for calculation of 95% confidence interval (CI) of survival estimates. Outcome of DS patients was also examined using Ponte di Legno (PdL) risk group [Low risk (LR) was defined as age at diagnosis ≤ 6 yr. and white cell count < 10X109/L and, remainder as high risk (HR)].(Blood 2014;123:70-7). Two-sided p values <0.05 were considered significant. Results: Of 1286 eligible pts aged 1-18 yrs. with de novo ALL enrolled on protocols 00-001 and 05-001, 38 (3%) had DS. There was no difference in demographic or presenting clinical features between DS and non-DS ALL pts except immunophenotype (absence of T-ALL in DS vs 11.7% in non-DS, p=0.017) and presence of high hyperdiploidy (51-65 chromosomes) (8.8% in DS vs 25.1% in non-DS, p=0.027) (Table 1). Two DS-ALL pts withdrew from the study after achieving CR. There was no difference in the CR rates (DS: 100% vs non-DS: 95.2%, p=0.47) or proportion of pts with low end of induction minimal residual disease (MRD) between DS and non-DS groups (p=0.73). Toxicities were comparable except DS pts had significantly higher rates of ≥Grade 3 mucositis (data available for protocol 05-001 only) (DS: 52.0% vs. non-DS: 12.0%, p<0.001), non-CNS thrombosis/bleed (18.4% vs. 8.2%; p=0.036), and seizure (15.8% vs. 4.7%, p=0.010). DS pts also had marginally higher rate of bacterial and fungal infections (55.3% vs. 41.3%, p=0.096) (Table 2). All 38 DS pts achieved a CR and there were 4 relapses with 1 death due to disease. There were no treatment-related deaths in DS-ALL pts. With a median follow-up of 6.2 yrs. the 5-yr EFS, DFS, and OS of DS pts were similar to non-DS pts (90.7% [81.1-100.0] vs. 83.7% [81.7-85.9]; 90.7% [81.1-100.0] vs. 87.4% [85.5-89.3]; 97.1% [91.8-100.0] vs. 91.4% [89.8-93.0]), with the 95% CI overlapping for each comparison (Figures 1a and 1b). There was no difference in outcomes of DS-ALL PdL LR pts (n=13) compared to PdL HR pts (n=25) (5-yr EFS 90.0% [73.2-100.0]. vs. 91.0% [79.9-100.0]; 5-yr OS 100.0% [100.0-100.0] vs. 95.8% [88.2-100.0]). Conclusion: DS pts treated on DFCI ALL Consortium protocols without dose reduction or modifications achieved similar outcomes to non-DS pts. DS pts had a higher frequency of mucositis, infection, and seizures, but did not experience any treatment-related deaths. Other than a higher risk of thrombotic complications, they did not develop excessive toxicity to asparaginase. The low rates of relapse and toxicity-related mortality support the approach of unified therapy protocol for DS and non-DS ALL pts with emphasis on supportive care interventions to prevent toxicities. Overall and event free survival Overall and event free survival Disclosures Asselin: Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Sigma Tau Pharamceuticals: Consultancy.

Frontline Hyper-CVAD with Ponatinib for Patients (pts) with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Results of a Phase II Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2496-2496
Author(s):  
Koji Sasaki ◽  
Susan O'Brien ◽  
Farhad Ravandi ◽  
Deborah A Thomas ◽  
Haim G Moore ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Event Free Survival ◽  
Vascular Events ◽  
Free Survival ◽  
Philadelphia Chromosome Positive

Abstract Background: Addition of tyrosine kinase inhibitors (TKIs) to chemotherapy improves outcome in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Ponatinib is a more potent BCR-ABL inhibitor, and covers the T315I clones. The combination of hyper-CVAD with ponatinib may contribute to better response rates and higher likelihood of eradication of minimal residual disease (MRD) than those reported with other TKIs. Methods: Pts with newly diagnosed Ph+ ALL received 8 cycles of hyper-CVAD alternating with high dose methotrexate and cytarabine every 21 days. Ponatinib was given at 45 mg/day for the first 14 days of cycle 1 then continuously for the subsequent 7 cycles. Pts in CR received maintenance with ponatinib 45 mg/day and vincristine and prednisone monthly for 2 years followed by ponatinib indefinitely. Results: From 11/2011 to 9/2013, 34 pts with untreated Ph+ ALL and 3 pts previously treated (2 pts not in CR were treated with one cycle of chemotherapy before the detection of BCR-ABL1; 1 pt in CCyR after 2 cycles of chemotherapy and dasatinib) have received a median of 6 cycles (2-8); 13 are receiving maintenance in CR; 9 underwent ASCT after a median of 4 cycles. Baseline pt characteristic and outcome are described in table 1. The overall CCyR, MMR, and CMR rates were 100%, 95%, and 78%, respectively. The median time to MMR and CMR were 3 (range, 2-14) and 11 (range, 2-96) weeks, respectively. The median time to MRD negativity was 3 weeks (range, 3-14). Median time to platelet and neutrophil recovery for cycle 1 was 22 and 18 days, respectively, and 22 and 16 days for subsequent cycles. Grade ≥ 3 toxicity included infections during induction (54%), increased liver functional tests (38%), thrombotic events (8%), myocardial infarction (14%), hypertension (16%), skin rash (22%), and pancreatitis (22%). With a median follow up of 26 months, 29 (78%) remain alive and in CR. Six pts died in CR: 1 pt died in CR from an unrelated cardiac event after being taken off therapy and placed on imatinib, 1 from MOF (C2D13), 1 from NSTEMI (C2D41; ponatinib 45 mg daily), 1 from potential MI (C4D42; ponatinib 30 mg daily), 1 from head injury sustained after a fall (C4D13), and 1 from sepsis post ASCT. Two (5%) in CMR relapsed with no identifiable T315I mutations after a median of 18 months. One of these pts achieved a second CR after blinatumomab and dasatinib therapy. To date, 13 pts are receiving maintenance therapy in CR. After the increased incidence of vascular toxicities was recognized, we offered our pts the option to switch TKIs or to reduce the dose of ponatinib to 30 mg and further decreased to 15 mg in pts in CMR. Thirteen pts remained on ponatinib at a dose of 15 mg daily in 12 and 30 mg daily in 1 (transcript levels of 0.04%). No further vascular events were observed in pts receiving lower doses of ponatinib. Nine pts elected to switch TKIs to dasatinib (n=7), nilotinib, or imatinib (1 each). One pt was lost to follow-up. Of 9 patients who underwent ASCT while in first CR (7 with MMR and 2 with CMR before transplantation), all but one are alive and disease-free after transplantation. There was no difference in OS by whether patients were censored or not at the time of ASCT. After transplantation, TKI therapy was resumed in all but one patient (1 imatinib, 4 dasatinib, 1 nilotinib, and 1 ponatinib). The 2-year event-free and overall survival rates are 81% and 80%, respectively (Figures 1). Conclusion: The combination of hyperCVAD with ponatinib is highly effective in pts with Ph+ ALL. Due to the vascular events observed, the ponatinib dose was modified to 30 mg daily during consolidation with subsequent reduction to 15 mg in pts in CMR without further episode of cardiovascular events. Table 1. Patient characteristic and outcome N(%); Median [range] N= 37 Age (yr) 51 [27-75] Age ≥50 20 (54%) Age ≥60 12 (32%) Performance status, No. (%)  0-1 31 (84)  2 6 (16)  WBC (x 109/L) 8 [1-630]  Presence of CNS disease, No. (%) 3 (8)  CD20 positivity, No. (%) 11 (30) Type of BCR-ABL1 transcript, No. (%)  p190 27 (73)  p210 10 (27) Cytogenetics abnormality, No. (%)  Diploid 5 (14)  Philadelphia-chromosome positive 32 (86) Baseline cardiovascular risk factors, No. (%)  Hypertension 18 (49)  Dyslipidemia 4 (11)  Coronary artery disease 4 (11)  Peripheral arterial disease 1 (3) Overall response, No. (%)  CR 36/36 (100)  CCyR 32/32 (100)  MMR 35/37 (95)  CMR 29/37 (78)  Flow negativity 35/36 (97)  Early death 0 Figure 1. a) Event-free survival, b) overall survival Figure 1. a) Event-free survival, b) overall survival Disclosures O'Brien: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding. Cortes:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; BMS: Consultancy, Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Chahoud:American Society of Hematology (ASH): Other: 2015 HONORS Award recipient. Wierda:Glaxo-Smith-Kline Inc.: Research Funding; Celgene Corp.: Consultancy.

scholarly journals Survival outcomes of a population-based cohort of adolescent and young adult (AYA), acute lymphoblastic leukemia (ALL) patients in Ontario, Canada: The IMPACT Cohort

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Cindy Lau ◽  
Jason Pole ◽  
Rinku Sutradhar ◽  
Nancy Baxter ◽  
Paul Nathan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Young Adult ◽  
Lymphoblastic Leukemia ◽  
Population Based ◽  
Adolescent And Young Adult ◽  
Survival Outcomes ◽  
Event Free Survival ◽  
Free Survival ◽  
The Impact

IntroductionAdolescents and young adults (AYA) are an understudied population in cancer research. The Initiative to Maximize Progress in Adolescent and Young Adult Cancer Therapy (IMPACT) cohort includes Ontario individuals aged 15-21 years, diagnosed with a malignancy during 1992-2011. This cohort contains a rich source of patient, disease, and treatment data. Objectives and ApproachThe IMPACT cohort was created using chart review and linkages to population-based health services databases. The cohort is comprised of AYA with a primary diagnosis of acute leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, sarcoma, or testicular cancer. For the current study, we focused on acute lymphoblastic leukemia (ALL) patients, and examined survival outcomes of those treated at pediatric vs adult centers, with adult vs pediatric protocols. We assessed 5-year event-free survival (first of relapse, progression, secondary malignant neoplasm, or death) and overall survival. ResultsThe IMPACT cohort contains 2,963 patients, of which 152/271 ALL patients were treated at adult centers. The 5-year event-free survival (EFS ± standard error) among those treated at a pediatric vs. adult center was 72%±4% vs. 56%±4% (p = 0.03), respectively. The 5-year overall survival (OS) was 82%±4% vs. 64%±4% (p Conclusion/ImplicationsALL patients treated with a pediatric protocol at a pediatric center experienced better, crude survival outcomes compared to those at an adult center. The IMPACT cohort offers the opportunity to study a myriad of questions on different cancer groups, with the ultimate goal of improving outcomes among the AYA population.

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