Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies.

The anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models.

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 (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 (range: 18-53) years, 92% were Hispanic, and 12 (50%) patients had Ph-like ALL.

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.

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.

Impact of Antifungal Prophylaxis Continuation or Discontinuation After Allogeneic Hematopoietic Cell Transplant on the Incidence of Invasive Mold Infection.

Background: Continuing antifungal prophylaxis (AFPx) to prevent invasive mold infections (IMIs) in recipients of allogeneic hematopoietic cell transplantation (alloHCT) after primary hospital discharge from alloHCT admission varies among transplant centers despite recommendations to continue prophylaxis through day +75. Characteristics driving AFPx prescribing at hospital discharge and outcomes are unknown.

Methods: In this retrospective analysis, we reviewed patients continuing AFPx vs no AFPx at hospital discharge.

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.

Outcomes of children treated for relapsed or refractory acute lymphoblastic leukemia: A single tertiary care center experience.

Background: Acute lymphoblastic leukemia (ALL) is one of the most common malignancies among children. Despite success in frontline treatment, 20% of children will relapse or show resistance to treatment.

Aim: The aim of this study is to evaluate the clinical characteristics of children diagnosed and treated for refractory or relapsed ALL and determine 3-year overall survival (OS) outcomes.

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors.

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.

Risk prediction for clonal cytopenia: multicenter real-world evidence.

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history.

Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD.

Acute graft-versus-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as the Minnesota risk identify standard and high-risk categories but lack a low-risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low-risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model's prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts.

Consolidation with First and Second Allogeneic Transplants in Adults with Relapsed/Refractory B-ALL Following Response to CD19CAR T Cell Therapy.

CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR-T therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT). Considering the limited published data for the utility of post CAR-T therapy consolidative alloHCT in r/r B-ALL, especially data related to patients receiving a second alloHCT, we sought to describe outcomes of patients with r/r B-ALL at our institution who received their first or second alloHCT following response to CAR-T therapy.

Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but published clinical experience is primarily with the first-generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope.

Implications and Optimization of Domain Structures in IV-VI High-Entropy Thermoelectric Materials.

High-entropy semiconductors are now an important class of materials widely investigated for thermoelectric applications. Understanding the impact of chemical and structural heterogeneity on transport properties in these compositionally complex systems is essential for thermoelectric design. In this work, we uncover the polar domain structures in the high-entropy PbGeSnSeTe system and assess their impact on thermoelectric properties.

Bone Marrow Harvest: A White Paper of Best Practices by the NMDP Marrow Alliance.

Data on recent bone marrow harvest (BMH) collections from the NMDP has shown that bone marrow (BM) quality has decreased based on total nucleated cell count in the product. To ensure that quality BM products are available to all recipients, the NMDP Marrow Alliance was formed in April 2021 to increase the capability of BM collection centers to safely deliver high-quality products consistently and to identify and disseminate guidelines for performing BMH. This white paper describes the best practices for BMH as defined by the NMDP Marrow Alliance.

Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD.

Graft-versus-host disease (GVHD) is a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Algorithms containing either the gastrointestinal (GI) GVHD biomarker amphiregulin (AREG) or a combination of 2 GI GVHD biomarkers (suppressor of tumorigenicity-2 [ST2] + regenerating family member 3 alpha [REG3α]) when measured at GVHD diagnosis are validated predictors of NRM risk but have never been assessed in the same patients using identical statistical methods. We measured the serum concentrations of ST2, REG3α, and AREG by enzyme-linked immunosorbent assay at the time of GVHD diagnosis in 715 patients divided by the date of transplantation into training (2004-2015) and validation (2015-2017) cohorts.