Maja Krajinovic

• MD PhD
• Professor (Full) at CHU Sainte-Justine, University of Montreal

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Despite a 90% five-year survival rate, survivors of childhood ALL (cALL) often suffer from late effects, including cardiometabolic disorders. Contributory factors such as inflammation and oxidative stress, in response to drug therapies, may induce premature aging and cellular s...

An example of chemotherapy‐induced cardiotoxicity in cancer survivors is acquired long QT syndrome (aLQTS), which may cause serious yet preventable life‐threatening consequences. Our objective was to identify and characterize childhood acute lymphoblastic leukemia (ALL) survivors with possible aLQTS using maximal exercise testing. In this cross‐sec...

Introduction: Chimeric antigen receptor (CAR) T-cells have revolutionized cancer treatment, showing significant success, including treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Despite their efficacy, cytokine release syndrome (CRS) emerges as a common early adverse effect that can be life threatening in severe cases, resulti...

Allogeneic HCT is a potentially curative treatment strategy for patients with inborn errors of immunities (IEIs). Objective of this study was to assess the optimal busulfan exposure prior to allogeneic HCT for patients with an IEI who received an intravenous busulfan-based conditioning regimen between 2000 and 2023. Patients from 17 international c...

Background Therapeutic drug monitoring (TDM) is crucial in optimizing the outcomes of hematopoietic stem cell transplantation by guiding busulfan (Bu) dosing. Limited sampling strategies show promise for efficiently adjusting drug doses. However, comprehensive assessments and optimization of sampling schedules for Bu TDM in pediatric patients are l...

Background Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) 10 years after diagnosis. We investigated risk factors for low BMD in long‐term cALL survivors. Methods We recruited 245 cALL survivors from the PETALE (Pré...

Acute lymphoblastic leukemia (ALL) is the most frequent pediatric cancer. 6-Mercaptopurine (6-MP) is a key component of ALL treatment. Its use, however, is also associated with adverse drug reactions, particularly myelosuppression. Thiopurine S-methyltransferase (TPMT) and, more recently, Nudix hydrolase 15 (NUDT15) deficiency, due to no-function v...

Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study...

Objectives: To understand why some long-term childhood cancer survivors experience positive adjustment in the long run,[Q1] this study aimed to (1) explore associations between well-being, health status, social support, and emotion regulation (ER) strategies in a cohort of long-term childhood lymphoblastic leukemia (cALL) survivors, (2) identify th...

Background An increased risk of neurocognitive deficits, anxiety, and depression has been reported in childhood cancer survivors. Methods We analyzed associations of neurocognitive deficits, as well as anxiety and depression, with common and rare genetic variants derived from whole-exome sequencing data of acute lymphoblastic leukemia (ALL) surviv...

Background: Children's exposure to chemotherapeutic agents causes several long-term adverse effects but physical activity has been evidenced to be an effective strategy to improve cardiac function. This cross-sectional study aimed to explore the association between physical activity levels, cardiorespiratory fitness, and cardiac parameters measure...

The characterization of cardiac mechanical properties may contribute to better understanding of doxorubicin-induced cardiotoxicity. Our study aims to investigate the relationship between cardiac mechanical properties, T1 and T2 relaxation times and partition coefficient. Fifty childhood acute lymphoblastic leukemia survivors underwent a cardiac mag...

Late effects such as neurocognitive issues and fatigue have been reported in childhood acute lymphoblastic leukemia (cALL) survivors. Yet, their association is often poorly understood. In this study, we wished to (1) describe neurocognitive difficulties and fatigue in a well-characterized cohort of long-term cALL survivors and (2) explore the risk...

Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exe...

Background: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopul...

Children with acute lymphoblastic leukemia (ALL) are treated with doxorubicin-based chemotherapy that can lead to cardiotoxicity which is a well-known cause of mortality. This study aims to characterize myocardial subtle changes induced by doxorubicin-related cardiotoxicity. We used the combination of cardiac magnetic resonance (CMR) imaging, cardi...

Background Genotype-phenotype analyses of rare diseases often suffer from a lack of power, due to small sample size, which makes identifying significant associations difficult. Sinusoidal obstruction syndrome (SOS) of the liver is a rare but life-threatening complication of hematopoietic stem cell transplantation (HSCT). The alkylating agent busulf...

Background: Childhood acute lymphoblastic leukemia survivors' anthracycline-induced cardiotoxicity could be prevented with good cardiorespiratory fitness levels and regular physical activity. This cross-sectional study aimed to assess the association between cardiorespiratory fitness and physical activity with cardiac magnetic resonance parameters...

Aim: We previously conducted exome-wide association study in acute lymphoblastic leukemia patients and identified association of five SNPs with asparaginase-related thrombosis. Here we aimed to replicate these findings in an independent patient cohort and through analyses in vitro. Patients & methods: SNPs located in IL16, MYBBP1A, PKD2L1, RIN3 and...

Acute lymphoblastic leukemia is the most frequent pediatric cancer. Approximately two third of survivors develop one or more health complications known as late adverse effects following their treatments. The existing measures offered to patients during their follow-up visits to the hospital are rather standardized for all childhood cancer survivors...

Introduction: Doxorubicin leads to dose dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. We investigated survivors' heart health using echocardiography and evaluated doxorubicin and dexrazoxane treatments on cardiac function. Methods: A total of 196 childhood ALL survivors were stratified (standard risk [SR], h...

Mediation analysis with a binary outcome is notoriously more challenging than with a continuous outcome. A new Bayesian approach for performing causal mediation with a binary outcome and a binary mediator, named the t-link approach, is introduced. This approach relies on the Bayesian multivariate logistic regression model introduced by O'Brien and...

Rationale and objectives: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Despite a 90% five-year survival rate, survivors of childhood ALL often suffer from late effects, including cardiometabolic disorders. Contributing factors such as inflammation and oxidative stress, combined with drug treatments, can induce premature a...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Institute of Cancer Research (ICR) of the Canadian Institutes ofHealth Research (CIHR), C17 Council Background Anthracycline-related cardiotoxicity is a major cause of mortality and morbidity in childhood acute lymphoblastic leukaemia...

Aims: To investigate the role of MYBBP1A gene and rs3809849 in pancreatic cancer (PANC1) and lymphoblastic leukemia (NALM6) cell lines and their response to asparaginase treatment. Materials & methods: The authors applied CRISPR-Cas9 to produce MYBBP1A knock-out (KO) and rs3809849 knock-in (KI) cell lines. The authors also interrogated rs3809849's...

A substantial number of survivors of childhood acute lymphoblastic leukemia (ALL) suffer from treatment-related late adverse effects. While multiple studies have identified the effects of chemotherapeutics and radiation therapy on musculoskeletal outcomes, few have investigated their associations with genetic factors. Here we analyzed musculoskelet...

Acute Graft versus Host Disease (aGvHD) grades 2–4 occurs in 15–60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role...

Background Sinusoidal occlusion syndrome (SOS) is a potentially severe complication following hematopoietic stem cell transplantation (HSCT) in pediatric patients. Treatment related risk factors such as intensity of conditioning, hepatotoxic co-medication and patient related factors such as genetic variants predispose individuals to develop SOS. Th...

Verbal fluency (VF) is a heterogeneous cognitive function that requires executive as well as language abilities. The purpose of this study was to elucidate the specificity of the resting state MEG correlates of the executive and language components. To this end, we administered a VF test, another verbal test (Vocabulary), and another executive test...

Doxorubicin leads to dose-dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. The first aim was to propose a contour-based estimation of T1 and T2 relaxation times based on the myocardial area, while our second aim was to evaluate native T1, post-gadolinium T1 and T2 relaxation time sensitivity to detect myocardial c...

The most frequent complication of allogeneic hematopoietic stem cell transplantation is acute Graft versus Host Disease (aGVHD). Proliferation and differentiation of donor T cells initiate inflammatory response affecting the skin, liver, and gastrointestinal tract. Besides recipient–donor HLA disparities, disease type, and the conditioning regimen,...

Background and Aims: Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in children, with a survival rate up to 90%. However, anthracycline-related cardiotoxicity is a major cause of mortality and morbidity in this population, and early detection of cardiac dysfunction remains a challenge. This study aims to explore vent...

Aim: Cardiovascular disease represents one of the main causes of secondary morbidity and mortality in patients with childhood cancer. Patients & methods: To further address this issue, we analyzed cardiovascular complications in relation to common and rare genetic variants derived through whole-exome sequencing from childhood acute lymphoblastic le...

Purpose This study aimed to retrospectively evaluate the genetic association of null variants of glutathione S-transferases GSTM1 and GSTT1 with relapse incidence in children with hematological malignancies (HMs) undergoing busulfan (BU)- containing allogeneic hematopoietic stem cell transplantation (HSCT) and to assess the impact of these variants...

Busulfan (Bu) is a common component of conditioning regimens before hematopoietic stem cell transplantation (HSCT) and is known for high interpatient pharmacokinetic (PK) variability. This study aimed to develop and externally validate a multicentric, population PK (PopPK) model for intravenous Bu in pediatric patients before HSCT to first study th...

Verbal fluency (VF) is a heterogeneous test that requires executive functions as well as language abilities. The purpose of this study was to elucidate the specificity of the resting state MEG correlates of the executive and language components. To this end, we administered a VFtest, another verbal test (Vocabulary), and another executive test (Tra...

Introduction Despite the significant survival improvement in childhood acute lymphoblastic leukemia (ALL), 15-20% of patients continue to relapse; outcomes following relapse remain suboptimal and have room for further improvement. Advances in genomics have shed new insights on the biology of ALL, led to the discovery of novel genomically-defined AL...

Background Childhood cancer survivors should be routinely screened for psychological distress. However, existing screening tools promoted by cancer care institutions, such as the Distress Thermometer (DT) generate high rates of errors. The aim of this study is to help refining strategies of screening psychological distress in this population by exp...

Sinusoidal obstruction syndrome (SOS) is a potentially life-threatening complication after hematopoietic stem cell transplantation (HSCT) or antineoplastic treatment without HSCT. Genetic variants were investigated for their association with SOS, but the evidence is inconclusive. We performed a systematic literature review to identify genes, gene v...

Background Relapse is the major cause of treatment failure in children with hematological malignancies (HMs) undergoing busulfan (BU)- based allogeneic hematopoietic stem cell transplantation (HSCT). Glutathione S-transferases (GSTs) isoforms that participate in BU detoxification and protect cells against stress and cell death may be linked to post...

Background: Relapse is the major cause of treatment failure in children with hematological malignancies (HMs) undergoing busulfan (BU)- based allogeneic hematopoietic stem cell transplantation (HSCT). Glutathione S-transferases (GSTs) isoforms that participate in BU detoxification and protect cells against stress and cell death may be linked to pos...

Cardiopulmonary exercise tests (CPET) focusing on analyses of heart rate (HR) responses and chronotropic incompetence (CI) could provide early information about treatment’s negative cardiac effects. We examined childhood acute lymphoblastic leukemia (ALL) survivors’ HR response during maximal CPET and identified survivors with CI. A total of 250 ch...

In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination....

PurposeThe purpose of this study was to demonstrate if childhood acute lymphoblastic leukemia (ALL) survivors exposed to chemotherapy (i.e., doxorubicin) are able to achieve a safe maximal cardiopulmonary exercise test (CPET).MethodsA total of 250 childhood ALL survivors were eligible to undergo a CPET on ergocycle. Analyses were performed in 216 s...

Survivors of childhood acute lymphoblastic leukemia (cALL) are at higher risk of developing cardiometabolic complications. We aimed at exploring the associations between biomarkers of inflammation, oxidative stress, endothelial function, endotoxemia and cardiometabolic risk factors. We conducted a cross-sectional analysis in 246 cALL survivors (mea...

To gain an in-depth understanding of human diseases , biologists typically mine patient data for relevant patterns. Clinical datasets are often unlabeled and involve features, a.k.a. markers, split into classes w.r.t. biological functions, whereby target patterns might well mix both levels. As such heterogeneous patterns are beyond the reach of cur...

Background: The prevalence of vertebral deformities in long-term survivors of childhood ALL is unknown. Our objectives were to identify the prevalence of vertebral deformities and their risk factors among long-term childhood ALL survivors. Methods / results: We recruited 245 (49% male) long-term childhood ALL survivors from the PETALE Cohort (Fr...

Purpose: This study aimed to: (1) describe the domains and levels of unmet needs of young adult survivors of childhood acute lymphoblastic leukemia (cALL) with comorbidities, and (2) to explore the factors associated with higher levels of unmet needs. Unmet need was considered as supportive care needs not met. Methods: The most vulnerable cALL sur...

Introduction: Cardiovascular diseases are the main cause of treatment-related morbidity and mortality in childhood cancer patients. Anthracyclines, one of the most common chemotherapeutic agents in treatment regimens, are implicated in chemotherapy-induced cardiotoxicity. Areas covered: This review describes the pharmacogenomic markers related t...

Purpose: The six-minute walk test (6MWT) is the most widely used test to assess the functional capacity of cancer patients. However, it is reported that the actual equations cannot accurately predict oxygen uptake (VO2 value) or walk distance (6MWD) in cancer survivors. Because of the importance for clinicians and physiologists to have a validated...

Purpose: Cancer survivors’ exposure to chemotherapeutic agents leads to multiple long-term side effects with a decrease in their cardiorespiratory fitness. The first aim was to determine whether cardiorespiratory fitness and physical activity levels were lower among survivors than healthy Canadians, while the second aim was to report associations b...

The pharmacokinetics of low dose busulfan (BU) were investigated as a non-myeloablative conditioning regimen for autologous gene therapy (GT) in pediatric subjects with adenosine deaminase-deficient severe combined immunodeficiency (ADA SCID). In three successive clinical trials, which included either γ-retroviral (γ-RV) or lentiviral (LV) vectors,...

Despite recent advances in immunotherapies, cytotoxic chemotherapy continues to be a first‐line treatment option for the majority of cancers. Unfortunately, a common side effect in patients undergoing chemotherapy treatment is neutropenia. To mitigate the risk of neutropenia and febrile neutropenia, prophylactic treatment with granulocyte‐colony st...

Introduction. Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of the treatment. Regular physical activity and a good cardiorespiratory fitness can decrease the risks of neurological disturbances and increase cognitive function scores. The aim of this study was...

Aim: To evaluate the association between human leukocyte antigen (HLA) alleles and native Escherichia coli asparaginase hypersensitivity (AH) in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Patients & methods: HLA-DQA1, HLA-DRB1 and HLA-DQB1 alleles were retrieved from available who...

Objectives The frequency of cognitive difficulties in childhood cancer survivors varies according to the measurement strategy. The goal of this research is to (1) describe agreements and differences between measures of working memory and attention (2) identify contributors of these differences, such as emotional distress, affects, and fatigue. Met...

Introduction: The 6-Minute Walking Test (6MWT) is a safe, standardized and well utilized method to assess the functional capacity. Recently, it was reported that the published prediction equations cannot accurately predict a valid maximal oxygen consumption ( V̇O2 peak) value in cancer survivors. Thus, the aim of this study was to establish and to...

Survivors of childhood acute lymphoblastic leukemia (cALL) are at high risk of developing dyslipidemia, including low HDL-cholesterol (HDL-C). This study aimed to examine the associations between food/nutrient intake and the levels of HDL-C in a cohort of children and young adult survivors of cALL. Eligible participants (n = 241) were survivors of...

Aim: To evaluate top-ranking genes identified through genome-wide association studies for an association with corticosteroid-related osteonecrosis in children with acute lymphoblastic leukemia (ALL) who received Dana–Farber Cancer Institute treatment protocols. Patients & methods: Lead SNPs from these studies, as well as other variants in the same...

Sinusoidal Obstruction Syndrome (SOS) is a well-recognized and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). SOS arises from endothelial cell damage and hepatocellular injury mostly due to the transplantation conditioning regimens but also to other patient, disease and treatment-related factors. Unders...

AIMS: Acute lymphoblastic leukemia (ALL) is one of the leading malignancies in children worldwide. The cardiotoxicity of anti-cancer treatments leads to a dysfunction of the cardiac autonomic nervous system. Protection strategies, with dexrazoxane treatments, were used to counter these adverse effects. The aim of this study was to investigate the e...

Introduction: More than two thirds of survivors have long-term adverse effects, and no study proposes a portrait of physical activity level in childhood acute lymphoblastic leukemia survivors. The aims of this study were to present the cardiorespiratory fitness (CRF) levels of survivors detailed overview sedentary activities portrait. Methods: A...

Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Treatments against ALL might lead to later cognitive effects and alterations in brain structure in survivors but to the authors' knowledge the observed variability in the severity of neurocognitive deficits is not fully understood. The objective of the current study...

Introduction. As the survival rate of childhood acute lymphoblastic leukemia (ALL) continues to improve, the physical deconditioning is becoming an increasingly common problem in survivors. The aim of this study was to compare the cardiorespiratory fitness and physical activity levels of survivors and control participants. Methods. A total of 221 c...

Asparaginase is a key component in leukemias and lymphomas treatment protocols and is suggested as a treatment for other malignancies in which an amino acid depletion strategy is indicated. Asparaginase intolerance is subject to inter-individual variability and can manifest as hypersensitivity reactions, pancreatitis, thrombosis, as well as metabol...

Background A substantial number of survivors of childhood acute lymphoblastic leukemia suffer from treatment-related late adverse effects including neurocognitive impairment. While multiple studies have described neurocognitive outcomes in childhood acute lymphoblastic leukemia (ALL) survivors, relatively few have investigated their association wit...

Background Haematopoietic stem cell transplantation (HSCT) is the only current curative treatment for Sickle Cell Disease (SCD), with potential life-threatening consequences. Busulfan is an alkylating agent used in HSCT conditioning regimen. Because of its narrow therapeutic window, determining the optimal first dose a priori remains a challenge. B...

Background Busulfan (Bu) is widely used as a component of myeloablative conditioning regimen before hematopoietic stem cell transplantation (HSCT) in children. Obtaining the ratio of Bu to its metabolite sulfolane i.e. metabolic ratio (MR) may serve as an indicator of Bu GSH conjugating capacity of an individual. Objective To evaluate the utility...

PURPOSE: Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of therapy. A regular practice of physical activity and a good cardiorespiratory fitness have the potential to reduce the risk of chronic diseases and to improve quality of life. It is currently unknown...

Exercise Prescription Based on a Six Minute Walk Test in Childhood Acute Lymphoblastic Leukemia Survivors 3564 Board #252 June 1 9:30 AM - 11:00 AM Duhamel, Gabrielle E.1; Caru, Maxime1; Lemay, Valérie1; Drouin, Simon2; Alos, Nathalie2; Bertout, Laurence2; Krajinovic, Maja2; Laverdière, Caroline2; Raboisson, Marie-Josée2; Sinnett, Daniel2; Andelfi...