ALL and philadelphia

Older adults who are diagnosed with acute lymphoblastic leukemia (ALL) and are treated with chemotherapy generally have poor outcomes. Blinatumomab is a CD19/CD3 bispecific T-cell engager that has been approved for the treatment of B-cell ALL in the relapsed/refractory setting or in patients with minimal residual disease (MRD) positivity. We previously reported on a small cohort of older adults with newly diagnosed Philadelphia chromosome negative B-cell ALL who were treated with blinatumomab monotherapy in the first line setting...

BACKGROUND/AIM: In precursor B-cell lineage acute lymphoblastic leukemia (BCP-ALL), leukemic cells harbor genetic abnormalities that play an important role in the diagnosis, prognosis, and treatment. A subgroup of BCP-ALL is characterized by the presence of a Philadelphia (Ph) chromosome and a chimeric BCR::ABL1 gene, whereas in another subgroup, leukemic cells exhibit near-haploidy with chromosome number 24-30. This study presents the third documented case of BCP-ALL in which a near haploid clone concurrently displayed a Ph chromosome/BCR::ABL1...

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This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality...

Introduction With the increasing use of Blinatumomab in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), including MRD-positive cases, awareness of its adverse effects has gradually improved. Pneumocystis jiroveci pneumonia (PCP) associated with Blinatumomab therapy is rare. Case Presentation We present a case of PCP in a patient undergoing Blinatumomab therapy. A 70-year-old female diagnosed with Philadelphia-like, CRLF2 overexpression B-cell precursor ALL received Blinatumomab as consolidation therapy after achieving complete remission with prior induction chemotherapy...

Background and objective Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+) is quite rare among pediatric patients. Its management has undergone significant changes in the past few years, leading to some variability in how it is approached. At the Portuguese Oncology Institute of Porto (IPOP), a tertiary oncological center, the standard of care has been aligned with the guidelines proposed by the European intergroup study of post-induction treatment of ALL Ph+ (EsPhALL). In this study, we aimed to examine the experience and outcomes related to the treatment of pediatric patients with ALL Ph+ at IPOP...

Breakpoint cluster region-Abelson ( BCR::ABL1 ) gene fusion is an essential oncogene in both chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+ ) B-cell acute lymphoblastic leukemia (B-ALL). While tyrosine kinase inhibitors (TKIs) are effective in up to 95% of CML patients, 50% of Ph+ B-ALL cases do not respond to treatment or relapse. This calls for new therapeutic approaches for Ph+ B-ALL. Previous studies have shown that inhibitors of the thioredoxin (TXN) system exert antileukemic activity against B-ALL cells, particularly in combination with other drugs...

Assessment of measurable residual disease (MRD) provides important prognostic information and can inform decision-making about appropriate consolidative therapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Many contemporary treatment protocols for Ph+ ALL achieve high rates of MRD negativity, and several analyses suggest that allogeneic hematopoietic stem cell transplant in first remission can be safely deferred in most patients who achieve MRD negativity by PCR for BCR::ABL1 within 3 months...

The BYOND study evaluated the efficacy and safety of bosutinib 500 mg once daily in patients with chronic myeloid leukemia (CML) resistant/intolerant to prior tyrosine kinase inhibitors (TKIs). These post-hoc analyses assessed the efficacy and safety of bosutinib by resistance or intolerance to prior TKIs (imatinib-resistant vs dasatinib/nilotinib-resistant vs TKI-intolerant), and cross-intolerance between bosutinib and prior TKIs (imatinib, dasatinib, nilotinib), in patients with Philadelphia chromosome-positive chronic phase CML...

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus ...

BACKGROUND: Widespread access to testing is critical to public health efforts to control the COVID-19 pandemic. Secondary distribution of COVID-19 self-test kits, where an individual distributes test kits to others in their social networks, is a potential strategy to improve access to testing. In this qualitative study, we identified salient beliefs about distributing and accepting COVID-19 self-test kits within one's social network, as well as ordering COVID-19 self-test kits from the government...

Childhood acute lymphoblastic leukemia (ALL) has witnessed substantial improvements in prognosis; however, a subset of patients classified as high-risk continues to face higher rates of relapse and increased mortality. While the National Cancer Institute (NCI) criteria have traditionally guided risk stratification based on initial clinical information, recent advances highlight the pivotal role of biological markers in shaping the prognosis of childhood ALL. This review delves into the emerging understanding of high-risk childhood ALL, focusing on molecular, cytogenetic, and immunophenotypic markers...

OBJECTIVE: Despite expanded guidelines, adolescent gonorrhea and chlamydia (GC/CT) screening rates remain low due to multiple psychosocial barriers and biases. This intervention aimed to improve screening and diagnosis rates at adolescent well visits by establishing a streamlined universal screening protocol for all patients ages 13-18 years old. METHODS: A universal sexually transmitted infection (STI) screening approach was introduced at an urban clinic affiliated with an academic medical center near Philadelphia, Pennsylvania (PA) in September 2018 for all adolescent well-visits...

Lack of adherence to antiretroviral therapy (ART) and poor retention in care are significant barriers to ending HIV epidemics. Treatment adherence support (TAS) effectiveness may be constrained by limited awareness and understanding of the benefits of ART, particularly the concepts of treatment as prevention and Undetectable=Untransmittable (U=U), for which substantial knowledge gaps persist. We used mixed methods to evaluate a straightforward visual and tactile tool, the B-OK Bottles ("B-OK"), that incorporates human-centered design and behavioral economics principles and is designed to change and strengthen mental models about HIV disease progression and transmission...

Philadelphia chromosome-positive B cell acute lymphoblastic leukemia (B-ALL), characterized by the BCR::ABL1 fusion gene, remains a poor prognosis cancer needing new therapeutic approaches. Transcriptomic profiling identified up-regulation of oncogenic transcription factors ERG and c-MYC in BCR::ABL1 B-ALL with ERG and c-MYC required for BCR::ABL1 B-ALL in murine and human models. Profiling of ERG- and c-MYC-dependent gene expression and analysis of ChIP-seq data established ERG and c-MYC coordinate a regulatory network in BCR::ABL1 B-ALL that controls expression of genes involved in several biological processes...

Ten cases of small intestinal tympany with or without volvulus were documented in Central American river turtles ( Dermatemys mawii ). These turtles were under managed care at the Philadelphia Zoo in Philadelphia, PA, USA, with one case followed after transfer to a different institution. The primary clinical presentation was abnormal buoyancy in nearly all cases (9/10) and anorexia in two cases (2/10). Five of 10 turtles with suspected or radiographically confirmed small intestinal tympany recovered (5/10), whereas five cases (5/ 10) resulted in death or euthanasia...

We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace Hyper-CVAD cycle 1 when combined with imatinib in adults with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response (MMR) rate measured by BCR::ABL1 quantification after cycle 4 (end of consolidation). All patients were eligible for allogeneic stem cell transplant (SCT), whereas those in MMR could receive autologous SCT, followed by 2-year imatinib maintenance in both cases...

INTRODUCTION: Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by mutations in the survival motor neuron 1 ( SMN1 ) gene. In clinical studies, gene replacement therapy with onasemnogene abeparvovec (formerly AVXS-101, Zolgensma® , Novartis) was efficacious in improving motor functioning in children with SMA. However, its effects on cognitive and language skills are largely unknown. METHODS: This longitudinal observational study evaluated changes in motor and neurocognitive functioning over a 1-year period after administration of onasemnogene abeparvovec in 12 symptomatic SMA type 1 patients with two copies of SMN2 aged 1...

A 25-year-old woman with a history of B-cell acute lymphoblastic leukemia over ten years ago was referred to our hospital with a chief complaint of leukoblastosis. She was participating in a JPLSG (Japanese Pediatric Leukemia/Lymphoma Study Group) clinical study at that time. We diagnosed ALL relapse by multi-color flow cytometric analysis of bone marrow samples at admission, with reference to previous JPLSG data. Because her leukemic cells were resistant to conventional cytotoxic agents, she proceeded to lymphocyte apheresis for chimeric antigen receptor T-cell (CAR-T, Tisagenlecleucel [Tisa-cel])...

A 27-year-old woman with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia received induction therapy with dasatinib and prednisolone. From the time of diagnosis, oocyte storage was planned in accordance with the patient's wishes. After progesterone administration for suppression of menstruation, and blood cell recovery, ovarian stimulation was performed and a sufficient number of eggs was collected. The patient was considered at high risk for ovarian stimulation syndrome (OHSS) and received cabergoline and letrozole...