Review
Oncology
Iman Abou Dalle, Ali Atoui, Ali Bazarbachi
Summary: Relapsed acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) is a challenging event, and the current treatment landscape is still facing difficulties. Recent research has allowed the development of new strategies that can improve remission rates and prolong survival.
FRONTIERS IN ONCOLOGY
(2022)
Article
Hematology
Dipenkumar Modi, Vijendra Singh, Seongho Kim, Lois Ayash, Abhinav Deol, Voravit Ratanatharathorn, Joseph P. Uberti
Summary: When comparing outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning and myeloablative conditioning regimens using thymoglobulin for GVHD prophylaxis, there was no significant difference in survival, relapse rates, or GVHD-free relapse-free survival between the two regimens. Thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with the reduced intensity conditioning regimen.
ANNALS OF HEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Farid Boulad, Aurelio Maggio, Xiuyan Wang, Paolo Moi, Santina Acuto, Friederike Kogel, Chayamon Takpradit, Susan Prockop, Jorge Mansilla-Soto, Annalisa Cabriolu, Ashlesha Odak, Jinrong Qu, Keyur Thummar, Fang Du, Lingbo Shen, Simona Raso, Rita Barone, Rosario Di Maggio, Lorella Pitrolo, Antonino Giambona, Maura Mingoia, John K. Everett, Pascha Hokama, Aoife M. Roche, Vito Adrian Cantu, Hriju Adhikari, Shantan Reddy, Eric Bouhassira, Narla Mohandas, Frederic D. Bushman, Isabelle Riviere, Michel Sadelain
Summary: This study reports the 6-8-year follow-up of four adult patients with transfusion-dependent beta-thalassemia who received autologous CD34(+) cells transduced with a lentiviral globin vector. The findings suggest that non-myeloablative conditioning can achieve durable stem cell engraftment, but a minimum CD34(+) cell transduction requirement is necessary for effective therapy. The study highlights the importance of monitoring patients with globin vectors.
Article
Hematology
Oscar B. Lahoud, Sean M. Devlin, Molly A. Maloy, Lindsey E. Roeker, Parastoo B. Dahi, Doris M. Ponce, Boglarka Gyurkocza, Guenther Koehne, James W. Young, Hugo R. Castro-Malaspina, Juliet N. Barker, Esperanza B. Papadopoulos, Ann A. Jakubowski, Andrew D. Zelenetz, Anthony R. Mato, Sergio A. Giralt, Miguel A. Perales, Craig S. Sauter
Summary: This study demonstrates that allogeneic hematopoietic stem cell transplantation (HSCT) can potentially cure patients with chronic lymphocytic leukemia (CLL), with favorable progression-free survival (PFS) and overall survival (OS) rates. The impact of novel agents on HSCT outcomes was found to be negligible. Reduced intensity conditioning (RIC) HSCT may be a successful treatment option for CLL patients with Richter's transformation and poor-risk CLL patients.
Article
Immunology
Danielle E. Arnold, Rofida Nofal, Connor Wakefield, Kai Lehmberg, Katharina Wustrau, Michael H. Albert, Emma C. Morris, Jennifer R. Heimall, Nancy J. Bunin, Ashish Kumar, Michael B. Jordan, Theresa Cole, Sharon Choo, Tim Brettig, Carsten Speckmann, Stephan Ehl, Malgorzata Salamonowicz, Justin Wahlstrom, Kanchan Rao, Claire Booth, Austen Worth, Rebecca A. Marsh
Summary: Patients with XIAP deficiency tolerate reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens well, with survival rates similar to hematopoietic cell transplantation (HCT) for other genetic HLH disorders. Acute GVHD and HLA mismatch negatively impact survival in XIAP-deficient patients undergoing allogeneic HCT.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Hematology
Shlomo Elias, Samantha Brown, Sean M. Devlin, Juliet N. Barker, Christina Cho, David J. Chung, Parastoo B. Dahi, Sergio Giralt, Boglarka Gyurkocza, Ann A. Jakubowski, Oscar B. Lahoud, Heather Landau, Richard J. Lin, Esperanza B. Papadopoulos, Ioannis Politikos, Doris M. Ponce, Michael Scordo, Brian C. Shaffer, Gunjan L. Shah, Roni Tamari, James W. Young, Miguel-Angel Perales, Roni Shouval
Summary: Comorbidity assessment is important before allogeneic haematopoietic cell transplantation (allo-HCT) to estimate non-relapse mortality (NRM) risk. The Simplified Comorbidity Index (SCI), which includes a small number of comorbidities and older age, has been shown to predict NRM. In this study, we validated the SCI in patients receiving reduced-intensity conditioning followed by allo-HCT from HLA-matched donors. Higher SCI scores were associated with increased NRM risk and reduced overall survival. These findings suggest that the SCI is a reliable tool for risk stratification in allo-HCT candidates.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Hematology
Brian D. Friend
Summary: In this study, the authors demonstrate that treatment intensification and improved supportive care measures have significantly improved long-term survival for childhood AML survivors. However, they also highlight the unwanted effects of treatment intensification, including increased burden of late effects and toxicity in recent patients.
Article
Oncology
Brendan Rasor, Tyler Dickerson, Qiuhong Zhao, Patrick Elder, Jonathan E. Brammer, Karilyn Larkin, Samantha Jaglowski, Alice Mims, Sam Penza, Sumithira Vasu, Sarah A. Wall, Basem William, Ayman Saad, Julianna V. F. Roddy, Hannah Choe, Marcin Puto
Summary: The retrospective cohort study compared the efficacy and tolerability of busulfan AUC target of 16.4 mg x Hr/L per day (FluBu4K) and a conventional RIC regimen (FluBu2) in patients with AML or MDS. The results suggest that for select patients, there may be benefit in choosing FluBu4K over FluBu2, as it showed a lower cumulative incidence of relapse at 18 months.
LEUKEMIA & LYMPHOMA
(2021)
Article
Biophysics
Dipenkumar Modi, Seongho Kim, Abhinav Deol, Lois Ayash, Voravit Ratanatharathorn, Joseph P. Uberti
Summary: Our study found no significant difference in outcomes between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) regimens in haploidentical peripheral blood stem cell transplant (haploPBSCT).
BONE MARROW TRANSPLANTATION
(2021)
Article
Biophysics
Nobuhiko Imahashi, Seitaro Terakura, Eisei Kondo, Koji Kato, Sung-Won Kim, Akihito Shinohara, Mizuki Watanabe, Takahiro Fukuda, Naoyuki Uchida, Hikaru Kobayashi, Jun Ishikawa, Keisuke Kataoka, Souichi Shiratori, Takashi Ikeda, Ken-ichi Matsuoka, Shuro Yoshida, Tadakazu Kondo, Takafumi Kimura, Makoto Onizuka, Tatsuo Ichinohe, Yoshiko Atsuta, Junya Kanda
Summary: The study showed that UCB transplantation with optimal conditioning and GVHD prophylaxis had better outcomes compared to MRD and MUD transplantation, suggesting it is a highly effective treatment for mature lymphoid malignancies. This indicates that UCB transplantation might be preferred over MRD or MUD transplantation in certain settings.
BONE MARROW TRANSPLANTATION
(2022)
Article
Immunology
Akira Nishimura, Yuki Aoki, Yasuyoshi Ishiwata, Takuya Ichimura, Junichi Ueyama, Yuta Kawahara, Takahiro Tomoda, Maiko Inoue, Kazuaki Matsumoto, Kento Inoue, Haruka Hiroki, Shintaro Ono, Motoi Yamashita, Tsubasa Okano, Mari Tanaka-Kubota, Miho Ashiarai, Satoshi Miyamoto, Reiji Miyawaki, Chika Yamagishi, Mari Tezuka, Teppei Okawa, Akihiro Hoshino, Akifumi Endo, Masato Yasuhara, Takahiro Kamiya, Noriko Mitsuiki, Toshiaki Ono, Takeshi Isoda, Masakatsu Yanagimachi, Daisuke Tomizawa, Masayuki Nagasawa, Shuki Mizutani, Michiko Kajiwara, Masatoshi Takagi, Hirokazu Kanegane, Kohsuke Imai, Tomohiro Morio
Summary: The purpose of the study was to compare the safety and efficacy of different conditioning regimens in hematopoietic cell transplantation for patients with primary immunodeficiency diseases. The results showed that FluBU regimen was effective in achieving high-level chimerism and long-term survival in SCID patients, while outcomes varied in non-SCID patients depending on the subtype of the disease. Further studies are needed to optimize the conditioning regimen for non-SCID PID patients.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Sharat Chandra, Kana Mizuno, Junfang Zhao, Stella M. Davies, Rebecca A. Marsh, Tsuyoshi Fukuda, Kenneth D. R. Setchell, Alexander A. Vinks, Parinda A. Mehta
Summary: The study demonstrates that using test-dose pharmacokinetics to predict full-dose pharmacokinetics of melphalan allows for accurate adjustment of melphalan dosage, preventing excess toxicity from increased systemic exposure, especially for patients with organ impairment.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Makoto Nakamura, Yusuke Meguri, Shuntaro Ikegawa, Takumi Kondo, Yuichi Sumii, Takuya Fukumi, Miki Iwamoto, Yasuhisa Sando, Hiroyuki Sugiura, Noboru Asada, Daisuke Ennishi, Shuta Tomida, Emi Fukuda-Kawaguchi, Yasuyuki Ishii, Yoshinobu Maeda, Ken-ichi Matsuoka
Summary: Alpha-galactosylceramide (alpha-GC) administration after reduced-dose posttransplantation cyclophosphamide (PTCy) efficiently restores GVHD-preventing activity and maintains the GVL effect, providing important insights for optimizing transplantation strategies.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Aniko Sijs-Szabo, Avinash G. Dinmohamed, Jurjen Versluis, Bronno van der Holt, Mar Bellido, Mette D. Hazenberg, Michel van Gelder, Nicolaas P. M. Schaap, Ellen Meijer, Lotte E. van der Wagen, Constantijn J. M. Halkes, Anita W. Rijneveld, Jan J. Cornelissen
Summary: In this retrospective study, RIC-alloHSCT was compared with MAC-alloHSCT in older adult patients with acute lymphoblastic leukemia. The results showed that RIC-alloHSCT had lower nonrelapse mortality but a significantly higher relapse rate compared to MAC-alloHSCT. These findings suggest that MAC-alloHSCT may be a more effective consolidation therapy for reducing relapse.
Editorial Material
Hematology
Marie Bleakley, Melinda Biernacki
Summary: In this study, it was found that inhibition of MDM2 enhances T-cell responses to AML and facilitates the GVL effect in murine models of allo-HCT.
Article
Biophysics
J. Loke, M. Labopin, C. Craddock, D. Niederwieser, J. Cornelissen, B. Afansayev, P. Jindra, J. Maertens, D. Blaise, K. Boriskina, M. Gramatzki, A. Ganser, B. Savani, M. Mohty, A. Nagler
Summary: A study of 937 AML patients undergoing transplantation from a mismatched unrelated donor found that patient age, adverse karyotype, and CMV seropositivity were correlated with decreased LFS and OS. There was no significant difference in LFS or OS between patients transplanted from donors mismatched at different HLA loci, but HLA-A mismatched transplants were associated with higher rates of acute GVHD and NRM. Patient CMV seropositivity was linked to increased NRM and acute GVHD, as well as reduced LFS and OS.
BONE MARROW TRANSPLANTATION
(2021)
Article
Biophysics
Jaime Sanz, Myriam Labopin, Miguel A. Sanz, Mahmoud Aljurf, Aida Botelho Sousa, Charles Craddock, Tsila Zuckerman, Helene Labussiere-Wallet, Antonio Campos, Giovanni Grillo, Zubeyde Nur Ozkurt, J. J. Cornelissen, Peter Remenyi, Massimo Martino, Rocio Parody Porras, Arnon Nagler, Norbert-Claude Gorin, Mohamad Mohty
Summary: The study compared outcomes of adult patients with APL in CR2 receiving alloHSCT or autoHSCT, showing higher non-relapse mortality in the alloHSCT group but no significant difference in relapse rate. AutoHSCT resulted in better Leukemia-free survival (LFS) and overall survival (OS) compared to alloHSCT, mainly due to reduced non-relapse mortality.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Charles Craddock, Aimee Jackson, Justin Loke, Shamyla Siddique, Andrea Hodgkinson, John Mason, Georgia Andrew, Sandeep Nagra, Ram Malladi, Andrew Peniket, Maria Gilleece, Rahuman Salim, Eleni Tholouli, Victoria Potter, Charles Crawley, Keith Wheatley, Rachel Protheroe, Paresh Vyas, Ann Hunter, Anne Parker, Keith Wilson, Jiri Pavlu, Jenny Byrne, Richard Dillon, Naeem Khan, Nicholas McCarthy, Sylvie D. Freeman
Summary: The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes for adults undergoing transplantation for high-risk AML or MDS, regardless of pretransplant MRD status. Pretransplant detectable MRD was associated with disease relapse, but acquisition of full donor T-cell chimerism improved overall survival.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Letter
Oncology
Charles Craddock, Aimee Jackson, Sylvie D. Freeman
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Hematology
Justin Loke, Marlen Metzner, Rebecca Boucher, Aimee Jackson, Louise Hopkins, Jiri Pavlu, Eleni Tholouli, Mark Drummond, Andy Peniket, Rebecca Bishop, Sonia Fox, Paresh Vyas, Charles Craddock
Summary: The ROMAZA trial established the maximum tolerated dose of combined ROM/AZA therapy for AML patients, with ROM 12 mg/m(2) on Days 8 and 15, and AZA 75 mg/m(2) administered for 7/28 day cycle. Among patients treated at the maximum tolerated dose, 23.7% were classified as responders by Cycle 6. Correlative next-generation sequencing studies provided important insights into therapy resistance.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Mhairi Copland, Daniel Slade, Graham McIlroy, Gillian Horne, Jenny L. Byrne, Kate Rothwell, Kristian Brock, Hugues De Lavallade, Charles Craddock, Richard E. Clark, Matthew L. Smith, Rachel Fletcher, Rebecca Bishop, Dragana Milojkovic, Christina Yap
Summary: The combination of ponatinib and FLAG-IDA demonstrated clinically meaningful activity and tolerability in patients with blast-phase chronic myeloid leukaemia, allowing for induction of a second chronic phase and preparation for allogeneic HSCT.
LANCET HAEMATOLOGY
(2022)
Article
Biophysics
Jesus Duque-Afonso, Juergen Finke, Myriam Labopin, Charles Craddock, Rachel Protheroe, Panagiotis Kottaridis, Eleni Tholouli, Jenny L. Byrne, Kim Orchard, Urpu Salmenniemi, Inken Hilgendorf, Hannah Hunter, Emma Nicholson, Adrian Bloor, John A. Snowden, Mareike Verbeek, Andrew Clark, Bipin N. Savani, Alexandros Spyridonidis, Arnon Nagler, Mohamad Mohty
Summary: This study compared the outcomes of two commonly used conditioning protocols, FluMel and FluTreo, for patients with acute myeloid leukemia. While both groups had similar overall survival rates, the FluMel group had a lower relapse incidence and slightly higher non-relapse mortality.
BONE MARROW TRANSPLANTATION
(2022)
Article
Oncology
Victoria Stavrou, Livingstone Fultang, Sarah Booth, Daniele De Simone, Arekdiusz Bartnik, Ugo Scarpa, Luciana Gneo, Silvia Panetti, Sandeep Potluri, Meaad Almowaled, Jonathan Barlow, Andris Jankevics, Gavin Lloyd, Andrew Southam, David A. Priestman, Paul Cheng, Warwick Dunn, Frances Platt, Hitoshi Endou, Charles Craddock, Karen Keeshan, Francis Mussai, Carmela De Santo
Summary: Acute myeloid leukaemia (AML) creates an immunosuppressive environment through induced arginine depletion. Serum amyloid A (SAA) in AML upregulates ARG2 expression, promotes cell viability, and activates iNKT cells, resulting in AML cell death. Therefore, stimulating iNKT cell activity has potential as an immunotherapy for AML.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Oncology
Naval G. Daver, Abhishek Maiti, Tapan M. Kadia, Paresh Vyas, Ravindra Majeti, Andrew H. Wei, Guillermo Garcia-Manero, Charles Craddock, David A. Sallman, Hagop M. Kantarjian
Summary: TP53-mutated MDS and AML are a distinct group of myeloid disorders with poor outcomes. Recent advances have identified novel pathogenic mechanisms and emerging therapies, including immunotherapeutic and nonimmune-based approaches, for the treatment of this entity.
Article
Hematology
Justin Loke, Nicholas McCarthy, Aimee Jackson, Shamyla Siddique, Andrea Hodgkinson, John Mason, Charles Crawley, Maria Gilleece, Andrew Peniket, Rachel Protheroe, Rahuman Salim, Eleni Tholouli, Keith Wilson, Georgia Andrew, Richard Dillon, Naeem Khan, Victoria Potter, Pramila Krishnamurthy, Charles Craddock, Sylvie Freeman
Summary: This study reports the prognostic impact of biomarkers including MRD, T-cell chimerism, and blast HLA-DR expression in AML/MDS patients receiving allogeneic stem-cell transplant. MRD positivity is associated with reduced overall survival, while MRD is infrequent and does not affect the outcome in patients with full donor T-cell chimerism.
Article
Biophysics
Enrico Maffini, Maud Ngoya, Jacques-Emmanuel Galimard, Samia Harbi, Nicolaus Kroeger, Uwe Platzbecker, Henrik Sengeloev, Charles Craddock, Victoria Potter, Goda Choi, Patrice Chevallier, Friedrich Stolzel, Eleni Tholouli, Johan Maertens, Fabio Ciceri, Jan Cornelissen, Jaime Sanz, Alexandros Spyridonidis, Francesco Lanza, Arnon Nagler, Mohamad Mohty
Summary: Allogeneic HCT programs are becoming accessible for older AML patients. Patients aged ≥70 years who received HCT from matched sibling, unrelated, or haploidentical donors showed good clinical outcomes, with reduced relapse rates and improved leukemia-free survival in haploidentical and unrelated donor transplantations compared to matched sibling transplantation.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Alexandros Spyridonidis, Myriam Labopin, Tobias Gedde-Dahl, Arnold Ganser, Matthias Stelljes, Charles Craddock, Eva Maria Wagner-Drouet, Jurjen Versluis, Thomas Schroeder, Igor Wolfgang Blau, Gerald. G. Wulf, Peter Dreger, Gitte Olesen, Henrik Sengeloev, Nicolaus Kroger, Victoria Potter, Edouard Forcade, Jakob Passweg, Regis Peffault de Latour, Johan Maertens, Keith M. O. Wilson, Jean Henri Bourhis, Juergen Finke, Eolia Brissot, Ali Bazarbachi, Sebastian Giebel, Bipin P. Savani, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
Summary: This study confirms the effectiveness of the recently developed transplant conditioning intensity (TCI) score in predicting mortality and relapse rates in hematopoietic cell transplantation.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Ram Malladi, Ikhlaaq Ahmed, Graham McIlroy, Fiona L. Dignan, Rachel Protheroe, Aimee Jackson, Paul Moss, Jane Nunnick, Shamyla Siddique, Rebecca Bishop, Mohamed Elhaneid, Andrea Hodgkinson, Charles Craddock
Summary: Chronic graft-versus-host disease (cGvHD) is a significant complication following allogeneic stem cell transplant, with a high rate of treatment resistance to standard therapies. The AZTEC trial investigating the use of azacitidine for cGvHD patients resistant to systemic steroids showed promising results in terms of both safety and efficacy, supporting further evaluation in a second stage of the study.
BONE MARROW TRANSPLANTATION
(2021)
Article
Hematology
Francesca A. Kinsella, Charlotte F. Inman, Wayne Croft, Jianmin Zuo, Hayden Pearce, Sara Barbieri, Charles Craddock, Ram Malladi, Paul Moss
Summary: CD52- T cells significantly increase after allo-hematopoietic stem cell transplantation and may be an independent risk factor for acute GVHD.
TRANSPLANTATION AND CELLULAR THERAPY
(2021)
Article
Hematology
Charles Craddock
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
