Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 944-950 ◽  
Author(s):  
Adele K. Fielding ◽  
Susan M. Richards ◽  
Rajesh Chopra ◽  
Hillard M. Lazarus ◽  
Mark R. Litzow ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Term Survival ◽  
First Remission ◽  
Previously Treated ◽  
Long Term Survivors ◽  
To Receive ◽  
Prevention Of Recurrence

Abstract Most adults with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR) will relapse. We examined the outcome of 609 adults with recurring ALL, all of whom were previously treated on the Medical Research Council (MRC) UKALL12/ECOG2993 study, where the overall survival (OS) of newly diagnosed patients is 38% (95% confidence interval [CI] = 36%-41%) at 5 years. By contrast, OS at 5 years after relapse was 7% (95% CI = 4%-9%). Factors predicting a good outcome after salvage therapy were young age (OS of 12% in patients younger than 20 years vs OS of 3% in patients older than 50 years; 2P < .001) and short duration of first remission (CR1) (OS of 11% in those with a CR1 of more than 2 years versus OS of 5% in those with a CR1 of less than 2 years; 2P < .001). Treatment received in CR1 did not influence outcome after relapse. In a very highly selected subgroup of patients who were able to receive HSCT after relapse, some were long-term survivors. We conclude from a large, unselected series with mature follow-up that most adults with recurring ALL, whatever their prior treatment, cannot be rescued using currently available therapies. Prevention of recurrence is the best strategy for long-term survival in this disease.

Chronic Progressive Cardiac Dysfunction Years After Doxorubicin Therapy for Childhood Acute Lymphoblastic Leukemia

2005 ◽  
Vol 23 (12) ◽  
pp. 2629-2636 ◽  
Author(s):  
Steven E. Lipshultz ◽  
Stuart R. Lipsitz ◽  
Stephen E. Sallan ◽  
Virginia M. Dalton ◽  
Suzanne M. Mone ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Left Ventricular ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Cardiac Abnormalities ◽  
Z Scores ◽  
Long Term Survivors ◽  
Fractional Shortening

Purpose Cross-sectional studies show that cardiac abnormalities are common in long-term survivors of doxorubicin-treated childhood malignancies. Longitudinal data, however, are rare. Methods Serial echocardiograms (N = 499) were obtained from 115 doxorubicin-treated long-term survivors of childhood acute lymphoblastic leukemia (median age at diagnosis, 4.8 years; median follow-up after completion of doxorubicin, 11.8 years). Results were expressed as z scores to indicate the number of standard deviations (SDs) above (+) or below (−) the normal predicted value. Median individual and cumulative doxorubicin doses were 30 mg/m2 per dose and 352 mg/m2, respectively. Results Left ventricular fractional shortening was significantly reduced after doxorubicin therapy, and the reduction was related to cumulative dose. z scores for fractional shortening transiently improved before falling to −2.76 more than 12 years after diagnosis. Reduced fractional shortening was related to impaired contractility and increasing afterload, consequences of a progressive reduction of ventricular mass, and wall thickness relative to body-surface area. Left ventricular contractility fell significantly over time and was depressed at last follow-up in patients receiving more than 300 mg/m2 of doxorubicin. Systolic and diastolic blood pressures were below normal more than 9 years after diagnosis. Even patients receiving lower cumulative doxorubicin doses experienced reduced mass and dimension. Fractional shortening and dimension at the end of therapy predicted these parameters 11.8 years later. Conclusion Cardiac abnormalities were persistent and progressive after doxorubicin therapy. Inadequate ventricular mass with chronic afterload excess was associated with progressive contractile deficit and possibly reduced cardiac output and restrictive cardiomyopathy. The deficits were worst after highest cumulative doses of doxorubicin, but appeared even after low doses.

scholarly journals Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

2016 ◽  
Vol 34 (22) ◽  
pp. 2644-2653 ◽  
Author(s):  
Kevin R. Krull ◽  
Yin Ting Cheung ◽  
Wei Liu ◽  
Slim Fellah ◽  
Wilburn E. Reddick ◽  
...  
Keyword(s):  
Executive Function ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Executive Dysfunction ◽  
Brain Regions ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Long Term Follow Up ◽  
Long Term Survivors

Purpose To examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol. Patients and Methods This longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education. Results Intelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI activity, with thicker cortices in dorsolateral prefrontal brain regions, and with white matter microstructure in the frontostriatal tact. Neurocognitive impairment was associated with these imaging findings as well. Associations did not change after adjustment for age or dose of leucovorin rescue. Conclusion Survivors of childhood acute lymphoblastic leukemia treated on contemporary chemotherapy-only protocols demonstrate executive dysfunction. A higher plasma concentration of methotrexate was associated with executive dysfunction as well as with a thicker cortex and higher activity in frontal brain regions, regions often associated with executive function.

Extended Follow-up of Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

2003 ◽  
Vol 349 (7) ◽  
pp. 640-649 ◽  
Author(s):  
Ching-Hon Pui ◽  
Cheng Cheng ◽  
Wing Leung ◽  
Shesh N. Rai ◽  
Gaston K. Rivera ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Long Term Survivors

scholarly journals Low-dose versus high-dose methotrexate during remission induction in childhood acute lymphoblastic leukemia (Protocol 81-01 update)

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2514-2519 ◽  
Author(s):  
CM Niemeyer ◽  
RD Gelber ◽  
NJ Tarbell ◽  
M Donnelly ◽  
LA Clavell ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Low Dose ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Remission Induction ◽  
High Dose ◽  
Childhood All ◽  
To Receive

We evaluated event-free survival (EFS) and leukemia-free interval (LFI) of children treated for acute lymphoblastic leukemia (ALL). Patients were randomized to receive either a low dose or high dose of methotrexate (MTX) as a single agent at the time of diagnosis. Five days later, multidrug therapy was begun. We assessed the early antileukemic efficacy of the two doses of MTX, as well as toxicity and long-term efficacy. An increase in cell kill, as indicated by a larger decrease in the percentage of viable cells in the bone marrow between days 0 and 5, was observed for the high-dose MTX group when compared with the low-dose MTX group (P = .04). At 7.1 years of median follow- up, the 38 children randomized to receive high-dose MTX had a better EFS and LFI compared with the 39 patients randomized to receive low- dose MTX. The 7-year percentages (+/- SE) for EFS were 82% +/- 6% for high-dose MTX and 69% +/- 7% for low-dose MTX (P = .13). The 7-year percentages for LFI were 91% +/- 5% and 69% +/- 7%, respectively (P = .01). We recommend that high-dose MTX be considered as an effective addition to induction therapy in childhood ALL.

scholarly journals L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 10 (19) ◽  
pp. 4419
Author(s):  
Madalina-Petronela Schmidt ◽  
Anca-Viorica Ivanov ◽  
Daniel Coriu ◽  
Ingrith-Crenguta Miron
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Free Survival ◽  
The Impact

Asparaginase is a basic component of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) and has played a crucial role in improving the long-term survival of this disease. The objectives of this retrospective study were to elucidate the toxicity profile associated with asparaginase in children and adolescents with ALL, to analyze the impact of each type of toxicity on long-term outcomes, and to identify risk factors. We analyzed the medical charts of 165 patients diagnosed with ALL at Sf. Maria Iasi Children’s Hospital from 2010 to 2019 and treated according to a chemotherapeutic protocol containing asparaginase. The median duration of follow-up was 5 years (0.1–11.5 years). Groups of patients with specific types of toxicity were compared to groups of patients without toxicity. We found the following incidence of asparaginase-associated toxicity: 24.1% clinical hypersensitivity, 19.4% hepatotoxicity, 6.7% hypertriglyceridemia, 4.2% hyperglycemia, 3.7% osteonecrosis, 3% pancreatitis, 2.4% thrombosis, and 1.2% cerebral thrombosis. Overall, 82 patients (49.7%) had at least one type of toxicity related to asparaginase. No type of toxicity had a significant impact on overall survival or event-free survival. Being older than 14 years was associated with a higher risk of osteonecrosis (p = 0.015) and hypertriglyceridemia (p = 0.043) and a lower risk of clinical hypersensitivity (p = 0.04). Asparaginase-related toxicity is common and has a varied profile, and its early detection is important for realizing efficient and appropriate management.

High Prevalence of Chronic Fatigue in Long Term Survivors of Childhood Acute Lymphoblastic Leukemia and Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4225-4225
Author(s):  
Hanne Hamre ◽  
Bernward Zeller ◽  
Adriani Kanellopoulos ◽  
Sophie Dorothea Fosså ◽  
Jon Håvar Loge ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
General Population ◽  
Lymphoblastic Leukemia ◽  
Chronic Fatigue ◽  
Diffusion Capacity ◽  
And Gender ◽  
Long Term Survivors ◽  
And Diffusion

Abstract Abstract 4225 Introduction: Chronic fatigue is a frequent and distressing late effect after successful cancer treatment. However, few studies have included survivors of childhood cancers. Aims: The primary aim of the study was to assess the prevalence of fatigue in long-term survivors of childhood acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), and to compare with the Norwegian general population. A secondary aim was to explore the association between cardiac or pulmonary late effects and fatigue in long-term survivors after NHL and HL. Material and method: This population-based cross-sectional study included tumor-free adult survivors of childhood ALL, NHL and HL diagnosed between 1970 and 2002 at an age of <19 years with at least 5 years follow-up time. The enrolled patients underwent extensive biochemical and clinical investigation including echocardiography and estimation of lung volumes and diffusion capacity. Clinical information was retrieved from the patient records. Chalder′s fatigue questionnaire (FQ) was used to assess fatigue. Chronic fatigue (CF) was defined as a substantially increased level of fatigue with duration of more than 6 months. 1423 age and gender matched individuals from the general Norwegian population served as controls. Results: A total of 290 patients completed the questionnaire (ALL 151, NHL 47, HL 92). Median age (range) at assessment was 29.9 (18.3–54.5) years. Median follow-up time from diagnosis was 21.3 (6.9–39.2) years. The overall prevalence of CF was 27% (ALL 23%, NHL 30%, HL 34%), as compared to 8.4% among the controls (p>0.001). There was a tendency towards a higher prevalence of CF by increasing age (32% among subjects aged ≥30 years at follow-up vs. 22% in subjects aged<30 years, p=0.063). This was most pronounced among the ALL survivors (36% among subjects aged ≥30 years years at follow-up vs. 13% among subjects aged <30 years, p=0.001). In ALL survivors, older age at diagnosis was associated with higher prevalence of CF (15% among subjects aged <6 years at diagnosis vs. 32% among subjects aged ≥6 years, p= 0.012). Indeed, among all survivors ≥6 years at diagnosis, the ALL group had a similar prevalence of CF as the two other diagnostic groups; 32%. No association was found between CF and gender, time from diagnosis, radiotherapy, cumulative anthracycline dose, body mass index, proBNP or hypothyreosis. Among the lymphoma survivors the presence of B-symptoms at diagnosis tended to be associated with CF (Presence: CF 48% vs. Absence: CF 29%, p=0.058). In long-term survivors of NHL and HL, no association was found between CF and aortic valve disease, total lung capacity and diffusion capacity. Conclusions: Compared to the general population the prevalence of CF is 3-fold increased in long-term survivors of childhood leukemia and lymphoma. The prevalence is highest in HL (34%), but, rather surprisingly, even ALL survivors have a high occurrence of CF (23%). The lack of association between CF and somatic co-morbidity or dysfunction warrants future studies exploring the etiology of CF in long-term survivors. Disclosures: No relevant conflicts of interest to declare.

Long-term survival in adult acute lymphoblastic leukemia: follow-up of a Southeastern Cancer Study Group trial.

1985 ◽  
Vol 3 (8) ◽  
pp. 1053-1058 ◽  
Author(s):  
G A Omura ◽  
M Raney
Keyword(s):  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Survival ◽  
Current Observation ◽  
First Remission

Current observation was obtained for adults treated on a protocol for acute lymphoblastic leukemia, which was open from 1972 to 1978, in order to determine the long-term outcome and to evaluate potential prognostic factors. Long-term survival (five + years) was seen in 32% (25/79) of patients who achieved complete remission; 16/79 remain in first remission and 2/79 are currently in second remission. Young age (less than 40) and female sex were significant prognostic factors for long-term survival, but the basis for this advantage is unclear. Further improvements in chemotherapy are needed.

scholarly journals Low-dose versus high-dose methotrexate during remission induction in childhood acute lymphoblastic leukemia (Protocol 81-01 update)

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2514-2519 ◽  
Author(s):  
CM Niemeyer ◽  
RD Gelber ◽  
NJ Tarbell ◽  
M Donnelly ◽  
LA Clavell ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Low Dose ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Remission Induction ◽  
High Dose ◽  
Childhood All ◽  
To Receive

Abstract We evaluated event-free survival (EFS) and leukemia-free interval (LFI) of children treated for acute lymphoblastic leukemia (ALL). Patients were randomized to receive either a low dose or high dose of methotrexate (MTX) as a single agent at the time of diagnosis. Five days later, multidrug therapy was begun. We assessed the early antileukemic efficacy of the two doses of MTX, as well as toxicity and long-term efficacy. An increase in cell kill, as indicated by a larger decrease in the percentage of viable cells in the bone marrow between days 0 and 5, was observed for the high-dose MTX group when compared with the low-dose MTX group (P = .04). At 7.1 years of median follow- up, the 38 children randomized to receive high-dose MTX had a better EFS and LFI compared with the 39 patients randomized to receive low- dose MTX. The 7-year percentages (+/- SE) for EFS were 82% +/- 6% for high-dose MTX and 69% +/- 7% for low-dose MTX (P = .13). The 7-year percentages for LFI were 91% +/- 5% and 69% +/- 7%, respectively (P = .01). We recommend that high-dose MTX be considered as an effective addition to induction therapy in childhood ALL.

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