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British Journal of Haematology Jul 2023
Topics: Child; Humans; Idarubicin; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Granulocyte Colony-Stimulating Factor; Vidarabine
PubMed: 37129267
DOI: 10.1111/bjh.18844 -
Bone Marrow Transplantation Feb 2024Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic...
Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.
Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m. We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT.
Topics: Humans; Adult; Melphalan; Carmustine; Thiotepa; Busulfan; Antineoplastic Combined Chemotherapy Protocols; Transplantation Conditioning; Transplantation, Homologous; Leukemia, Myeloid, Acute; Recurrence; Pathologic Complete Response; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Alkylating Agents; Retrospective Studies; Vidarabine
PubMed: 38040842
DOI: 10.1038/s41409-023-02150-w -
Experimental and Clinical... Nov 2023Allogeneic hematopoietic stem cell transplant is the only curative treatment for patients with transfusion-dependent thalassemia major. In recent years, a number of...
Busulfan-Based and Treosulfan-Based Myeloablative Conditioning for Allogeneic Transplantation in Children with Thalassemia Major: a Single-Center Experience From Southern Turkey.
OBJECTIVES
Allogeneic hematopoietic stem cell transplant is the only curative treatment for patients with transfusion-dependent thalassemia major. In recent years, a number of novel approaches have improved patient outcomes and quality of life by minimizing the toxicity of conditioning regimens. The objective of this study was to compare the role of treosulfan- and busulfan-based conditioning in transfusion-dependent thalassemia.
MATERIALS AND METHODS
Data were collected retrospectively on 121 children with beta thalassemia major who underwent hematopoietic stem cell transplant using treosulfan-based (n = 37) or busulfan-based (n = 84) conditioning regimens between 2012 and 2022.
RESULTS
Two-year overall survival was 87.5% in the busulfan-based conditioning group and 91.1% in the treosulfan-based conditioning group.The group given the busulfan regimen compared with treosulfan regimen had significantly increased number of side effects (58.3% vs 21.6%, respectively; P < .001). When the busulfan-based regimen by level was evaluated, we observed no significant differences between the frequency of side effects according to drug serum levels. In addition, no significant differences were shown between the 2 regimen groups for cumulative incidence of acute and chronic graft-versus-host disease.
CONCLUSIONS
The safety and effectiveness of a treosulfan-based myeloablative conditioning regimen has been confirmed by ourretrospective investigation of pediatric patients with beta thalassemia.
Topics: Humans; Child; Busulfan; beta-Thalassemia; Retrospective Studies; Quality of Life; Turkey; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease; Vidarabine
PubMed: 38140932
DOI: 10.6002/ect.2023.0143 -
International Journal of Hematology Jan 2024Various reduced-intensity conditioning (RIC) regimens are used to decrease toxicity while providing comparable outcomes to myeloablative regimens. We compared toxicity...
Fludarabine melphalan versus fludarabine treosulfan for reduced intensity conditioning regimen in allogeneic hematopoietic stem cell transplantation: a retrospective analysis.
Various reduced-intensity conditioning (RIC) regimens are used to decrease toxicity while providing comparable outcomes to myeloablative regimens. We compared toxicity and outcomes between two RIC regimens, fludarabine with melphalan (Flu-Mel) and fludarabine with treosulfan (Flu-Treo), retrospectively over a 10-year period in two donor groups, matched related donor (MRD)/matched unrelated donor (MUD) and haploidentical (Haplo) transplants. The study included 138 patients, of which 105 received MRD/MUD (Flu-Mel: 94, Flu-Treo: 11) and 33 Haplo (Flu-Mel: 17, Flu-Treo: 16) transplants. In the MRD/MUD group, 44 (47%) of patients who received Flu-Mel had grade 3/4 oral mucositis compared to 1 (9%) who received Flu-Treo (P = 0.02). Corresponding numbers in the Haplo group were 7 (41%) and 1 (6%). Grade 3/4 diarrhoea was more frequent with Flu-Mel than Flu-Treo in the Haplo group (41% vs 6%; P = 0.039), but not the MRD/MUD group. Median follow-up time for all patients was 4.8 years. Five-year OS in the MRD/MUD group was 62% with Flu-Mel versus 53% with Flu-Treo (P = 0.0694). Similarly, 5-year OS was 41% with Flu-Mel and 28% with Flu-Treo (P = 0.770) in the Haplo group. Severe mucositis and diarrhoea were significantly less frequent with Flu-Treo than Flu-Mel. Flu-Treo provided comparable outcomes to Flu-Mel in all donor transplants.
Topics: Humans; Melphalan; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Vidarabine; Unrelated Donors; Transplantation Conditioning; Diarrhea; Graft vs Host Disease
PubMed: 37952243
DOI: 10.1007/s12185-023-03674-z -
Methods in Molecular Biology (Clifton,... 2024Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic treatment for many patients with high-risk hematologic malignancies and...
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic treatment for many patients with high-risk hematologic malignancies and bone marrow failure syndromes. While allo-HCT can be highly effective, it is met with significant bone marrow conditioning regimen-related toxicities and complications such as infections related to poor immune reconstitution. This chapter describes the measurement of clofarabine and fludarabine concentrations to support clinical trials whose goal is to determine the optimal therapeutic ranges in order to maximize effectiveness while minimizing variability and regimen-related adverse events and toxicities. Moreover, the same holds true for patients receiving fludarabine as part of their lymphodepleting chemotherapy for chimeric antigen receptor T-cells (CAR T-cells). It is believed that one of the causes of variable outcomes after CAR T-cell therapy is lymphodepletion due to the variable fludarabine concentrations.This chapter describes a HPLC-MS/MS method to measure both compounds simultaneously. Clofarabine and fludarabine are extracted with solvent from plasma by the addition of deuterated internal standards prepared in methanol. Chromatographic separation is attained using a reversed-phase column followed by mass spectrometry which is performed in the positive ion mode. Herein, the described method to quantify both compounds in plasma is fast, accurate, and sensitive and allows for rapid drug concentration monitoring and timely dose adjustments.
Topics: Humans; Clofarabine; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Vidarabine
PubMed: 38036821
DOI: 10.1007/978-1-0716-3541-4_17 -
Journal of the Egyptian National Cancer... May 2024Total body irradiation (TBI) for hematopoietic stem cell transplant (HSCT) has certain distinct advantages, such as uniform dose distribution and lack of drug...
BACKGROUND
Total body irradiation (TBI) for hematopoietic stem cell transplant (HSCT) has certain distinct advantages, such as uniform dose distribution and lack of drug resistance, but it is not widely available in resource-constrained settings. To overcome the limitations of in-house radiotherapy services in hematology centers, we evaluated the feasibility of conducting HSCT programs in coordination with two physically distant centers using a reduced-intensity TBI protocol.
METHODS
Thirty-two patients with a median age of 20.5 years were included in the study. Fifteen patients were diagnosed with aplastic anemia, 10 patients with acute myeloid leukemia (AML), 3 patients with acute lymphocytic leukemia (ALL), and 4 patients with other hematological conditions. Conditioning regimens used were fludarabine plus cyclophosphamide in 29 cases, fludarabine-cytarabine ATG in 2 cases, and busulfan plus fludarabine in 1 case. The TBI dose was 3 Gy in 28 cases and 2 Gy in 4 cases. Patients were followed monthly after TBI, and the major toxicities were recorded.
RESULTS
The median follow-up was 22 months. The most common acute complication was acute graft-versus-host disease (GVHD), which occurred in 15.6% of patients. The major late complications were chronic GVHD (9.3%), Cytomegalovirus (CMV) infection (34.3%), and CMV-induced secondary graft failure (6.2%). Seventy-five percent of patients were alive, 21.9% were dead, and 1 patient was lost to follow-up.
CONCLUSIONS
HSCT based on TBI is feasible even if the center lacks a radiotherapy facility by coordinating with a remote radiotherapy facility. without compromising the patient's outcome.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Male; Female; Adult; Transplantation Conditioning; Whole-Body Irradiation; Young Adult; Adolescent; Graft vs Host Disease; Child; Middle Aged; Child, Preschool; Vidarabine
PubMed: 38764073
DOI: 10.1186/s43046-024-00221-7 -
Blood Advances Feb 2024
Topics: Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Cell- and Tissue-Based Therapy; Vidarabine
PubMed: 38191740
DOI: 10.1182/bloodadvances.2023012068 -
Pediatric Transplantation May 2024We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD).
OBJECTIVE
We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD).
METHODS
A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate.
RESULTS
Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018).
CONCLUSION
BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.
Topics: Humans; Child; Child, Preschool; Adolescent; Busulfan; Retrospective Studies; Graft vs Host Disease; Transplantation Conditioning; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Antilymphocyte Serum; Adrenoleukodystrophy; Vidarabine
PubMed: 38602169
DOI: 10.1111/petr.14735 -
Frontiers in Pharmacology 2023var. angustifolia Thw. (Annonaceae), is a famous traditional medicinal plant in Asia. Ample data specifies that the medicinal plant has anticancer activity; however,...
var. angustifolia Thw. (Annonaceae), is a famous traditional medicinal plant in Asia. Ample data specifies that the medicinal plant has anticancer activity; however, the detailed mechanisms of action still need to be well studied. Recent studies have revealed the cytotoxicity potential of leaf against HeLa cells. Therefore, the current study was conducted to examine the regulation of miRNAs in HeLa cancer cells treated with the standardized methanolic leaf extract (PLME). The regulation of miRNAs in HeLa cancer cells treated with the standardized PLME extract was studied through Illumina, Hi-Seq. 2000 platform of Next-Generation Sequencing (NGS) and various bioinformatics tools. The PLME treatment regulated a subset of miRNAs in HeLa cells. Interestingly, the PLME treatment against HeLa cancer cells identified 10 upregulated and 43 downregulated ( < 0.05) miRNAs associated with apoptosis induction. Gene ontology (GO) term analysis indicated that PLME induces cell death in HeLa cells by inducing the pro-apoptotic genes. Moreover, the downregulated oncomiRs modulated by PLME treatment in HeLa cells were identified, targeting apoptosis-related genes through gene ontology and pathway analysis. The LC-ESI-MS/MS analysis identified the presence of Vidarabine and Anandamide compounds that were previously reported to exhibit anticancer activity. The findings of this study obviously linked the cell cytotoxicity effect of PLME treatment against the HeLa cells with regulating various miRNAs expression related to apoptosis induction in the HeLa cells. PLME treatment induced apoptotic HeLa cell death mechanism by regulating multiple miRNAs. The identified miRNAs regulated by PLME may provide further insight into the mechanisms that play a critical role in cervical cancer, as well as novel ideas regarding gene therapeutic strategies.
PubMed: 37693900
DOI: 10.3389/fphar.2023.1198425 -
Leukemia Research Sep 2023Daunorubicin and Cytarabine (DA; 3 + 7) has been the standard frontline Acute Myeloid Leukemia (AML) induction regimen resulting in Complete Remission (CR) rates of...
Daunorubicin and Cytarabine (DA; 3 + 7) has been the standard frontline Acute Myeloid Leukemia (AML) induction regimen resulting in Complete Remission (CR) rates of 50-70%. It is associated with induction mortality of 15-30%. We report a comparative analysis of DA versus fludarabine, cytarabine, G-CSF (FLAG) + /- Venetoclax in resource constrained settings. We conducted a single center, retrospective analysis of 37 treatment naïve fit AML patients from May 2021 to December 2022 who received either standard DA regimen (Group 1) or FLAG + /- Venetoclax (Group 2). The median patient age was 36.6 years in DA arm (n = 18) as compared to 40.1 years in FLAG arm (n = 19). CR rates at day 28 were 55.5% in group 1 and 89.4% in group 2 (odds ratio [OR], 7.20; 95% confidence interval [CI], 1.274 -40.678; P = 0.012). Patients in FLAG based therapy arm had shorter duration of neutropenia (P = 0.003), fewer episodes of grade 3 febrile neutropenia (P = 0.0228), shorter duration of antibiotic therapy (P = 0.03), lesser need of 3rd line antibiotic therapy (P = 0.0228). Mortality rates were 16.6% (n = 3) in (group 1) and 0% (n = 0) in (group 2) (p = 0.105). Our analysis supports that FLAG based induction regimen is an effective and well-tolerated therapy in treatment naïve fit AML patients.
Topics: Humans; Adult; Anthracyclines; Retrospective Studies; Induction Chemotherapy; Antineoplastic Combined Chemotherapy Protocols; Leukemia, Myeloid, Acute; Remission Induction; Cytarabine; Vidarabine; Anti-Bacterial Agents; Granulocyte Colony-Stimulating Factor
PubMed: 37467566
DOI: 10.1016/j.leukres.2023.107346