15 results on '"Massoud, Radwan"'
Search Results
2. Individualized busulfan dosing improves outcomes compared to fixed-dose administration in pre-transplant minimal residual disease-positive acute myeloid leukemia patients with intermediate-risk undergoing allogeneic stem cell transplantation in CR.
- Author
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Klyuchnikov E, Langebrake C, Badbaran A, Dadkhah A, Massoud R, Freiberger P, Ayuk F, Janson D, Wolschke C, Bacher U, and Kröger N
- Subjects
- Humans, Busulfan adverse effects, Neoplasm, Residual, Transplantation, Homologous, Recurrence, Transplantation Conditioning, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute etiology, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
Pre-transplant minimal residual disease (MRD) impacts negatively on post-transplant relapse risk in acute myeloid leukemia (AML). Therapeutic drug monitoring by calculating area under the curve (AUC) was developed to optimize busulfan (Bu) exposure. Here, we compared post-transplant outcomes after individualized versus fixed busulfan dosage in intermediate-risk AML who achieved CR prior to allograft focusing on pre-transplant flow-MRD. Eighty-seven patients (median, 56 years) with intermediate-risk AML and pre-transplant flow-MRD ("different from normal") were included. Thirty-two patients received individualized busulfan; 54 fixed dosages. Individualized dosage was adjusted in 25/32 patients: increased, n = 18/25 (72%); decreased: n = 7/25 (28%). After median follow-up of 27 months, we observed lower 3-year relapses (6%, 2%-19% vs. 35%, 23%-49% p = 0.02), improved 3-year leukemia-free survival (LFS) (78%, 54%-91% vs. 55%, 40%-70% p = 0.009) and - overall survival (OS) (82%, 60%-93% vs. 69%, 54%-81% p = 0.05) after individualized compared to fixed Bu. Non-relapsed mortality (NRM) and acute graft versus host disease (GvHD) were not different. In multivariate analysis, fixed Bu showed unfavorable impact on OS (hazard ratio [HR] 4.6, p = 0.044), LFS (HR 3.6, p = 0.018) and relapses (HR 3.6, p = 0.033). Fixed Bu also had unfavorable impact on LFS (3.6, 1.1-12.6, p = 0.041) in pre-transplant MRD-positive patients. Individualized, AUC-based, busulfan is associated with lower relapses in intermediate-risk AML patients allografted in CR and may overcome pre-transplant MRD-positivity., (© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
3. Post-Transplantation Day +100 Minimal Residual Disease Detection Rather Than Mixed Chimerism Predicts Relapses after Allogeneic Stem Cell Transplantation for Intermediate-Risk Acute Myelogenous Leukemia Patients Undergoing Transplantation in Complete Remission.
- Author
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Klyuchnikov E, Badbaran A, Massoud R, Fritzsche-Friedland U, Freiberger P, Ayuk F, Wolschke C, Bacher U, and Kröger N
- Subjects
- Adult, Aged, Chimerism, Female, Humans, Male, Middle Aged, Neoplasm, Residual diagnosis, Recurrence, Transplantation, Homologous adverse effects, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute diagnosis
- Abstract
Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplantation relapse in patients with acute myelogenous leukemia (AML). Nevertheless, the predictive value of both approaches in homogeneous populations remains underinvestigated. Here we suggest that MRD may have greater predictive value for relapse than mixed chimerism (MC) in intermediate-risk AML patients. Seventy-nine patients with intermediate-risk AML (40 males; median age, 57 years [range, 19 to 77 years]) were included. MRD detection on day +100 was performed in bone marrow via multiparameter flow cytometry (MFC) and quantitative real-time PCR (qPCR) for patients with an NPM1 mutation. Chimerism analysis was performed in peripheral blood. MC was defined as the persistence of <99.9% of donor alleles. The area under the receiver operating characteristic curve was highest for qPCR-MRD (.93), followed by MFC-MRD (.80) and MC (.65). The highest rate of relapse at 3 years was observed in day +100 qPCR-MRD-positive patients (100%), followed by MFC-MRD-positive patients (55%; P < .001). No patients with MC and without detectable MRD experienced relapse. The median 3-year overall survival (OS) and leukemia-free survival (LFS) for patients with MC without detectable MRD were both 86% (range, 61% to 96%), significantly higher than the values in day +100 MFC-MRD-positive patients (OS, 61% [range, 36% to 84%]; LFS: 30% [range, 11% to 59%]) and with day +100 qPCR-MRD-positive patients (OS: 17% [range, 3% to 56%], P = .001; LFS: 0%, P < .001). In patients with intermediate-risk AML, the qPCR-MRD on day +100 was highly predictive for relapse and long-term survival after allogeneic stem cell transplantation, followed closely by MFC-MRD. In contrast, chimerism status had limited predictive potential. Thus, molecular and flow cytometry MRD monitoring rather than MC in the first several months post-transplantation can identify patients at increased risk of relapse who may benefit from early post-transplantation preemptive intervention., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
4. Post-Transplantation Multicolored Flow Cytometry-Minimal Residual Disease Status on Day 100 Predicts Outcomes for Patients With Refractory Acute Myeloid Leukemia.
- Author
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Klyuchnikov E, Badbaran A, Massoud R, Fritsche-Friedland U, Janson D, Ayuk F, Christopeit M, Wolschke C, Bacher U, and Kröger N
- Subjects
- Flow Cytometry methods, Humans, Male, Neoplasm, Residual genetics, Recurrence, Retrospective Studies, Leukemia, Myeloid, Acute therapy
- Abstract
Patients with relapsed/refractory acute myeloid leukemia (AML) have a dismal prognosis. Allogeneic stem cell transplantation (allo-SCT) provides a curative approach; however, the overall survival (OS) remains low (20% to 40%). In this setting, although some effective approaches have been evaluated in recent years, the management of such patients still remains challenging. In this study we evaluated the predictive role of post-transplant day 100 minimal residual disease (MRD) detection for post-transplantation outcomes for patients with refractory AML. Fifty-six adult patients with refractory AML (median age 58, range 20-76; male, 61%) who underwent allo-SCT were included in this retrospective monocentric study. Twenty-nine patients (52%) received fludarabine, amsacrine, and cytarabine (FLAMSA)-based conditioning. MRD was assessed using multicolored flow cytometry (MFC) according to European Leukemia Net guidelines ("different from normal" and leukemia-associated phenotype). The sensitivity of the method was 10
-4 to 10-5 . The median marrow blast count at allo-SCT was 25% (range 6% to 91%). At day 100 after transplantation, 40 patients (71%) experienced MFC-MRD negativity, and 16 patients (29%) were MRD positive. All included patients survived at least 100 days after transplantation without relapse. Univariate and multivariate analysis based on Kaplan-Meier and Cox proportional hazards method were performed. The median follow-up was 16 months (range 3 to 66). The post-transplantation day 100 MRD-negative patients instead received 2 allografts (27% versus 6%, P = .08). In multivariate analysis, day 100 MRD status (negative versus positive) (OS: 0.23 [0.1 to 0.54], P =0.001; relapses: 0.20 [0.1 to 0.49], P = .0005) and FLAMSA versus other regimens (0.34 [0.1 to 0.83], P = .018; relapses: 0.43 [0.17 to 1.1], P = .07) independently impacted post-transplantation survival. We suggest that post-transplantation day 100 MFC-MRD detection plays predictive role in refractory AML patients and may help to define possible candidates for early post-transplantation interventions aiming to decrease the relapse risk and improve survival., Competing Interests: Conflict of interest statement There are no conflicts of interest to report., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
5. A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c acute myeloid leukemia.
- Author
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Hleihel R, El Hajj H, Wu HC, Berthier C, Zhu HH, Massoud R, Chakhachiro Z, El Sabban M, De The H, and Bazarbachi A
- Subjects
- Humans, NIMA-Interacting Peptidylprolyl Isomerase genetics, NIMA-Interacting Peptidylprolyl Isomerase metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism, Oncogene Proteins, Fusion metabolism, Tretinoin pharmacology, Tretinoin therapeutic use, Tumor Suppressor Protein p53 genetics, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Promyelocytic, Acute drug therapy, Leukemia, Promyelocytic, Acute genetics, Leukemia, Promyelocytic, Acute metabolism
- Abstract
Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis. Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Such PML induction drives P53 activation, favoring blast response to chemotherapy or arsenic in vivo. This RA/PML/P53 cascade could mechanistically explain RA-facilitated chemotherapy response in patients with NPM-1c mutated acute myeloid leukemia.
- Published
- 2021
- Full Text
- View/download PDF
6. Enhanced Immune Reconstitution of γδ T Cells after Allogeneic Stem Cell Transplantation Overcomes the Negative Impact of Pretransplantation Minimal Residual Disease-Positive Status in Patients with Acute Myelogenous Leukemia.
- Author
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Klyuchnikov E, Badbaran A, Massoud R, Fritsche-Friedland U, Janson D, Ayuk F, Wolschke C, Bacher U, and Kröger N
- Subjects
- Humans, Middle Aged, Neoplasm, Residual, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Immune Reconstitution, Leukemia, Myeloid, Acute therapy
- Abstract
Minimal/measurable residual disease (MRD) before allogeneic stem cell transplantation (allo-SCT) in patients with acute myelogenous leukemia (AML) is a poor risk factor for outcome. γδ T cells represent a unique minority lymphocyte population that is preferentially located in peripheral tissues, can recognize antigens in a non-MHC-restricted manner, and plays a "bridging" role between the innate and adaptive immune systems. In this study, we investigated a potential graft-versus-leukemia effect of γδ T cell reconstitution post-transplantation in AML patients with pretransplantation positive MRD status (MRD
+ ). MRD assessment was performed in 202 patients using multicolored flow cytometry ("different from normal" strategy); 100 patients were deemed MRD+ . Analysis for absolute concentrations of CD3+ , CD4+, CD8+ , natural killer, and γδ T cells were performed by flow cytometry according to an internal protocol at day +30 and +100 post-transplantation. Differences between categorical and continuous variables were determined using the chi-square and Student t test, respectively. The Mann-Whitney U test was used to compare medians of continuous variables. Spearman's correlation was used for nonparametric assessment of correlation between different cell subsets during immune reconstitution. Kaplan-Meier survival analysis and Cox regression analysis were used to investigate the associations between immune reconstitution and survival outcomes. Gray's analysis was used to compute incidences of relapse, nonrelapse mortality, and graft-versus-host disease (GVHD). The median follow-up of survivors was 28 months (range 3 to 59 months). Younger age (≤58 years) of recipient and donor (<30 years), sex mismatch, use of a matched donor, cytomegalovirus reactivation, and administration of antithymocyte globulin were associated with a faster γδ T cell reconstitution. In multivariable analysis for MRD+ patients, a higher than median level of γδ T cells on days +30 and +100 resulted in significantly improved leukemia-free survival (hazard ratio [HR], 0.42 [P = .007] and 0.42 [P = .011], respectively) and overall survival (HR, 0.44 [P = .038] and 0.33 [P = .009], respectively). Furthermore, a higher γδ T cell level on day +30 was associated with a significantly reduced risk of relapse (HR, 0.36; P = .019). No impact of γδ T cell level on relapse at days +30 and +100 could be seen in MRD-negative patients, and no correlation with occurrence of GVHD was observed. Our data indicate that enhanced immune reconstitution of γδ T cells post-transplantation may overcome the higher relapse risk of pretransplantation MRD+ status in patients with AML., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
7. Allogeneic stem cell transplantation in acute leukemia patients after COVID-19 infection.
- Author
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Christopeit M, Reichard M, Niederwieser C, Massoud R, Klyuchnikov E, Haase N, Wolschke C, Ayuk F, Heidenreich S, and Kröger N
- Subjects
- Humans, SARS-CoV-2, COVID-19, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Published
- 2021
- Full Text
- View/download PDF
8. Risk adapted therapeutic strategy in newly diagnosed acute myeloid leukemia: Refining the outcomes of ELN 2017 intermediate-risk patients.
- Author
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Mohty R, Massoud R, Chakhachiro Z, Mahfouz R, Nassif S, El-Cheikh J, Bazarbachi A, and Abou Dalle I
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Leukemia, Myeloid, Acute classification, Male, Middle Aged, Retrospective Studies, Risk Factors, Transplantation, Homologous, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Induction Chemotherapy methods, Leukemia, Myeloid, Acute drug therapy, Maintenance Chemotherapy methods
- Abstract
Introduction: Despite advances in the treatment of acute myeloid leukemia (AML), cytotoxic chemotherapy remains the standard induction regimen., Patients and Methods: In this single center retrospective study, we assessed outcomes of 99 consecutive adult AML patients treated with a risk-adapted strategy with a median follow-up of 35.5 months., Results: We identified 24 (24 %), 55 (56 %) and 20 (20 %) patients classified as favorable-, intermediate-, and adverse- risk group respectively, according to the European LeukemiaNet (ELN) 2017 classification. Patients either received idarubicin and cytarabine induction chemotherapy with or without FLT3 inhibitors or hypomethylating agents based on age and comorbidity. The complete response (CR) rate was 76 % (82 % and 61 % in patients aged < 60 and ≥ 60, respectively). For the whole cohort, the 3-year overall survival (OS) was 53 %, being 62 % and 30 % in patients aged < 60 and ≥ 60, respectively. The 3-year leukemia-free survival (LFS) was 54 %, with 56 % and 45 % in patients aged < 60 and ≥ 60, respectively. The 3-year LFS were 58 %, 62 % and 25 % for patients within ELN favorable-, intermediate-, and adverse-risk groups respectively. Twenty-seven (36 %) out of 75 patients with intermediate- and adverse-risk disease underwent allogeneic hematopoietic cell transplantation (allo-HCT) in first CR with 92 % of them receiving post-transplant maintenance consisting of azacitidine in 19 (76 %) patients or sorafenib in 6 (24 %) patients. Of these patients younger than 60 years, the 3-year OS and LFS were 85 % and 69 %, respectively., Conclusion: These results indicate an improved OS for AML patients especially in intermediate-risk category who were treated with a total therapy consisting of induction chemotherapy followed by allo-HCT and post-transplant maintenance., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
9. Haploidentical related donor allogeneic hematopoietic stem cell transplantation for patient aged older than 76 years with refractory acute myeloid leukemia.
- Author
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El-Cheikh J, Salem R, Massoud R, Salem C, Ghaoui N, Kanj SS, Mahfouz R, and Bazarbachi A
- Subjects
- Aged, Allografts, Humans, Leukemia, Myeloid, Acute blood, Leukemia, Myeloid, Acute genetics, Male, Recurrence, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Tissue Donors
- Published
- 2020
- Full Text
- View/download PDF
10. Efficacy and Feasibility of Sorafenib as a Maintenance Agent After Allogeneic Hematopoietic Stem Cell Transplantation for Fms-like Tyrosine Kinase 3 Mutated Acute Myeloid Leukemia: An Update.
- Author
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Battipaglia G, Massoud R, Ahmed SO, Legrand O, El Cheikh J, Youniss R, Aljurf M, Mohty M, and Bazarbachi A
- Subjects
- Adolescent, Adult, Cohort Studies, Combined Modality Therapy, Feasibility Studies, Female, Follow-Up Studies, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Maintenance Chemotherapy, Male, Middle Aged, Mutation, Prognosis, Remission Induction, Survival Rate, Transplantation, Homologous, Young Adult, fms-Like Tyrosine Kinase 3 antagonists & inhibitors, fms-Like Tyrosine Kinase 3 genetics, Hematopoietic Stem Cell Transplantation mortality, Leukemia, Myeloid, Acute drug therapy, Protein Kinase Inhibitors therapeutic use, Sorafenib therapeutic use
- Abstract
Background: Patients diagnosed with acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 (FLT3) mutations have a very poor prognosis, despite use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and salvage treatments., Patients and Methods: We previously reported the safety and efficacy of sorafenib, an FLT3 inhibitor, as a maintenance agent after allo-HSCT in patients diagnosed with AML with FLT3 mutations. We provide an update on the 27 patients with FLT3-mutated AML in our original report, who received sorafenib as a single maintenance agent., Results: Since our previous report, others have confirmed our reported significant overall survival and progression-free survival in patients who received sorafenib before and/or after allo-HSCT. In this update on the 27 patients with FLT3-mutated AML in our original report, we show persistence of the previously reported impressive long-term disease control., Conclusion: Our results, with longer follow-up than in our previous report, together with those of others, further support the use of sorafenib as a maintenance agent after allo-HSCT., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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11. Mutant H3 histones drive human pre-leukemic hematopoietic stem cell expansion and promote leukemic aggressiveness.
- Author
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Boileau M, Shirinian M, Gayden T, Harutyunyan AS, Chen CCL, Mikael LG, Duncan HM, Neumann AL, Arreba-Tutusaus P, De Jay N, Zeinieh M, Rossokhata K, Zhang Y, Nikbakht H, Mouawad C, Massoud R, Frey F, Nasr R, El Cheikh J, El Sabban M, Kleinman CL, Mahfouz R, Minden MD, Jabado N, Bazarbachi A, and Eppert K
- Subjects
- Animals, Animals, Genetically Modified, Antineoplastic Agents pharmacology, Base Sequence, Bone Marrow Cells, Cell Differentiation, Cell Transformation, Neoplastic, DNA genetics, Drosophila melanogaster genetics, Gene Expression Regulation, Leukemic drug effects, Hematopoiesis physiology, Hematopoietic Stem Cells metabolism, Humans, Mice, Mutation, Neoplasms, Experimental, Epigenomics, Gene Expression Regulation, Leukemic physiology, Histones metabolism, Leukemia, Myeloid, Acute metabolism
- Abstract
Our ability to manage acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption central to leukemogenesis, including improper histone methylation. Here we examine 16 histone H3 genes in 434 primary AML samples and identify Q69H, A26P, R2Q, R8H and K27M/I mutations (1.6%), with higher incidence in secondary AML (9%). These mutations occur in pre-leukemic hematopoietic stem cells (HSCs) and exist in the major leukemic clones in patients. They increase the frequency of functional HSCs, alter differentiation, and amplify leukemic aggressiveness. These effects are dependent on the specific mutation. H3K27 mutation increases the expression of genes involved in erythrocyte and myeloid differentiation with altered H3K27 tri-methylation and K27 acetylation. The functional impact of histone mutations is independent of RUNX1 mutation, although they at times co-occur. This study establishes that H3 mutations are drivers of human pre-cancerous stem cell expansion and important early events in leukemogenesis.
- Published
- 2019
- Full Text
- View/download PDF
12. Feasibility of Venetoclax-based combinations for adult patients with acute myeloid leukemia relapsing after allogenic stem cell transplantation.
- Author
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Moukalled NM, El Darsa H, Haibe Y, Massoud R, Kanj SS, Mahfouz R, Bazarbachi A, and El-Cheikh J
- Subjects
- Adult, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Feasibility Studies, Female, Humans, Male, Middle Aged, Recurrence, Sulfonamides pharmacology, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute drug therapy, Sulfonamides therapeutic use, Transplantation Conditioning methods, Transplantation, Homologous methods
- Published
- 2019
- Full Text
- View/download PDF
13. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia.
- Author
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Battipaglia G, Ruggeri A, Massoud R, El Cheikh J, Jestin M, Antar A, Ahmed SO, Rasheed W, Shaheen M, Belhocine R, Brissot E, Dulery R, Eder S, Giannotti F, Isnard F, Lapusan S, Rubio MT, Vekhoff A, Aljurf M, Legrand O, Mohty M, and Bazarbachi A
- Subjects
- Adolescent, Adult, Chemotherapy, Adjuvant, Disease-Free Survival, Feasibility Studies, Female, Graft vs Host Disease, Humans, Leukemia, Myeloid, Acute genetics, Maintenance Chemotherapy, Male, Middle Aged, Niacinamide therapeutic use, Retrospective Studies, Sorafenib, Transplantation, Homologous, Treatment Outcome, Young Adult, fms-Like Tyrosine Kinase 3 genetics, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use
- Abstract
Background: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results., Methods: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia., Results: The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively., Conclusions: Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867-74. © 2017 American Cancer Society., (© 2017 American Cancer Society.)
- Published
- 2017
- Full Text
- View/download PDF
14. A Pin1/PML/P53 axis activated by retinoic acid in
- Author
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Hleihel, Rita, El Hajj, Hiba, Wu, Hsin-Chieh, Berthier, Caroline, Zhu, Hong-Hu, Massoud, Radwan, Chakhachiro, Zaher, El Sabban, Marwan, de The, Hugues, and Bazarbachi, Ali
- Subjects
NIMA-Interacting Peptidylprolyl Isomerase ,Leukemia, Myeloid, Acute ,integumentary system ,Leukemia, Promyelocytic, Acute ,Oncogene Proteins, Fusion ,Editorials ,Humans ,Nuclear Proteins ,Tretinoin ,Tumor Suppressor Protein p53 ,Article - Abstract
Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis. Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Such PML induction drives P53 activation, favoring blast response to chemotherapy or arsenic in vivo. This RA/PML/P53 cascade could mechanistically explain RA-facilitated chemotherapy response in patients with NPM-1c mutated acute myeloid leukemia.
- Published
- 2020
15. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia
- Author
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Battipaglia, Giorgia, Ruggeri, Annalisa, Massoud, Radwan, El Cheikh, Jean, Jestin, Matthieu, Antar, Ahmad, Ahmed, Syed Osman, Rasheed, Walid, Shaheen, Marwan, Belhocine, Ramdane, Brissot, Eolia, Dulery, Remy, Eder, Sandra, Giannotti, Federica, Isnard, Françoise, Lapusan, Simona, Rubio, Marie-Thérèse, Vekhoff, Anne, Aljurf, Mahmoud, Legrand, Ollivier, Mohty, Mohamad, Bazarbachi, Ali, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Università degli studi di Napoli Federico II, American University of Beirut Faculty of Medicine and Medical Center (AUB), King Faisal Specialist Hospital and Research Centre, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Battipaglia, G., Ruggeri, A., Massoud, R., El Cheikh, J., Jestin, M., Antar, A., Ahmed, S. O., Rasheed, W., Shaheen, M., Belhocine, R., Brissot, E., Dulery, R., Eder, S., Giannotti, F., Isnard, F., Lapusan, S., Rubio, M. -T., Vekhoff, A., Aljurf, M., Legrand, O., Mohty, M., and Bazarbachi, A.
- Subjects
Adult ,Male ,Niacinamide ,Phenylurea Compound ,Fms-like tyrosine kinase 3 (FLT3) ,Adolescent ,[SDV]Life Sciences [q-bio] ,Graft vs Host Disease ,Antineoplastic Agents ,Disease-Free Survival ,maintenance ,Maintenance Chemotherapy ,Antineoplastic Agent ,Young Adult ,acute myeloid leukemia (AML) ,allogeneic stem cell transplantation ,Retrospective Studie ,Humans ,Transplantation, Homologous ,Transplantation, Homologou ,ComputingMilieux_MISCELLANEOUS ,Retrospective Studies ,Phenylurea Compounds ,Hematopoietic Stem Cell Transplantation ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Middle Aged ,Sorafenib ,Feasibility Studie ,Leukemia, Myeloid, Acute ,Treatment Outcome ,fms-Like Tyrosine Kinase 3 ,Chemotherapy, Adjuvant ,Feasibility Studies ,Female ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Human - Abstract
BACKGROUND: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results. METHODS: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia. RESULTS: The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively. CONCLUSIONS: Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867–74. © 2017 American Cancer Society.
- Published
- 2017
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