Publications by authors named "Pinilla-Ibarz J"

Transcription factors control genes to maintain normal hemopoiesis, and dysregulation of some factors can lead to acute lymphoblastic leukemia (ALL). Mycoviruses are known to alter the genetics of their fungal host. The present study evaluates the effects of the products of a mycovirus-containing (MCAF), isolated from the home of a patient with ALL, on certain transcription factors of normal and ALL cell lines.

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  • * Patients reported improvements in physical functioning and fatigue within a year post-treatment, but indicators of pain, anxiety, and depression remained stable or worsened in those with active disease.
  • * While overall toxicity decreased for the first 180 days, it increased again by day 360; prior therapies influenced worsening pain and anxiety in patients with extensive treatment histories.
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  • Preclinical studies have shown that in vitro-differentiated Th17 cells can be effective in solid tumors, but their potential in enhancing adoptive cell therapy (ACT) for hematological cancers like chronic lymphocytic leukemia (CLL) is not yet explored.
  • CLL, a type of B-cell cancer, faces issues with resistance to targeted therapies, and existing T-cell treatments like CAR T cells have seen limited success due to T-cell dysfunction and immunosuppressive responses.
  • This research highlights the successful polarization of CD4 T cells into a Th17 phenotype from a CLL mouse model, demonstrating improved memory properties and persistence in treating leukemia, marking a significant step towards enhancing ACT efficacy in CLL with Th17 CAR T
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Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch.

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  • Advancements in CLL/SLL treatments have led to a study exploring a new frontline therapy combining high-dose methylprednisolone, ofatumumab, and lenalidomide for treatment-naive patients.
  • In a phase 2 study involving 45 patients, the treatment showed a 96% overall response rate and a median progression-free survival of 54.4 months, with 29% achieving a complete response.
  • Although the treatment was generally well tolerated, with manageable side effects, the effectiveness compared to existing treatments remains uncertain, highlighting the need for further research in the frontline setting.
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  • Ponatinib is a third-generation tyrosine-kinase inhibitor (TKI) effective against all known resistance mutations of the BCR::ABL1 gene, showing strong results in chronic-phase chronic myeloid leukemia (CP-CML) patients resistant to other TKIs in the PACE trial.
  • The OPTIC trial introduced a response-based, dose-reduction strategy for ponatinib and assessed its efficacy and safety among patients with CP-CML and multiple TKI resistance or T315I mutation.
  • Results indicated that the lower dosing strategy in OPTIC led to improved treatment tolerance, lower cardiovascular risks, and similar or better patient outcomes compared to the PACE trial.
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  • - The study investigates the challenges faced by patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T-cell therapy, highlighting poor outcomes associated with this treatment.
  • - Researchers identified specific serum proteins linked to severe immune-related toxicities and worse clinical responses, leading to a new risk stratification tool using pre-lymphodepletion C reactive protein (CRP) and ferritin levels.
  • - Validated with international cohorts, the findings suggest that this easy-to-use model can effectively classify patients by risk and improve decision-making for CAR T-cell therapy, optimizing patient selection.
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Importance: Patients with chronic myeloid leukemia (CML) who have a sustained deep molecular response using tyrosine kinase inhibitors (TKIs) can safely attempt to stop their use. As these medications are very costly, this change in treatment protocols may result in large savings.

Objective: To estimate future savings from attempting to stop TKI use among patients with CML who have deep molecular response.

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  • The study investigates the relationship between non-melanoma skin cancers (keratinocyte carcinomas) and survival rates in patients with melanoma and chronic lymphocytic leukemia (CLL), focusing on the co-occurrence of these cancers.
  • Utilizing a retrospective cohort approach from 2008 to 2020, researchers analyzed patient data to examine the impact of keratinocyte carcinoma history on survival outcomes for both melanoma and CLL.
  • Results indicated that a history of keratinocyte carcinoma was linked to better survival rates for the first four years after a melanoma diagnosis, but did not significantly affect CLL survival, highlighting the need for further research on blood parameters related to these conditions.
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The Virtual Opinions poll Independent Centered on CLL patients' Experience (VOICE) evaluated patients' knowledge about chronic lymphocytic leukemia (CLL), their perspectives on diagnosis and treatment, and their unmet needs. Clinicians and patient advocacy group representatives developed and distributed the survey from March through December 2022 in 12 countries, and 377 patients with ≥1 line of previous CLL treatment responded from Europe, Latin America, the United States, Australia, Egypt, and Turkey. A majority of them (90%; 336/374) relied on their physicians for information regarding CLL and treatment.

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The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and 29 932 CD3+CD4+ and CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-sequencing of 26,411 CD3+CD4+ and CD26+/CD7+ and 33 841 CD3+CD4+ and CD26-/CD7- lymphocytes, we show that tumor cells in Sézary syndrome and mycosis fungoides (MF) exhibit different phenotypes and trajectories of differentiation. When compared to MF, Sézary cells exhibit narrower repertoires of TCRs and exhibit clonal enrichment.

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  • CD19-directed CAR T cell therapy (axi-cel and tisa-cel) is approved for treating various types of large B cell lymphoma (LBCL) but not specifically for transformed nonfollicular lymphomas (tNFLs).
  • A retrospective study evaluated the effectiveness of these therapies in tNFL patients treated at Moffitt Cancer Center from 2017 to 2021, analyzing outcomes in different lymphoma types.
  • Overall response rates for tCLL/SLL and tMZL were 66.7% and 92.9%, respectively, with no significant differences in progression-free survival between tNFL and DLBCL/tFL groups
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Immune thrombocytopenia (ITP) is a known autoimmune complication of chronic lymphocytic leukemia (CLL). Currently, there is limited data regarding the risk CLL confers on hospitalization outcomes in patients admitted with ITP.The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases (ICD) codes to identify hospitalizations for ITP and then subclassified the data into hospitalizations with and without CLL.

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Tyrosine kinase inhibitor therapy revolutionized chronic myeloid leukemia treatment and showed how targeted therapy and molecular monitoring could be used to substantially improve survival outcomes. We used chronic myeloid leukemia as a model to understand a critical question: why do some patients have an excellent response to therapy, while others have a poor response? We studied gene expression in whole blood samples from 112 patients from a large phase III randomized trial (clinicaltrials gov. Identifier: NCT00471497), dichotomizing cases into good responders (BCR::ABL1 ≤10% on the International Scale by 3 and 6 months and ≤0.

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  • * In CLL, patients exhibit elevated levels of Th17 cells and interleukin 17, which relate to disease progression, prognosis, and changes in the tumor microenvironment compared to healthy individuals.
  • * The review emphasizes the need for further study on how Th17 cells influence CLL and discusses their potential in therapies, aiming to improve immune balance and treatment outcomes for patients.
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  • - Ponatinib is a third-generation drug that effectively treats chronic-phase chronic myeloid leukemia (CP-CML) patients who didn't respond to previous second-generation treatments, including those with the tough T315I mutation.
  • - Results from the PACE and OPTIC trials showed that after 24 months, a significant percentage of patients achieved a favorable response (≤1% BCR::ABL1), with overall survival rates being 85% in PACE and 91% in OPTIC.
  • - The OPTIC trial's dose-reduction strategy enhanced safety outcomes without sacrificing effectiveness, resulting in fewer serious side effects compared to PACE while maintaining robust efficacy rates.
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Activation-induced cytidine deaminase (AID) has been implicated as both a positive and a negative factor in the progression of B cell chronic lymphocytic leukemia (CLL), but the role that it plays in the development and progression of this disease is still unclear. We generated an AID knockout CLL mouse model, AID/Eμ-TCL1, and found that these mice die significantly earlier than their AID-proficient counterparts. AID-deficient CLL cells exhibit a higher ER stress response compared to Eμ-TCL1 controls, particularly through activation of the IRE1/XBP1s pathway.

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Regulatory T cells (Tregs) are responsible for maintaining immune homeostasis by controlling immune responses. They can be characterized by concomitant expression of FoxP3, CD25 and inhibitory receptors such as PD-1 and CTLA-4. Tregs are key players in preventing autoimmunity and are dysregulated in cancer, where they facilitate tumor immune escape.

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CD19 targeted chimeric antigen receptor-modified T cell therapy (CAR-T) leads to B cell aplasia and low serum immunoglobulin levels. Long-lived CD19-negative plasma cells may persist through the therapy and generate antibodies. There is a paucity of data describing how CAR-T impacts the persistence of antibodies against vaccine-related antigens and the degree to which CAR-T recipients may respond to vaccines.

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Introduction: Frontline treatment of hairy cell leukemia (HCL) with a single course of the purine nucleoside analog (PNA) produces a high rate of complete remission (CR) with prolonged durations. At the time of relapse, although treatment guidelines recommend re-treatment with a PNA alone or in combination with rituximab (R), practice patterns vary and data supporting each approach are limited.

Methods: We conducted a multisite outcomes analysis of patients treated for HCL between 1995 and 2018 at six US medical centers.

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Background: The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used.

Methods: To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions.

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