Survival In Acute Lymphoblastic Leukemia Research Articles

The paradigm of total body irradiation in acute lymphoblastic leukaemia: Therapeutic effectiveness versus the challenges of toxicity

IntroductionTotal body irradiation (TBI) is part of the myeloablative conditioning for hematopoietic stem cell transplantation (HSCT) in malignant hematologic disorders. This therapy has recently shown improved survival in acute lymphoblastic leukemia (ALL) compared to chemotherapy-based regimens. However, side effects are a significant limitation, especially in the pediatric population. Patients and methodsWe retrospectively analyzed the survival of patients with ALL who underwent an HSCT at a tertiary hospital between 1996 and 2009 (N = 69 HSCT in 57 patients). We differentiated a cohort that received TBI (N = 44) from another that did not (N = 25). Subsequently, we interviewed the survivors from the TBI group with a minimum of 10 years of follow-up (N = 18), asking about the presence of side effects. ResultsThe overall survival (OS) at 2 and 5 years was 79.1% and 65.2% respectively for the TBI group and 66.2% and 55.8% for the non-TBI group, although this difference was not significant (P=.31). The event-free survival (EFS) at 2 and 5 years was 77.3% and 63.6% respectively for the TBI group and 56% and 32% for the non-TBI group (P=.02). The probability of relapse (PR) at 2 years for those who received TBI was 10% compared to 28.6% for those who did not receive TBI (P=.005). Survivors who received TBI developed secondary neoplasms (39%), dyslipidemia (67%), cognitive impairments affecting memory (44%), recurrent respiratory infections (39%), thyroid abnormalities (45%), premature ovarian failure (89%), cataracts (22%), and psychological problems (44%). However, the quality of life, as self-assessed by the patients, was considered good for 83% of the participants.. ConclusionsPatients who received TBI had significantly higher EFS and lower PR. However, adverse effects are frequent and significant, although they do not subjectively affect quality of life.

Childhood acute lymphoblastic leukemia survival and spatial analysis of socio-environmental risks in Mexico.

Acute lymphoblastic leukemia (ALL) etiology remains largely unknown; incidence patterns by age, sex, and geographical distribution suggest a potential environmental role. To identify ALL clusters from four contrasting urban areas of Mexico and to characterize the sources of environmental carcinogens. Hospital-based ALL cases (n = 443) diagnosed in children <19 years old from the Metropolitan Zones of Merida and San Luis Potosi, the State of Mexico, and Tijuana were analyzed (2015-2020). ALL cases were coded according to the International Classification of Diseases for Oncology. ALL clusters were identified by Kernel Density, and excess risk was estimated. Data of particulate matter ≤2.5 µm (PM2.5) concentrations measured by community-monitoring stations were analyzed. Geocoded datasets of benzene, polycyclic aromatic hydrocarbons, and PM2.5 sources were analyzed to characterize patterns of exposure in ALL clusters. The survival rate for ALL ranged from 61.5% to 78.6%. Seven ALL clusters with excess risk (RR 1.4-2.3, p < 0.05) were identified. The carcinogen sources included artisanal brick kilns, gas stations, cement works, carpentry, paint, and chemical manufacturing establishments. PM2.5 levels ranged from 15 µg/m3 to 37 µg/m3 among study areas. ALL clusters were identified at the community level; the excess risk could be explained by small-scale carcinogen sources. The levels of PM2.5 in outdoor air ranged from 3 to 6 times above the World Health Organization (WHO) air quality guidelines. Healthcare providers must raise awareness of the increased risk of ALL in children living near sources of environmental carcinogens; cancer control and prevention strategies must be steered from a multi-sectoral and multi-action perspective to protect children's health.

Multiple Reactions and Increased Infusion Time During Desensitization May Decrease the Efficacy of Pegaspargase Chemotherapy

Asparaginase therapy improves survival in Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma and is considered a critical component of chemotherapy. However, 10-25% of patients experience immediate hypersensitivity reactions to the preferred asparaginase chemotherapeutic agent, pegaspargase. In the setting of limited supply of the main alternative agent, Erwinia asparaginase, patients may not be able to receive asparaginase therapy unless they undergo desensitization. While cases of successful desensitizations to pegaspargase have been described, our center’s experience has demonstrated challenges in effectively desensitizing these patients.

Dominant-negative transforming growth factor-β receptor-armoured mesothelin-targeted chimeric antigen receptor T cells slow tumour growth in a mouse model of ovarian cancer

Ovarian cancer is a major cause of death among all gynaecological cancers. Although surgery, chemotherapy and targeted therapy have yielded successful outcomes, the 5-year survival rate remains < 30%. Adoptive immunotherapy, particularly chimeric antigen receptor (CAR) T-cell therapy, has demonstrated improved survival in acute lymphoblastic leukaemia with manageable toxicity. We explored CAR T-cell therapy in a preclinical mouse model of ovarian cancer. Second-generation CAR T cells were developed targeting mesothelin (MSLN), which is abundantly expressed in ovarian cancer. Cytotoxicity experiments were performed to verify the lethality of CAR T cells on target cells via flow cytometry. The in vivo antitumour activity of MSLN CAR T cells was also verified using a patient-derived xenograft (PDX) mouse model with human tumour-derived cells. We also evaluated the potency of CAR T cells directed to MSLN following co-expression of a dominant-negative transforming growth factor-β receptor type II (dnTGFβRII). Our data demonstrate that anti-MSLN CAR T cells specifically eliminate MSLN-expressing target cells in an MSLN density-dependent manner. This preclinical research promises an effective treatment strategy to improve outcomes for ovarian cancer, with the potential for prolonging survival while minimizing risk of on-target off-tumour toxicity.

Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL).

Simple SummaryThe improved understanding of acute lymphoblastic leukemia has brought with it several new therapy strategies as well as novel treatment agents. The aim of our review was to create a well-arranged overview of the currently available treatment strategies for ALL.Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy characterized by proliferation and accumulation of premature lymphoid blasts. Depending on risk factors, the survival of acute lymphoblastic leukemia has significantly improved over the last decades. During the last years, measurable residual disease (MRD) assessment has evolved into one of the most sensitive markers for prognosis and risk of relapse. For this reason, measurable residual disease detection and monitoring count as standard evaluation in patients with acute lymphoblastic leukemia. Allogeneic stem cell transplantation is still the recommended treatment option for patients with high and highest risk profiles as well as for relapsed or refractory settings. The increased understanding of the pathomechanism and heterogeneity of acute lymphoblastic leukemia has led to the development of several novel therapeutic opportunities such as tyrosine-kinase inhibitors, antibody-based therapies and CAR-T cells with the aim of improving clinical outcomes. Furthermore, the major advances in disease understanding of ALL have led to the identification of different subgroups and better disease stratification. Even though novel therapy targets are constantly developed, acute lymphoblastic leukemia remains a challenging and life-threatening disease. To improve the historically unsatisfying result in therapy of adult acute lymphoblastic leukemia many clinical trials have recently been initiated to determine the optimum combination regimens of novel and old agents for adult acute lymphoblastic leukemia.

Unravelling ALL: The Keys to Improved Post-Transplant Survival in Acute Lymphoblastic Leukemia

Unravelling ALL: The Keys to Improved Post-Transplant Survival in Acute Lymphoblastic Leukemia

Depletion of d- and l-asparagine in cerebrospinal fluid in acute lymphoblastic leukemia during PEGasparaginase therapy.

l-Asparaginase hydrolyzes l-asparagine and not its enantiomer d-asparagine. Unlike l-asparagine, d-asparagine is nonessential for the survival of acute lymphoblastic leukemia (ALL) cells. Studies showed that serum asparagine is depleted below 0.5 μM in ≥96% of the patients during pegylated Escherichia coli l-asparaginase (PEGasparaginase) treatment; however, cerebrospinal fluid (CSF) asparagine levels are depleted in only 20%-30% of the patients. Thus far, studies only reported the total CSF asparagine (sum of d- and l-asparagine) concentrations. Data on the pharmacological goal, which is l-asparagine depletion, are lacking. Therefore, we studied this in 30 patients (95 samples) with newly diagnosed ALL. They received two doses of PEGasparaginase on day 4 and 18 in induction. Median age at diagnosis was 5.7 years (range 1.5-17.1 years). d-Asparagine and l-asparagine concentrations (median (range)) before PEGasparaginase treatment were 0.038 (0.0-0.103) μM and 6.1 (1.82-11.5) μM, respectively. CSF l-asparagine concentrations were reduced by 85% (76%-100%) and approximately one-third of the patients (32%) had CSF l-asparagine depletion below 0.5 μM 11 days after the second PEGasparaginase dose administration. CSF d-asparagine and l-glutamine levels remained stable before and after administration of PEGasparaginase. The percentage of d-asparagine as a fraction of total asparagine (sum of d- and l-asparagine) was 0.62% before and 4.5% after PEGasparaginase treatment. No correlation was found between higher serum PEGasparaginase activity and CSF l-asparagine concentration. l-Asparagine is not a better parameter than total asparagine in CSF due to the negligible amount of d-asparagine in the CSF before and after PEGasparaginase treatment.

Effect of Treatment in a Specialized Pediatric Hemato-Oncology Setting on 5-Year Survival in Acute Lymphoblastic Leukemia: A Quasi-Experimental Study.

Simple SummaryAdolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have a worse prognosis than children. In addition to differences in biology—such as higher incidence of unfavorable genetic alterations in the AYA population—this might be related to the fact that ALL patients under a certain age (often 18 years) are generally treated in special pediatric hemato-oncology settings, which is associated with improved survival, while patients above that age are treated in adult hemato-oncology care settings. Based on previous research, adult treatment settings have increasingly adopted pediatric-inspired protocols, which appear to have led to increased survival of adolescent ALL patients. This study aims to assess whether there remains an effect of treatment of ALL patients in a specialized pediatric hemato-oncology setting on 5-year survival. This study provides insight into the effects of such treatment for ALL patients, and may stimulate further research into causal relationships in other oncological conditions.Survival rates of adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) are inferior to those of pediatric ALL patients. In part, this may be caused by differences in treatment setting. Generally, children are treated in specialized pediatric hemato-oncology settings, whereas AYAs are treated in adult hemato-oncology settings. Since 2005, adult treatment protocols have included pediatric-inspired chemotherapy, which has been the standard of care for AYAs from 2008 onwards. This study aims to assess whether, despite protocols in both settings having become more similar, there remains an effect of treatment in specialized pediatric hemato-oncology settings on 5-year survival for ALL patients in the Netherlands. We used nationwide registry data (2004–2013) on 472 ALL patients aged between 10 and 30 years old. A fuzzy regression discontinuity design was applied to estimate the treatment effect using two-stage least squares regression with the treatment threshold at 17 years and 7 months of age, adjusting for sex, age at diagnosis, and immunophenotype. We found a risk difference of 0.419 (p = 0.092; 95% CI = −0.0686; 0.907), meaning a 41.9 percentage point greater probability of surviving five years after diagnosis for ALL patients treated in specialized pediatric hemato-oncology settings. Our results suggest that ALL patients around the threshold could benefit from increased collaboration between pediatric and adult hemato-oncology in terms of survival.

Clinical and molecular-biologic features of infant acute leukemia

Acute leukemia (AL) in children up 1 year old is very rare disease, comprise less 5 % of all pediatric AL cases. The clinical course of infant AL is extremely aggressive with frequent extramedullar dissemination, initial hyperleukocytosis and MLL aberrations. Predominance of unfavorable clinical and laboratory features leads to unsatisfactory treatment results by modern curative protocols in children up to 1 year old: 4-year event-free survival for acute lymphoblastic leukemia is 50.9 ± 4.5 % and 3-year event-free survival for acute myeloid leukemia – 72–74 %. Optimization of therapeutic programs for infant AL with consideration to anatomy and physiologic features of infants, inclusion of targeted drugs (blinatumomab), epigenetic and cell technologies is actual and not resolved problem in modern pediatric oncology-hematology.

The Effect of B-Cell Lymphoma 2 and BCL2-Associated X Polymorphisms on the Survival of Acute Lymphoblastic Leukemia Patients: Application of Frailty Survival Models

Background:B-cell lymphoma 2 (BCL-2) and BCL-2 associated X (BAX) polymorphisms are important in the apoptosis process, response to treatment and survival in Acute Lymphoblastic Leukemia (ALL) patients. We aimed to investigate the effect of these genes with other predictors corresponding to the survival of ALL patients with an appropriate frailty survival model.Methods:Our study was performed in 2020 on sixty-two cases of childhood aged 3–16 (year) with ALL disease who were selected by convenience sampling from the two hospitals of Tabriz, Iran. RFLPPCR method was used for genotyping the promoter region of the BAX and BCL-2 genes. We used different frailty survival models, to control heterogeneity between individuals due to unmeasured factors affecting their survival. All analyses were implemented using Stata 16.Results:Based on the result of log-logistic model along with frailty gamma, the proportional odds (standard error) of survival for a CC allele of BCL-2 patient compared to a AA allele patient were 6.0 (1.47); P<0.001 and for a AC of BCL-2 allele patient were 0.57 (1.23); P=0.009. Patients with AG allele of BAX had 2.05 (1.26) times greater odds of surviving than a AA allele patient (P=0.003). The odds of survival of patients with abnormal white blood cell (WBC) were 92% less than normal WBC (P<0.001).Conclusion:With controlling unmeasured factors affecting, the BCL-2 and BAX genes promoter polymorphism are effective in the survival rates for ALL.

Impact of Insurance on Overall Survival in Acute Lymphoblastic Leukemia: A SEER Database Study

IntroductionInsurance status at diagnosis remains an important barrier to health care access and adherence to treatment. Here, we aim to assess the impact of insurance status, and age on overall survival (OS) in patients with acute lymphoblastic leukemia (ALL). Materials and methodsUsing the Surveillance, Epidemiology, and End Results database, we identified all patients younger than 65 years of age diagnosed with ALL from 2010 to 2016. OS was estimated for each group using the Kaplan Meier curves and compared based on insurance type using a log-rank test. Multivariate analysis using Cox proportional hazard regression model was used to assess the effect of insurance status on OS. ResultsA total of 9057 patients were included in the analysis. Medicaid beneficiaries had worse 5-year OS than insured patients (HR 1.33, 95% CI 1.08-1.63, P = .006) in 0-18 years age group. Despite chemotherapy, patients older than 18 years showed poor OS in all insurance categories. Patients on Medicaid showed inferior OS compared to insured in 19-40 years (HR 1.46, 95% CI 1.21-1.76, P < .001) and 41-65 years age group (HR 1.27, 95% CI 1.09-1.49, P = .003). Interestingly, no significant difference was observed in the OS between the Medicaid and uninsured groups in each age category. ConclusionOur large database study demonstrates that insured status is associated with better OS in ALL across all age groups. Further studies to develop effective strategies to bridge health care disparities areessential.

Total body irradiation-based versus busulfan-based myeloablative conditioning for single-unit cord blood transplantation in adults

Comparative studies between total body irradiation (TBI)-based and busulfan-based myeloablative conditioning (MAC) regimens for cord blood transplantation (CBT) have been limited. We retrospectively analyzed the results of single-unit CBT in 333 adult patients who received either TBI-based (n = 258) or busulfan-based (n = 75) MAC regimens at our institute. After adjusting for significant variables in the univariate analysis, there were no significant differences in neutrophil recovery (hazard ratio (HR), 0.88; p = .460), grade III–IV acute graft-versus-host disease (GVHD) (HR: 1.40, p = .410), extensive chronic GVHD (HR: 0.73, p = .380), relapse (HR: 0.61, p = .270), non-relapse mortality (HR: 1.38, p = .420), overall survival (HR: 1.18, p = .637), or event-free survival (HR: 1.08, p = .773), although platelet recovery was lower with marginal significance for the busulfan-based regimen (HR: 0.67, p = .068). In subgroup analysis, TBI-based regimens were superior to busulfan-based regimens in terms of survival for acute lymphoblastic leukemia, but not for myeloid malignancies. Further investigation is warranted even for CBT.

Survival benefit of pediatric-based regimen for adults with acute lymphoblastic leukemia: A single-center retrospective cohort

Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens. Considering these results, We decided to treat newly diagnosed ALL patients according to age and risk factors. The goal of this study was to describe the results of this intensive chemotherapy treatment approach for ALL adult patients diagnosed at our institution. Fifty-eight ALL patients, diagnosed from 2004 to 2013, were included in the analysis. Patients were assigned to either the St. Jude Total Therapy XIIIB high-risk arm (St Jude) or the CALGB 8811 (CALGB). The Kaplan-Meier survival curve was used for the survival analyses and the Cox proportional hazard regression, for multivariable analysis. The overall survival was 22.9% at 10 years. The St. Jude improved survival, compared to the CALGB (p=0.007), with 32.6% vs. 7.4% survival rate at 10 years. However, no survival benefit was found for patients younger than 20 years old (p=0.32). The multivariable analysis demonstrated that undetectable minimal residual disease (MRD) and hematopoietic stem cell transplantation (HSCT) had beneficial impact on survival (p=0.0007 and p=0.004, respectively). ALL is a disease of poor prognosis for adults. The joint effort to standardize treatment and seek solutions is the way to start improving this scenario.

Modulation of CD22 Antigen Density Improves Efficacy of CD22 Chimeric Antigen Receptor (CAR) T Cells Against CD22lo B-Lineage Leukemia and Lymphoma

While overall survival for acute lymphoblastic leukemia (ALL) in children treated with risk-adapted, multi-agent chemotherapeutic regimens is greater than 85%, relapsed ALL remains a major challenge. Chimeric antigen receptor (CAR) T cell therapy targeting CD19 provides these patients with a remission induction rate of 70-90% across multiple clinical trials, but loss of the targeted epitope results in relapse following CD19 CAR T cells. In the setting of these relapses, our group conducted a CD22 CAR T cell trial, which induces remission in approximately 70% percent of patients with relapsed/refractory CD22-positive pre-B cell ALL, including those relapsing after CD19 CAR therapy (NCT02315612). However, relapse associated with reduced CD22 site density has shortened remission duration in some patients. To test the impact of low CD22 site density on CD22 CAR T cell functionality, we modified Nalm6 ALL cell lines using CRISPR/Cas9 to eliminate the CD22 gene, followed by lentiviral transduction of full-length CD22 and single-cell cloning based on CD22 expression levels. CD22 site density was assessed with the Quantibrite-PE Assay Kit and four cell lines were identified for a spectrum of CD22 expression: CD22 negative (CD22neg); CD22 low (CD22lo) - site density comparable to that seen in ALL patients relapsing following CD22 CAR therapy; CD22 normal (Nalm6) - site density comparable to ALL CD22 expression; and CD22 high (CD22hi) - site density comparable to CD19 levels. As CD22 site density decreases, CD22 CAR T cells produce incrementally less interferon-gamma and do not produce IL-2 against CD22lo ALL. CD22 CAR delayed, but was unable to prevent, progression of CD22lo ALL in murine xenografts. We next evaluated two potential approaches to overcoming low site density antigen escape: improving CAR activity or increasing tumor sensitivity. To improve CAR activity, we generated a high-binding affinity CD22 CAR (CD22 CARH1) using an affinity-enhanced version of the scFv from the CD22 CAR construct in our ongoing trial. Despite higher affinity, the CD22 CARH1 T cell did not improve in vitro killing or in vivo clearance of CD22lo ALL. To increase tumor sensitivity, we sought to increase CD22 site density using the PKC inhibitor Bryostatin1, a drug previously shown to increase CD22 expression in CLL. Bryostatin1 increases CD22 site density on a panel of pre-B cell ALL and diffuse large B cell lymphoma (DLBCL) cell lines. Interestingly, the CD22 increase is durable for at least 1 week after exposure to Bryostatin1. Bryostatin1-mediated CD22 increased site density improves cytokine production by CD22 CAR T cells. To evaluate the mechanism of Bryostatin1-mediated upregulation of CD22 expression, RNAseq was performed on Bryostatin1-exposed ALL. Preliminary analysis demonstrates that Bryostatin1 does not directly affect CD22 mRNA expression levels, but modulates early transcription factors within the B-cell receptor pathway. Based on these results, we are further evaluating pathways affected by Bryostatin1 through protein expression analysis and assessing in vivo function of Bryostatin1 in the setting of a patient-derived CD22 CAR-resistant xenograft model. In conclusion, these results demonstrate a clear threshold antigen site density, below which the CD22 CAR is unable to clear CD22-expressing ALL. We further demonstrate that increased CD22 CAR affinity does not seem to improve CD22 CAR activity against CD22lo ALL. Bryostatin1-mediated CD22 modulation can improve CD22 CAR response against leukemia and lymphoma providing a potential rational combination to rescue CD22 CAR activity and remission durability. DisclosuresNo relevant conflicts of interest to declare.

Absolute Lymphocyte Count after First Induction Is Associated with Relapse Free Survival in Acute Myeloid Leukemia

Introduction. Absolute lymphocyte count (ALC) nowadays is a well known independent prognostic factor of survival in acute lymphoblastic leukemia (ALL): higher counts of ALC in period of induction therapy predict better results. The opposite situation remains with ALC and acute myeloid leukemia. Recent researches showed inverse dependence with higher initial ALC and worse response rate or shorter remission in AML. However, there is still limited data of ALC value in AML patients (pts) after chemotherapy courses. This criterion of prognosis is quite cheap and can be widely used in almost every clinic.Aims. To explore ALC in de novo AML pts after 1 induction course and compare it with clinical outcomes.Methods. From March 2016 to March 2017 in hematology department of National Research Center for Hematology in the study included 35 pts with de novo AML. All pts were treated with standard protocol and 1 induction course included cytarabine (100mg/m2 twice/day tag 1-7) and daunorubicine (60mg/m2 tag 1-3). In period on 28th - 40th days (depends of recovery) after therapy we performed blood samples with ALC analysis using Flow Cytometry. Kaplan-Meier method with log-rank test was used for disease free survival (DFS) analysis. 8 pts had resistant leukemia after 1st course and 8 another pts had relapse in short time.Results. We found out that DFS after 1st course was associated with certain amount of ALC (pic.1). ALC more than 0,8 x109/l predicted poor DFS in contrast with pts of low ACL (<0,8x109/l)(median survival 226 days vs not reached, p=0,03) . Limitation of study was the short follow up period (under 1,5 years). Data had retrospective analysis and there were no standardized methods and time points.Conclusion. Our findingsidentify ALC after 1st induction course in AML isprobably dysfunctional and may cause worse response to leukemia and short DFS. These studies need further researches in bigger cohort of pts. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Enolase 2-Mediated Glucose Metabolism Promotes Cell Proliferation and Survival in Acute Lymphoblastic Leukemia

Background: The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. Expression of glycolytic enzyme enolase 2(ENO2) was found to be closely related with clinical features of acute lymphoblastic leukemia (ALL) patients, but its functions are still unclear in ALL.Methods: We evaluated the association between ENO2 mRNA expression of bone marrow mononuclear cells(BM-MCs) and efficacy of chemotherapy, and further explored the function of ENO2 in ALL.Results: The results showed that ENO2 mRNA expression in BM-MCs was significantly decreased when patients completed induction chemotherapy and reached complete remission(CR). ENO2 mRNA expression was increased when patients suffered relapse. Functional study demonstrated that ENO2 promoted cell growth, glycolysis, and glucocorticoid-resistance, all of which were effectively inhibited when ENO2 was silenced with shRNAs. Further study found that ENO2 upregulated various glycolysis-related genes, and ENO2 enhanced Akt activity with subsequent Glycogen synthase kinase3β(GSK-3β) phosphorylation, inducing cell proliferation and glycolysis. The combination of silencing ENO2 and 2-deoxyglucose (2-DG) synergistically inhibited leukemia cell survival.Conclusion: These results indicate that ENO2 may be a biological marker for monitoring chemotherapeutic efficacy and relapse in ALL. ENO2 may provide a potential therapeutic strategy for ALL. DisclosuresNo relevant conflicts of interest to declare.

Minimal residual disease level determined by flow cytometry provides reliable risk stratification in adults with T-cell acute lymphoblastic leukaemia.

Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B-cell ALL, reports of adult T-cell ALL (T-ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)-based MRD at the end of induction (EOI-MRD). The present retrospective study included 94 adult patients with T-ALL. MRD was detected by six- to eight-colour FCM. Patients who were EOI-MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P=0·0020), and a lower relapse-free survival (RFS) (5·4% vs. 61·0%, P=0·0005) and overall survival (OS) (32·7% vs. 69·7%, P<0·0001) than those who were EOI-MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) at their first remission, EOI-MRD positivity was predictive of post-transplant relapse (2-year CIR: 68·2% vs. 4·0%, P=0·0003). Multivariate analysis showed that EOI-MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P=0·046], RFS (HR 2·125, P=0·048) and OS (HR 2·987, P=0·017). In conclusion, EOI-MRD based on FCM was an independent prognostic factor for relapse and survival in adult T-ALL. For patients who underwent HSCT, EOI-MRD could be used to identify patients with a high risk of relapse after allo-HSCT.

Long-term and quality of survival in patients treated for acute lymphoblastic leukemia during the pediatric age.

Long-term survival for acute lymphoblastic leukemia (ALL) in children improved over the last three decades up to 80-90% of affected patients. Consequently, the quality of life of survivors has become increasingly important. This study analyses the clinical features and outcome of 119 children with ALL, focusing on the quality of long-term survival in a subset of 22 patients over 18 years of age. Among this group, the 10-year event-free survival and overall survival were 83.1% (C.I. 74.0-89.2) and 88.4% (C.I. 80.9-93.1), respectively. Treatment related long-term medical complications were reported only in 2 patients (9.1%). Secondary school was completed successfully in 20 of 22 patients (89.9%). The remaining 2 patients were still attending at the time of the analysis. In conclusion, current treatment for ALL is well tolerated and does not compromise significantly the quality of life of survivors.

Clinical utility of complex assessment with evoked potentials in acute lymphoblastic leukemia survivors: comparison of various treatment protocols

BackgroundOne of the greatest success of pediatric hematology is a prominent improvement of survival in acute lymphoblastic leukemia (ALL). Therefore, special attention needs to be paid to long-term side effects of the treatment such as neurotoxicity. One of the few diagnostic methods that allow an objective assessment of sensory systems are evoked potentials (EP).MethodsThe analyzed group consisted of 167 ALL long-term survivors, aged 4.9–28.4 years, without auditory, visual and sensory deviations. Patients were treated with New York (NY, n = 35), previous modified Berlin-Frankfurt-Münster (pBFM, n = 47) and BFM95 (n = 85) protocols. In order to assess the impact of radiotherapy on recorded EP, a joint analysis of NY and pBFM groups was performed. The control group consisted of 35 patients, aged 6–17 years. The analyzed patients underwent a complex assessment with visual EP (VEP), somatosensory EP (SEP) and brainstem auditory EP (BAEP) in accordance with current standards.ResultsALL treatment contributed to the shortening of wave I latency (1.59 vs 1.90, P = 0.003) and prolongation of I-III (2.23 vs 2.04, P = 0.004) and I-V (4.57 vs 4.24, P = 0.002) interwave latencies of BAEP. A significant effect was also noticed in P100 (106.32 vs 101.57, P < 0.001) and N135 (151.42 vs 138.22, P < 0.001) latencies of VEP and N18 amplitude (3.24 vs 4.70, P = 0.007) and P25 latency (21.32 vs 23.39, P < 0.001) of SEP. The distribution of abnormalities between protocols was similar in BAEP (NY - 68.6%, pBFM - 61.7%, BFM95–69.4%, P = 0.650), VEP (NY - 68.6%, pBFM - 42.5%, BFM95–58.3%, P = 0.053) and significantly different for SEP (NY - 62.9%, pBFM - 36.2%, BFM95–53.0%, P = 0.045). The harmful effect of radiotherapy was most clearly marked in numerous disturbances of SEP parameters.ConclusionsThe presented analysis indicates a high frequency of subclinical abnormalities in EP regardless of the analyzed protocol. To our knowledge current study is the largest and one of the most complex research examining the role of EP in ALL patients. The obtained results indicate the possibility of using a single, objective and non-invasive measurement of EP in ALL survivors in order to stratify the risk of developing sensory abnormalities in adulthood.

Acute Lymphoblastic Leukaemia Survival in Children Covered by Seguro Popular in Mexico: A National Comprehensive Analysis 2005–2017

The aim of the study was to measure survival of children with acute lymphoblastic leukemia (ALL) under Mexico’s public health insurance for the population treated under Seguro Popular. A retrospective cohort study using claims data from Mexico’s Seguro Popular program, covering cancer treatment from 2005 to 2015 was conducted. Overall 5-year national and state-specific survival for children with ALL across Mexico who initiated cancer treatment under this program was estimated. From 2005 to 2015, 8,977 children with ALL initiated treatment under Seguro Popular. Under this financing scheme, the annual number of treated children doubled from 535 in 2005 to 1,070 in 2015. The estimates for 5-year overall survival of 61.8% (95%CI 60.8, 62.9) remained constant over time. We observed wide gaps in risk-standardized 5-year overall survival among states ranging from 74.7% to 43.7%. We found a higher risk of mortality for children who received treatment in a non-pediatric specialty hospital (Hazards Ratio, HR = 1.18; 95%CI 1.09, 1.26), facilities without a pediatric oncology/hematology specialist (HR = 2.17; 95%CI 1.62, 2.90), and hospitals with low patient volume (HR = 1.22; 95%CI 1.13, 1.32). In a decade Mexico’s Seguro Popular doubled access to ALL treatment for covered children and by 2015 financed the vast majority of estimated ALL cases for that population. While some progress in ALL survival may have been achieved, nationwide 5-year overall survival did not improve over time and did not achieve levels found in comparable countries. Our results provide lessons for Mexico’s evolving health system and for countries moving toward universal health coverage.