Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment modality for primary myelofibrosis (MF) and related myeloproliferative neoplasms. Older age at diagnosis and age-related comorbidities make most patients ineligible for allo-HCT, given concerns for nonrelapse mortality (NRM). Here we report the outcomes of 37 consecutive recipients of allo-HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol. Most patients received ruxolitinib before HCT (n = 32), and those with splenomegaly >22 cm received pretransplantation splenic irradiation. The median age at HCT was 60 years (range, 40 to 74 years), and 68% of the cohort carried a JAK2 driver mutation. All patients received fludarabine/busulfan-based conditioning; 22 patients (59%) received a reduced-intensity conditioning regimen. All patients received peripheral blood grafts, from a matched sibling donor in 16 patients (43%), an unrelated donor in 20 patients, and a haploidentical-related donor in 1 patient. Sixty-one percent had a Hematopoietic Cell Transplantation Comorbidity Index 3, 40% had a Karnofsky Performance Status score <90, and 24% had a high-risk DIPSS Plus score. With a median follow-up of 40.2 months (range, 16.9 to 115 months), the 3-year overall survival and relapse-free survival were 81.1% (95% confidence interval [CI], 64.4% to 90.5%) and 78.4% (95% CI, 61.4% to 88.5%), respectively. Only 2 patients relapsed/progressed after transplant. NRM at 2 years was 16.2% (95% CI, 6.5% to 29.9%). All patients engrafted. Sixteen patients were treated with ruxolitinib post-transplantation for graft-versus-host disease, graft rejection/relapse, or persistent MF. These results suggest that pretransplantation ruxolitinib, fludarabine/busulfan-based conditioning, and splenic management are keys to improved transplantation outcomes in patients undergoing allo-HCT for MF.

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Background With the rising number of chimeric antigen receptor (CAR) T cell treated patients, it is increasingly important to understand the treatment’s impact on patient-reported outcomes (PROs) and, ideally, identify biomarkers of central nervous system (CNS) adverse effects. Methods The purpose of this exploratory study was to assess short-term PROs and serum kynurenine metabolites for associated neurotoxicity among patients treated in an anti-CD20, anti-CD19 (LV20.19) CAR T cell phase I clinical trial (NCT03019055). Fifteen CAR T treated patients from the parent trial provided serum samples and self-report surveys 15 days before and 14, 28, and 90 days after treatment. Results Blood kynurenine concentrations increased over time in patients with evidence of neurotoxicity (p = 0.004) and were increased in self-reported depression (r = 0.52, p = 0.002). Depression improved after CAR T infusion (p = 0.035). Elevated 3-hydroxyanthranilic acid (3HAA) concentrations prior to cell infusion were also predictive of neurotoxicity onset (p = 0.031), suggesting it is a biomarker of neurotoxicity following CAR T cell therapy. Conclusions Elevated levels of kynurenine pathway metabolites among CAR T cell recipients are associated with depressed mood and neurotoxicity. Findings from this exploratory study are preliminary and warrant validation in a larger cohort.

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