scholarly journals Thromboembolism Prophylaxis in Adult Patients with Acute Lymphoblastic Leukemia Treated in the GRAALL-2005 Study

Blood ◽  
2020 ◽  
Author(s):  
Corentin Orvain ◽  
Marie Balsat ◽  
Emmanuelle Tavernier ◽  
Jean-Pierre Marolleau ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Fresh Frozen Plasma ◽  
Adult Patients ◽  
Bleeding Complications ◽  
Thromboembolism Prophylaxis ◽  
Prophylactic Measures ◽  
Increased Risk ◽  
Fresh Frozen ◽  
Grade 3

Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP). Antithrombin (AT) replacement has been suggested to prevent VTE and thus might increase exposure to ASP. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Between 2006 and 2014, 784 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 16% with 69% of them occurring during induction therapy. Most patients received AT supplementation (87%). After excluding patients who did not receive L-ASP or developed thrombosis before L-ASP, AT supplementation did not have a significant impact on VTE (8% versus 14%, OR: 0.6, p=0.1). Fibrinogen concentrates administration was associated with an increased risk of VTE (17% versus 9%, OR 2.2, p=0.02) whereas transfusion of fresh-frozen plasma had no effect. Heparin prophylaxis was associated with an increased risk of VTE (13% versus 7%, OR 1.9, p=0.04). Prophylactic measures were not associated with an increased risk of grade 3-4 bleeding complications. The rate of VTE recurrence after L-ASP reintroduction was 3% (1/34). In ALL patients receiving L-ASP therapy, the use of fibrinogen concentrates may increase the risk of thrombosis and should be restricted to rare patients with hypofibrinogenemia-induced hemorrhage. Patients developed VTE despite extensive AT supplementation which advocates for additional prophylactic measures. While this large descriptive study was not powered to demonstrate the efficacy of these prophylactic measures, it provides important insight to guide future trial design. NCT00327678.

Impact of Prophylactic Fresh Frozen Plasma On Venous Thromboembolism in Adults Treated for Acute Lymphoblastic Leukemia Receiving Asparaginase,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3345-3345
Author(s):  
Mandy N Lauw ◽  
Bronno Van der Holt ◽  
Saskia Middeldorp ◽  
Joost CM Meijers ◽  
Bart J Biemond
Keyword(s):  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Treatment Period ◽  
Plasma Levels ◽  
Lymphoblastic Leukemia ◽  
Fresh Frozen Plasma ◽  
Prophylactic Measures ◽  
Total Treatment ◽  
Fresh Frozen ◽  
Frozen Plasma

Abstract Abstract 3345 Background: Acute lymphoblastic leukemia (ALL) is frequently complicated by venous thromboembolism (VTE). The reported incidence varies from 2% to 37%, with the highest risk arising in the first weeks after treatment initiation. VTE leads to morbidity, mortality and premature termination of therapy. Prevention of VTE in ALL is complicated, as thrombotic and bleeding factors need to be balanced. The efficacy of prophylactic antithrombotic measures is not clear yet, and standardized guidelines are lacking. We assessed the effect of various prevention protocols on the VTE risk in adults treated for ALL. Methods: Between April 1999 and November 2005, 240 consecutive patients aged 16–59 years with newly diagnosed ALL were treated with the same anti-leukemic protocol in a Dutch-Belgian multicenter study, which included L-asparaginase in cycle 1 (5000 U/m2/day, day 15–28). All VTE events during treatment were prospectively recorded. VTE prophylaxis was applied only in cycle 1 during asparaginase administration, and varied between different centers: no prophylaxis, fresh frozen plasma (FFP), or antithrombin (AT) concentrate. A centers' prevention protocol was used as a proxy for all patients treated in that center. AT plasma levels were assessed of patients with VTE and 22 controls without VTE. We determined VTE incidence in cycle 1, the impact of the various prophylactic measures, and VTE incidence during the total treatment period for ALL. Secondly, we assessed the clinical relevance of VTE on ALL outcome. Results: 25 of 240 patients (10.4%; 95% CI 6.6–14.3) experienced objectively diagnosed, symptomatic VTE in cycle 1 (10 cerebral thromboses of which 8 in the sagittal sinus, 11 upper limb vein thromboses (10 central venous catheter (CVC)-related), 3 deep vein thromboses of the leg, 1 pulmonary embolism). VTE incidence in patients receiving FFP prophylaxis was reduced by 70% as compared to patients without prophylactic measures (7.2% vs. 23.9%; RR 0.3; 95% CI 0.1–0.6; Table 1). Age, sex, ALL-type and CVC-placement did not differ significantly between patients with and without FFP prophylaxis. The effect of prophylactic AT concentrate could not be properly assessed as it was only rarely given in two centers. Mean AT plasma levels did not differ significantly between VTE patients with or without FFP, neither between patients with VTE and controls without VTE (Figure 1). During the total treatment period, VTE occurred in 36 of 240 patients (15.0%; 95% CI 10.5–19.5). Patients with VTE in cycle 1 were less likely to obtain complete remission after cycle 1 (HR 0.5; 95% CI 0.3–0.9), but did not have a significantly decreased overall survival (HR 1.5; 95% CI 0.9–2.6). Conclusions: FFP significantly reduced VTE incidence by 70% during ALL treatment, without reversing the AT deficiency induced by asparaginase. Our observation is in contrast with two previous studies on the effect of FFP on VTE in ALL. The mechanisms by which FFP accomplishes this antithrombotic effect are not clear yet and require further investigation. Since this was a retrospective, observational study, the effect of prophylactic FFP on VTE risk in adults treated for ALL should be confirmed by a randomized controlled trial. Disclosures: No relevant conflicts of interest to declare.

The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase

Blood ◽  
2009 ◽  
Vol 114 (25) ◽  
pp. 5146-5151 ◽  
Author(s):  
Lesleigh S. Abbott ◽  
Mariana Deevska ◽  
Conrad V. Fernandez ◽  
David Dix ◽  
Victoria E. Price ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Health Centre ◽  
Expectant Management ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
The Impact ◽  
Frozen Plasma

Abstract Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.

Toxicities in Adults with Acute Lymphoblastic Leukemia (ALL) Treated with Regimens Using Pegasparaginase.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1924-1924 ◽  
Author(s):  
Michael Rytting ◽  
Marc Earl ◽  
Dan Douer ◽  
Brenda Muriera ◽  
Anjali Advani ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cleveland Clinic ◽  
Adult Patients ◽  
Close Monitoring ◽  
Multiple Doses ◽  
Elevated Liver Enzymes ◽  
Grade 3 ◽  
Long Acting ◽  
Age Range

Abstract Background: The current therapeutic strategy of applying pediatric-based regimens for acute lymphoblastic leukemia (ALL) to adults with ALL exposes these patients to multiple doses of asparaginase (ASP). Exposure to long-acting or pegylated ASP is particularly prominent due to dosing convenience, since pegylated ASP can be administered intravenously and requires fewer doses than shorter-acting forms. Previously, adult patients were much less likely to be treated with ASP-containing regimens due to reports from the 1970s of increased toxicity from ASP in adults compared with children. We report on the toxicities encountered in 3 protocols that include multiple doses of pegylated ASP as part of therapy for ALL in adult patients. Methods: Thus far, the 3 protocols have enrolled 92 patients between the ages of 14 and 71 years. The pegylated ASP dose ranges from 2000–2500 IU/m2. Approximately 330 doses of pegylated ASP have been given. Results: Grade 3–4 hepatic toxicity is the most prominent; grade 3–4 transaminase elevation occurred in 47 (51%) patients, and grade 3–4 hyperbilirubinemia was seen in 22 (24%) patients (Table). Hyperglycemia was grade 3–4 toxicity in 30 (33%) patients. Grade 3–4 allergic reactions to pegylated ASP occurred in 5 (5%) patients. Twelve (13%) patients developed thromboses. Of note, 3 (3%) patients have had leukoencephalopathy on magnetic resonance imaging scans with reversible stroke-like symptoms. The majority of hepatic toxicities resolve spontaneously, allowing patients to continue chemotherapy. All of the patients with stroke-like symptoms have fully recovered. Conclusions: Considerable hepatotoxicity and hyperglycemia occur in adult ALL patients treated with polychemotherapy that includes long-acting ASP. Other toxicities occur with a frequency similar to that seen in pediatric patients treated with a long-acting ASP. This toxicity profile warrants close monitoring and continued data collection from clinical trials that use pegylated ASP in adults with ALL. USC Cleveland Clinic M.D. Anderson Total *No. of patients with grade 3–4 toxicities. Median age (years) 33 46 20 33 Age range (years) 18–57 20–71 14–34 14–71 No. doses/patients 127/39 56/25 147/28 330/92 Toxicity* Elevated liver enzymes 23 7 17 47 Hyperbilirubinemia 7 6 9 22 Hyperglycemia 12 5 13 30 Clinical pancreatitis 5 N/A 3 8 Fatigue 3 1 7 11 Thrombosis 3 (SVC only) 2 7 12 Hypofibrinogenemia N/A 8 N/A 8 Elevated PT / INR N/A 1 N/A 1 Bleeding 0 N/A 0 0 Nausea / vomiting 1 4 2 7 Allergy / hypersensitivity 0 2 3 5 Neuropathy 1 1 N/A 2 CNS stroke-like syndrome 0 0 3 3

scholarly journals Risk Factors for Induction Related Mortality in Adults Patients with Acute Lymphoblastic Leukemia: Report from a Hispanic Population

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5162-5162
Author(s):  
Sergio I Inclan-Alarcon ◽  
Christianne Bourlon ◽  
Oscar Manuel Fierro-Angulo ◽  
Jesus A Garcia-Ramos ◽  
Santiago Riviello-Goya ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Adult Patients ◽  
Hispanic Population ◽  
Increased Risk ◽  
The Impact ◽  
Hispanic Adult

Abstract Introduction Acute lymphoblastic leukemia (ALL) represents 20-30% of acute leukemia in adults. Higher incidence and inferior outcomes in Hispanic population have been described. In Latin Americans induction mortality (IM) is a major cause of death representing 20-50% vs.7-11% in developed countries. Our aim was to determine risk factors (RF) related to IM in ALL Hispanic adult patients. Methods We retrospectively analyzed clinical data of ≥18yo patients with ALL diagnosed and treated at our institution within 2009 and 2016. Results A total of 170 patients were included. Median age was 29 years (16-70), 64% were AYA, 96.8% had B-cell ALL, and 62.3% received Hyper-CVAD. IM rate was 13.4%. In 64.1% IM was related to an infectious cause. The most frequent infection was pneumonia (39.8%). Gram-negative etiology was more prevalent (35.5% vs. 10.2%), however, IM rate was higher in gram-positive infections (26.3% vs .13.6%; p=.028). RF related to IM in univariate analysis were: CNS involvement (OR4.6,95%IC2.8-9.5;p=<.001), tumor lysis syndrome (TLS) (OR 5.6, 95% CI 2.2-14.1; p=<.001), need for dialysis (OR 28.9, 95% CI 5.3-157.1; p=<.001), primary hypertension (OR 3.5, 95% CI 1.0-12.7; p=.052), shock status (OR 10.3, 95% CI 3.9-27.3; p=<.001), ECOG³2 (OR 1.9, 95% IC 1.1-3.4; p=.022), T-ALL (OR 2.2, 95% IC 1.1-4.3; p=.026), Hyper-CVAD (OR 1.9, 95% IC 1.1-3.8; p=0.51), ventilation assistance (OR 7.7, 95% IC 2.8-21; p=<.001), and vasopressor use (OR 7.6, 95% IC 2.8-20.6; p=<.001). In multivariate analysis TLS, need for dialysis and shock, kept statistical significance. Conclusions To our knowledge, this is the largest study that evaluates the impact over IM of biological, social, and economic factors in Hispanic adult patients with ALL. We identified factors not previously described such as hypertension and need for dialysis. Multicenter prospective studies most be urged to asses and validate these RF, and design a bedside prognostic score that can predict an increased risk of IM at ALL diagnosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cerebral infarction in a patient with acute lymphoblastic leukemia after fresh-frozen plasma replacement during l-asparaginase therapy

1992 ◽  
Vol 41 (4) ◽  
pp. 295-296 ◽  
Author(s):  
Hideshi Ishii ◽  
Hakumei Oh ◽  
Nobuko Ishizuka ◽  
Yasuhiro Matsuura ◽  
Hirotoshi Nakamura ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cerebral Infarction ◽  
Lymphoblastic Leukemia ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
Frozen Plasma

scholarly journals Prevention of Venous Thrombotic Events in Adult Patients with Acute Lymphoblastic Leukemia Treated in a Pediatric-Inspired Protocol - a Graall Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2776-2776 ◽  
Author(s):  
Corentin Orvain ◽  
Marie Balsat ◽  
Véronique Lhéritier ◽  
Emmanuelle Tavernier ◽  
Jean-Pierre Marolleau ◽  
...  
Keyword(s):  
Platelet Count ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
E Coli ◽  
Intravenous Injections ◽  
Increased Risk ◽  
Consolidation Phase ◽  
To Receive

Abstract Background: Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP) and subsequent antithrombine (AT) deficiency. Previous reports showed that patients with venous thrombotic events (VTE) have a lower event-free survival that may be due to early discontinuation of L-ASP. It has been suggested that AT replacement could decrease the rate of thrombosis and prevent L-ASP discontinuation. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Methods: All patients received a 5-drug induction therapy with 8 native E. Coli-ASP intravenous injections (6,000 UI/m2/injection). Patients in complete remission (CR) received two consolidation courses each containing two L-ASP intravenous injections (10000 UI/m2/injection). All patients in persistent CR for whom allogeneic stem cell transplantation was not indicated in first CR received a late intensification with the same drugs as in the induction course, followed by the repetition of one consolidation course. Platelet transfusion support was recommended for platelets below 20 x 109/L, fresh frozen plasma (FFP) or fibrinogen concentrates were recommended if fibrinogen levels fell below 0.5 g/L, and AT concentrate substitution therapy was recommended in order to maintain AT levels above 60%. Prophylactic heparin was recommended during induction and late intensification. All cases of VTE were identified prospectively by clinical signs and confirmed by radiological imaging based on institutional guidelines. Results: Between 2006 and 2014, 787 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 14.4% (113 VTEs in 110 patients). VTEs included 72 (64%) deep vein thromboses (DVT), with one third in the lower limb and two thirds in the upper limb, 32 (28%) cerebral venous thrombosis (CVT), and 13 (12%) pulmonary embolism (PE). No disease characteristic was associated with a higher risk of thrombosis. Patients with DVT and/or PE were older (median age of 40 versus 38 for those with CVT versus 35 for those without VTE, p=0.04), had a higher BMI (median BMI of 26 versus 23 for those with CVT and 24 for those without VTE, p=0.01), and had a higher platelet count at diagnosis (median platelet count of 100 G/l versus 84 G/l for those with CVT versus 68 G/l for those without VTE, p=0.06) whereas patients with CVT had higher hemoglobin levels (median hemoglobin level of 11.7 g/dl versus 10.1 g/dl for those with DVT/PE versus 10.2 g/dl for those without VTE, p=0.03). Sixty-seven percent of VTEs occurred during induction therapy. Other VTEs occurred as follows: 17 (15%) during consolidation phase 1 (688 patients), 4 (4%) during consolidation phase 2 (537 patients), 9 (8%) during late intensification (356 patients), and 7 (6%) in 335 during consolidation phase 3 (335 patients). The type of thrombosis was different according to treatment phase as most CVT occurred during induction therapy (29 versus 3 CVTs during subsequent phases of treatment, p=0.003). During induction therapy, patients with VTE were more likely to have received heparin prophylaxis (82% versus 60% for those without VTE, odds ratio (OR) 1.8, p=0.06) and fibrinogen prophylaxis (14% versus 8% for those without VTE, OR 2, p=0.05) whereas they received less AT prophylaxis (82% versus 88% for those without VTE, OR 0.5, p=0.05). Patients with VTE received less L-ASP infusions during induction therapy (median number of 7 versus 8 injections for those without VTE, p<0.001) and they were less likely to receive L-ASP during late intensification (64% versus 69% for those without TVE during induction and who went on to receive late intensification, p<0.001). Among 25 patients who experienced VTE during induction and in whom L-ASP, either native E. Coli-ASP or Erwiniase-ASP, was reintroduced during late intensification, none presented with recurrence of VTE. Conclusion: In ALL patients receiving L-ASP therapy, appropriate AT prophylaxis was associated with less VTE and should be used extensively. Maintaining higher AT levels in patients at increased risk for VTE should be evaluated. L-ASP can be reintroduced in patients who experienced VTE during induction as none had thrombotic recurrence. Fibrinogen concentrates may increase the risk of thrombosis and should be restricted to patients with hemorrhage. Disclosures Dombret: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Venous Thrombosis in Children with Acute Lymphoblastic Leukemia Treated on DCOG ALL-9 and ALL-10 Protocols: The Effect of Fresh Frozen Plasma

TH Open ◽  
2019 ◽  
Vol 03 (02) ◽  
pp. e109-e116
Author(s):  
Irene Klaassen ◽  
Charlotte Zuurbier ◽  
Barbara Hutten ◽  
Cor van den Bos ◽  
A. Schouten ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Plasma Levels ◽  
Medical Center ◽  
Lymphoblastic Leukemia ◽  
Academic Medical Center ◽  
Fresh Frozen Plasma ◽  
Thrombotic Risk ◽  
Fresh Frozen ◽  
Frozen Plasma

Background Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children. Especially, ALL treatment, with therapeutics such as asparaginase and steroids, increases the thrombotic risk by reduction in procoagulant and anticoagulant proteins. Replacement of deficient natural anticoagulants by administration of fresh frozen plasma (FFP) may have a preventive effect on the occurrence of VTE. Methods We retrospectively analyzed all consecutive children (≤18 years) with ALL, treated on the Dutch Childhood Oncology Group (DCOG) ALL-9 and ALL-10 protocols at the Emma Children's Hospital Academic Medical Center between February 1997 and January 2012, to study the effect of FFP on VTE incidence, antithrombin and fibrinogen plasma levels, and VTE risk factors. Results In total, 18/205 patients developed VTE (8.8%; 95% confidence interval [CI]: 4.9–12.7%). In all patients, VTE occurred after asparaginase administration. In total, 82/205 patients (40%) received FFP. FFP supplementation did not prevent VTE or alter plasma levels of antithrombin or fibrinogen. In the multivariate analysis, VTE occurred significantly more frequently in children ≥12 years (odds ratio [OR]: 3.89; 95% CI: 1.29–11.73) and treated according to the ALL-10 protocol (OR: 3.71; 95% CI: 1.13–12.17). Conclusion FFP supplementation does not seem to be beneficial in the prevention of VTE in pediatric ALL patients. In addition, age ≥12 years and treatment according to the DCOG ALL-10 protocol with intensive and prolonged administration of asparaginase in combination with prednisone are risk factors. There is a need for effective preventive strategies in ALL patients at high risk for VTE.

scholarly journals Pegasperagase Toxicity in Adult Patients with Acute Lymphoblastic Leukemia: A Single Center Experience Comparing Patients Older and Younger Than 35 Years of Age

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5067-5067
Author(s):  
Jun H Choi ◽  
Jacques Azzi ◽  
Tsivia Hochman ◽  
Mary Lynn R. Nierodzik ◽  
Shella Saint Fleur-Lominy ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Adult Population ◽  
Prospective Trial ◽  
Philadelphia Chromosome ◽  
Treatment Protocol ◽  
Adult Patients ◽  
Grade 3

Background: The treatment paradigm of adult patients with acute lymphoblastic leukemia (ALL) is primarily derived from successful pediatric chemotherapy regimens. Pegasparagase (PEG) is a key component of pediatric therapy and is the backbone of cytotoxic ALL regimens. However, among the adult population the use of PEG has been limited by the difficulty in tolerating prolonged asparagine depletion. Hepatotoxicity is among the most common adverse events reported with the use of PEG, with grade 3/4 hepatotoxicity seen in 20% of young adults compared to 40-60% of older adults. Incorporating PEG into the treatment of ALL patients under 40 remains an accepted practice despite some studies that report up to 75% of patients have grade 3/4 adverse events as a result of asparagine depletion. In a study of 85 patients with ALL, 3-year overall survival (OS) was significantly different between patients older and younger than 35 (52% vs 83% p = 0.003). Whether this difference is due to PEG toxicity or to other factors remains to be determined. At NYU hospitals, PEG-containing protocols are frequently deployed to treat adult ALL. In our study, we sought to look at the difference in PEG toxicity and response rate (RR) in patients older and younger than 35 and whether these toxicities contributed to a delay in subsequent treatments and to a worse outcome. Methods: We conducted a retrospective chart review of patients older than 18 diagnosed with ALL or lymphoblastic lymphoma, who received at least 1 dose of PEG at our institution between 2014 and 2018. All patients received PEG as part of their first line treatment protocol. Our main objective was to compare the tolerability and toxicity profile of intravenous PEG in patients ≥35 years old versus <35. Our secondary objective was to investigate its effects on chemotherapy delay, RR, and relapse rate. Results: Out of a total of 50 patients, 23 were age ≥ 35 (46%). Mean age was 34.4 (Range: 18.9-63.1). The 2 groups shared similar distributions in gender, race, and Philadelphia chromosome (Ph) subtypes (Table 1). The older group received significantly less PEG, 5114.8 vs. 25353.7 units (p=0.0007) and 1.65 vs. 3.59 doses (p<0.0001) compared to the younger group. Grade 1-4 toxicity profiles were similar as both groups had high hepatotoxicity rates: transaminitis 100% vs. 89% (p=0.079) and hyperbilirubinemia 78% vs. 78% (p=0.104) in the older vs younger group, respectively. Grade 3-4 hepatotoxicity was significantly more pronounced in patients ≥35 years old (transaminitis 65% vs. 33% [p=0.0245], hyperbilirubinemia 48 vs. 15% [p=0.0111]). Coagulopathy rates evaluated with hypofibrinogenemia and thrombosis were similar between the older and the younger groups at 52% vs. 44% [p=0.104] and 17% vs. 7%, [p=0.855], respectively, and the frequency of pancreatitis and anaphylaxis were 4% vs. 18.5% (p=0.422) and 0% vs. 14.8% (p=0.115), respectively. In the older group, only 13% completed the planned PEG dosages compared to 59% in the younger group (p=0.0008), and delay in other chemotherapy by more than 30 days due to PEG hepatotoxicity occurred in 55% of older patients compared to 22% of younger patients (p=0.02). MRD negativity rate after induction was similar in the older and younger group (50% vs. 60% [p=0.491], respectively), but the 12-month relapse free survival was significantly lower in the older group (41%, [95% CI: 55.7%-89%] vs. 77%, [95% CI: 21%-61%], p=0.022) (Figure 1). Conclusions: Patients aged ≥ 35 received significantly less PEG during their treatments but were more likely to develop severe grade 3-4 hepatotoxicity compared to their younger counterparts. The response rates were similar with comparable MRD negativity rates after induction regardless of total amount of PEG administered. However, relapse occurred more frequently in the older group, possibly resulting from more frequent delays in administering other chemotherapy agents due to PEG toxicity. Incorporation of PEG is important in the treatment of ALL but should be used with caution in patients ≥35 years old, and will likely require dose and schedule modifications. A larger prospective trial investigating adequate dosing and scheduling of PEG in this age group is warranted, specifically comparing delays in chemotherapy, relapse, and survival rates in regimens with and without PEG. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcomes of Down-Syndrome Associated Acute Lymphoblastic Leukemia in Adults: A Single Center Retrospective Review

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3717-3717
Author(s):  
Sita D. Bhella ◽  
Eshetu G Atenafu ◽  
Joseph Brandwein ◽  
Vikas Gupta ◽  
Johann Hitzler ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Acute Lymphoblastic Leukemia ◽  
Successful Treatment ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Outcome Data ◽  
Adult Patients ◽  
Multiparameter Flow Cytometry ◽  
Cancer Center ◽  
Increased Risk

Abstract Background: Children and adults with Down Syndrome (DS) have an approximately 20-fold increased risk of developing acute lymphoblastic leukemia, which in the majority of cases is of the B-cell precursor (BCP) type, and have significantly inferior outcomes due to both higher relapse rates and increased treatment-related mortality.During treatment for ALL, children with DS are at a higher risk of complications such as prolonged neutropenia, severe mucositis and longer hospitalizations. In view of the significant barriers to successful treatment for pediatric DS-ALL and the absence of outcome data for DS-ALL in adults, we retrospectively reviewed the outcomes of adult patients with DS-ALL treated at our center. Methods: All patients greater than 18 years of age diagnosed with DS-ALL who were followed at Princess Margaret Cancer Center/University Health Network (PMH/UHN) between January 1, 2000 and June 30, 2014 were identified using the institutional leukemia database. Diagnosis of ALL was established by standard FAB WHO Criteria using multiparameter flow cytometry for immunophenotyping according to ISCN guidelines. Treatment of adult DS patients with de novo ALL and those with relapsed ALL who had not previously received intensive asaparaginas therapy, were treated according to a modified Dana Farber Cancer Institute (DFCI) ALL regimen; reduced doses of methotrexate were used due to the increased risk of mucositis reported in children with DS. This regimen includes an at least four fold higher total dose of E. coli derived asparaginase compared to other adult regimens. Results: Seven adult patients with DS-ALL were treated at our center from 2000 to 2014. Four of these were diagnosed with de novo DS-ALL (after age of 18 years) and three patients developed a late isolated bone marrow relapse of DS-ALL as adults after previous treatment for childhood DS-ALL. Approximately half of our patients had favourable cytogenetics and half had intermediate risk cytogenetics . Treatment was not altered based on cytogenetics. The median age of 4 patients, with de novo adult DS-ALL, was 26 years (range 21-42 years). 75% achieved a CR after initial induction; one patient died during induction from sepsis. Two of the four de novo adult DS-ALL patients relapsed after CR1 durations of 11 and 35 mon.. One patient received palliative chemotherapy. At the time of last follow up, 3 of these patients have died. The one remaining patient is alive in continuous CR at 41 mos. The three adult DS patients with relapsed ALL had a median age of 14 years (7-15 years) at diagnosis of primary DS-ALL and 29 years (21-36) at the diagnosis of relapse. Two of these received DFCI as re-induction while the third received Hyper-CVAD. Despite achieving an initial remission all patients with relapsed DS-ALL died , two from subsequent relapsed and one from an invasive aspergillosis. One patient relapsed while on therapy at 4.7 months. The other patient relapsed while off therapy at 15.2 months. The overall and relapsed-free survival of adult patients with DS and de novo ALL at 3 years was 50% and 33.3%, respectively, and thus markedly inferior to results of a similarly treated population of adults (aged 18-35 years) without DS ( 3-year OS 83%, 3-year RFS 77%) at our center. Conclusions: The results of our series of adult patients with DS and ALL suggest that the barriers to successful treatment of ALL in adults with DS are similar to those observed in children. Although the rarity of adult ALL in general, and that of adult DS-ALL in particular, limits sample size and conclusions, this report is to our knowledge the first describing survival outcomes of adults with DS and ALL and highlights that treatment of primary adult DS-ALL is feasible but significantly less successful compared to adults without DS. As in children, subsequent relapse and treatment-related mortality impacting outcome are equally problematic. Disclosures Gupta: Incyte: Honoraria, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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