I was walking down a side street in Florence, Italy, sipping a cappuccino, when our quirky tour guide, (who I recall reminded me of Mary Poppins with her umbrella, carpet bag, and hint of magical powers), waved us over to a side door of the Galleria dell'Accademia di Firenze. After she rushed us through the door, she navigated us through the crowd of people, waving her umbrella at one masterpiece after another until she halted abruptly directly in front of the pièce de resistance, Michelangelo’s David. After walking us around the colossal marble masterpiece and commenting on her favorite aspect (the veins of his hand), she shared how Michelangelo came to sculpt David. The block of Carrara marble he used was actually discarded and damaged by three different artists before him. He envisioned David in the marred metamorphic rock, and then chipped away until uncovering the masterpiece within the marble. At this year’s ASH, scientists and clinicians have revealed many masterpieces in our understanding and approach to the management of bone marrow failure (BMF) syndromes and clonal hematopoiesis (CH). As a specialist caring for patients with BMF and clonal hematopoiesis of indeterminate potential (CHIP), it is not hard to appreciate progress in these areas as anything short of a masterpiece. Though I don’t think I have any magical powers or any resemblance to Mary Poppins, I will serve as your tour guide through the ASH Galleria dell’BMF Syndromes and CH.
On Dec. 10, the recently launched ASH journal, Blood Neoplasia, hosted a Poster Walk on the Progression of Clonal Hematopoiesis to Hematologic Neoplasms. This illuminating event unveiled six exemplary posters detailing a wide range of concepts, from whole exome detection of genetic drivers of CH to the implementation of machine learning using blood count data to identify high-risk CH. The poster walk platform afforded an intimate and lively setting that allowed presenters to expound on the complex and significant findings from their research. Though the abstracts presented culminated in a masterpiece theater, I was particularly enthralled by Christopher Maximilian Arends’, MD, presentation on the exploratory analysis of CH in ovarian cancer patients undergoing Poly(ADP-ribose) polymerase (PARP) inhibitor therapy. With therapy-related myeloid neoplasms increasingly recognized for those receiving PARP inhibitors, having a more comprehensive understanding of CH under the pressure of PARP inhibition is exceedingly necessary. Investigators not only evaluated CH in whole blood of patient plasma, but also tumor-derived mutations in cell-free DNA. There was a strong association between PARP inhibitor exposure and CH, as well as the number of CH mutations. Further, patients with CH detected had shorter progression-free survival and more frequent infections during study treatment. Overall, this was an intriguing analysis highlighting that CH in this setting is linked to inferior outcomes and associated with potential adverse effects while on PARP inhibition.
If you followed along with me and my metaphorical umbrella, our next stop on our artisan tour was the Education Program session Inherited Bone Marrow Failure Syndromes - From Pediatrics to Adult. Emma M. Groarke, MD, an incomparable BMF authority hailing from the National Institutes of Health, served as chair of this session, which was a treasure trove of BMF syndrome pearls. Recognizing and accurately diagnosing inherited BMF syndromes (IBMFS) is crucial, and more awareness is necessary to ensure IBMFS are not missed. This session provided education, awareness, and so much more. Managing patients with IBMFS is challenging. Timothy S. Olson, MD, PhD, tackled the management of adolescents and young adults with Fanconi nemia (FA), as it is becoming increasingly recognized in this population with unique treatment and surveillance challenges. To close out the masterful program, Marena R. Niewisch, MD, outlined detection, management, and surveillance of telomere biology disorders. Expanding on IBMFS further, an imperative discussion on the extraordinarily complex role and timing of stem cell transplant took place during the Education Program session Goldilocks and Transplant Timing in Inherited Marrow Failure Syndromes: Too Early, Too Late, Just Right?
Michelangelo was quoted as saying, “In every block of marble I see a statue as plain as though it stood before me, shaped and perfect in attitude and action. I have only to hew away the rough walls that imprison the lovely apparition to reveal it to the other eyes as mine see it.” To the scientists, clinicians, and investigators who shared your stunning work on CH and BMF syndromes this year, please know that you have taken the challenging rocks (that many would not dare approach) and have chipped away for us all to see the enlightening revelations buried within. To close out our masterpiece tour, I will leave you with an assortment of CH and BMF abstracts to review if you did not have the chance to do so while in San Diego: Abstracts 811, 229, 937, 948, 369, 812, and 725.
Dr. Ragon indicated no relevant conflicts of interest.
