ATM germ line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological malignancies.

ABSTRACT: Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder caused by pathogenic variants (PVs) of the ATM gene, predisposing children to hematological malignancies. We investigated their characteristics and outcomes to generate data-based treatment recommendations. In this multinational, observational study we report 202 patients aged ≤25 years with A-T and hematological malignancies from 25 countries. Ninety-one patients (45%) presented with mature B-cell lymphomas, 82 (41%) with acute lymphoblastic leukemia/lymphoma, 21 (10%) with Hodgkin lymphoma and 8 (4%) with other hematological malignancies. Four-year overall survival and event-free survival (EFS) were 50.8% (95% confidence interval [CI], 43.6-59.1) and 47.9% (95% CI 40.8-56.2), respectively. Cure rates have not significantly improved over the last four decades (P = .76). The major cause of treatment failure was treatment-related mortality (TRM) with a four-year cumulative incidence of 25.9% (95% CI, 19.5-32.4). Germ line ATM PVs were categorized as null or hypomorphic and patients with available genetic data (n = 110) were classified as having absent (n = 81) or residual (n = 29) ATM kinase activity. Four-year EFS was 39.4% (95% CI, 29-53.3) vs 78.7% (95% CI, 63.7-97.2), (P < .001), and TRM rates were 37.6% (95% CI, 26.4-48.7) vs 4.0% (95% CI, 0-11.8), (P = .017), for those with absent and residual ATM kinase activity, respectively. Absence of ATM kinase activity was independently associated with decreased EFS (HR = 0.362, 95% CI, 0.16-0.82; P = .009) and increased TRM (hazard ratio [HR] = 14.11, 95% CI, 1.36-146.31; P = .029). Patients with A-T and leukemia/lymphoma may benefit from deescalated therapy for patients with absent ATM kinase activity and near-standard therapy regimens for those with residual kinase activity.

Haploidentical HSCT in the Treatment of Pediatric Hematological Disorders.

Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD.

Neuroblastoma-A Review of Combination Immunotherapy.

Neuroblastoma is the most common extracranial solid tumor found in childhood and is responsible for 15% of deaths among children with cancer. Although multimodal therapies focused on surgery, chemotherapy, radiotherapy, and stem cell transplants have favorable results in many cases, the use of conventional therapies has probably reached the limit their possibility. Almost half of the patients with neuroblastoma belong to the high-risk group. Patients in this group require a combination of several therapeutic approaches. It has been shown that various immunotherapies combined with conventional methods can work synergistically. Due to the development of such therapeutic methods, we present combinations and forms of combining immunotherapy, focusing on their mechanisms and benefits but also their limitations and potential side effects.

Clinical Implications of Isocitrate Dehydrogenase Mutations and Targeted Treatment of Acute Myeloid Leukemia with Mutant Isocitrate Dehydrogenase Inhibitors-Recent Advances, Challenges and Future Prospects.

Despite the better understanding of the molecular mechanisms contributing to the pathogenesis of acute myeloid leukemia (AML) and improved patient survival in recent years, AML therapy still remains a clinical challenge. For this reason, it is important to search for new therapies that will enable the achievement of remission. Recently, the Food and Drug Administration approved three mutant IDH (mIDH) inhibitors for the treatment of AML. However, the use of mIDH inhibitors in monotherapy usually leads to the development of resistance and the subsequent recurrence of the cancer, despite the initial effectiveness of the therapy. A complete understanding of the mechanisms by which IDH mutations influence the development of leukemia, as well as the processes that enable resistance to mIDH inhibitors, may significantly improve the efficacy of this therapy through the use of an appropriate synergistic approach. The aim of this literature review is to present the role of IDH1/IDH2 mutations in the pathogenesis of AML and the results of clinical trials using mIDH1/IDH2 inhibitors in AML and to discuss the challenges related to the use of mIDH1/IDH2 inhibitors in practice and future prospects related to the potential methods of overcoming resistance to these agents.

Infant Acute Lymphoblastic Leukemia-New Therapeutic Opportunities.

Infant acute lymphoblastic leukemia (Infant ALL) is a kind of pediatric ALL, diagnosed in children under 1 year of age and accounts for less than 5% of pediatric ALL. In the infant ALL group, two subtypes can be distinguished: KMT2A-rearranged ALL, known as a more difficult to cure form and KMT2A- non-rearranged ALL with better survival outcomes. As infants with ALL have lesser treatment outcomes compared to older children, it is pivotal to provide novel treatment approaches. Progress in the development of molecularly targeted therapies and immunotherapy presents exciting opportunities for potential improvement. This comprehensive review synthesizes the current literature on the epidemiology, clinical presentation, molecular genetics, and therapeutic approaches specific to ALL in the infant population.

Electrochemical and Optical Sensors for the Detection of Chemical Carcinogens Causing Leukemia.

The incidence and mortality due to neoplastic diseases have shown an increasing tendency over the years. Based on GLOBOCAN 2020 published by the International Agency for Research on Cancer (IARC), leukemias are the thirteenth most commonly diagnosed cancer in the world, with 78.6% of leukemia cases diagnosed in countries with a very high or high Human Development Index (HDI). Carcinogenesis is a complex process initiated by a mutation in DNA that may be caused by chemical carcinogens present in polluted environments and human diet. The IARC has identified 122 human carcinogens, e.g., benzene, formaldehyde, pentachlorophenol, and 93 probable human carcinogens, e.g., styrene, diazinone. The aim of the following review is to present the chemical carcinogens involved or likely to be involved in the pathogenesis of leukemia and to summarize the latest reports on the possibility of detecting these compounds in the environment or food with the use of electrochemical sensors.

Recent Updates in Venetoclax Combination Therapies in Pediatric Hematological Malignancies.

Venetoclax is a strongly effective B-cell lymphoma-2 inhibitor (BCL-2) with an ability to selectively restore the apoptotic potential of cancerous cells. It has been proven that in combination with immunotherapy, targeted therapies, and lower-intensity therapies such as hypomethylating agents (HMAs) or low-dose cytarabine (LDAC), the drug can improve overall outcomes for adult patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM), amongst other hematological malignancies, but its benefit in pediatric hematology remains unclear. With a number of preclinical and clinical trials emerging, the newest findings suggest that in many cases of younger patients, venetoclax combination treatment can be well-tolerated, with a safety profile similar to that in adults, despite often leading to severe infections. Studies aim to determine the activity of BCL-2 inhibitor in the treatment of both primary and refractory acute leukemias in combination with standard and high-dose chemotherapy. Although more research is required to identify the optimal venetoclax-based regimen for the pediatric population and its long-term effects on patients' outcomes, it can become a potential therapeutic agent for pediatric oncology.

Overview on Aneuploidy in Childhood B-Cell Acute Lymphoblastic Leukemia.

Recent years have brought significant progress in the treatment of B-cell acute lymphoblastic leukemia (ALL). This was influenced by both the improved schemes of conventionally used therapy, as well as the development of new forms of treatment. As a consequence, 5-year survival rates have increased and now exceed 90% in pediatric patients. For this reason, it would seem that everything has already been explored in the context of ALL. However, delving into its pathogenesis at the molecular level shows that there are many variations that still need to be analyzed in more detail. One of them is aneuploidy, which is among the most common genetic changes in B-cell ALL. It includes both hyperdiploidy and hypodiploidy. Knowledge of the genetic background is important already at the time of diagnosis, because the first of these forms of aneuploidy is characterized by a good prognosis, in contrast to the second, which is in favor of an unfavorable course. In our work, we will focus on summarizing the current state of knowledge on aneuploidy, along with an indication of all the consequences that may be correlated with it in the context of the treatment of patients with B-cell ALL.

Characteristics and treatment results of refractory and relapsed acute myeloid leukaemia in paediatric patients treated in Polish Paediatric Leukaemia/Lymphoma Study Group institutions according to the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 and a review of novel treatment possibilities in paediatric acute myeloid leukaemia.

Introduction: This study aimed to present the clinical features and results of treatment of patients diagnosed with refractory or relapsed acute myeloid leukaemia (AML) in Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG) institutions, treated in accordance with the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012, as their first-line therapy. Material and methods: The outcome data of 10 patients with refractory AML (median age 9.5 years) and 30 with relapsed AML (median age 12 years) were analysed retrospectively. Re-induction was usually based on idarubicin, fludarabine, and cytarabine along with allogeneic haematopoietic stem cell transplant (allo-HSCT) in 5 patients with refractory AML and 7 relapsed AML children. Results: 37.5% (3/8) of refractory AML patients achieved second complete remission second complete remission (CRII). One of ten patients (1/10; 10%) was alive and stayed in complete remission for 34 months after the allo-HSCT. The probability of 3-year event-free survival (pEFS) in this group was 0.125 ±0.11. In the group of relapsed AML patients, the CRII was achieved in 9 patients (34%), and the probability of survival was: pEFS = 0.24 ±0.08; probability overall survival (pOS) = 0.34 ±0.09, with significantly better results achieved in patients who underwent allo-HSCT (pOS = 0.54 ±0.14 vs. 0.08 ±0.08, p < 0.0001). Conclusions: The prognosis of refractory AML and the first AML recurrence in children who were first-line treated in PPL/LSG centres according to Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 is poor. Failures of re-induction treatment particularly result from difficulties in achieving remission. Allogeneic HSCT improves prognosis in children with refractory and first recurrent AML, under the condition it is performed in complete remission. Novel therapeutic approaches are needed to increase the remission rate and improve the outcomes.

Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Despite the enormous progress in ALL therapy, resulting in achieving a 5-year survival rate of up to 90%, the ambitious goal of reaching a 100% survival rate is still being pursued. A typical ALL treatment includes three phases: remission induction and consolidation and maintenance, preceded by a prednisone prephase. Poor prednisone response (PPR) is defined as the presence of ≥1.0 × 109 blasts/L in the peripheral blood on day eight of therapy and results in significantly frequent relapses and worse outcomes. Hence, identifying risk factors of steroid resistance and finding methods of overcoming that resistance may significantly improve patients' outcomes. A mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) pathway seems to be a particularly attractive target, as its activation leads to steroid resistance via a phosphorylating Bcl-2-interacting mediator of cell death (BIM), which is crucial in the steroid-induced cell death. Several mutations causing activation of MAPK-ERK were discovered, notably the interleukin-7 receptor (IL-7R) pathway mutations in T-cell ALL and rat sarcoma virus (Ras) pathway mutations in precursor B-cell ALL. MAPK-ERK pathway inhibitors were demonstrated to enhance the results of dexamethasone therapy in preclinical ALL studies. This report summarizes steroids' mechanism of action, resistance to treatment, and prospects of steroids therapy in pediatric ALL.

Neurotoxicity Associated with Treatment of Acute Lymphoblastic Leukemia Chemotherapy and Immunotherapy.

Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) and is expected to improve treatment outcomes and reduce doses of conventional chemotherapy without compromising the effectiveness of the therapy. However, both chemotherapy and immunotherapy cause side effects, including neurological ones. Acute neurological complications occur in 3.6-11% of children treated for ALL. The most neurotoxical chemotherapeutics are L-asparaginase (L-ASP), methotrexate (MTX), vincristine (VCR), and nelarabine (Ara-G). Neurotoxicity associated with methotrexate (MTX-NT) occurs in 3-7% of children treated for ALL and is characterized by seizures, stroke-like symptoms, speech disturbances, and encephalopathy. Recent studies indicate that specific polymorphisms in genes related to neurogenesis may have a predisposition to MTX toxicity. One of the most common complications associated with CAR T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS). Mechanisms of neurotoxicity in CAR T-cell therapy are still unknown and may be due to disruption of the blood-brain barrier and the effects of elevated cytokine levels on the central nervous system (CNS). In this review, we present an analysis of the current knowledge on the mechanisms of neurotoxicity of standard chemotherapy and the targeted therapy in children with ALL.

Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) accounts for approximately 15-20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result of numerous mutations and epigenetic changes occurring in this disease that adversely affect the susceptibility to treatment and relapse rate. We describe various molecular-targeted therapies that have been developed in recent years to meet these challenges and were or are currently being studied in clinical trials. First introduced in adult AML, novel forms of treatment are slowly beginning to change the therapeutic approach to pediatric AML. Despite promising results of clinical trials investigating new drugs, further clinical studies involving greater numbers of pediatric patients are still needed to improve the outcomes in childhood AML.

Expression of CD73 on leukemic blasts increases during follow-up - a promising candidate marker for minimal residual disease detection in pediatric B-cell precursor acute lymphoblastic leukemia.

Flow cytometry (FCM) is a precise and well-established tool to assess the minimal residual disease (MRD) level in childhood acute lymphoblastic leukemia (ALL). It is crucial to distinguish leukemic cells from their normal counterparts; thus new markers should be evaluated, to increase the accuracy of the analysis. The expression of CD73 on blast cells was measured and compared at the day of diagnosis and at days 15 and 33 of treatment. To determine antigen expression levels, a normalized scale based on median fluorescence intensity (nMFI) was used. The study group consisted of 188 patients from the Polish Pediatric Leukemia and Lymphoma Study Group. From 177 patients with positive MRD at day 15 of treatment, in 147 (83.1%) cases an increase of CD73 expression was observed (mean increase of +17 nMFI units). In addition, an increase of CD73 expression was noted in 26 of 31 (83.9%) patients at day 33 of treatment. In turn, a decrease of CD73 expression was observed only in 13/177 (7.3%) and 1/31 (3.2%) cases at days 15 and 33 of treatment, respectively. In 17 (9.6%) patients no change in expression of CD73 between diagnosis and day 15 of treatment was observed. In the great majority of cases the expression of CD73 is not only stable but increases during the early stages of treatment, which makes it a very useful marker to be used for MRD monitoring in childhood B-cell precursor (BCP)-ALL patients.

Comprehensive Overview of Gene Rearrangements in Childhood T-Cell Acute Lymphoblastic Leukaemia.

Acute lymphoblastic leukaemia (ALL) is a relevant form of childhood neoplasm, as it accounts for over 80% of all leukaemia cases. T-cell ALL constitutes a genetically heterogeneous cancer derived from T-lymphoid progenitors. The diagnosis of T-ALL is based on morphologic, immunophenotypic, cytogenetic, and molecular features, thus the results are used for patient stratification. Due to the expression of surface and intracellular antigens, several subtypes of T-ALL can be distinguished. Although the aetiology of T-ALL remains unclear, a wide spectrum of rearrangements and mutations affecting crucial signalling pathways has been described so far. Due to intensive chemotherapy regimens and supportive care, overall cure rates of more than 80% in paediatric T-ALL patients have been accomplished. However, improved knowledge of the mechanisms of relapse, drug resistance, and determination of risk factors are crucial for patients in the high-risk group. Even though some residual disease studies have allowed the optimization of therapy, the identification of novel diagnostic and prognostic markers is required to individualize therapy. The following review summarizes our current knowledge about genetic abnormalities in paediatric patients with T-ALL. As molecular biology techniques provide insights into the biology of cancer, our study focuses on new potential therapeutic targets and predictive factors which may improve the outcome of young patients with T-ALL.

Genomic Analyses of Pediatric Acute Lymphoblastic Leukemia Ph+ and Ph-Like-Recent Progress in Treatment.

Pediatric acute lymphoblastic leukemia (ALL) with t(9;22)(q34;q11.2) is a very rare malignancy in children. Approximately 3-5% of pediatric ALL patients present with the Philadelphia chromosome. Previously, children with Ph+ had a poor prognosis, and were considered for allogeneic stem cell transplantation (allo-HSCT) in their first remission (CR1). Over the last few years, the treatment of childhood ALL has significantly improved due to standardized research protocols. Hematopoietic stem cell transplantation (HSCT) has been the gold standard therapy in ALL Ph+ patients, but recently first-generation tyrosine kinase inhibitor (TKI)-imatinib became a major milestone in increasing overall survival. Genomic analyses give the opportunity for the investigation of new fusions or mutations, which can be used to establish effective targeted therapies. Alterations of the IKZF1 gene are present in a large proportion of pediatric and adult ALL Ph+ cases. IKZF1 deletions are present in ~15% of patients without BCR-ABL1 rearrangements. In BCR-ABL1-negative cases, IKZF1 deletions have been shown to have an independent prognostic impact, carrying a three-fold increased risk of treatment failure. The prognostic significance of IKZF1 gene aberrations in pediatric ALL Ph+ is still under investigation. More research should focus on targeted therapies and immunotherapy, which is not associated with serious toxicity in the same way as classic chemotherapy, and on the improvement of patient outcomes. In this review, we provide a molecular analysis of childhood ALL with t(9;22)(q34;q11.2), including the Ph-like subtype, and of treatment strategies.

The Use of Inhibitors of Tyrosine Kinase in Paediatric Haemato-Oncology-When and Why?

The fundamental pathophysiology of malignancies is dysregulation of the signalling pathways. Protein tyrosine kinases (PTKs) are among the enzymes which, if mutated, play a critical role in carcinogenesis. The best-studied rearrangement, which enhances PTK activity and causes atypical proliferation, is BCR-ABL1. Abnormal expression of PTKs has proven to play a significant role in the development of various malignancies, such as chronic myelogenous leukaemia, brain tumours, neuroblastoma, and gastrointestinal stromal tumours. The use of tyrosine kinase inhibitors (TKIs) is an outstanding example of successful target therapy. TKIs have been effectively applied in the adult oncology setting, but there is a need to establish TKIs' importance in paediatric patients. Many years of research have allowed a significant improvement in the outcome of childhood cancers. However, there are still groups of patients who have a poor prognosis, where the intensification of chemotherapy could even cause death. TKIs are designed to target specific PTKs, which lead to the limitation of severe adverse effects and increase overall survival. These advances will hopefully allow new therapeutic approaches in paediatric haemato-oncology to emerge. In this review, we present an analysis of the current data on tyrosine kinase inhibitors in childhood cancers.

The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia.

Childhood acute lymphoblastic leukemia is a genetically heterogeneous cancer that accounts for 10-15% of T-cell acute lymphoblastic leukemia (T-ALL) cases. The T-ALL event-free survival rate (EFS) is 85%. The evaluation of structural and numerical chromosomal changes is important for a comprehensive biological characterization of T-ALL, but there are currently no genetic prognostic markers. Despite chemotherapy regimens, steroids, and allogeneic transplantation, relapse is the main problem in children with T-ALL. Due to the development of high-throughput molecular methods, the ability to define subgroups of T-ALL has significantly improved in the last few years. The profiling of the gene expression of T-ALL has led to the identification of T-ALL subgroups, and it is important in determining prognostic factors and choosing an appropriate treatment. Novel therapies targeting molecular aberrations offer promise in achieving better first remission with the hope of preventing relapse. The employment of precisely targeted therapeutic approaches is expected to improve the cure of the disease and quality of life of patients. These include therapies that inhibit Notch1 activation (bortezomib), JAK inhibitors in ETP-ALL (ruxolitinib), BCL inhibitors (venetoclax), and anti-CD38 therapy (daratumumab). Chimeric antigen receptor T-cell therapy (CAR-T) is under investigation, but it requires further development and trials. Nelarabine-based regimens remain the standard for treating the relapse of T-ALL.

Targeted Therapy in the Treatment of Pediatric Acute Lymphoblastic Leukemia-Therapy and Toxicity Mechanisms.

Targeted therapy has revolutionized the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) with specific genetic abnormalities. It is still being described as a new landmark therapeutic approach. The main purpose of the use of molecularly targeted drugs and immunotherapy in the treatment of ALL is to improve the treatment outcomes and reduce the doses of conventional chemotherapy, while maintaining the effectiveness of the therapy. Despite promising treatment results, there is limited clinical research on the effect of target cell therapy on the potential toxic events in children and adolescents. The recent development of highly specific molecular methods has led to an improvement in the identification of numerous unique expression profiles of acute lymphoblastic leukemia. The detection of specific genetic mutations determines patients' risk groups, which allows for patient stratification and for an adjustment of the directed and personalized target therapies that are focused on particular molecular alteration. This review summarizes the knowledge concerning the toxicity of molecular-targeted drugs and immunotherapies applied in childhood ALL.

Varicella-zoster virus infection in the pediatric population with acute lymphoblastic leukemia in Poland.

Varicella-zoster virus (VZV) infection in pediatric hemato-oncology patients can be a therapeutic problem when children are exposed to immunosuppression. The aim of this study is to evaluate the incidence of VZV infection, antiviral therapy and outcome in children with ALL treated in polish hemato-oncological centers between 2012 and 2019 years. This study included medical records of 1874 patients, aged 1 to 18 years, with newly diagnosed acute lymphoblastic leukemia. During chemotherapy, 406 children out of 1874 (21.6%) experienced viral infections. The incidence of VZV infection in the whole group children with ALL was 1.8%. Among them, 34 (8.4%) patients were diagnosed with VZV infection. Thirty-five episodes of viral infections were identified. The median time of VCV therapy was 12 days. Herpes zoster infection occurred in 24 (70.6%) children, and varicella in 10 (29.4%) ones. The average time from the start of chemotherapy to the appearance of herpes zoster was 7.26 ± 4.05 months. VZV infection occurred mainly during the maintenance therapy, the reinduction and induction phases. There was no correlation between steroid dosage or type and subsequent zoster. The total lymphocyte count of these patients on the first day of zoster was reduced. No serious complications were observed due to this infection. All patients survived. In conclusion, a low incidence of VZV infection was observed among pediatric patients with ALL in Poland. This analysis indicates that currently used therapeutic methods are effective in children with cancer and VZV infection. The main focus should be on the prevention of delayed chemotherapy.

Mixed phenotype acute leukemia: Biological profile, clinical characteristic and treatment outcomes: Report of the population-based study.

OBJECTIVES: The aim of this population-based, retrospective study was to analyze biological and clinical features and treatment results in children diagnosed with MPAL in all Polish pediatric oncology centers between 2007 and 2018. METHODS: Among 2893 children and adolescents diagnosed and treated for acute leukemia, 39 (1.35%) patients fulfilled the WHO criteria of MPAL. The T/myeloid phenotype was most prevalent. RESULTS: Cytogenetics findings were seen in 2 (5.1%), while chromosomal abnormalities were found in 14 (35.9%) patients. Thirty-two patients achieved CR-1, including 23 (92.0%) treated with ALL-directed chemotherapy and 9 (64.3%) treated with AML-type induction regimens. Within these patients, 4 (12.5%) died due to treatment-related complications and 11 (34.4%) relapsed. Nineteen (63.3%) patients underwent allo-HSCT in CR-1 and 14 (73.7%) of them have been in CR-1. In total, 17 (43.6%) patients remain in CR-1 for 1-12 years, including 14 (58.3%) with T/myeloid MPAL. The 5-year pOS and pEFS were 51.8% and 44.2%, respectively. The overall survival for ALL-directed therapy was significantly better than the one for AML-type chemotherapy (P = .001). It was also better for patients who underwent HSCT in CR-1 (P = .001). CONCLUSIONS: The prognosis of MPAL is unsatisfactory, but initial treatment with ALL-directed chemotherapy consolidated with allo-HSCT improves the outcomes in MPAL.