Grafapex (treosulfan)

This case represents, to our knowledge, one of the very few-if not the first-reported instances of successful HSCT for JMML in a patient with TAR syndrome. It underscores the importance of vigilant surveillance in TAR patients for potential malignant transformation and demonstrates the curative potential of HSCT in rare congenital-hematologic overlap syndromes.

P2, N=132, Not yet recruiting, Masonic Cancer Center, University of Minnesota

P2, N=40, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Jul 2027 --> Jul 2028 | Trial primary completion date: Jul 2027 --> Jul 2028

P4, N=289, Recruiting, Medizinische Hochschule Hannover | N=128 --> 289

P2, N=40, Completed, Fred Hutchinson Cancer Center | Active, not recruiting --> Completed

P4, N=128, Recruiting, Medizinische Hochschule Hannover | N=52 --> 128

P=N/A, N=300, Not yet recruiting, The Children's Hospital at Westmead

P2, N=60, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Jan 2028 --> Mar 2029 | Trial primary completion date: Feb 2026 --> Apr 2027

Conditioning was based on total body irradiation (TBI) in 30 patients and on chemotherapy in 27 patients, mainly with reduced-toxicity conditioning (RTC; Treosulfan, Fludarabine, and Thiotepa). Our data support the use of TBI-free conditioning and suggest improved outcomes with unrelated donors receiving ATLG prophylaxis. NCT00317408.

The use of non-treosulfan-based myeloablative conditioning (MAC) regimens increased the risk of endothelial complications compared to reduced-intensity conditioning (RIC) (HR, 4.9; 95% CI, 1.1-22.0; P=0.040), whereas outcomes with treosulfan-based MAC were comparable to RIC. In summary, allogeneic HSCT is a viable curative strategy for ED when performed before transformation to an aggressive malignancy i.e. myelodysplasia with excess blasts or acute myeloid leukemia. However, the elevated incidence of endothelial toxicity highlights the importance of optimizing conditioning intensity and enhancing peritransplant monitoring in this population.

P2, N=24, Not yet recruiting, Federal Research Institute of Pediatric Hematology, Oncology and Immunology

This is the first published case suggesting a potential role for leukotriene receptor antagonists in CYSLTR2-mutant UM. These findings support further preclinical and clinical investigation of montelukast as a repurposed therapy in this challenging disease entity.