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1. 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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6. 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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7. 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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8. 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

11. 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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13. 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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14. 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

19. 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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21. 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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22. Mutations in Human Histone H3 are Pre-Leukemic Events and Promote Hematopoietic Stem Cell Expansion and Leukemic Aggressiveness

Author

Boileau, Meaghan, primary, Shirinian, Margret, additional, Gayden, Tenzin, additional, Harutyunyan, Ashot, additional, Chen, Carol, additional, Mikael, Leonie, additional, Duncan, Heather, additional, Neumann, Andrea, additional, Arreba-Tutusaus, Patricia, additional, De Jay, Nicolas, additional, Zeinieh, Michele, 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, additional, Mahfouz, Rami, additional, Minden, Mark, additional, Jabado, Nada, additional, Bazarbachi, Ali, additional, and Eppert, Kolja, additional

Published
2018
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24. Incidence of Cytomegalovirus (CMV) Reactivation after Autologous Peripheral Blood Stem Cell Transplantation (ASCT) in 324 Patients with Multiple Myeloma and Lymphoma: A Single-Center Study at the American University of Beirut Medical Center (AUBMC)

Author

Massoud, Radwan, primary, Assi, Rita, additional, Fares, Elie, additional, Kreidieh, Nabila, additional, Mahfouz, Rami, additional, Kanj, Souha, additional, El-Zakhem, Aline, additional, Kharfan-Dabaja, Mohamed A., additional, Bazarbachi, Ali, additional, and El Cheikh, Jean, additional

Published
2016
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27. 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, primary, Ruggeri, Annalisa, additional, Jestin, Matthieu, additional, Massoud, Radwan, additional, El Cheikh, Jean, additional, Antar, Ahmad, additional, Ahmed, Syed Osman, additional, Rasheed, Walid, additional, Belhocine, Ramdane, additional, Brissot, Eolia, additional, Dulery, Remy, additional, Eder, Sandra, additional, Giannotti, Federica, additional, Isnard, Francoise, additional, Lapusan, Simona, additional, Rubio, Marie-Thérèse, additional, Vekhoff, Anne, additional, Aljurf, Mahmoud, additional, Legrand, Ollivier, additional, Mohty, Mohamad, additional, and Bazarbachi, Ali, additional

Published
2016
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30. Leukemic Stem Cells (LSCs) As Peri-Transplant MRD Assessment in AML Patients Undergoing Allogeneic Stem Cell Transplantation in CR

Author

Klyuchnikov, Evgeny, Badbaran, Anita, Massoud, Radwan, Freiberger, Petra, Wolschke, Christine, Ayuk, Francis A., Bacher, Ulrike, and Kroeger, Nicolaus

Abstract

Background:Several studies have shown that the leukemic stem cells (LSCs: CD34 +CD38 -CD45RA +/Combi-6 +) play a crucial role in the development of relapses in AML patients (pts). LSCs are less sensitive to conventional therapy; moreover, their phenotypical characteristics may allow immune evasion promoting relapses after allo-SCT. Although ELN guidelines recommend including LSCs into MRD assessment, this approach has not yet been studied extensively in the allogeneic setting. Here we suggested that peri-transplant LSCs detection may provide additional prognostic information to conventional (c)MRD in AML pts allografted in CR.

Published
2023
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31. 3010 - Mutations in Human Histone H3 are Pre-Leukemic Events and Promote Hematopoietic Stem Cell Expansion and Leukemic Aggressiveness

Author

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

Published
2018
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34. Interim Disease Evaluation Post Induction Chemotherapy for Acute Myeloid Leukemia

Author

Moukalled, Nour, Massoud, Radwan, Mahfouz, Rami, Chakhachiro, Zaher, Nassif, Samer, Elcheikh, Jean, and Bazarbachi, Ali

Abstract

Introduction:Interim disease evaluation and its timing during induction chemotherapy (day 14 or day 21) for patients with acute myeloid leukemia (AML) remains controversial. It has been suggested that failure to achieve complete remission (CR) at day 21 is associated with a poor prognosis. Nonetheless, the significance of persistent disease and the need for an early double induction is questionable.

Published
2017
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35. Safety and Efficacy of Thiotepa Based Conditioning Regimen in Patients Undergoing Allogeneic Stem Cell Transplantation: A Retrospective Single Center Experience

Author

Elcheikh, Jean, Massoud, Radwan, Moukalled, Nour, Haffar, Basel, Zaherddine, Ammar, Maya, Charafeddine, Mahfouz, Rami, and Bazarbachi, Ali

Abstract

Introduction:Allogeneic hematopoietic stem cell transplantation (allo-SCT) offers the only chance of long-term remission and possibly cure for almost all hematologic malignancies. The conditioning regimen plays an important role and its choice is influenced by various factors, such as, age of patient, performance status, disease risk, and remission status at the time of transplantation.

Published
2017
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36. Sequential Regimen with Thiotepa, Cyclophosphamide, Etoposide, Fludarabine and Busulfan in Allogeneic Stem Cell Transplantation for the Treatment of Relapsed and Refractory Hematological Malignancies

Author

El Darsa, Haidar, Massoud, Radwan, Haffar, Basel, Zaherddine, Ammar, Bazarbachi, Ali, and Elcheikh, Jean

Abstract

INTRODUCTION:Relapsed / Refractory leukemia and lymphoma (R/R, L/L) patients have a very poor prognosis despite all the well-known therapeutic strategies. Sequential conditioning followed by allogeneic stem cell transplantation (allo-SCT) provides an efficient disease control in those high risk patients.

Published
2017
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37. Haploidentical stem cell transplantation with post-transplant cyclophosphamide challenges and outcome from a tertiary care center in Lebanon.

Author

El Cheikh J, Bidaoui G, Sharrouf L, Zahreddine A, Massoud R, Nehme R, Kreidieh N, Moukalled N, Abou Dalle I, Mahfouz R, and Bazarbachi A

Abstract

This letter describes the experience of the American University of Beirut Medical Center in Lebanon with haploidentical stem cell transplant (haplo-SCT) for hematological malignancies in adult patients. Haplo-SCT made it possible through universal and rapid donor availability for most of the adult patients with leukemia or lymphoma not only in the Middle East but also globally. Moreover, the use of post-transplant cyclophosphamide (PTCy) and reduced intensity conditioning (RIC) regimens when indicated improved the outcome and decreased the toxicity of haploidentical stem cell transplant.RIC regimens also allowed its use in the elderly population. Patients from throughout the Middle East come to our center, the American university of Beirut Medical Center, to receive this transformative type of stem cell transplant. In this paper, we discuss the results of haplo-SCT with PTCy done on adult patients with hematological malignancies in our center from 2015 to 2021. The results are encouraging and show that haplo-SCT should be considered more often in the Middle Eastern countries. The subgroup analysis showed the importance of achieving complete remission of the disease prior to transplant to improve outcomes in our center. There is a paucity of literature on the outcomes of haplo-SCT in the Middle East which may contribute to the limited number of centers that offer this type of SCT. Herein, we aim to fill this gap in the hopes of encouraging the implementation of this potentially curative modality of treatment to a larger extent in the Middle East., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors JE-C and RM declared that they were editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 El Cheikh, Bidaoui, Sharrouf, Zahreddine, Massoud, Nehme, Kreidieh, Moukalled, Abou Dalle, Mahfouz and Bazarbachi.)

Published
2023
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38. Antibody response after vaccination against SARS-CoV-2 in adults with hematological malignancies: a systematic review and meta-analysis.

Author

Gagelmann N, Passamonti F, Wolschke C, Massoud R, Niederwieser C, Adjallé R, Mora B, Ayuk F, and Kröger N

Subjects
Adult, Antibody Formation, COVID-19 Vaccines, Humans, SARS-CoV-2, Vaccination, COVID-19 prevention & control, Hematologic Neoplasms therapy
Abstract

Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in fragile patients. We aimed to systematically analyze the outcomes of patients with hematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (2 doses of mRNA or one dose of vectorbased vaccines). We identified 49 studies comprising 11,086 individuals. Overall risk of bias was low. The pooled response for hematological malignancies was 64% (95% confidence interval [CI]: 59-69; I²=93%) versus 96% (95% CI: 92-97; I²=44%) for solid cancer and 98% (95% CI: 96-99; I²=55%) for healthy controls (P<0.001). Outcome was different across hematological malignancies (P<0.001). The pooled response was 50% (95% CI: 43-57; I²=84%) for chronic lymphocytic leukemia, 76% (95% CI: 67-83; I²=92%) for multiple myeloma, 83% (95% CI: 69-91; I²=85%) for myeloproliferative neoplasms, 91% (95% CI: 82-96; I²=12%) for Hodgkin lymphoma, and 58% (95% CI: 44-70; I²=84%) for aggressive and 61% (95% CI: 48-72; I²=85%) for indolent non-Hodgkin lymphoma. The pooled response for allogeneic and autologous hematopoietic cell transplantation was 82% and 83%, respectively. Being in remission and prior COVID-19 showed significantly higher responses. Low pooled response was identified for active treatment (35%), anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). Studies on timing, value of boosters, and long-term efficacy are needed. This study is registered with PROSPERO (clinicaltrials gov. Identifier: CRD42021279051).

Published
2022
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39. 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 R, Gagelmann N, Fritzsche-Friedland U, Zeck G, Heidenreich S, Wolschke C, Ayuk F, Christopeit M, and Kröger N

Subjects
CD4-Positive T-Lymphocytes, Cyclophosphamide therapeutic use, Herpesvirus 4, Human, Humans, Retrospective Studies, Epstein-Barr Virus Infections complications, Globulins therapeutic use, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation methods, Immune Reconstitution, Peripheral Blood Stem Cell Transplantation adverse effects
Abstract

Anti-T-cell lymphocyte globulin (ATLG) and posttransplant cyclophosphamide (PTCy) are now widely used strategies to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Data comparing immune reconstitution (IR) between ATLG and PTCy is scarce. This retrospective study conducted at the University Medical Center Hamburg-Eppendorf (UKE) compares PTCy (n=123) and ATLG (n=476) after myeloablative allogeneic peripheral blood stem cell transplant. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100 and 180 posttransplant. Incidence of infections, viral reactivations, GVHD and relapse were collected. Neutrophil engraftment was significantly delayed in the PTCy group (median day 12 vs. day 10, P<0.001) with a high incidence of infection before day+100 in the PTCy arm but a higher Epstein-Barr virus reactivation in the ATLG arm and comparable cytomegalovirus reactivation. Overall incidence of acute GVHD was similar but moderate/severe chronic GVHD was seen more often after PTCy (44% vs. 38%, P=0.005). ATLG resulted in a faster reconstitution of CD8+ T, NK, NKT and gdT cells while CD4 T cells and B cells reconstituted faster after PTCy. Similar reconstitution was observed for T-regulatory cells and B cells. Non-relapse mortality relapse incidence, disease-free survival, and overall survival did not differ significantly between both arms. Even though differences in IR were related to a decreased incidence of infection and moderate/severe cGVHD in the ATLG group they had no impact on any of the other long-term outcomes. However, it remains undetermined which regimen is better as GVHD prophylaxis.

Published
2022
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