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Blood rheology after allogeneic hematopoietic stem cell transplantation or gene therapy in sickle cell disease.

Allogeneic hematopoietic cell transplantation (HCT) and autologous hematopoietic stem cell-based gene therapies are potentially curative for sickle cell disease (SCD). Although most patients experience resolution of overt clinical symptoms associated with SCD with donor-dominant myeloid chimerism after undergoing HCT or the induction of a substantial amount of alternative hemoglobin (Hb) after gene therapy (GT), whether the underlying subclinical physiology is normalized in these individuals is unknown. One approach to evaluating the underlying physiology is to characterize the blood rheology …

Autologous stem cell transplantation meets CAR-T therapy: A synergistic strategy for B-cell lymphoma.

B-cell lymphoma, the most common subtype of non-Hodgkin lymphoma, presents major therapeutic challenges due to molecular heterogeneity and high relapse rates. While autologous hematopoietic stem cell transplantation (ASCT) has been a cornerstone for relapsed/refractory (R/R) B-cell lymphoma, its efficacy is often compromised by minimal residual disease (MRD) persistence and an immunosuppressive tumor microenvironment. Chimeric antigen receptor (CAR)-T cell therapy has transformed treatment paradigms but faces limited long-term durability due to antigen escape and T-cell exhaustion. The integra…

Comprehensive risk stratification for adult T-cell lymphoblastic lymphoma undergoing allogeneic haematopoietic stem cell transplantation.

Relapse remains the primary cause of transplant failure in T-cell lymphoblastic lymphoma (T-LBL) after allogeneic haematopoietic stem cell transplantation (allo-HSCT), yet prognostic data are scarce. We conducted a multicentre retrospective study of 104 adult T-LBL patients in complete metabolic remission (CMR) undergoing allo-HSCT. Pretransplant Deauville score (DS) was evaluated, and a risk model integrating DS, immunophenotype and donor type was developed. Patients with DS of 3 had significantly inferior 2-year overall survival (OS) (70.5% vs. 77.4% vs. 86.8%, p < 0.001), progression-free s…

Bridging therapy with valemetostat to allogeneic hematopoietic cell transplantation for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus-1. Patients diagnosed with aggressive ATL have a poor prognosis. As response duration to conventional multiagent chemotherapy is short, upfront allogeneic hematopoietic cell transplantation (allo-HCT) is recommended. As disease status at the time of allo-HCT is the primary prognostic factor, bridging therapy to allo-HCT is sometimes necessary during donor coordination. However, conventional chemotherapies are often toxic, particularly for older patients and those with inadequate hematop…

CD56bright NK cell expansion correlated with EBV reactivation control post allogeneic hematopoietic stem cell transplantation.

Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however, whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 11 patients who occurred EBV reactivation post allo-HSCT and 11 patients without EBV infection as control. We found that that EBV infection induced the expansion of CD56bright and NKG2A+KIR- NK subsets,and decreased the cytotoxicity function of NK cells. The frequency of NKG2A+KIR- NK cells …

Insights into cytomegalovirus-associated T cell receptors in recipients following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) reactivation is a serious problem in recipients of allogeneic hematopoietic stem cell transplantation. Long-term latency depends on specific T cell immune reconstitution, which identifies various pathogens by T cell receptors (TCRs). However, the mechanisms underlying the selection of CMV-specific TCRs in recipients after transplantation remain unclear. METHODS: Using high-throughput sequencing and bioinformatics analysis, the T cell immune repertoire of seven CMV reactivated recipients (CRRs) were analyzed and compared to those of seven CMV non-activated rec…

Myelodysplastic syndrome following chimeric antigen receptor T-cell therapy treated with allogenic stem cell transplantation.

Chimeric antigen receptor (CAR) T-cell therapy is currently approved for the treatment of B-cell non-Hodgkin lymphomas and B-cell acute lymp … ng the follow-up, the diagnosis of MDS was made. The patient underwent allogenic hematological stem cell transplantation. The patient remains in complete remission of his lymphoma and MDS 19 months after hematological stem cell transplantation.

Disseminated Invasive Mucormycosis Infection Following Autologous Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma.

Invasive fungal infections (IFI) are challenging to predict, diagnose and treat, and are associated with a particularly high mortality among patients with hematological malignancies. They are relatively uncommon in patients with lymphoma, compared with those with acute leukemia or undergoing allogeneic transplantation. We present a patient, autografted for recurrent lymphoma, with fever and refractory diarrhea persisting post engraftment, eventually attributable to disseminated mucor infection. This case illustrates the challenge of timely diagnosis and initiation of treatment for IFI in lymph

Hematopoietic stem cell mobilization for allogeneic stem cell transplantation by motixafortide, a novel CXCR4 inhibitor.

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… TO THE EDITOR: Granulocyte colony-stimulating factor (G-CSF) is the most common agent used for mobilizing peripheral blood (PB) hematopoietic stem and progenitor cells (HSPCs) for allogeneic hematopoietic cell transplantation (allo-HCT). … transplantation in patients with multiple myeloma Blood 113 23 2009 5720 5726 19363221 10.1182/blood-2008-08-174946 11 Schroeder MA Rettig MP Lopez S Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft Blood 129 19 2017 2680 2692 28292947 …

What is the role of up-front autologous stem cell transplantation in mantle cell lymphoma?

Up-front autologous stem cell transplantation (ASCT) is the established standard of care for younger, transplant-eligible MCL patients and is associated with a prolonged progression-free survival (PFS) benefit. However, there is no randomized controlled trial data, with therapy including rituximab and cytarabine, that has established a PFS and overall survival (OS) benefit with ASCT in the modern era. Multiple retrospective studies have failed to identify an OS benefit associated with ASCT in younger MCL patients. The high-risk patient subgroup with evidence of baseline TP53 mutation has a dis…

Retrospective analysis of hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: conditioning intensity matters.

Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare myeloid malignancy with a generally poor prognosis. Although preliminary evidence suggests that hematopoietic cell transplantation (HCT) could improve outcome in patients with BPDCN, the individual contributions of conditioning and graft-versus-tumor (GVT) effects to HCT success are undefined. We present a retrospective study of 162 adult patients who underwent a first HCT (allogeneic 146, autologous 16) between 2009 and 2017, and were registered with the EBMT. Median age was 57 (range 20-73) years, and disease status at HCT was f…

Hepatosplenic T-Cell Non-Hodgkin Lymphoma Cured with Tandem Autologous and Allogeneic Stem Cell Transplantation.

Hepatosplenic T-cell lymphoma is a very difficult lymphoma to deal with, almost impossible to cure. "Tandem" consolidation therapy with auto-stem cell transplant and allo-stem cell transplant can induce a long-lasting response and potentially cure this disease.

Immunoprofiling reveals cell subsets associated with the trajectory of cytomegalovirus reactivation post stem cell transplantation.

Human cytomegalovirus reactivation is a major opportunistic infection after allogeneic haematopoietic stem cell transplantation and has a complex relationship with post-transplant immune reconstitution. Here, we use mass cytometry to define patterns of innate and adaptive immune cell reconstitution at key phases of human cytomegalovirus reactivation in the first 100 days post haematopoietic stem cell transplantation. Human cytomegalovirus reactivation is associated with the development of activated, memory T-cell profiles, with faster effector-memory CD4+ T-cell recovery in patients with low-l…

Haploidentical Allogeneic Stem Cell Transplantation in Sickle Cell Disease: A Systematic Review and Meta-Analysis.

Allogeneic hematopoietic stem cell transplantation (SCT) is the sole established curative treatment option for patients with sickle cell disease (SCD). However, a lack of HLA-identical sibling donors is a limiting factor. Haploidentical related donors are a promising donor pool, potentially extending SCT as a curative treatment option to a larger group of patients with no other meaningful treatment options for their severe SCD. In the present study, we aimed to systematically review the results of haploidentical SCT in patients with SCD. A comprehensive search was performed in MEDLINE/PubMed a…

Targeted recruitment of optimal donors for unrelated hematopoietic cell transplantation: The Stem Cell Club process.

OBJECTIVE/BACKGROUND: Patients in need of hematopoietic stem cell transplantation often cannot find a suitable HLA-matched donor in their families and rely on unrelated donors. Individuals can register with their country's donor registry either online or at a stem cell drive by providing consent and a tissue sample for typing. METHODS: Stem Cell Club is a donor recruitment organization in Canada that recruits Canadians as stem cell donors. This article outlines the Stem Cell Club's protocol for donor recruitment at stem cell drives including five core components: prescreening, informed consen…

Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era.

The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression-free survival (PFS) 17% (13-23%), and overall survival (OS) 28% (22-35%). Karnofsky performance sta…

A case of hepatosplenic T-cell lymphoma successfully treated by HLA haploidentical stem cell transplantation.

We report a case of hepatosplenic T-cell lymphoma (HSTL) transplanted from an HLA-haploidentical daughter. A 51-year-old man was referred due to liver function test abnormalities and fever. He was confirmed to have γδ-type HSTL by bone marrow and liver biopsies. He was treated with five cycles of a CHOP regimen. Although metabolic complete response (CR), as defined by positron emission tomography, was achieved, his bone marrow still contained tumor cells on polymerase chain reaction (PCR). He underwent transplantation using unmanipulated peripheral blood stem cells from his HLA-haploidentical

Body mass index does not impact hematopoietic progenitor cell mobilization for autologous hematopoietic cell transplantation.

BACKGROUND: Obesity has implications for hematopoietic progenitor cell (HPC) mobilization, chemotherapy administration, and medication dosing. We analyzed the impact of obesity on HPC mobilization as well as key outcomes that are associated with cell dose in autologous hematopoietic cell transplantation (AHCT) recipients. METHODS: We conducted a retrospective cohort study on 556 consecutive eligible AHCT recipients at our institution from 1/2004 to 12/2009. Patients were categorized into four groups based on the body mass index (BMI): underweight (BMI < 18.5), normal (18.5-24.9), overweight (…