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Acta Haematologica 2023
High Incidences of Acute and Chronic Graft-Versus-Host Disease after Hematopoietic Cell Transplants for Acute Myeloid Leukemia Using Thiotepa, Busulfan, and Fludarabine Pretransplant Conditioning.
Topics: Humans; Busulfan; Thiotepa; Hematopoietic Stem Cell Transplantation; Bronchiolitis Obliterans Syndrome; Incidence; Leukemia, Myeloid, Acute; Vidarabine; Transplantation Conditioning; Graft vs Host Disease; Retrospective Studies
PubMed: 36446340
DOI: 10.1159/000528306 -
Pediatric Transplantation Mar 2023Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections.... (Review)
Review
BACKGROUND
Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for CID; however, little is known about the necessity and benefits of HSCT in patients with STK4 deficiency.
METHODS
We report two siblings with STK4 deficiency transplanted from two unrelated donors with the same conditioning regimen.
RESULTS
In the conditioning regimen, rituximab was given on Day -11 (375 mg/m ), and sirolimus was added on the same day. Busulfan was administered at a myeloablative dose (3.2 mg/kg; Days -7 to -4) with 150 mg/m of fludarabine (Days -7 to -3). They were transplanted with peripheral blood stem cells, and graft-versus-host disease (GVHD) prophylaxis was administered with 10 mg/m methotrexate on Days 1, 3, and 6. In addition, mycophenolate mofetil (MMF) was started on Day 1 with ongoing use of sirolimus. We did not encounter veno-occlusive disease (VOD), high-grade acute GVHD, or significant organ toxicity in either patient. Both patients were well at the end of the first year after HSCT with complete donor chimerism.
CONCLUSIONS
Serine/threonine kinase 4 deficiency is a disease with high mortality post-HSCT; therefore, the conditioning regimen and GVHD prophylaxis strategies are important considerations in these patients. In our opinion, the conditioning regimen, which includes rituximab and busulfan and fludarabine (BU-FLU), GVHD prophylaxis with sirolimus and MMF, and short-term methotrexate, offers favorable outcomes and is well tolerated in our STK4-deficient patients.
Topics: Humans; Busulfan; Methotrexate; Rituximab; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Sirolimus; Mycophenolic Acid; Unrelated Donors; Protein Serine-Threonine Kinases; Serine; Transplantation Conditioning; Vidarabine; Intracellular Signaling Peptides and Proteins
PubMed: 36394186
DOI: 10.1111/petr.14439 -
American Journal of Hematology Feb 2023
Efficacy of front-line ibrutinib versus fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: A retrospective multicenter "Real-World" study.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Cyclophosphamide; Vidarabine; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36349541
DOI: 10.1002/ajh.26779 -
Bone Marrow Transplantation Jan 2023
Fludarabine- and low-dose cyclophosphamide-based conditioning regimens provided favorable survival and engraftment for unmanipulated hematopoietic cell transplantation from unrelated donors and matched siblings in patients with Fanconi anemia: results from the CBMTR.
Topics: Humans; Fanconi Anemia; Unrelated Donors; Siblings; Hematopoietic Stem Cell Transplantation; Vidarabine; Cyclophosphamide; Transplantation Conditioning; Graft vs Host Disease
PubMed: 36257981
DOI: 10.1038/s41409-022-01838-9 -
Computational and Mathematical Methods... 2022Data from single-cell RNA sequencing (RNA-seq) of CLL patients were obtained from the Gene Expression Omnibus database. The R package was utilized to analyze the data,...
Analysis of Data on Fludarabine, Cyclophosphamide, and Rituximab Chemoimmunotherapy for Chronic Lymphocytic Leukemia Shows High Patient Heterogeneity and the Need for More Consideration of Individualized Treatment.
METHODS
Data from single-cell RNA sequencing (RNA-seq) of CLL patients were obtained from the Gene Expression Omnibus database. The R package was utilized to analyze the data, and the relation of results was predicted via the GeneMANIA website. The information of 7 samples covered three stages: observation stage, pretreatment by CIT with rituximab, fludarabine, and cyclophosphamide (pre-CIT), and post-CIT. The differentially expressed genes (DEGs) were identified, and functional enrichment analyses were performed. B cell subpopulations and pseudotime trajectories analysis was conducted.
RESULTS
A total of 70,659 DEGs were identified. Each patient's DEGs presented their own characteristics, with low similarity. Therefore, it is difficult to identify potential hub genes. Similarly, pathway enrichment analysis showed significant tumor heterogeneity among CLL patients. Analysis of relapsed post-CIT compared to the observation stage suggested that the pathway should be taken seriously as it is closely related to treatment strategy and patient prognosis.
CONCLUSIONS
Tumor heterogeneity may be a more common manifestation of CLL. Individualized treatment should be considered for CLL. abnormality and its regulatory factors should still be the focus of CLL diagnosis and treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Vidarabine
PubMed: 36226246
DOI: 10.1155/2022/7451395 -
Bone Marrow Transplantation Jan 2023For acute lymphoblastic leukemia (ALL) patients, total body irradiation (TBI)- based conditioning regimens are the first choice specially in young population. However,...
Thiotepa, busulfan and fludarabine conditioning-regimen is a promising approach for older adult patients with acute lymphoblastic leukemia treated with allogeneic stem cell transplantation.
For acute lymphoblastic leukemia (ALL) patients, total body irradiation (TBI)- based conditioning regimens are the first choice specially in young population. However, several studies have shown an equivalence in clinical outcomes with thiotepa-based conditioning regimen. We performed a retrospective study to evaluate the outcome of adult ALL patients who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with a thiotepa-busulfan-fludarabine (TBF) myeloablative conditioning regimen with reduced toxicity. Fifty-five patients received a TBF regimen. The median age of the patients was 51 years (range, 17 to 72.4). Most patients had a diagnosis of B-ALL (93%) with 7% having T-ALL. Two - and 5-year overall survival was 73.2% and 64%, respectively. At 2 years, leukemia-free survival and GVHD-free, relapse-free survival were 59.5% and 57.6%, and at 5 years, 53.4% and 51.8%, respectively. The 5-year non-relapse mortality was 15%. The day 180 cumulative incidence (CI) of grade II-IV acute GVHD and grade III-IV acute GVHD were 38.2% and 5.5%, respectively. At 2 years, the CI of chronic GVHD and extensive chronic GVHD was 16.9% and 1.9%, respectively. Our study results do suggest that using TBF as the conditioning regimen in adult ALL patients is a promising option with acceptable toxicity.
Topics: Humans; Aged; Adolescent; Young Adult; Adult; Middle Aged; Busulfan; Thiotepa; Retrospective Studies; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Vidarabine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Graft vs Host Disease; Transplantation Conditioning
PubMed: 36224494
DOI: 10.1038/s41409-022-01841-0 -
ChemMedChem Dec 2022Repurposing of antiviral drugs affords a rapid and effective strategy to develop therapies to counter pandemics such as COVID-19. SARS-CoV-2 replication is closely...
Effects of the 5'-Triphosphate Metabolites of Ribavirin, Sofosbuvir, Vidarabine, and Molnupiravir on CTP Synthase Catalysis and Filament Formation: Implications for Repurposing Antiviral Agents against SARS-CoV-2.
Repurposing of antiviral drugs affords a rapid and effective strategy to develop therapies to counter pandemics such as COVID-19. SARS-CoV-2 replication is closely linked to the metabolism of cytosine-containing nucleotides, especially cytidine-5'-triphosphate (CTP), such that the integrity of the viral genome is highly sensitive to intracellular CTP levels. CTP synthase (CTPS) catalyzes the rate-limiting step for the de novo biosynthesis of CTP. Hence, it is of interest to know the effects of the 5'-triphosphate (TP) metabolites of repurposed antiviral agents on CTPS activity. Using E. coli CTPS as a model enzyme, we show that ribavirin-5'-TP is a weak allosteric activator of CTPS, while sofosbuvir-5'-TP and adenine-arabinofuranoside-5'-TP are both substrates. β-d-N -Hydroxycytidine-5'-TP is a weak competitive inhibitor relative to CTP, but induces filament formation by CTPS. Alternatively, sofosbuvir-5'-TP prevented CTP-induced filament formation. These results reveal the underlying potential for repurposed antivirals to affect the activity of a critical pyrimidine nucleotide biosynthetic enzyme.
Topics: Humans; Ribavirin; Sofosbuvir; Antiviral Agents; SARS-CoV-2; Vidarabine; Escherichia coli; COVID-19; Cytidine
PubMed: 36184568
DOI: 10.1002/cmdc.202200399 -
Bone Marrow Transplantation Dec 2022Different doses of treosulfan plus fludarabine have shown advantage over reduced intensity regimens. However, data comparing higher doses of treosulfan to myeloablative...
Comparative study of treosulfan plus Fludarabine (FT14) with busulfan plus Fludarabine (FB4) for acute myeloid leukemia in first or second complete remission: An analysis from the European Society for Blood and Marrow Transplantation (EBMT) Acute Leukemia Working Party (ALWP).
Different doses of treosulfan plus fludarabine have shown advantage over reduced intensity regimens. However, data comparing higher doses of treosulfan to myeloablative busulfan are limited. Thus, we compared outcomes between FT14 (fludarabine 150/160 mg/m and treosulfan 42 g/m, or FT14) over FB4 (fludarabine 150/160 mg/m and busulfan 12.8 mg/kg). We retrospectively studied patients from European Society for Blood and Marrow Transplantation registry: a) adults diagnosed with acute myeloid leukemia (AML), b) recipients of first allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated or sibling donor (2010-2020), c) HSCT at first or second complete remission, d) conditioning with FT14 or FB4. FT14 recipients (n = 678) were older, with higher rates of secondary AML, unrelated donors, peripheral blood grafts, and adverse cytogenetics, but lower percentage of female donor to male recipient compared to FB4 (n = 2025). Analysis was stratified on age. In patients aged < 55 years, FT14 was associated with higher relapse incidence (RI) and lower Leukemia-Free Survival (LFS). In patients aged≥55 years, acute GVHD CI was higher in FB4, without significant differences in other outcomes. Although FT14 has been used for higher-risk HSCT patients, our large real-world multicenter study suggests that FB4 is associated with better outcomes compared to FT14 in younger patients.
Topics: Adult; Humans; Male; Female; Busulfan; Retrospective Studies; Bone Marrow; Vidarabine; Transplantation Conditioning; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Acute Disease
PubMed: 36138068
DOI: 10.1038/s41409-022-01830-3 -
Bone Marrow Transplantation Dec 2022
Topics: Humans; Pentostatin; Vidarabine; Cyclophosphamide; Transplantation Conditioning; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation
PubMed: 36115868
DOI: 10.1038/s41409-022-01819-y -
Bone Marrow Transplantation Nov 2022
Topics: Humans; Aged; Vidarabine; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Leukemia, Myeloid, Acute; Transplantation Conditioning; Graft vs Host Disease; Busulfan; Retrospective Studies
PubMed: 36097041
DOI: 10.1038/s41409-022-01821-4