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Outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult acute lymphoblastic leukemia (ALL) have improved over time. Studies have shown that total body irradiation (TBI) is the preferable type of myeloablative conditioning (MAC). However, outcomes based on central nervous system (CNS) involvement, namely CNS-positive versus CNS-negative, have not been compared. Here, we evaluated outcomes of 547 patients (CNS-positive = 96, CNS-negative = 451) who were allografted in the first complete remission (CR1) between 2009 and 2019. Primary endpoint was leukemia-free survival (LFS). Median follow-up was not different between the CNS-positive and CNS-negative groups (79 versus 67.2 months, P = 0.58). The CNS-positive group were younger (median age 31.3 versus 39.7 years, P = 0.004) and were allografted more recently (median year 2012 versus 2010, P = 0.003). In both groups, MAC was the preferred approach (82.3% versus 85.6%, P = 0.41). On multivariate analysis, the CNS-positive group had higher incidence of relapse (RI) (hazard ratio [HR] = 1.58 [95% confidence interval (CI) = 1.06-2.35], P = 0.025), but no adverse effect on LFS (HR = 1.38 [95% CI = 0.99-1.92], P = 0.057) or overall survival (OS) (HR = 1.28 [95% CI = 0.89-1.85], P = 0.18). A subgroup multivariate analysis limited to CNS-positive patients showed that a TBI-based MAC regimen resulted in better LFS (HR = 0.43 [95% CI = 0.22-0.83], P = 0.01) and OS (HR = 0.44 [95% CI = 0.21-0.92], P = 0.03) and lower RI (HR = 0.35 [95% CI = 0.15-0.79], P = 0.01). Another subgroup analysis in CNS-negative patients showed that MAC-TBI preparative regimens also showed a lower RI without a benefit in LFS or OS. While a MAC-TBI allo-HCT regimen may not be suitable to all, particularly for older patients with comorbidities, this approach should be considered for patients who are deemed fit and able to tolerate.

Patients with myelofibrosis (MF) experience an array of symptoms that impair health-related quality of life (HRQoL). Fedratinib, an oral, selective Janus-kinase 2 (JAK2) inhibitor, was investigated in the randomized, placebo-controlled, phase III JAKARTA study in adult patients with intermediate- or high-risk JAK-inhibitor-naïve MF. The effect of fedratinib 400 mg/d on patient-reported MF symptoms and HRQoL in JAKARTA was assessed. Participants completed the modified Myelofibrosis Symptom Assessment Form (MFSAF v2.0), which evaluates 6 key MF symptoms (night sweats, early satiety, pruritus, pain under ribs on the left side, abdominal discomfort, bone/muscle pain). The modified MFSAF v2.0 was completed during the first 6 treatment cycles and at end of cycle 6 (EOC6). Symptom response was a ≥50% improvement from baseline in total symptom score (TSS). Overall HRQoL was assessed by EQ-5D-3L health utility index (HUI) score. The MFSAF-evaluable population comprised 91/96 patients randomized to fedratinib 400 mg and 85/96 patients randomized to placebo. Mean baseline TSS was 17.6 and 14.7 for fedratinib and placebo, respectively, and mean EQ-5D-3L HUI was 0.70 and 0.72. Fedratinib elicited statistically significant and clinically meaningful improvements in TSS from baseline versus placebo at all postbaseline visits. Symptom response rates at EOC6 were 40.4% with fedratinib and 8.6% with placebo (OR 7.0 [95% CI, 2.9-16.9]; P

Myelofibrosis symptoms compromise health-related quality of life (HRQoL). Ruxolitinib can reduce myelofibrosis symptom severity, but many patients discontinue ruxolitinib due to loss of response or unacceptable toxicity. Fedratinib is an oral, selective JAK2 inhibitor approved in the United States for treatment of patients with intermediate-2 or high-risk myelofibrosis. The single-arm, phase II JAKARTA2 trial assessed fedratinib 400 mg/d (starting dose) in patients with myelofibrosis previously treated with ruxolitinib. Patient-reported changes in myelofibrosis symptom severity using the modified Myelofibrosis Symptom Assessment Form (MFSAF), and overall HRQoL and functional status using the EORTC QLQ-C30, were evaluated at each cycle. Clinically meaningful changes from baseline HRQoL scores were based on effect sizes. Ninety patients were MFSAF-evaluable. Myelofibrosis symptoms were mild-to-moderate at baseline. Patients showed statistically significant and clinically meaningful improvements in total symptom scores from baseline on the MFSAF at all post baseline visits through the end of cycle 6 (EOC6). Baseline global health status/QoL and functional domain scores on the EORTC QLQ-C30 were meaningfully worse than in the general population. At EOC6, 44% of patients reported clinically meaningful improvements in global health status/QoL, and 30%–53% of patients experienced clinically meaningful improvement in QLQ-C30 functional domains across post baseline timepoints. Over 80% of ongoing patients perceived fedratinib as beneficial on the Patient’s Global Impression of Change questionnaire. Fedratinib effects were consistent among prognostically relevant patient subgroups. Patients with myelofibrosis previously treated with ruxolitinib experienced clinically meaningful improvements in myelofibrosis symptom burden, overall HRQoL, and functional status in the first 6 months of fedratinib treatment.