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4. Development and Validation of a Concise Objectifiable Risk Evaluation Score for Non-Relapse Mortality after Allogeneic Hematopoietic Stem Cell Transplantation

Author

Weise, Gunnar, primary, Massoud, Radwan, additional, Krause, Rolf, additional, Heidenreich, Silke, additional, Janson, Dietlinde, additional, Klyuchnikov, Evgeny, additional, Wolschke, Christine, additional, Zeck, Gaby, additional, Kröger, Nicolaus, additional, and Ayuk, Francis, additional

Published
2024
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12. Allogeneic hematopoetic stem cell transplant for patients with refractory T‐Cell lymphomas.

Author

Massoud, Radwan, Naim, Hassan, Klyuchnikov, Evgeny, Janson, Dietlinde, Wolschke, Christine, Ayuk, Francis, and Kröger, Nicolaus

Subjects
*STEM cell transplantation, *T cells, *LYMPHOMAS, *GRAFT versus host disease, *OVERALL survival, *REFRACTORY materials
Abstract

Objective: Allogeneic stem cell transplantation (allo‐SCT) may have a curative potential due to the graft versus lymphoma effect. In this study, we aimed to compare transplant outcomes between refractory‐T‐NHL (ref‐NHL) and Chemosensitive‐T‐NHL (CS‐T‐NHL). Materials and Methods: We retrospectively reviewed the records of 26 ref‐NHL and 29 CS‐T‐NHL consecutive patients who underwent allo‐SCT at our center and compared the transplant outcomes between the groups. Results: All patients were heavily pretreated with 27% of patients relapsing post‐auto‐SCT and two patients in the ref‐T‐NHL post‐allo‐SCT. Patients were transplanted mainly from unrelated donors. There were no differences in leucocytes and platelet engraftment between the two groups. At 3 years, the relapse incidence was 34% in Ref‐TNHL and 19% in CS‐TNHL (p =.33), with non‐relapse mortality rates of 28% and 22%, respectively (p =.52). Female patients and those with a previous auto‐SCT had lower relapse incidence (p =.045, p =.003). The 3‐year overall survival was 39% in Ref‐TNHL and 56% in CS‐TNHL (p =.15). Trends for improved progression‐free survival (PFS) and graft‐versus‐host disease relapse‐free survival (GRFS) were observed in the CS‐TNHL group (PFS: 60% vs. 30%, p =.075; GRFS: 38% vs. 21%, p =.1). Conclusion: Acknowledging the retrospective nature of our study, our results indicate that allo‐SCT has a curative potential in patients with T‐NHL even in refractory status. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Anti-T-lymphocyte globulin (ATLG) compared to post-transplant cyclophosphamide as GvHD prophylaxis in ALL patients undergoing allogeneic stem cell transplantation

Author

Steiner, Normann, Massoud, Radwan, Klyuchnikov, Evgeny, Gagelmann, Nico, Richter, Johanna, Niederwieser, Christian, Rathje, Kristin, Urbanowicz, Tatjana, Kunte, Ameya, Engelmann, Janik, Ihne, Christina, Lastovytska, Iryna, Lindhauer, Cecilia, Marquard, Franziska, Reichard, Mirjam, Ryzhkova, Alla, Sabauri, Rusudan, Schäfersküpper, Mathias, Seyedi, Niloufar, Kalogeropoulos, Georgios, Heidenreich, Silke, Rudolph, Ina, Zeck, Gaby, Janson, Dietlinde, Wolschke, Christine, Ayuk, Francis, and Kröger, Nicolaus

Abstract

We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n= 74) or PTCy (n= 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p= 0.9 and 0.5, respectively). CIR and NRM rate at three years was 12 and 21% after PTCy and 19 and 20% after ATLG (p= 0.4 and p= 0.9, respectively). Acute GvHD grades II-IV and grades III/IV at 100 days was 46 and 19% after PTCy and 33 and 10% after ATLG (p= 0.08 and p= 0.9, respectively). Chronic GvHD of all grade at two years was higher after PTCy: 55% versus 26% (p< 0.001). Based on the propensity score matching (PSM) analysis, aGvHD grades II-IV was trending higher in the PTCy group compared to the ATLG group (p= 0.07). In contrast to the PSM analysis, on multivariate analysis the receipt of PTCy compared with ATLG was associated with a reduced CIR (p= 0.026). Our retrospective single-center analysis shows a lower incidence of acute and chronic GvHD while displaying similar LFS and OS after ATLG compared to PTCy in TBI based allogeneic stem cell transplantation for high-risk ALL.

Published
2024
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20. 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

Klyuchnikov, Evgeny, primary, Langebrake, Claudia, additional, Badbaran, Anita, additional, Dadkhah, Adrin, additional, Massoud, Radwan, additional, Freiberger, Petra, additional, Ayuk, Francis, additional, Janson, Dietlinde, additional, Wolschke, Christine, additional, Bacher, Ulrike, additional, and Kröger, Nicolaus, additional

Published
2022
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21. Viral Reactivation and Immune Reconstitution after CAR-T Cell Treatment in Patients with Hematologic Malignancies

Author

Kunte, Ameya Shrinivas, primary, Gagelmann, Nico, additional, Badbaran, Anita, additional, Berger, Carolina, additional, Massoud, Radwan, additional, Klyuchnikov, Evgeny, additional, Wolschke, Christine, additional, Janson, Dietlinde, additional, Fritsche-Friedland, Ulrike, additional, Fehse, Boris, additional, Kroeger, Nicolaus, additional, and Ayuk, Francis A., additional

Published
2022
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23. Individualized busulfan dosing improves outcomes compared to fixed dose administration in pre-transplant MRD positive AML patients with intermediate risk undergoing allogeneic stem cell transplantation in CR

Author

Klyuchnikov, Evgeny, Langebrake, Claudia, Badbaran, Anita, Dadkhah, Adrin, Massoud, Radwan, Freiberger, Petra, Ayuk, Francis, Janson, Dietlinde, Wolschke, Christine, Bacher, Ulrike, and Kröger, Nicolaus

Subjects
610 Medizin und Gesundheit
Abstract

Pre-transplant minimal residual disease (MRD) impacts negatively on post-transplant relapse risk in AML. Therapeutic drug monitoring by calculating area-under-the-curve (AUC) was developed to optimize busulfan 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. 87 patients (median, 56 years) with intermediate-risk AML and pre-transplant flow-MRD ("different from normal") were included. 32 patients received individualized busulfan; 54 fixed dosage. 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 LFS (78%, 54-91% vs 55%, 40-70% p = 0.009) and -OS (82%, 60-93% vs 69%, 54-81% p = 0.05) after individualized compared to fixed Bu. NRM and acute GvHD were not different. In multivariate analysis, fixed Bu showed unfavorable impact on OS (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.

Published
2022
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24. Post-transplant day +100 MRD detection rather than mixed chimerism predicts relapses after allo-SCT for intermediate risk AML patients transplanted in CR

Author

Klyuchnikov, Evgeny, Badbaran, Anita, Massoud, Radwan, Fritsche-Friedland, Ulrike, Freiberger, Petra, Ayuk, Francis, Wolschke, Christine, Bacher, Ulrike, and Kröger, Nicolaus

Subjects
body regions, hemic and lymphatic diseases, 610 Medicine & health
Abstract

BACKGROUND Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplant relapses in AML patients. Nevertheless, the predictive values of both approaches in homogeneous population remain underinvestigated. Here, we suggest that MRD may have a higher predictive value for relapses than mixed chimerism (MC) in intermediate risk AML patients. PATIENTS AND METHODS 79 patients with intermediate risk AML (male, n=40, median age, 57 (19-77)) were included. MRD detection on day +100 was performed in bone marrow (multiparameter flow cytometry and quantitative real-time PCR for NPM1-mutated patients). Chimerism analysis was measured in peripheral blood. MC was defined as persistence of

Published
2022
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25. 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

Klyuchnikov, Evgeny, Langebrake, Claudia, Badbaran, Anita, Dadkhah, Adrin, Massoud, Radwan, Freiberger, Petra, Ayuk, Francis, Janson, Dietlinde, Wolschke, Christine, Bacher, Ulrike, and Kröger, Nicolaus

Subjects
STEM cell transplantation, ACUTE myeloid leukemia, GRAFT versus host disease, BUSULFAN, DRUG monitoring, HEMATOPOIETIC stem cell transplantation, KIDNEY failure
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. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Enhanced immune reconstitution of γδ T cells after allograft overcomes negative impact of pre-transplant MRD positive status in AML patients.: γδ T cells and MRD+ AML

Author

Klyuchnikov, Evgeny, Badbaran, Anita, Massoud, Radwan, Fritsche-Friedland, Ulrike, Janson, Dietlinde, Ayuk, Francis, Wolschke, Christine, Bacher, Vera, and Kröger, Nicolaus

Subjects
hemic and lymphatic diseases, 610 Medicine & health
Abstract

BACKGROUND Minimal residual disease (MRD) prior to allogeneic stem cell transplantation (allo-SCT) in AML is a poor risk factor for outcome. The γδ T cells represents a unique minority lymphocyte population which is preferentially located in peripheral tissues, can recognize antigens in non-MHC restricted manner and plays a "bridging" role between innate and adaptive immune system. OBJECTIVES In this study, we investigated a potential graft-vs-leukaemia effect of γδ T cells reconstitution post-transplant in AML patients with pre-transplant positive minimal/measurable disease status (MRD+). STUDY DESIGN We investigated a potential graft-vs-leukaemia effect of γδ T cells reconstitution post-transplant in AML patients with pre-transplant positive MRD+. MRD assessment was performed in 202 patients (MRD+, n=100) with multicolored flow cytometry ("different from normal" strategy). Analysis for absolute concentrations of CD3+, CD4+, CD8+, NK, and γδ T cells were performed by flow cytometry according to an internal protocol at day +30 and +100 post-transplant. Differences between categorical and continuous variables were determined by Chi-square and Student's T-test, respectively. The Mann-Whitney test was used to compare medians of continuous variables. Spearman 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. Grays' analysis was used to compute incidences of relapses, non-relapse mortality (NRM) and graft-vs-host disease (GvHD). RESULTS Follow-up for survivors was 28 months (3-59). Younger age (≤58) of recipient and donor (

Published
2021

29. Comparison of and Immune Reconstitution and Graft Versus Host Disease in 30mg/Kg Anti-T-Lymphocyte Globuline with 60mg/Kg ATLG As Graft Versus Host Disease Prophylaxis in Matched Unrelated Donor Myeloablative Peripheral Blood Stem Cell Transplantation

Author

Massoud, Radwan, primary, Klyuchnikov, Evgeny, additional, Gagelmann, Nico, additional, Zabelina, Tatjana, additional, Christine, Wolschke, additional, Ayuk, Francis Ayuketang, additional, Fritsche-Friedland, Ulrike, additional, Zander, Axel R., additional, and Kröger, Nicolaus, additional

Published
2021
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31. Comparison of immune reconstitution between anti-T-lymphocyte globulin and posttransplant cyclophosphamide as acute graft-versus-host disease prophylaxis in allogeneic myeloablative peripheral blood stem cell transplantation

Author

Massoud, Radwan, primary, Gagelmann, Nico, additional, Fritzsche-Friedland, Ulrike, additional, Zeck, Gaby, additional, Heidenreich, Silke, additional, Wolschke, Christine, additional, Ayuk, Francis, additional, Christopeit, Maximilian, additional, and Kröger, Nicolaus, additional

Published
2021
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32. A Pin1/PML/P53 axis activated by retinoic acid in

Author

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

36. Impact of Adding Antithymocyte Globulin to Posttransplantation Cyclophosphamide in Haploidentical Stem-Cell Transplantation

Author

El-Cheikh, Jean, primary, Devillier, Raynier, additional, Dulery, Remy, additional, Massoud, Radwan, additional, Al Chami, Farouk, additional, Ghaoui, Nohra, additional, Moukalled, Nour, additional, Pagliardini, Thomas, additional, Marino, Fabrizio, additional, Malard, Florent, additional, Bazarbachi, Abdul Hamid, additional, Mohty, Razan, additional, Bazarbachi, Ali, additional, Castagna, Luca, additional, Mohty, Mohamad, additional, and Blaise, Didier, additional

Published
2020
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42. Mutant H3 histones drive human pre-leukemic hematopoietic stem cell expansion and promote leukemic aggressiveness

Author

Boileau, Meaghan, primary, Shirinian, Margret, additional, Gayden, Tenzin, additional, Harutyunyan, Ashot S., additional, Chen, Carol C. L., additional, Mikael, Leonie G., additional, Duncan, Heather M., additional, Neumann, Andrea L., additional, Arreba-Tutusaus, Patricia, additional, De Jay, Nicolas, additional, Zeinieh, Michele, additional, Rossokhata, Katya, additional, Zhang, Yelu, additional, Nikbakht, Hamid, additional, Mouawad, Carine, additional, Massoud, Radwan, additional, Frey, Felice, additional, Nasr, Rihab, additional, El Cheikh, Jean, additional, El Sabban, Marwan, additional, Kleinman, Claudia L., additional, Mahfouz, Rami, additional, Minden, Mark D., additional, Jabado, Nada, additional, Bazarbachi, Ali, additional, and Eppert, Kolja, additional

Published
2019
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46. 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

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

47. Trends in hematopoietic stem cell transplant activity in Lebanon

Author

Bazarbachi, Ali, Zahreddine, Ammar, Massoud, Radwan, Cheikh, Jean, Hanna, Colette, Nasr, Fadi, Abboud, Miguel, and Ibrahim, Ahmad

Abstract

Hematopoietic stem cell transplantation (HSCT) has been accessible to the population residing in Lebanon and surrounding countries since 1997. HSCT programs were developed in two major hospitals in Beirut: American University of Beirut Medical Center (AUBMC) and Makassed General Hospital. Mount Lebanon Hospital initiated an autologous HSCT activity later. Between 2012 and 2016, the HSCT activity in Lebanon reached a total of 897 transplants, among which 303 (33.8%) were allogeneic HSCT and 594 (66.2%) were autologous HSCT. Overall, autologous HSCT activity has remained stable over the past 5years, whereas allogeneic HSCT activity has seen a steep increase between 2012 and 2013 followed by a modest increase later. Haploidentical transplantation has mushroomed and represented almost half of allogeneic HSCT activity in 2016. AUBMC and Makassed General Hospital are members of the European Blood and Marrow Transplantation (EBMT) and East Mediterranean Blood and Marrow Transplantation groups, and AUBMC has been accredited by JACIE (Joint Accreditation Committee – ISCT & EBMT) since 2016. The past 5years have seen an increase in HSCT-related research and publications, mainly from AUBMC. These research activities were predominantly focused on personalized conditioning for allogeneic HSCT and post-transplant maintenance therapy.

Published
2024
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