scholarly journals Sociodemographic and Medical Determinants of Quality of Life in Long-Term Childhood Acute Lymphoblastic Leukemia Survivors Enrolled in EORTC CLG Studies

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 152
Author(s):  
Charlotte Sleurs ◽  
Jammbe Musoro ◽  
Ali Rowsell ◽  
Michal Kicinski ◽  
Stefan Suciu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Personal Growth ◽  
Older Patients ◽  
Lymphoblastic Leukemia ◽  
Life Challenges ◽  
Risk Patients ◽  
Component Scores

Background: due to increasing survival rates in childhood acute lymphoblastic leukemia (ALL), the number of survivors has been expanding. A significant proportion of these survivors can experience long-term emotional and psychosocial problems. However, the exact risk factors remain inconclusive. We investigated potential risk factors for decreased daily life quality and life challenges in long-term childhood ALL survivors enrolled between 1971 and 1998 in EORTC studies. Methods: self-report questionnaires were collected from 186 survivors (109 females; mean age at diagnosis 5.62 years, range 0.2–14.7; median time since diagnosis of 20.5 years (12.9–41.6)), including the Short-Form Health Survey (SF-12) and Impact of Cancer-Childhood Survivors (IOC-CS). Multivariable linear regression models were used to assess the impact of gender, age at diagnosis, relapse/second neoplasm, National Cancer Institute (NCI) risk group and cranial radiotherapy on 2 subscales of the SF-12 (physical and mental health) and five subscales of the IOC-CS (life challenges, body and health, personal growth, thinking and memory problems and socializing). Results: mental component scores of SF-12 were not significantly associated with any risk factor. Physical component scores were lower in relapsed, irradiated and NCI high-risk patients. Regarding IOC-CS negative impact subscales, life challenges was more negatively impacted by cancer in female, younger (i.e., <6 years) and relapsed patients. Regarding the positive impact scales, personal growth was more positively impacted in relapsed patients, whereas body and health, and socializing, were less positively impacted in these patients, compared to non-relapsed patients. Socializing was more positively impacted in older patients (>6 years). Conclusions: this study demonstrates that long-term outcomes can be both adverse and positive, depending on the patient’s demographic and clinical characteristics. Younger, female, and relapsed patients might encounter more life challenges years after their disease, while physical challenges could occur more often in relapsed and high-risk patients. Finally, the positive effect on socializing in the older patients sheds new light on the importance of peer interactions for this subgroup. Specific individual challenges thus need specialized support for specific subgroups.

Risk Factors in Childhood Acute Lymphoblastic Leukemia: A Single Center Experience in a Developing Country.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4475-4475
Author(s):  
Sema S. Anak ◽  
Leyla Agaoglu ◽  
Arzu Akcay ◽  
Ebru T. Saribeyoglu ◽  
Didem Y. Atay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
Pediatric All

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with the survival rates up to 80–90%, but in high-risk patients the survival rate is still unsatisfactory. The aim of this study is to analyze the pediatric ALL data of a single pediatric university center between 1987–2005 retrospectively to identify risk factors effecting the event free survival (EFS). In order to determine the risk factors possibly effecting the survival, we analyzed gender, age, physical examination findings, blood cell count, FAB morphology, immunophenotyping results, translocations and extramedullary involvement. During the same period, chemotherapy regimens used and response to these protocols were also analyzed. A total of 372 cases [220 male (60%) and 151 female (41%)] were diagnosed and treated in our center between 1987–2005. The age distribution was as follows: 7% patients under 2 years, 68% between 2–10 years, 25% above 10 years of age. At diagnosis, 76% patients had a hemoglobin level <10gr/dl, 56% WBC >10.000/mm3, 74% platelet <100.000/mm3. Primary CNS involvement was positive in 2.5%, mediastinal mass in 8% of all patients. The morphological subtypes were as follows: L1 64%, L2 32%, L3 4%. Immunophenotypic results revealed T ALL in 22%, mature B ALL in 8% and B ALL (common, pre B, proB) in 70%. All patients received CCG modified BFM protocol (80% of all patients) until 1999. Since then high-risk patients were treated with the augmented BFM protocol and L3 patients BFM NHL 95 Protocol, while standard risk patients continued to get the CCG modified BFM protocol. The remission rate at day 33 was 97.8%. Eighty-one patients relapsed (68% patients isolated bone marrow, 16% bone marrow + extramedullary, 9% CNS, 7% testes). According to the univariate analysis of our patient population, the factors negatively effecting the EFS were age <1 year, hepatomegaly >2cm., white blood cell >50.000/mm3 and platelet count <20.000/mm3, L3 FAB morphology, ≥M2 bone marrow status at day 14; CD3, HLADR, CD45 and Tdt negativity. According to the multivariate analysis the most important negative risk factors effecting the EFS were age <1 year, hepatomegaly >2cm. and ≥M2 bone marrow status at day 14 and CD 45 negativity. After a follow up of 72±59 months (1–300 months) 58% of patients are alive & well, 28% were lost to follow up and 14% patients succumbed to death. Overall survival (OS) for 60&120 months follow up were 83%, 83% and event free survival (EFS) 72%, 70% respectively. In conclusion, in ALL patients risk assessment is very important to conduct appropriate therapy. Identifying such factors and implementing risk adapted therapy will improve our treatment results decreasing the toxicity rates in pediatric ALL. Therefore treatment of all ALL patients still remains a challenge.

scholarly journals Intensive Multiagent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide, Irinotecan, and Radiation, in Patients With High-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group

2016 ◽  
Vol 34 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Brenda J. Weigel ◽  
Elizabeth Lyden ◽  
James R. Anderson ◽  
William H. Meyer ◽  
David M. Parham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
High Risk ◽  
Bone Marrow Involvement ◽  
High Risk Group ◽  
Historical Cohort ◽  
Dismal Prognosis ◽  
Risk Patients ◽  
Metastatic Sites

Purpose Patients with metastatic rhabdomyosarcoma (RMS), except those younger than 10 years with embryonal RMS, have an estimated long-term event-free survival (EFS) of less than 20%. The main goal of this study was to improve outcome of patients with metastatic RMS by dose intensification with interval compression, use of the most active agents determined in phase II window studies, and use of irinotecan as a radiation sensitizer. Patients and Methods Patients with metastatic RMS received 54 weeks of therapy: blocks of therapy with vincristine/irinotecan (weeks 1 to 6, 20 to 25, and 47 to 52), interval compression with vincristine/doxorubicin/cyclophosphamide alternating with etoposide/ifosfamide (weeks 7 to 19 and 26 to 34), and vincristine/dactinomycin/cyclophosphamide (weeks 38 to 46). Radiation therapy occurred at weeks 20 to 25 (primary) but was also permitted at weeks 1 to 6 (for intracranial or paraspinal extension) and weeks 47 to 52 (for extensive metastatic sites). Results One hundred nine eligible patients were enrolled, with a median follow-up of surviving patients of 3.8 years (3-year EFS for all patients, 38% [95% CI, 29% to 48%]; survival, 56% [95% CI, 46% to 66%]). Patients with one or no Oberlin risk factor (age > 10 years or < 1 year, unfavorable primary site of disease, ≥ three metastatic sites, and bone or bone marrow involvement) had a 3-year EFS of 69% (95% CI, 52% to 82%); high-risk patients with two or more risk factors had a 3-year EFS of 20% (95% CI, 11% to 30%). Toxicity was similar to that on prior RMS studies. Conclusion Patients with metastatic RMS with one or no Oberlin risk factor had an improved 3-year EFS of 69% on ARST0431 compared with an historical cohort from pooled European and US studies; those with two or more risk factors have a dismal prognosis, and new approaches are needed for this very-high-risk group.

scholarly journals Venous Thromboembolism and Its Risk Factors in Children with Acute Lymphoblastic Leukemia in Israel: A Population-Based Study

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2759
Author(s):  
Shlomit Barzilai-Birenboim ◽  
Ronit Nirel ◽  
Nira Arad-Cohen ◽  
Galia Avrahami ◽  
Miri Ben Harush ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Population Based ◽  
Population Based Study ◽  
Inherited Thrombophilia ◽  
Severe Hypertriglyceridemia

Venous thromboembolism (VTE) is a serious complication of acute lymphoblastic leukemia (ALL) therapy. The aim of this population-based study was to evaluate the rate, risk factors, and long-term sequelae of VTE in children treated for ALL. The cohort included 1191 children aged 1–19 years diagnosed with ALL between 2003–2018, prospectively enrolled in two consecutive protocols: ALL-IC BFM 2002 and AIEOP-BFM ALL 2009. VTEs occurred in 89 patients (7.5%). Long-term sequelae were uncommon. By univariate analysis, we identified four significant risk factors for VTEs: Severe hypertriglyceridemia (p = 0.005), inherited thrombophilia (p < 0.001), age >10 years (p = 0.015), and high-risk ALL group (p = 0.039). In addition, the incidence of VTE was significantly higher in patients enrolled in AIEOP-BFM ALL 2009 than in those enrolled in ALL-IC BFM 2002 (p = 0.001). Severe VTE occurred in 24 children (2%), all of whom had at least one risk factor. Elevated triglyceride levels at diagnosis did not predict hypertriglyceridemia during therapy. In a multivariate analysis of 388 children, severe hypertriglyceridemia and inherited thrombophilia were independent risk factors for VTE. Routine evaluation for these risk factors in children treated for ALL may help identify candidates for intervention.

scholarly journals Personalized therapy in pediatric high-risk B-cell acute lymphoblastic leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072092757 ◽  
Author(s):  
Seth E. Karol ◽  
Ching-Hon Pui
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Risk Patients ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Disease Stratification ◽  
Cure Rates ◽  
Minimal Residual

Although cure rates for pediatric acute lymphoblastic leukemia (ALL) have now risen to more than 90%, subsets of patients with high-risk features continue to experience high rates of treatment failure and relapse. Recent work in minimal residual disease stratification and leukemia genomics have increased the ability to identify and classify these high-risk patients. In this review, we discuss this work to identify and classify patients with high-risk ALL. Novel therapeutics, which may have the potential to improve outcomes for these patients, are also discussed.

Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital.

1998 ◽  
Vol 16 (12) ◽  
pp. 3761-3767 ◽  
Author(s):  
A W Walter ◽  
M L Hancock ◽  
C H Pui ◽  
M M Hudson ◽  
J S Ochs ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Brain Tumors ◽  
Lymphoblastic Leukemia ◽  
Low Grade ◽  
High Grade ◽  
Research Hospital ◽  
Dose Dependent

PURPOSE To evaluate the incidence of and potential risk factors for second malignant neoplasms of the brain following treatment for childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS The study population consisted of 1,612 consecutively enrolled protocol patients treated on sequential institutional protocols for newly diagnosed ALL at St Jude Children's Research Hospital (SJCRH) between 1967 and 1988. The median follow-up duration is 15.9 years (range, 5.5 to 29.9 y). RESULTS The cumulative incidence of brain tumors at 20 years is 1.39% (95% confidence interval [CI], 0.63% to 2.15%). Twenty-two brain tumors (10 high-grade gliomas, one low-grade glioma, and 11 meningiomas) were diagnosed among 21 patients after a median latency of 12.6 years (high-grade gliomas, 9.1 years; meningiomas, 19 years). Tumor type was linked to outcome, with patients who developed high-grade tumors doing poorly and those who developed low-grade tumors doing well. Risk factors for developing any secondary brain tumor included the presence of CNS leukemia at diagnosis, treatment on Total X therapy, and the use of cranial irradiation, which was dose-dependent. Age less than 6 years was associated with an increased risk of developing a high-grade glioma. CONCLUSION This single-institution study, with a high rate of long-term data capture, demonstrated that brain tumors are a rare, late complication of therapy for ALL. We report many more low-grade tumors than others probably because of exhaustive long-term follow-up evaluation. The importance of limiting cranial radiation is underscored by the dose-dependent tumorigenic effect of radiation therapy seen in this study.

Minimal Residual Disease At 3 Months, Combined to the Presence of IKZF1 Deletion in B-Lineage or Absence of NOTCH1 pathway Mutation in T-Lineage, Recapitulates the Disease Risk Assessment in Adults with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia - A GRAALL Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 572-572 ◽  
Author(s):  
Kheira Beldjord ◽  
Elizabeth Macintyre ◽  
Véronique Lhéritier ◽  
Marie-Laure Boulland ◽  
Thibaut Leguay ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Disease Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cns Involvement ◽  
Risk Patients ◽  
Minimal Residual

Abstract Abstract 572 Aim. In recent series of adults with acute lymphoblastic leukemia (ALL), the GRAALL (ASH 2009, abstract 577) and other cooperative groups have confirmed the strong prognostic value of Ig/TCR minimal residual disease (MRD) on patient outcome. Despite this, age, WBC, CNS involvement, recurrent chromosomal translocations, and early response to steroids and chemotherapy remain frequently used to tailor post-remission therapy and envision allogeneic stem cell transplantation (SCT) in most adult ALL trials. We updated our MRD study, now with 262 patients who all achieved complete remission (CR) after the first induction and were assessed for MRD after induction (MRD1, at 6 weeks) and consolidation (MRD2, at 12 weeks). One hundred and fifty-eight patients had Philadelphia chromosome (Ph)-negative B-cell precursor ALL (BCP-ALL), while 104 had T-cell ALL (T-ALL). Since 107 of the BCP-ALL (68%) were studied for IKZF1 deletion and 90 of the T-ALL patients (87%) for NOTCH1/FBXW7 mutations, we were able to reassess the MRD significance according to these newly described oncogenic markers. These two covariates (i.e. MRD and IKZF1/NOTCH1/FBXW7 genetics) allowed us to redefine a much simpler yet more powerful stratification of disease risk in both BCP- ALL and T-ALL subsets. Methods. All 262 patients studied (median age, 31.5 years) were treated in the GRAALL-2003 and GRAALL-2005 trials. Although they were younger and had more frequently circulating blasts, other characteristics and outcome did not differ from patients treated in the same trials but not assessed for MRD. Ig/TCR MRD levels were determined according to Euro-MRD guidelines (Leukemia 2007;21:604). IKZF1 deletions were assessed by multiplex multi-fluorescent PCR. NOTCH1/FBXW7 mutations were assessed as previously described (Blood 2009;113:3918). Multivariate backward stepwise selection Cox models were used for the cumulative incidence of relapse (CIR), disease-free (DFS) and overall survival (OS) endpoints, after censoring transplanted patients at SCT. Models were always adjusted on age (35-year cutoff), WBC (30 and 100 G/L cutoff for BCP- and T-ALL, respectively), CNS involvement, and trial. Additional BCP-specific covariates included CD20 expression, t(4;11) and t(1;19) translocations, and IKZF1 deletion. Additional T-specific covariates included cortical immunophenotype according to the EGIL classification, TLX1 overexpression, and NOTCH1/FBXW7 mutation. Finally, allogeneic SCT was re-evaluated in the newly defined risk subsets, as a time-dependent covariate. Results. An initial multivariate analysis revealed that among blood response after 1 week of steroid, bone marrow response after 2 weeks of therapy, and molecular response at both MRD1 and MRD2 time-points, the MRD2 level was the main and sole independent predictor of relapse (P=0.003). In BCP-ALL patients, persistent MRD2 and IKZF1 deletion were the only two independent factors identified, the presence of at least one factor defining 51% high-risk patients with 52% versus 15% CIR (HR, 3.8; P= 0.008), 41% versus 81% DFS (HR, 3.6; P= 0.005), and 54% versus 80% OS (HR, 3.9; P= 0.015) at 4 years. Allogeneic SCT in first CR significantly decreased relapse incidence and prolonged DFS in these new high-risk BCP-ALL patients (HR, 0.23 and 0.40; P= 0.016 and 0.05, respectively). In T-ALL patients, persistent MRD2 and lack of NOTCH1/FBXW7 mutation were the only two independent factors identified, the presence of at least one factor defining 49% high-risk patients with 64% versus 12% CIR (HR, 6.4; P= 0.002), 36% versus 88% DFS (HR, 6.4; P= 0.002), and 41% versus 95% OS (HR, 7.3; P= 0.015) at 4 years. SCT had no significant effect on relapse incidence and DFS in these new high-risk T-ALL patients. Conclusion. In adult patients with Ph-negative ALL treated with the pediatric-inspired GRAALL regimen, IKZF1 deletion in BCP-ALL, NOTCH1/FBXW7 mutation in T-ALL, and MRD at 3 months in both subsets replace all classical risk factors, leading to a new simplified prognostic scoring system based only on IKZF1 and NOTCH1/FBXW7 genetics and MRD clearance. This new risk score identifies approximately half of the patients as good-risk, with a relapse incidence as low as 10–15%. It will be validated and used prospectively in the next generation of GRAALL trials, to stratify both new drug evaluation and SCT in first CR. Disclosures: No relevant conflicts of interest to declare.

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