scholarly journals Delays in Start of Intensification Therapy Are Common for Adults with Acute Lymphoblastic Leukemia, and Are Associated with Decreased Survival in Patients Who Undergo Allogeneic Stem Cell Transplant (SCT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 208-208
Author(s):  
Anita J. Kumar ◽  
Phyllis A. Gimotty ◽  
Joel Gelfand ◽  
Georgina Buck ◽  
Jacob M. Rowe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Phase I ◽  
Multivariate Regression ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Term Survival ◽  
Black Race ◽  
Female Sex ◽  
The Impact

Abstract Acute lymphoblastic leukemia (ALL) has a high relapse rate in adults. While the biology of the patient may be responsible for the marked difference in survival seen in comparison to children, variable adherence to complex chemotherapy regimens may also play a role. However, there is very little understanding about the risk factors for delays in therapy and the impact of delays on survival. To study delays in newly diagnosed adult ALL patients, we conducted an observational study using data from ECOG 2993/ MRC_UKALLXII (Rowe, Blood 2005). We analyzed Ph- patients who started intensification after documented complete remission (CR). A long delay (LD) was defined as > 98 days from start of induction to start of intensification (IS), which was >2 weeks delay beyond the 84 days recommended per protocol. A Very Long Delay (VLD) was defined as a >4 weeks delay. Of 2109 patients enrolled, 1247 patients met inclusion criteria for analysis. Of note, 435 Ph- patients who achieved CR after induction but did not proceed to intensification were excluded. In univariate analysis, female sex (p<0.001), Black race (p=0.01), and older age (p<0.001) were associated with increased odds of LD. During induction presence of infection (p=0.01), dose reductions (p=0.001), duration of neutropenia (p=0.007), thrombocytopenia (p<0.001), and hospitalization duration (p<0.001) were associated with LD. In multivariate regression, age, female sex, dose reduction, Black race, and hospitalization duration were significantly associated with LD and VLD (Table I). At 2 years after diagnosis, 801/1247 (64.2%) patients were alive. Of the surviving patients, 181 (22.5%) had VLD, and 620 (77.4%), had delay <4 weeks, p=0.073. Of the alloHCT patients, 333 were alive: 57/333 (17%) had VLD, and 276/333 (83%) had been delayed <4 weeks (p=0.036). As of July 2014, 687/1247 (55%) patients have died, with a median time to death from start of intensification of 13.3 months (range 0.8-231). Survival analysis was stratified by post-remission therapy, with living patients censored at date last seen. Patients who received myeloablative allogeneic HCT (allo HCT) had poorer overall survival from start of intensification (OS-IS) and event free survival (EFS-IS) after LD or VLD. While OS-IS and EFS-IS were significantly worse for alloHCT patients after VLD (p=0.02 and p=0.03) respectively, survival was not worse for non-transplant patients after VLD (p=0.24 and p=0.10) (Figure I). In a multivariate Cox regression, adjusting for other high-risk disease features (age, cell lineage, and white cell count at diagnosis), patients who underwent allo HCT had significantly worse OS-IS (HR 1.4, p=0.02) and EFS-IS (HR 1.4, p=0.02) after experiencing VLD compared to alloHCT patients who experienced <4 weeks delay. When evaluating OS and EFS from diagnosis, VLD was still associated with poorer OS (HR 1.34, p=0.04) and EFS (HR 1.34, p=0.03). There was no difference in OS or EFS in patients who received non-transplant post-remission therapy based on delay. In a comprehensive analysis of the largest adult ALL study ever reported, we identified significant risk factors predictive of LD and VLD (>2 and >4 weeks beyond mandatory rest period). Our findings highlighted that patients were delayed because of chemotherapy toxicity and also identified healthcare disparities. VLD was associated with poorer OS and EFS in patients undergoing alloHCT, but not in patients undergoing non-transplant post remission therapy. Further studies are planned to prospectively identify patient barriers to on-schedule treatment with a goal of earlier intervention. The ability to better predict and intervene on risk factors for delay can improve adherence to protocol and optimize long-term survival. Table I: Multivariate Regression for LD and VLD Risk Factors Variable Odds Ratio 95% Confidence Interval p-value Days in the hospital Phase I Induction 1.01 1.00-1.02 0.04 Duration of Thrombocytopenia, Phase I 1.02 1.01-1.03 0.001 Age by Decade 1.2 1.08-1.31 <0.001 Reduced Dose in Induction 1.54 1.08-2.22 0.019 Sex, Female 1.56 1.22-2.0 <0.001 Race, Black 3.4 1.41-7.96 0.006 Figure 1 Figure 1. p=0.023 Disclosures No relevant conflicts of interest to declare.

Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia

2011 ◽  
Vol 29 (31) ◽  
pp. 4143-4150 ◽  
Author(s):  
Mariël L. te Winkel ◽  
Rob Pieters ◽  
Wim C.J. Hop ◽  
Hester A. de Groot-Kruseman ◽  
Maarten H. Lequin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Multivariate Regression ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Long Term Outcome ◽  
Female Sex ◽  
Incidence Risk

Purpose We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). Patients and Methods Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with the dexamethasone-based Dutch Child Oncology Group–ALL9 protocol. Osteonecrosis was defined by development of symptoms (National Cancer Institute grade 2 to 4) during treatment or within 1 year after treatment discontinuation, confirmed by magnetic resonance imaging. We evaluated risk factors for osteonecrosis using logistic multivariate regression. To describe outcome, we reviewed clinical and radiologic information after antileukemic treatment 1 year or more after osteonecrosis diagnosis. Results Cumulative incidence of osteonecrosis at 3 years was 6.1%. After adjustment for treatment center, logistic multivariate regression identified age (odds ratio [OR], 1.47; P < .01) and female sex (OR, 2.23; P = .04) as independent risk factors. Median age at diagnosis of ALL in patients with osteonecrosis was 13.5 years, compared with 4.7 years in those without. In 21 (55%) of 38 patients with osteonecrosis, chemotherapy was adjusted. Seven patients (18%) underwent surgery: five joint-preserving procedures and two total-hip arthroplasties. Clinical follow-up of 35 patients was evaluated; median follow-up was 4.9 years. In 14 patients (40%), symptoms completely resolved; 14 (40%) had symptoms interfering with function but not with activities of daily living (ADLs; grade 2); seven (20%) had symptoms interfering with ADLs (grade 3). In 24 patients, radiologic follow-up was available; in six (25%), lesions improved/disappeared; in 13 (54%), lesions remained stable; five (21%) had progressive lesions. Conclusion Six percent of pediatric patients with ALL developed symptomatic osteonecrosis during or shortly after treatment. Older age and female sex were risk factors. After a median follow-up of 5 years, 60% of patients had persistent symptoms.

scholarly journals Chemotherapy Delays Are Associated with Inferior Outcome in Acute Lymphoblastic Leukemia: A Retrospective Study from a Tertiary Cancer Center in South India

2021 ◽  
Vol 42 (01) ◽  
pp. 051-060
Author(s):  
Vineet Agrawal ◽  
Smita Kayal ◽  
Prasanth Ganesan ◽  
Biswajit Dubashi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Cancer Center ◽  
Survival Outcomes ◽  
Separate Analysis ◽  
Term Survival ◽  
Free Survival ◽  
Intensive Phase ◽  
The Impact

Abstract Background Treatment protocols for acute lymphoblastic leukemia (ALL) have evolved over time to give excellent cure rates in children and moderate outcomes in adults; however, little is known how delays in chemotherapy affect long-term survival. Objectives To find the association of delays during different treatment phases on the survival outcomes. Materials and Methods Data from 149 ALL cases treated between 2009 and 2015 were retrospectively analyzed. Treatment course in commonly used protocols was divided into three phases—induction, consolidation (postremission), maintenance, and also a combined intensive phase (induction plus consolidation) for the purpose of analysis, and delay in each phase was defined based on clinically acceptable breaks. Analysis was done to find the impact of treatment delay in each phase on the survival outcomes. Results The median age was 12 years (range, 1–57). Multi-center Protocol-841 (MCP-841) was used for 72%, German Multicenter Study Group for Adult ALL (GMALL) for 19%, and Berlin, Frankfurt, Muenster, 95 protocol (BFM-95) for 9% of patients. Delay in induction was seen in 52%, consolidation in 66%, and during maintenance in 42% of patients. The median follow-up was 41 months, and 3-year survival outcomes for the entire cohort were event-free survival (EFS)—60%, relapse-free survival (RFS)—72%, and overall survival (OS)—68%. On univariate analysis, delay in induction adversely affected EFS (hazard ratio [HR] = 1.78, p = 0.04), while delay in intensive phase had significantly worse EFS and RFS (HR = 2.41 [p = 0.03] and HR = 2.57 [p = 0.03], respectively). On separate analysis of MCP-841 cohort, delay in intensive phase affected both EFS (HR = 3.85, p = 0.02) and RFS (HR = 3.42, p = 0.04), whereas delay in consolidation significantly affected OS with (HR = 4.74, p = 0.04) independently. Conclusion Treatment delays mostly in intensive phase are associated with worse survival in ALL; attempts should be made to maintain protocol-defined treatment intensity while adequately managing toxicities.

scholarly journals The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

2019 ◽  
Vol 3 (4) ◽  
pp. 670-680 ◽  
Author(s):  
Moshe Yeshurun ◽  
Daniel Weisdorf ◽  
Jacob M. Rowe ◽  
Martin S. Tallman ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Low Grade ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Graft Versus Leukemia ◽  
The Impact ◽  
Risk Of Relapse

Abstract Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

Multi-Agent Phase I Trials in Childhood Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4528-4528
Author(s):  
Richard Sposto ◽  
Elizabeth A. Raetz ◽  
Charles P. Reynolds ◽  
Paul S. Gaynon
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Cell Transplant ◽  
Phase I Trials ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Background: Single agent phase I trials with conventional methodology may not be suitable for children with relapsed leukemia. Accrual of children with ALL in relapse to single-agent phase I trials is poor due to clinical urgency and a &gt; 30% likelihood of complete response (CR) with a variety conventional agents combinations (Br J Haematol.2005; 131(5): 579) with the option of hematopoietic stem cell transplant in remission. As most drugs are ultimately used in combination, a Phase I trial testing a new agent in combination with conventional agents would seem most useful and might increase accrual. However, with conventional phase I methodologies determination of a maximum tolerated dose is complicated by the toxicities of the accompanying conventional agents and by the background morbidity of relapsed leukemia. Methods: The Children’s Oncology Group (COG) study, AALL01P2, employed vincristine, prednisone, doxorubicin, and pegylated asparaginase for children with ALL in first marrow relapse. We determined the incidence of conventional non-hematologic dose limiting toxicities (DLT’s) and modeled the impact on a hypothetical phase I trial of a candidate agent with no additional toxicity. Results: Among 111 patients on AALL01P2, 19% had conventional non-hematologic DLT’s. Induction therapy was judged clinically acceptable. With a traditional Phase I escalation scheme that accepts 0/3 and 1/6 DLT’s at a dose-level and rejects 2/3 and 2/6 DLT’s, an agent that adds no morbidity would be rejected as too toxic at any dose 30% of the time. Conclusion: Background morbidity confounds identification of an acceptable dose of a non-toxic new agent tested in combination with conventional drugs for recurrent ALL. We propose a modification to the traditional Phase I design that increases the DLT thresholds to 1/3 and 2/6, which effectively compensates for background toxicity and reduces the chance of falsely rejecting an acceptable agent.

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 Acute Lymphoblastic Leukemia in Adolescents and Young Adults in Finland.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1885-1885
Author(s):  
Anu Usvasalo ◽  
Ulla Saarinen-Pihkala ◽  
Erkki Elonen ◽  
Riikka Raty ◽  
Kim Vettenranta
Keyword(s):  
Young Adults ◽  
Risk Factor ◽  
Acute Lymphoblastic Leukemia ◽  
Treatment Group ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Total Duration ◽  
Cell Transplant ◽  
Adult Treatment ◽  
Term Survival

Abstract Background: Long-term survival in pediatric acute lymphoblastic leukemia has dramatically improved during the past three decades through intensification of therapy. Progress has also been made regarding therapy of adult ALL. Recent reports in the literature suggest better outcome on pediatric protocols, as compared with adult ones. In pediatric ALL, age over 10 years is a high-risk factor in many protocols. The arbitrary age limit of 16 years may not truly reflect the biologic differences in ALL between adolescents vs. young adults. The purpose of the present work was to evaluate the outcome of adolescents with ALL in Finland, treated on pediatric vs. adult ALL protocols. Materials and methods: All patients aged 10–25 years diagnosed with ALL during 1990–2005 in Finland were included. There were 120 patients (aged 10–16 yrs) treated on pediatric common Nordic (NOPHO) protocols with a total duration of 2 yrs, and 100 patients (aged 17–25 yrs) treated on Finnish National ALL adult protocols with a total duration of 3.5 yrs. In total 15 underwent allo-SCT in first remission. Data had been collected to the pediatric Nordic NOPHO database, as well as to the Finnish Leukemia Group ALL database. Events were defined as death, relapse, or second malignancy. Results: The 5-year EFS was 68 % for children (n=62) and 55% for adults (n=72) (p=0.04), and the 5-year OS was 75 % for children and 68 % for adults (p=0.075), respectively. When only patients treated with conventional chemotherapy were included (stem cell transplant recipients in 1CR excluded), the 5-year EFS was 65 % for children (n=53) and 55 % for adults (n=66) (p=0.09), and the 5-year OS was 80 % for children and 65 % for adults (p=0.09), respectively. Regardless of protocol, EFS in the age group of 10–15 years was 74 % and in the group 15–25 years 57 % (p=0,06). Conclusions: EFS regarding all patients was better on pediatric than on adult protocols. All the other comparisons reached statistically only a trend level. The difference in outcome between pediatric and adult protocols in Finland is less clear than reported elsewhere. Age seems to be a prognostic factor also in the adolescent age groups. The non-transplanted patients seemed to have a better outcome, suggesting that those with higher risk probably ended up with transplant. Although therapy is an important risk factor, our further analysis of cytogenetic features including CGH array may reveal other risk factors that may turn out to be even more powerful. EFS, pediatric vs. adult treatment group EFS, pediatric vs. adult treatment group

scholarly journals Outcomes of Acute Lymphoblastic Leukemia with KMT2A (MLL) rearrangement - The MD Anderson Experience

2021 ◽  
Author(s):  
Guillaume Richard-Carpentier ◽  
Hagop M Kantarjian ◽  
Guilin Tang ◽  
C. Cameron Yin ◽  
Joseph D. Khoury ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Poor Prognosis ◽  
Stem Cell Transplant ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Md Anderson ◽  
The Impact

Acute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23) - KMT2A-AFF1 is associated with a poor prognosis. The impact of KMT2A rearrangements other than t(4;11) is uncertain and the benefit of allogeneic stem cell transplant (HSCT) is unclear. We reviewed adult patients with ALL treated at our institution from 1984 to 2019 and identified 50/1102 (5%) with KMT2A rearrangement: 42 (84%) with t(4;11)/KMT2A-AFF1 and 8 (16%) with other gene partners. The median age was 45 years old (range, 18 - 78 years); median white blood cell count was 109.0 x 109/L (range, 0.5 - 1573.0). The complete remission (CR) rate was 88% and the rate of measurable residual disease negativity by flow cytometry at CR was 41% (76% overall during follow-up). At the last follow-up, 14 patients were alive. The 5-year overall survival (OS) rate was 18% (95% CI, 9 - 35%) with no difference between t(4;11) and other KMT2A rearrangements (p=0.87). In a 4-month landmark analysis, the 5-year OS rate was 32% (95% CI, 14 - 70%) in patients who underwent HSCT versus 11% (95% CI, 3 - 39) in others (p=0.10). Our study confirms the poor prognosis of ALL with any KMT2A rearrangement and the role of HSCT in these patients.

scholarly journals Risk Factors for Childhood Leukemia: Radiation and Beyond

2021 ◽  
Vol 9 ◽  
Author(s):  
Janine-Alison Schmidt ◽  
Sabine Hornhardt ◽  
Friederike Erdmann ◽  
Isidro Sánchez-García ◽  
Ute Fischer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Mouse Models ◽  
Environmental Risk ◽  
Childhood Leukemia ◽  
Background Radiation ◽  
Lymphoblastic Leukemia ◽  
International Workshop ◽  
Experimental Studies ◽  
The Impact

Childhood leukemia (CL) is undoubtedly caused by a multifactorial process with genetic as well as environmental factors playing a role. But in spite of several efforts in a variety of scientific fields, the causes of the disease and the interplay of possible risk factors are still poorly understood. To push forward the research on the causes of CL, the German Federal Office for Radiation Protection has been organizing recurring international workshops since 2008 every two to three years. In November 2019 the 6th International Workshop on the Causes of CL was held in Freising and brought together experts from diverse disciplines. The workshop was divided into two main parts focusing on genetic and environmental risk factors, respectively. Two additional special sessions addressed the influence of natural background radiation on the risk of CL and the progress in the development of mouse models used for experimental studies on acute lymphoblastic leukemia, the most common form of leukemia worldwide. The workshop presentations highlighted the role of infections as environmental risk factor for CL, specifically for acute lymphoblastic leukemia. Major support comes from two mouse models, the Pax5+/− and Sca1-ETV6-RUNX1 mouse model, one of the major achievements made in the last years. Mice of both predisposed models only develop leukemia when exposed to common infections. These results emphasize the impact of gene-environment-interactions on the development of CL and warrant further investigation of such interactions — especially because genetic predisposition is detected with increasing frequency in CL. This article summarizes the workshop presentations and discusses the results in the context of the international literature.

scholarly journals Therapy-related acute lymphoblastic leukemia is a distinct entity with adverse genetic features and clinical outcomes

2019 ◽  
Vol 3 (24) ◽  
pp. 4228-4237 ◽  
Author(s):  
Caner Saygin ◽  
Ashwin Kishtagari ◽  
Ryan D. Cassaday ◽  
Natalie Reizine ◽  
Ilana Yurkiewicz ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Clinical Outcomes ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Small Subset ◽  
Distinct Entity ◽  
Term Survival ◽  
Cytotoxic Therapies ◽  
The Impact ◽  
Prior Malignancy

Abstract Patients with therapy-related acute lymphoblastic leukemia (t-ALL) represent a small subset of acute lymphoblastic leukemia (ALL) patients who received genotoxic therapy (ie, chemotherapy or radiation) for a prior malignancy. These patients should be distinguished from patients with de novo ALL (dn-ALL) and ALL patients who have a history of prior malignancy but have not received cytotoxic therapies in the past (acute lymphoblastic leukemia with prior malignancy [pm-ALL]). We report a retrospective multi-institutional study of patients with t-ALL (n = 116), dn-ALL (n = 100), and pm-ALL (n = 20) to investigate the impact of prior cytotoxic therapies on clinical outcomes. Compared with patients with pm-ALL, t-ALL patients had a significantly shorter interval between the first malignancy and ALL diagnosis and a higher frequency of poor-risk cytogenetic features, including KMT2A rearrangements and myelodysplastic syndrome-like abnormalities (eg, monosomal karyotype). We observed a variety of mutations among t-ALL patients, with the majority of patients exhibiting mutations that were more common with myeloid malignancies (eg, DNMT3A, RUNX1, ASXL1), whereas others had ALL-type mutations (eg, CDKN2A, IKZF1). Median overall survival was significantly shorter in the t-ALL cohort compared with patients with dn-ALL or pm-ALL. Patients who were eligible for hematopoietic cell transplantation had improved long-term survival. Collectively, our results support t-ALL as a distinct entity based on its biologic and clinical features.

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.

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