Blinatumomab for First-Line Treatment of Children and Young Persons With B-ALL.

PURPOSE: We tested whether blinatumomab (Blina) is effective as a toxicity-sparing alternative to first-line intensive chemotherapy in children and young persons (CYP) with B-ALL who were chemotherapy-intolerant or chemotherapy-resistant. METHODS: Data were collected for consecutive CYP (age 1-24 years) with Philadelphia chromosome-positive or Philadelphia chromosome-negative B-ALL who received Blina as first-line therapy. Blina was given as replacement for postremission intensive chemotherapy to patients with chemotherapy intolerance or resistance. Blina responders received further chemotherapy (Blin-CT) or first remission hematopoietic stem-cell transplant (Blin-HSCT) if indicated. Event-free survival (EFS) and overall survival (OS) of the Blin-CT group were compared with those of matched controls treated with standard chemotherapy in the UKALL 2003 trial. Events were defined as death, relapse, or secondary cancer. RESULTS: From February 2018 to February 2023, 105 patients were treated, of whom 85 were in the Blin-CT group and 20 were in the Blin-HSCT group. A majority of Blin-CT patients received Blina for chemotherapy intolerance (70 of 85, 82%), and the group had a higher-risk profile than unselected patients with B-ALL. Blina was well tolerated with only one patient having a grade 3/4-related toxicity event, and of the 60 patients who were minimal residual disease-positive pre-Blina, 58 of 60 (97%) responded. At a median follow-up of 22 months, the 2-year outcomes of the 80 matched Blin-CT group patients were similar to those of 192 controls (EFS, 95% [95% CI, 85 to 98] v 90% [95% CI, 65 to 93] and OS, 97% [95% CI, 86 to 99] v 94% [95% CI, 89 to 96]). Of the 20 in the HSCT group, three died because of transplant complications and two relapsed. CONCLUSION: Blina is safe and effective in first-line treatment of chemotherapy-intolerant CYP with ALL.

Benefits for children with suspected cancer from routine whole-genome sequencing.

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.

Clinical and historical aspects of the Elephant Man: exploring the facts and the myths.

Joseph Merrick, the Elephant Man, presented to the Royal London Hospital in 1884 with an obscure condition that puzzled his contemporaries, and fascinates clinicians to this day. Throughout the 1900s, a number of theories were advanced to explain the numerous growths that covered his body: neurofibromatosis, Proteus syndrome, and a combination of childhood injury, fibrous dysplasia, and pyarthrosis. The debate continued throughout the 20th century without resolution. Today, new consensus on the genetic and clinical diagnosis of neurofibromatosis and Proteus syndrome has allowed advancements in the Elephant Man's diagnosis. Using recent clinical diagnostic criteria it is now possible to conclude that Joseph Merrick was in all likelihood suffering from Proteus syndrome. Nevertheless, details of his genotype remain unknown. Obtaining intact DNA from the Elephant Man's skeleton is challenging, yet it is possible that sequencing Merrick's genome could provide genetic confirmation of his clinical diagnosis, and shed light on the process of tumourigenesis.

Pycnodysostosis and the making of an artist.

Henri de Toulouse-Lautrec, a 19th century artist celebrated for his depictions of the Moulin Rouge and Parisian nightlife, suffered from an unknown disorder. His symptoms were not only rare, but also difficult to determine. Both during his lifetime and following his death potential diagnoses have proved controversial, including the most popularly supported suggestion of pycnodysostosis. Addressing the ongoing debate of Toulouse-Lautrec's diagnosis, this article reconsiders the evidence. It summarises multiple perspectives and draws on more recent medical research, while acknowledging that the available sources are often unreliable. Ultimately, while there may be no definitive solution to the mystery of Toulouse-Lautrec's diagnosis, it is possible to draw one conclusion. Observing its impact on his life and work, it is clear that the condition formed the foundation of Toulouse-Lautrec's artistic career, shaping the way he perceived the world and defining the artworks that are now so widely admired.