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Blood Advances Jan 2022Adolescent and young adult patients with acute lymphoblastic leukemia (ALL) have superior outcomes when treated on pediatric regimens. Pediatric ALL regimens rely...
Adolescent and young adult patients with acute lymphoblastic leukemia (ALL) have superior outcomes when treated on pediatric regimens. Pediatric ALL regimens rely heavily on corticosteroids and asparaginase and are known to increase the risk of osteonecrosis (ON) and fractures in children, particularly adolescents. Orthopedic toxicity among young adults treated on pediatric-inspired regimens is not well described. Here, we report the symptomatic orthopedic toxicities of patients aged 15 to 50 years treated on sequential Dana-Farber Cancer Institute ALL Consortium protocols. Among 367 patients with a median age of 23 years (range, 15-50 years; 68% aged <30 years), 60 patients were diagnosed with ON (5-year cumulative incidence, 17%; 95% confidence interval [CI], 13-22), and 40 patients experienced fracture (5-year cumulative incidence, 12%; 95% CI, 8-15). Patients aged <30 years were significantly more likely to be diagnosed with ON (5-year cumulative incidence, 21% vs 8%; P = .004). Patients treated more recently on pegaspargase-based protocols were significantly more likely to be diagnosed with ON compared with those treated on earlier trials with native Escherichia coli asparaginase (5-year cumulative incidence, 24% vs 5%; P < .001). Of the 54 ON events for which adequate information was available, surgery was performed in 25 (46%). Patients with ON had superior overall survival (OS) compared with those without (multivariable OS hazard ratio, 0.15; 95% CI, 0.05-0.46; P = .001; ON included as a time-varying exposure). Increased rates of orthopedic toxicity in late-generation protocols may be driven by the pharmacokinetic drug interaction between pegaspargase and dexamethasone, leading to higher dexamethasone exposure.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Disease-Free Survival; Humans; Incidence; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proportional Hazards Models; Young Adult
PubMed: 34610104
DOI: 10.1182/bloodadvances.2021005278 -
Genes & Diseases Nov 2023
PubMed: 37554212
DOI: 10.1016/j.gendis.2023.02.011 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Jun 2020This study aimed to explore the clinical characteristics, survival rate, and prognostic factors of advanced-stage extranodal nasal type NK/T cell lymphoma (ENKTL)...
This study aimed to explore the clinical characteristics, survival rate, and prognostic factors of advanced-stage extranodal nasal type NK/T cell lymphoma (ENKTL) patients. The clinical data of 51 advanced-stage ENKTL patients in Peking Union Medical College Hospital from January 2012 to September 2019 were retrospectively analyzed. The clinical characteristics, treatment responses, survival rate, and prognostic factors were elucidated. The differences between nasal and non-nasal type and the significance of EBV-DNA in treatment response assessment and prognosis analysis were also evaluated. The male-to-female ratio in the whole group was 2.9∶1 with a median age of 42 years old (range, 14-67 years) . The median follow-up time was 30 months (range, 1-78 months) . The one- and three-year progression-free survival (PFS) rates for the whole cohort were 34.1% and 24.6%, respectively, and the one- and three-year overall survival (OS) rates were 39.9% and 26.6%, respectively. The ratio of nasal to non-nasal type was 1.6∶1. The proportion of hemophagocytic lymphohistiocytosis (HLH) was significantly higher in non-nasal-type patients than nasal-type (=0.039) , and the complete response (CR) rate of first-line chemotherapy is significantly lower in non-nasal type patients (=0.008) . The median OS for nasal and non-nasal types were nine months and four months, respectively. The three-year PFS rates of nasal and non-nasal type patients were 36.0% and 10.0% (=0.029) , respectively, and the three-year OS rates were 37.9% and 11.4% (=0.050) , respectively. The correlation between the Epstein-Barr virus DNA (EBV-DNA) and treatment response were satisfactory. Survival curve between baseline EBV-DNA-negative and EBV-DNA-positive patients showed no significant difference. The three-year OS rates of EBV-DNA-negative and EBV-DNA-positive patients after one cycle of treatment were 77.9% and 8.1% (=0.002) , respectively. In a multivariate analysis, EBV-DNA-positive following one cycle of treatment was an independent adverse prognostic factor for OS. The efficacy of pegaspargase-based chemotherapy and long-term survival of advanced-stage ENKTL patients were still poor. Clinical characteristics, treatment response, and long-term survival of non-nasal-type patients were worse than that of nasal-type patients. In a multivariate analysis, EBV-DNA-positive after one cycle of treatment was an independent adverse prognostic factor for OS. It can be used for early prediction of treatment response and prognosis.
Topics: Adolescent; Adult; Aged; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 32654458
DOI: 10.3760/cma.j.issn.0253-2727.2020.06.005 -
Frontiers in Oncology 2020Asparaginase-associated pancreatitis (AAP) is one of the most common complications occurring in patients with asparaginase-treated acute lymphoblastic leukemia (ALL)....
BACKGROUND
Asparaginase-associated pancreatitis (AAP) is one of the most common complications occurring in patients with asparaginase-treated acute lymphoblastic leukemia (ALL). Peg-asparaginase (peg-asp), a chemically recombined asparaginase with lower hyposensitivity and better patient tolerance, is now approved as the first line asparaginase formulation in ALL chemotherapy regimens. Due to the differences in pharmacokinetic characteristics and administration procedure between l-asp and peg-asp, this study aimed to investigate the clinical manifestations of peg-asp-associated pancreatitis.
METHOD
Patients with peg-asp-associated pancreatitis diagnosed within a 5-year period (July 2014 to July 2019) were identified and retrospectively studied. The clinical manifestations, laboratory findings, and imaging results of patients with AAP were analyzed. AAP patients were further classified into mild/moderate and severe groups based on criteria used in previous studies. Clinical outcomes were compared between groups.
RESULTS
A total of 38 patients were enrolled in this study. The underlying disease included ALL (n=35) and lymphoma (n=3). The majority of patients developed AAP during the first phase, called remission induction (n=26, 68.4%), after a median of 2 peg-asp doses (range: 1-11). The DVLP regimen (n=23) is the most common peg-asp regimen used in AAP patients. Abdominal pain occurred after a median of 14.5 days (range: 1-50) from the last peg-asp administration, accompanied by abdominal distension (n=14), nausea (n=17), vomiting (n=21), and fever (n=19). Serum amylase elevation was reported in all AAP patients, of whom 65.8% (n=25) exhibited an elevation in the level of this enzyme three times the upper normal level, fulfilling the Atlanta criteria. The level of serum lipase (median days of elevation=23 days, range: 4-75) was significantly elevated compared with that of serum amylase (median days of elevation=9 days, range: 2-71) and persisted at a markedly high level after the level of serum amylase returned to normal. Common local complications included abdominal ascites (n=10) and peripancreatic fluid collection (n=8). Approximately 42.1% (n=16) of patients with severe AAP experienced systemic complications (septic shock or hypovolemic shock) or severe local complications (pseudocyst), among whom 5 failed to recover. Approximately 84.8% (n=28/33) of the remaining patients resumed chemotherapy; among them, peg-asp formulation in 30.3% (n=10/33) of these patients was adjusted, while asparaginase treatment in 39.4% (n=13/33) was permanently discontinued. Five patients experienced an AAP relapse in later stages of asparaginase treatment. Comparison between mild/moderate and severe AAP patients showed a statistically significant difference in the number of pediatric intensive care unit stays (p=0.047), survival rate (p=0.009), AAP prognosis (p=0.047), and impacts on chemotherapy (p=0.024), revealing a better clinical outcome in mild/moderate AAP patients.
CONCLUSION
Early recognition and management of AAP is essential in reversing the severity of AAP. The existing AAP criteria had a low strength in determining the severity of pediatric AAP. A well-defined AAP definition could help distinguish patients with high anticipated risk for redeveloping AAP and ALL relapse, in order to prevent unnecessary withdrawal of asparaginase. Our study could serve as a basis for conducting future large cohort studies and for establishing an accurate definition of pediatric AAP.
PubMed: 33194600
DOI: 10.3389/fonc.2020.538779 -
Scientific Reports Jan 2017Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell...
Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell lymphoma. However, its prognostic value in extranodal natural killer (NK)/T-cell lymphoma (ENKL) remains unclear. Here, we conducted a retrospective study to determine the impact of PET/CT in ENKL. Fifty-two patients newly diagnosed with ENKL were enrolled. Baseline maximum standardized uptake values (SUVmax), whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG) were recorded. Additionally, interim PET/CT (I-PET) and end-of-treatment PET/CT (E-PET) results were scored using a 5-point scale. Patients were divided into groups using baseline parameter cut-off values; significant differences were found in overall survival (OS) and progression-free survival (PFS) between the high and low WBMTV and WBTLG groups and in OS between the two SUVmax groups. Positive I-PET and E-PET results predicted inferior PFS and OS. A multivariate analysis showed that baseline WBTLG, I-PET and E-PET results were associated with PFS and OS, and baseline SUVmax was an independent predictor of OS. Thus, baseline WBTLG, I-PET and E-PET results are good predictors of PFS and OS in ENKL patients who received L-asparaginase/pegaspargase in their first-line treatment, and baseline SUVmax is a valuable tool for assessing OS.
Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Asparaginase; Female; Fluorodeoxyglucose F18; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Polyethylene Glycols; Positron Emission Tomography Computed Tomography; Prognosis; Retrospective Studies; Young Adult
PubMed: 28117395
DOI: 10.1038/srep41057 -
Journal of Clinical Oncology : Official... Feb 2020Children's Oncology Group (COG) AALL0331 tested whether intensified postinduction therapy that improves survival in children with high-risk B-cell acute lymphoblastic... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Children's Oncology Group (COG) AALL0331 tested whether intensified postinduction therapy that improves survival in children with high-risk B-cell acute lymphoblastic leukemia (ALL) would also improve outcomes for those with standard-risk (SR) ALL.
PATIENTS AND METHODS
AALL0331 enrolled 5,377 patients between 2005 and 2010. All patients received a 3-drug induction with dexamethasone, vincristine, and pegaspargase (PEG) and were then classified as SR low, SR average, or SR high. Patients with SR-average disease were randomly assigned to receive either standard 4-week consolidation (SC) or 8-week intensified augmented Berlin-Frankfurt-Münster (BFM) consolidation (IC). Those with SR-high disease were nonrandomly assigned to the full COG-augmented BFM regimen, including 2 interim maintenance and delayed intensification phases.
RESULTS
The 6-year event-free survival (EFS) rate for all patients enrolled in AALL0331 was 88.96% ± 0.46%, and overall survival (OS) was 95.54% ± 0.31%. For patients with SR-average disease, the 6-year continuous complete remission (CCR) and OS rates for SC versus IC were 87.8% ± 1.3% versus 89.1% ± 1.2% ( = .52) and 95.8% ± 0.8% versus 95.2% ± 0.8% ( = 1.0), respectively. Those with SR-average disease with end-induction minimal residual disease (MRD) of 0.01% to < 0.1% had an inferior outcome compared with those with lower MRD and no improvement with IC (6-year CCR: SC, 77.5% ± 4.8%; IC, 77.1% ± 4.8%; = .71). At 6 years, the CCR and OS rates among 635 nonrandomly treated patients with SR-high disease were 85.55% ± 1.49% and 92.97% ± 1.08%, respectively.
CONCLUSION
The 6-year OS rate for > 5,000 children with SR ALL enrolled in AALL0331 exceeded 95%. The addition of IC to treatment for patients with SR-average disease did not improve CCR or OS, even in patients with higher MRD, in whom it might have been predicted to provide more value. The EFS and OS rates are excellent for this group of patients with SR ALL, with particularly good outcomes for those with SR-high disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Consolidation Chemotherapy; Disease-Free Survival; Female; Humans; Induction Chemotherapy; Infant; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome
PubMed: 31825704
DOI: 10.1200/JCO.19.01086 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Aug 2023To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. The clinical data of 656 ENKTL patients... (Randomized Controlled Trial)
Randomized Controlled Trial
To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% 63.8% ; =0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Topics: Male; Humans; Middle Aged; Asparaginase; Prognosis; Retrospective Studies; Lymphoma, Extranodal NK-T-Cell; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Cyclophosphamide; Methotrexate; DNA; Treatment Outcome
PubMed: 37803837
DOI: 10.3760/cma.j.issn.0253-2727.2023.08.005 -
Blood Apr 2021Truncation of asparaginase treatment due to asparaginase-related toxicities or silent inactivation (SI) is common and may increase relapse risk in acute lymphoblastic... (Randomized Controlled Trial)
Randomized Controlled Trial
Truncation of asparaginase treatment due to asparaginase-related toxicities or silent inactivation (SI) is common and may increase relapse risk in acute lymphoblastic leukemia (ALL). We investigated relapse risk following suboptimal asparaginase exposure among 1401 children aged 1 to 17 years, diagnosed with ALL between July 2008 and February 2016, treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol (including extended asparaginase exposure [1000 IU/m2 intramuscularly weeks 5-33]). Patients were included with delayed entry at their last administered asparaginase treatment, or detection of SI, and followed until relapse, death, secondary malignancy, or end of follow-up (median, 5.71 years; interquartile range, 4.02-7.64). In a multiple Cox model comparing patients with (n = 358) and without (n = 1043) truncated asparaginase treatment due to clinical toxicity, the adjusted relapse-specific hazard ratio (HR; aHR) was 1.33 (95% confidence interval [CI], 0.86-2.06; P = .20). In a substudy including only patients with information on enzyme activity (n = 1115), the 7-year cumulative incidence of relapse for the 301 patients with truncation of asparaginase treatment or SI (157 hypersensitivity, 53 pancreatitis, 14 thrombosis, 31 other, 46 SI) was 11.1% (95% CI, 6.9-15.4) vs 6.7% (95% CI, 4.7-8.6) for the 814 remaining patients. The relapse-specific aHR was 1.69 (95% CI, 1.05-2.74, P=.03). The unadjusted bone marrow relapse-specific HR was 1.83 (95% CI, 1.07-3.14, P=.03) and 1.86 (95% CI, 0.90- 3.87, P=.095) for any central nervous system relapse. These results emphasize the importance of therapeutic drug monitoring and appropriate adjustment of asparaginase therapy when feasible. This trial was registered at www.clinicaltrials.gov as #NCT03987542.
Topics: Adolescent; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Infant; Male; Neoplasm Recurrence, Local; Netherlands; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Prospective Studies; Risk Factors; Survival Rate
PubMed: 33150360
DOI: 10.1182/blood.2020006583 -
The Journal of Allergy and Clinical... Jan 2022
Topics: Asparaginase; COVID-19; COVID-19 Vaccines; Humans; Hypersensitivity, Immediate; Polyethylene Glycols; RNA, Messenger; SARS-CoV-2
PubMed: 34678498
DOI: 10.1016/j.jaip.2021.09.051