Relapse In Pediatric Acute Lymphoid Leukemia

Background: The extensive genetic heterogeneity found in the B cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype of childhood ALL represents a potential repository of biomarkers. To explore this potential, we have carried out in silico analysis of publicly available ALL datasets to identify genetic biomarkers for childhood BCP-ALL, which could be used either individually or in combination as markers for early detection, risk stratification, and prognosis. Methods: To explore novel genes that show promising clinical and molecular signatures, we examined the cBioPortal online tool for publicly available datasets on lymphoid cancers...

Acute Myeloid Leukemia (AML) is a complex and highly aggressive disease. To characterize the prognostic factors of pediatric patients with AML relapse, a retrospective cohort study was performed to collect data from children and adolescents, at a hematological oncology reference center, over 11 years. We selected 51 cases of the disease, diagnosed and treated uniformly, divided into two groups: with complete remission (n = 33; 65 %) and with relapse (n = 18; 35 %). The groups were homogeneous concerning demographic characteristics and hematological parameters at diagnosis...

Acute lymphoblastic leukemia (ALL) is a heterogenous hematological malignancy representing 25% of all cancers in children less than 15 years of age. Significant improvements in survival and cure rates have been made over the past four decades in pediatric ALL treatment. Asparaginases, derived from Escherichia coli and Erwinia chrysanthemi , have become a critical component of ALL therapy since the 1960s. Asparaginases cause depletion of serum asparagine, leading to deprivation of this critical amino acid for protein synthesis, and hence limit survival of lymphoblasts...

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a blood cancer that originates from the abnormal proliferation of B-lymphoid progenitors. Cell population components and cell-cell interaction in the bone marrow microenvironment are significant factors for progression, relapse, and therapy resistance of BCP-ALL. In this study, we identified specifically expressed genes in B cells and myeloid cells by analyzing single-cell RNA sequencing data for seven BCP-ALL samples and four healthy samples obtained from a public database...

There is limited data regarding pediatric mixed phenotype acute leukemia (MPAL) and there is no global consensus on its management yet. In this retrospective study, we analyzed the outcomes of children diagnosed with MPAL at our institute. This study included children ≤ 14 years with MPAL who presented to a tertiary cancer center in India from January 1st 2009 to December 31st 2015. Over a seven-year period, 1390 patients with leukemia presented to our institute of which 22 patients (1.5%) had MPAL. Sixteen patients (72...

PURPOSE OF REVIEW: Chimeric antigen receptor T-cell (CAR-T) therapy is a form of adoptive cellular therapy that has revolutionized the treatment landscape in hematologic malignancies, especially B-cell lymphomas. In this review, we will discuss some of the landmark data behind these therapies and then lay out our approach to utilizing this new therapy. RECENT FINDINGS: CD19-directed CAR-Ts are the most common type currently used in treatment of relapsed B-cell lymphoid neoplasms...

BACKGROUND: Pediatric oncology patients have high rates of hospital readmission but there is a dearth of research into risk factors for unplanned 30-day readmissions among this high-risk population. AIM: In this study, we built a statistical model to provide insight into risk factors of unplanned readmissions in this pediatric oncology. METHODS: We retrieved 32 667 encounters from 10 418 pediatric patients with a neoplastic condition from 16 hospitals in the Cerner Health Facts Database and built a mixed-effects model with patients nested within hospitals for inference on 75% of the data and reserved the remaining as an independent test dataset...

Acute lymphoblastic leukemia (ALL) is an aggressive hematological cancer that mainly affects children. Relapse and chemoresistance result in treatment failure, underlining the need for improved therapies. BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription repressor recognized as a tumor suppressor in lymphomas, but little is known about its function and regulatory network in pediatric ALL (p-ALL). Herein, we found aberrant BACH2 expression at new diagnosis not only facilitated risk stratification of p-ALL but also served as a sensitive predictor of early treatment response and clinical outcome...

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a common pediatric leukemia caused by lymphoid precursor proliferation. We analyzed immunophenotyping and hematological findings, as the risk of relapse, of pediatric ALL patients at diagnosis and relapse. METHODS: Peripheral blood and bone marrow samples of 30 pediatric ALL patients were collected at diagnosis and at relapse. The latter was evaluated for immunophenotyping and cytochemical staining (Periodic Acid Schiff stain (PAS)), while hematological findings were assessed in the former one...

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Current immunotherapies exploit the performance of antibodies through several different mechanisms, including naked antibodies, antibodies linked to cytotoxic agents, and T-cell re-directing antibodies...

B-cell acute lymphoblastic lymphoma (B-ALL) is a disease found mainly in children and in young adults. B-ALL is characterized by the rapid proliferation of poorly differentiated lymphoid progenitor cells inside the bone marrow. In the United States, ~4,000 of these patients are diagnosed each year, accounting for ~30% of childhood cancer types. The tumorigenesis of the disease involves a number of abnormal gene expressions (including TEL-AML1, BCR-ABL-1, RAS and PI3K ) leading to dysregulated cell cycle. Risk factors of B-ALL are the history of parvovirus B 19 infection, high birth weight and exposure to environmental toxins...

Childhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer. It is characterized by bone marrow lymphoid precursors that acquire genetic alterations, resulting in disrupted maturation and uncontrollable proliferation. More than a dozen molecular subtypes of variable severity can be used to classify cALL cases. Modern therapy protocols currently cure 85-90% of cases, but other patients are refractory or will relapse and eventually succumb to their disease. To better understand intratumor heterogeneity in cALL patients, we investigated the nature and extent of transcriptional heterogeneity at the cellular level by sequencing the transcriptomes of 39,375 individual cells in eight patients (six B-ALL and two T-ALL) and three healthy pediatric controls...

BACKGROUND: Donor lymphocyte infusion (DLI) is often used to treat leukemic relapse after hematopoietic cell transplantation (HCT). However, the relationship between outcomes and distinct DLI cellular composition has not been previously reported. Additionally, there are limited published data on efficacy in pediatrics. We evaluated whether DLI cellular content and development of graft-versus-host disease (GVHD) impacted disease and influenced overall survival (OS) in children receiving DLI for recurrent leukemia...

Prognosis of relapsed leukemia patients after second allogeneic hematopoietic stem cell transplantation (HSCT2) is historically considered very poor. We report the outcome of 18 pediatric patients after failure of HSCT2. The 2-year overall survival was 26% (95% confidence interval [CI], 6-47). The lymphoid malignancies were associated with better survival (40% [95% CI, 12-68]) than myeloid malignancies (0%, P=0.002), together with time to relapse after the HSCT2 (≥5 mo: 44% [95% CI, 12-76] vs. 0% for patients who relapsed within 5 mo from HSCT2, P=0...

The current treatment for pediatric acute lymphoblastic leukemia (ALL) is highly successful with high cure rate. However, the treatment of adult ALL remains a challenge, particularly for refractory and/or relapsed (R/R) ALL. The advent of new targeted agents, blinatumomab, inotuzumab ozogamycin, and chimeric antigen receptor (CAR) T cells, are changing the treatment paradigm for ALL. Tisagenlecleucel (kymriah, Novartis) is an autologous CD19-targeted CAR T cell product approved for treatment of R/R B cell ALL and lymphoma...

Purpose Somatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22...

LESSONS LEARNED: Clofarabine can be active in relapsed and refractory lymphoid malignancies on a weekly dosing schedule.Responses were seen in patients with T-cell lymphomas, including cutaneous T-cell lymphoma, but not in patients with aggressive B-cell lymphomas. BACKGROUND: Clofarabine is a second-generation purine nucleoside analog currently approved for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. In adults, clofarabine has been investigated in several phase I and II trials as a single agent and in combination for relapsed or refractory acute leukemia...

Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Thiopurine is a widely used drug in the maintaining treatment of ALL. After a period of chemotherapy, 20% of pediatric patients and over 50% of adult patients will relapse. To investigate the mechanisms of drug resistance in vitro , we established the thiopurine resistant cell lines Reh-6MPR (6-MP Resistant cell) and Reh-6TGR (6-TG Resistant cell) by stepwise selection of the ALL cell line Reh...

As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-cell ALL; however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL...

Several retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T, B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells) compartments...