Article
Hematology
Ceri Bygrave, Charlotte Pawlyn, Faith Davies, Zoe Craig, David Cairns, Anna Hockaday, Matthew Jenner, Gordon Cook, Mark Drayson, Roger Owen, Walter Gregory, Gareth Morgan, Graham Jackson, Martin Kaiser
Summary: Despite equal access to subsequent therapies, myeloma patients who relapse early within 12 months of autologous stem cell transplant have significantly worse progression-free survival and overall survival compared to later relapsing patients, highlighting the urgent need for improved outcome prediction and early intervention strategies.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Despina Fotiou, Foteini Theodorakakou, Efstathios Kastritis
Summary: Systemic AL amyloidosis is a rare hematological disorder caused by clonal plasma cells producing amyloidogenic immunoglobulins. Prognosis is determined by organ involvement, biology of the plasma cell clone, and response to treatment markers. Current staging systems focus on cardiac dysfunction and renal damage. Discovery of sensitive biomarkers for early diagnosis and comprehensive disease biology assessment is crucial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Mehmet Kemal Samur, Marco Roncador, Anil Aktas Samur, Mariateresa Fulciniti, Abdul Hamid Bazarbachi, Raphael Szalat, Masood A. Shammas, Adam S. Sperling, Paul G. Richardson, Florence Magrangeas, Stephane Minvielle, Aurore Perrot, Jill Corre, Philippe Moreau, Anjan Thakurta, Giovanni Parmigiani, Kenneth C. Anderson, Herve Avet-Loiseau, Nikhil C. Munshi
Summary: High-dose melphalan improves progression-free survival in multiple myeloma, but it causes more mutations in surviving myeloma cells at relapse. These newly acquired mutations are associated with DNA damage and double-stranded breaks, and are predominantly found on the transcribed strand. A machine learning model based on this unique pattern can predict patients who will receive high-dose melphalan with high accuracy.
Article
Hematology
Hamza Hassan, Karina Verma, Grace Ferri, Dina Brauneis, Karen Quillen, J. Mark Sloan, Vaishali Sanchorawala, Camille Vanessa Edwards
Summary: High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is well tolerated in older patients with AL amyloidosis. Compared to the mHDM group, patients in the HDM group had a higher proportion of very good partial response at 12 months and longer progression-free survival. However, transplant-related non-hematologic toxicities were more common in the HDM group.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Oncology
Robert Puckrin, Neil Chua, Mona Shafey, Douglas A. Stewart
Summary: HD-MTX-based induction followed by TBMR/ASCT has the potential to achieve long-term survival in a substantial proportion of patients with SCNSL.
LEUKEMIA & LYMPHOMA
(2022)
Article
Hematology
Giovanni Palladini, Giampaolo Merlini
Summary: The treatment of AL amyloidosis is a challenge for hematologists, but early diagnosis and personalized therapy can improve patient outcomes.
Article
Oncology
Raphael Koch, Hans Gelderblom, Lianne Haveman, Benedicte Brichard, Heribert Juergens, Sona Cyprova, Henk van den Berg, Wolf Hassenpflug, Anna Raciborska, Torben Ek, Daniel Baumhoer, Gerardine Egerer, Hans Theodor Eich, Marleen Renard, Peter Hauser, Stefan Burdach, Judith Bovee, Fiona Bonar, Peter Reichardt, Jarmila Kruseova, Jendrik Hardes, Thomas Kuhne, Torsten Kessler, Stephane Collaud, Marie Bernkopf, Trude Butterfass-Bahloul, Catharina Dhooge, Sebastian Bauer, Janos Kiss, Michael Paulussen, Angela Hong, Andreas Ranft, Beate Timmermann, Jelena Rascon, Volker Vieth, Jukka Kanerva, Andreas Faldum, Markus Metzler, Wolfgang Hartmann, Lars Hjorth, Vivek Bhadri, Uta Dirksen
Summary: The study evaluated the effect of high-dose chemotherapy followed by reinfusion of autologous hematopoietic stem cells on survival in high-risk Ewing sarcoma patients. The results showed no benefit of TreoMel-HDT for the entire cohort, but it may be beneficial for patients younger than 14 years. This observation is supported by other studies.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Cedric Gillich, Dilara Akhoundova, Michael Hayoz, Yolanda Aebi, Carlo R. Largiader, Katja Seipel, Michael Daskalakis, Ulrike Bacher, Thomas Pabst
Summary: Upfront treatment consolidation with TreoMel HDCT and ASCT has promising efficacy and safety in MM patients, achieving a complete response rate of 84% and an OS rate of 83%. Treosulfan pharmacokinetics showed no significant correlation with MM responses, but higher exposure and peak value in female patients were associated with longer hospitalizations.
Article
Hematology
Eli Muchtar, Angela Dispenzieri, Shaji K. Kumar, Martha Q. Lacy, Francis K. Buadi, David Dingli, Suzanne R. Hayman, Nelson Leung, Prashant Kapoor, Wilson Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Yi Lisa Hwa, Amie Fonder, Miriam Hobbs, Ronald S. Go, S. Vincent Rajkumar, Robert A. Kyle, William J. Hogan, Morie A. Gertz
Summary: This study assessed the utility of ASCT2 in AL amyloidosis and found that progression-free and overall survival were significantly longer after ASCT2 for patients with durable remission after ASCT1 and those who did not receive therapy between the two transplants.
TRANSPLANTATION AND CELLULAR THERAPY
(2021)
Editorial Material
Hematology
Giampaolo Merlini, Giovanni Palladini
Summary: The study demonstrates the effectiveness and good tolerability of passive antiamyloid immunotherapy using the monoclonal antibody CAEL-101 in patients with LC amyloidosis, with significant treatment outcomes achieved in a short period of time.
Article
Pharmacology & Pharmacy
Giovanni Palladini, Paolo Milani
Summary: Systemic light chain (AL) amyloidosis is a rapidly progressive disease caused by a small B cell clone producing toxic light chains. The major affected organs are the heart and kidney, but others can also be involved. Adequate technology and expertise are essential for the diagnosis and workup of patients, and specialized centers should be considered. Treatment options include daratumumab-based therapy and autologous stem cell transplant for eligible patients. Clinical trials are ongoing to test immunotherapy targeting amyloid deposits and the amyloid clone.
Article
Oncology
Lalit Kumar, Ranjit Kumar Sahoo, Sudhir Kumar, Annie K. K. Baa, Ghazal Tansir, Neha Pathak, Prabhat S. S. Malik, Om Dutt Sharma, Anisha Mathew, Ankit Jha, Ritu Gupta, Atul Sharma, Ahitagni Biswas, Rakesh Kumar, Sanjay Thulkar, Soumyaranjan Malik, Ashish Dutt, AIIMS Myeloma Grp
Summary: The impact of melphalan dose on transplant outcomes for multiple myeloma was evaluated. Patient response to transplantation and overall survival were similar regardless of melphalan dose. The initial treatment played a crucial role in preparing patients for subsequent transplant outcomes.
LEUKEMIA & LYMPHOMA
(2023)
Article
Biophysics
Francesca Guijarro, Alex Bataller, Marina Diaz-Beya, Ana Garrido, Christelle Coll-Ferra, Susana Vives, Olga Salamero, David Valcarcel, Mar Tormo, Montserrat Arnan, Antonia Sampol, Sandra Castano-Diez, Carmen Martinez, Maria Suarez-Lledo, Francesc Fernandez-Aviles, Juan Carlos Hernandez-Boluda, Josep Maria Ribera, Montserrat Rovira, Salut Brunet, Jorge Sierra, Jordi Esteve
Summary: This study analyzed the long-term outcomes of a sequential regimen based on IDA-FLAG and high-dose melphalan in patients with relapsed/refractory acute myeloid leukemia. The results showed that this regimen achieved a high complete response rate and a lower cumulative relapse incidence, but also had a high non-relapse mortality and a significant incidence of grade 3-4 acute graft-versus-host disease. Long-term survivors enjoyed a good quality of life.
BONE MARROW TRANSPLANTATION
(2022)
Article
Hematology
Murielle Roussel, Valerie Lauwers-Cances, Margaret Macro, Xavier Leleu, Bruno Royer, Cyrille Hulin, Lionel Karlin, Aurore Perrot, Cyrille Touzeau, Marie-Lorraine Chretien, Sophie Rigaudeau, Mamoun Dib, Emmanuelle Nicolas-Virelizier, Martine Escoffre-Barbe, Karim Belhadj, Clara Mariette, Anne-Marie Stoppa, Carla Araujo, Chantal Doyen, Jean Fontan, Brigitte Kolb, Laurent Garderet, Sabine Brechignac, Jean-Valere Malfuson, Arnaud Jaccard, Pascal Lenain, Cecile Borel, Benjamin Hebraud, Omar Benbrahim, Veronique Dorvaux, Salomon Manier, Karine Augeul-Meunier, Marie-Christiane Vekemans, Edouard Randriamalala, Driss Chaoui, Jo Caers, Carine Chaleteix, Lofti Benboubker, Laure Vincent, Sylvie Glaisner, Patricia Zunic, Borhane Slama, Jean-Richard Eveillard, Catherine Humbrecht-Kraut, Veronique Morel, Philippe Mineur, Jean-Claude Eisenmann, Helene Demarquette, Valentine Richez, Marguerite Vignon, Denis Caillot, Thierry Facon, Philippe Moreau, Anne-Laurene Colin, Pascale Olivier, Soraya Wuilleme, Herve Avet-Loiseau, Jill Corre, Michel Attal
Summary: This study found that the combination of bortezomib and high-dose melphalan did not improve outcomes or efficacy endpoints in patients with multiple myeloma compared to high-dose melphalan alone.
Article
Multidisciplinary Sciences
Pamina Kazman, Ramona M. Absmeier, Harald Engelhardt, Johannes Buchner
Summary: The study characterizes the lag phase of a patient-derived truncated LC using biochemical and biophysical experiments, identifying structural transitions that occur prior to fibril formation.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Angela Dispenzieri, Efstathios Kastritis, Ashutosh D. Wechalekar, Stefan O. Schoenland, Kihyun Kim, Vaishali Sanchorawala, Heather J. Landau, Fiona Kwok, Kenshi Suzuki, Raymond L. Comenzo, Deborah Berg, Guohui Liu, Arun Kumar, Douglas V. Faller, Giampaolo Merlini
Summary: In relapsed/refractory AL amyloidosis patients, there was no significant difference in hematologic response rate and complete response rate between the ixazomib-dexamethasone treatment group and physician's choice treatment group, but patients in the ixazomib-dexamethasone group had a significantly longer median time to vital organ deterioration or mortality.
Article
Hematology
Raphael E. Szalat, Joshua Gustine, J. Mark Sloan, Camille Edwards, Vaishali Sanchorawala
Summary: Daratumumab as a single agent or in combination with chemotherapies shows impressive efficacy in AL amyloidosis patients, but predictive factors associated with outcomes remain unclear. Achieving at least VGPR and presence of 1q21 gain are independently associated with better progression free survival and overall survival. Patients receiving more than 12 cycles of daratumumab therapy have significantly longer survival outcomes.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Review
Medicine, General & Internal
Maya Abdallah, Vaishali Sanchorawala
Summary: The management of AL amyloidosis is complex and requires careful consideration of various factors. Emerging data have suggested promising results for novel therapeutic agents. High-dose melphalan and stem cell transplantation is recommended for eligible patients, while bortezomib-based regimens are recommended for transplant-ineligible patients. For relapsed/refractory disease, novel therapeutics such as proteosome inhibitors, immunomodulatory agents, and monoclonal antibodies have shown promising outcomes.
AMERICAN JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Vaishali Sanchorawala, Mario Boccadoro, Morie Gertz, Ute Hegenbart, Efstathios Kastritis, Heather Landau, Peter Mollee, Ashutosh Wechalekar, Giovanni Palladini
Summary: These guidelines comprehensively assess the eligibility criteria and strategies for stem cell transplantation treatment in AL amyloidosis patients, including stem cell collection, drug therapy, and supportive care, aiming to improve survival rates and reduce complications for patients.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Ashutosh D. Wechalekar, M. Teresa Cibeira, Simon D. Gibbs, Arnaud Jaccard, Shaji Kumar, Giampaolo Merlini, Giovanni Palladini, Vaishali Sanchorawala, Stefan Schonland, Christopher Venner, Mario Boccadoro, Efstathios Kastritis
Summary: This guideline recommends non-transplant chemotherapy treatment for AL amyloidosis patients, based on clinical presentation and patient tolerance. Targeted therapy evaluation and treatment methods for amyloid fibrils are urgently needed.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Hematology
Vaishali Sanchorawala, Ashutosh D. D. Wechalekar, Kihyun Kim, Stefan O. O. Schonland, Heather J. J. Landau, Fiona Kwok, Kenshi Suzuki, Angela Dispenzieri, Giampaolo Merlini, Raymond L. L. Comenzo, Dasha Cherepanov, Vanessa C. C. Hayden, Arun Kumar, Richard Labotka, Douglas V. V. Faller, Efstathios Kastritis
Summary: Patient-reported outcomes in AL amyloidosis have not been thoroughly studied. However, analysis of data from the TOURMALINE-AL1 trial showed that patients treated with ixazomib-dexamethasone had similar or better health-related quality of life and symptoms compared to those treated with chemotherapy.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Andrew Staron, Lisa M. Mendelson, Tracy Joshi, Frederick L. Ruberg, Vaishali Sanchorawala
Summary: Through a retrospective review of referrals to the Amyloidosis Centre from 2010 to 2021, it was found that 6% of cases lacked amyloid pathology upon extensive assessment at the centre. The main sources of misdiagnosis were erroneous staining of tissue specimens and misinterpretation of cardiac imaging, with misinterpretation of cardiac imaging becoming a major source in recent years.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Pathology
Karina Verma, Tina Zhang, David Mueller, Julie Li, Vaishali Sanchorawala, Andrew Staron
Summary: This study reports a case of hyperammonemic encephalopathy (HE) as the presenting symptom in a patient with non-producer multiple myeloma (NPMM). The patient successfully reversed HE symptoms through various treatments. This case challenges the previously suggested mechanism that excess ammonia in multiple myeloma arises from degradation of M-proteins, and postulates amplified amino acid metabolism in neoplastic plasma cells of NPMM.
DIAGNOSTIC PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lisa Mendelson, Tatiana Prokaeva, K. H. Vincent Lau, Vaishali Sanchorawala, Kristen McCausland, Brian Spencer, Surendra Dasari, Ellen D. McPhail, Michelle C. Kaku
Summary: This article describes the clinical features of hereditary gelsolin (AGel) amyloidosis, a systemic disease characterized by neurological, ophthalmological, dermatological, and other organ involvements. Neurological manifestations were observed in 15 patients, including cranial neuropathy, peripheral neuropathy, and carpal tunnel syndrome. A novel gelsolin variant was identified and associated with a unique clinical phenotype.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Editorial Material
Oncology
Vaishali Sanchorawala
JCO ONCOLOGY PRACTICE
(2023)
Article
Health Care Sciences & Services
Avery A. Rizio, Michelle K. White, Anita D'Souza, Kristen Hsu, Paula Schmitt, Tiffany P. Quock, James Signorovitch, Isabelle Lousada, Vaishali Sanchorawala
Summary: Systemic AL amyloidosis is a rare protein misfolding disorder that affects various organs, leading to organ dysfunction and failure. The Amyloidosis Forum aims to accelerate the development of effective treatments for AL amyloidosis through a public-private partnership. The Health-Related Quality of Life (HRQOL) Working Group within the forum identified patient-reported outcome (PRO) assessments of HRQOL that are relevant for clinical trials and practice. They found that the SF-36v2 Health Survey and PROMIS-29 Profile are suitable instruments for AL amyloidosis patients, but further work is needed to establish clinically meaningful change thresholds.
PATIENT-RELATED OUTCOME MEASURES
(2023)
Article
Hematology
Morie A. Gertz, Adam D. Cohen, Raymond L. Comenzo, Efstathios Kastritis, Heather J. Landau, Edward N. Libby, Michaela Liedtke, Vaishali Sanchorawala, Stefan Schoenland, Ashutosh Wechalekar, Jeffrey A. Zonder, Giovanni Palladini, Jackie Walling, Spencer Guthrie, Christie Nie, Carol Karp, Yuying Jin, Gene G. Kinney, Giampaolo Merlini
Summary: The VITAL trial assessed the efficacy and safety of birtamimab in combination with standard of care in AL amyloidosis patients. Although no significant difference was observed in the overall results, a post hoc analysis showed significant improvement in survival time at month 9 for Mayo stage IV patients treated with birtamimab.
Article
Hematology
Joshua N. Gustine, Andrew Staron, Lisa Mendelson, Tracy Joshi, Deepa M. Gopal, Omar K. Siddiqi, Frederick L. Ruberg, Vaishali Sanchorawala
Summary: Patients with advanced cardiac AL amyloidosis have a poor prognosis. Early hematologic and cardiac responses can prolong survival. This study identified factors predictive of treatment outcomes and survival.
Letter
Biochemistry & Molecular Biology
K. H. Vincent Lau, Tatiana Prokaeva, Luke Zheng, Gheorghe Doros, Michelle C. Kaku, Brian Spencer, John Berk, Vaishali Sanchorawala
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Hematology
Hamza Hassan, Karina Verma, Grace Ferri, Dina Brauneis, Karen Quillen, J. Mark Sloan, Vaishali Sanchorawala, Camille Vanessa Edwards
Summary: High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is well tolerated in older patients with AL amyloidosis. Compared to the mHDM group, patients in the HDM group had a higher proportion of very good partial response at 12 months and longer progression-free survival. However, transplant-related non-hematologic toxicities were more common in the HDM group.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
