Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality)
Methods: A SOP was developed at a single institution to improve screening, referral, and delivery of LDSRT for patients with MF and palpable splenomegaly proceeding to RIC alloHSCT. Palpable splenomegaly (≥5cm 5cm below the costal margin) or spleen size >15cm on imaging (CT or US) was required for referral for consideration of LDSRT. Patients younger than 18, those with prior abdominal, total lymphoid, or total body irradiation (>4Gy) were excluded. Symptomatic splenomegaly was assessed at the time of consultation using the validated 10 question Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF TSS) before radiation treatment and at day 90 of follow up. Splenic size (dimensions, volume) was assessed by the radiation oncology team with pre-treatment CT, on d5 (post-treatment cone beam CT), and d90+/- 14 days post-transplant (d90 CT scan preferred but optional). LDSRT started within 3 weeks of simulation and the planning target volume (PTV) was prescribed 5Gy over 5 daily fractions. A cone beam (CBCT) was performed on d1, d5. A CBC was collected prior to treatment on d1, d3, and d5 of radiation treatment. Feasibility was determined by completion of the SOP followed by alloHSCT within 10 days of LDSRT. Additional outcomes included safety and tolerability, improvement in symptomatic splenomegaly (MPN-SAF TSS), splenic size, and transplant related outcomes including engraftment rate and time, overall survival, and non-relapse mortality. Outcomes are reported using descriptive statistics.
Results: A prespecified interim analysis was performed for 10 patients treated between June 2023- July 2024. The median pre-treatment spleen size assessed by simulation CT was 1806 cc (volume) and 21.7 cm (greatest diameter), with an average splenic density of 37.1 HU. Seven patients had ruxolitinib-resistant splenomegaly. No significant changes in thrombocytopenia grade were observed during radiation treatment compared with baseline. All 10 patients successfully completed the SOP without treatment interruption or delay and proceeded to alloHSCT as planned within 6 +/- 1.9 days (median) of completion of LDSRT. All 10 patients successfully completed engraftment within 19 +/- 3.8 days of transplant (median, standard dev). Four patients experienced acute GVHD (maximum grade 3 skin) and 2 patients experienced chronic GVHD. Spleen size was reduced following LDSRT, as demonstrated by a reduction in splenic volume on Day 5 CBCT by 15.9% (median, range=7-39% decrease) and by day 90, 52.6% (median, range=decrease 70%-+31%). Symptomatic splenomegaly was improved as assessed by comparing pre-splenic RT and D90 post-transplant MPN-SAF-TSS scores; a median score improvement of 20 points was observed. At a median last follow up of 297 days (range: 83-335), 10/10 patients were alive without relapse.
Conclusion: Interim analysis of a SOP for LDSRT for patients with MF is safe, feasible, and resulted in reduction in spleen size and patient reported symptomatic splenomegaly when combined with alloHSCT. Standardization of combination therapies which improve patient quality of life without compromising treatment outcomes is important for patients with rare diseases such as MF.
Disclosures: Shomali: Blueprint Medicines: Research Funding; Incyte Inc: Consultancy, Research Funding.