The efficacy of targeted and immune-based therapies in adults with TP53-mutated acute lymphoblastic leukaemia.

We retrospectively evaluated the treatment outcomes of 47 adult patients with TP53-mutated acute lymphoblastic leukaemia (ALL) treated with either blinatumomab, inotuzumab or/and CD19 CAR T-cell therapy. The complete remission with or without count recovery (CR/CRi) (negative minimal residual disease (MRD-) rate) following treatment with blinatumomab (n = 46), inotuzumab (n = 26) and CD19 CAR T cells (n = 6) was 58.7% (96.

Extramedullary sites of disease in B-cell acute lymphoblastic leukemia: incidence, biology, and treatment.

Treatment outcomes of relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) have improved with the introduction of targeted agents and immunotherapeutics that allow successful bridging to allogeneic hematopoietic cell transplantation. Nonetheless, the risk of subsequent relapse remains significant. Although the most common site of relapse after salvage therapies is the bone marrow, extramedullary relapse is increasingly reported both in the central nervous system (CNS) and in non-CNS sites, especially after treatment with blinatumomab.

Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial.

Background: Two doses of subcutaneous blinatumomab in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia were identified as preliminary recommended phase 2 doses, based on the dose-escalation phase of this multicentre single-arm, phase 1/2 trial. Here, we aim to further study the safety, activity, and pharmacokinetics of these doses in all participants who have received them, including those treated in the completed phase 1b expansion part of the study.

Methods: We did a post-hoc analysis of data from patients enrolled in the dose-escalation and dose-expansion phases and in the pharmacokinetic evaluation cohort of this multicentre, single-arm, phase 1/2 study.

The integration of blinatumomab consolidation in the CALGB 10403 regimen for adults with B-cell precursor acute lymphoblastic leukaemia in measurable residual disease-negative remission.

Blinatumomab consolidation was recently approved for patients with acute lymphoblastic leukaemia (ALL) who achieve measurable residual disease (MRD) negative remission based on the survival benefit yielded in the E1910 trial. The CALGB 10403 (C10403) is the most frequently used paediatric inspired regimen for young adults treated in the United States; however, data and guidance on how to best incorporate blinatumomab consolidation into the C10403 regimen are lacking. Here, we describe our experience of adding blinatumomab consolidation to the C10403 regimen per our institutional consensus.

The Role of Transplant for Philadelphia-positive B-cell Acute Lymphoblastic Leukemia in 2025.

Purpose Of Review: This review expands upon the evolving role of allo-HSCT, integrating current clinical evidence, emerging therapies, and novel risk-adapted strategies for managing adult with Ph + ALL in the contemporary era.

Recent Findings: Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia (ALL) is the most common genetically defined subtype of B-cell ALL. The treatment of Ph + ALL has witnessed significant advancements over the past two decades following the introduction of BCR::ABL1 tyrosine kinase inhibitors (TKIs).

Optimizing stroke lesion segmentation: A dual-approach using Gaussian mixture models and nnU-Net.

Machine learning-based stroke lesion segmentation models are widely used in biomedical imaging, but their ability to detect treatment effects remains largely unexplored. Gaussian Mixture Models (GMM) and nnU-Net are among the most prominent and well-established segmentation workflows. GMM has been widely used for probabilistic tissue classification for decades, while nnU-Net has established itself as a leading deep learning framework for biomedical image segmentation, with hundreds of applications in preclinical and clinical research.

Hypomethylating agent and venetoclax are effective salvage therapies in relapsed/refractory early T-cell precursor acute lymphoblastic leukaemia.

Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a distinct biological subtype of T-ALL and is associated with poor clinical outcomes due to the lack of effective salvage regimens that can induce remission and bridge patients to allogeneic stem cell transplantation. Targeting antiapoptotic BCL-2 family proteins has demonstrated therapeutic efficacy in ETP-ALL with agents such as venetoclax. We present a case series of five adult patients with relapsed or refractory (R/R) ETP-ALL who were treated with a hypomethylating agent (HMA) in combination with venetoclax (HMA-VEN) and demonstrate that this therapy is efficacious and can bridge responders to allogeneic stem cell transplantation with curative intent.

Impact of hyperhydration on fluid overload and hematopoietic cell transplant after post-transplant cyclophosphamide-based graft-versus-host-disease prophylaxis.

Introduction: Hemorrhagic cystitis (HC) is an early complication after hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy). Hyperhydration can reduce HC, but may lead to fluid overload (FO), which has been associated with higher non-relapse mortality (NRM) after HCT.

Methods: The objectives of this study were to grade FO between days 3 and 8 based on weight gain, diuretic therapy, and FO-related organ dysfunction and analyze the impact of FO on non-relapse mortality (NRM) and subsequently on overall survival (OS) of patients undergoing HCT with PTCy-based GvHD prophylaxis.

Melphalan-based conditioning with post-transplant cyclophosphamide for peripheral blood stem cell transplantation: donor effect.

Fludarabine and melphalan (FM) conditioning offers effective disease control with an acceptable toxicity profile. Post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has improved transplant outcomes. We retrospectively reviewed patients receiving FM-based transplants with PTCy at City of Hope.

TP53 mutations are associated with CD19- relapse and inferior outcomes after blinatumomab in adults with ALL.

Despite the success of the CD19 × CD3 T-cell engager blinatumomab in B-cell acute lymphoblastic leukemia (B-ALL), treatment failure is common and can manifest with antigen loss and extramedullary disease (EMD) relapse. To understand the impact of leukemia genetics on outcomes, we reviewed 267 adult patients with B-ALL treated with blinatumomab and used next-generation sequencing to identify molecular alterations. Patients received blinatumomab for relapsed/refractory (R/R) disease (n = 150) and minimal residual disease (MRD; n = 88), upfront as induction (n = 10) or as consolidation in MRD-negative state (n = 19).

Donor regulatory T-cell therapy to prevent graft-versus-host disease.

Allogeneic hematopoietic cell transplantation is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies, enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity. We enrolled 44 patients in an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg therapy manufactured from donor-mobilized peripheral blood improves 1-year GVHD-free relapse-free survival (GRFS) after myeloablative conditioning.

Fludarabine melphalan reduced intensity conditioning vs radiation-based myeloablative conditioning in patients undergoing allogeneic transplantation for acute myeloid leukemia with measurable residual disease.

Patients with AML and measurable residual disease (MRD) undergoing allogeneic hematopoietic cell transplantation (HCT) may benefit from myeloablative conditioning (MAC) when feasible to reduce relapse risk. Fludarabine-Melphalan (FluMel) is a common reduced intensity conditioning (RIC) regimen; however, data in MRD+ patients is sparse. We performed a retrospective review of AML patients who underwent their first HCT (2016-2021) without morphologic disease at City of Hope who had pre-transplant marrow evaluated for MRD using multicolor flow cytometry (MFC) and received radiation-based MAC or FluMel conditioning.

Combined Cytokine Blockade Therapy (CCBT) Using Basiliximab and Infliximab for Treatment of Steroid-Refractory Graft-Versus-Host Disease (SR-GvHD).

Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature.

Methods: Sixty patients with steroid-refractory aGVHD were analyzed.

Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia.

BCL-2 protein overexpression, common in B-cell acute lymphoblastic leukemia (B-ALL), including the Philadelphia chromosome (Ph)-like subtype, mediates leukemic cell survival. We treated 24 patients with 14 days of BCL-2 inhibitor, venetoclax, 400 mg daily (dose level 1) during induction and consolidation cycles combined with the CALGB 10403 regimen in newly diagnosed adults with Ph-negative B-ALL. Median age was 31 years (range: 18-53), 92% were Hispanic, and 12 (50%) patients had Ph-like ALL.

Delaying pegaspargase during induction in adults with acute lymphoblastic leukaemia is associated with lower risk of high-grade hepatotoxicity without adversely impacting outcomes.

Pegaspargase is a key drug for the treatment of younger adults with acute lymphoblastic leukaemia (ALL). Pegaspargase-associated hepatotoxicity is most common during induction, and its incidence increases with age and body mass index (BMI). We hypothesized that the delayed administration of pegaspargase during induction is associated with lower risk of hepatotoxicity while retaining efficacy.

Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation.

Introduction: Allogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes.

Clinical review of substitutions or alternatives for critical chemotherapy drug shortages in hematologic malignancies.

Purpose: Over the past decade, drug shortages have become increasingly more problematic for clinicians, with over 300 drug shortages reported in the first quarter of 2023. Shortages of chemotherapy drugs can have a negative impact on patient care, as omission or delay of treatment can lead to worse outcomes. Although many articles have been published on this topic, currently no review articles discuss strategies for using alternative regimens or substitutions in the event of severe chemotherapy drug shortages.

Comparing transplant outcomes in ALL patients after myeloablative conditioning in mismatch-related or unrelated donor settings.

The optimal myeloablative conditioning regimen for ALL patients undergoing hematopoietic cell transplant (HCT) with an alternative donor is unknown. We analyzed HCT outcomes ALL patients (n = 269) who underwent HCT at our center from 2010 to 2020 in complete remission (CR) after FTBI-etoposide and CNI-based GvHD prophylaxis for matched donor HCT (ETOP-package; n = 196) or FTBI-Fludarabine and post-transplant cyclophosphamide (PTCy)-based prophylaxis for HLA- mismatched (related or unrelated) donors (FLU-package; n = 64). Patients in FLU-package showed a significant delay in engraftment (p < 0.

Total Body Irradiation and Fludarabine with Post-Transplantation Cyclophosphamide for Mismatched Related or Unrelated Donor Hematopoietic Cell Transplantation.

Allogeneic hematopoietic cell transplantation (HCT) remains the sole curative treatment for most patients with hematologic malignancies. A well-matched donor (related or unrelated) remains the preferred donor for patients undergoing allogeneic HCT; however, a large number of patients rely on alternative donor choices of mismatched related (haploidentical) or unrelated donors to access HCT. In this retrospective study, we investigated outcomes of patients who underwent mismatched donor (related or unrelated) HCT with a radiation-based myeloablative conditioning MAC regimen in combination with fludarabine, and post-transplantation cyclophosphamide (PTCy) as higher-intensity graft-versus-host disease (GVHD) prophylaxis.