Sequential High‐Dose Ruxolitinib and Low‐Dose Splenic Irradiation for Pretransplant Management of Splenomegaly Before Allogeneic Hematopoietic Cell Transplantation With Fludarabine/Busulfan‐Based Conditioning in Myelofibrosis

ABSTRACT

Background

Significant splenomegaly remains a major barrier to successful allogeneic hematopoietic cell transplantation (allo‐HCT) in myelofibrosis (MF), contributing to delayed engraftment and an increased risk of graft failure. Systemic JAK inhibition and splenic irradiation are commonly used as independent pretransplant strategies; however, evidence regarding their sequential use and integration into contemporary conditioning platforms remains limited.

Methods

We conducted a single‐center retrospective study of nine patients with MF who underwent allo‐HCT between 2020 and 2025. Patients received sequential high‐dose ruxolitinib followed by low‐dose splenic irradiation (LDSI) as pretransplant spleen‐directed therapy prior to a fludarabine/busulfan‐based conditioning regimen. Spleen response, engraftment kinetics, and transplant outcomes were evaluated.

Results

High‐dose ruxolitinib reduced median spleen length from 185 to 172 mm, followed by a further decrease to 137 mm after LDSI. All patients achieved engraftment, with median times to neutrophil and platelet recovery of 15 and 19 days, respectively. The cumulative incidence of any‐grade acute graft‐versus‐host disease (GVHD) was 22.2%, and moderate chronic GVHD occurred in 11.1%. The estimated 2‐year overall survival was 88.9%, and the estimated 2‐year GVHD‐free and relapse‐free survival (GRFS) was 76.2%. The estimated 2‐year cumulative incidence of relapse was 12.7%, and estimated non‐relapse mortality was 11.1%.

Conclusion

Sequential high‐dose ruxolitinib followed by LDSI appeared feasible and was associated with stepwise pretransplant spleen reduction and encouraging early transplant outcomes following allogeneic HCT with fludarabine/busulfan‐based conditioning. Given the small sample size and absence of a comparator group, this combined systemic and local spleen‐directed strategy warrants further evaluation in prospective multicenter studies.

Trial Registration

The authors have confirmed clinical trial registration is not needed for this submission.

1. Introduction

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm comprising primary MF (PMF) and secondary MF (SMF), the latter arising from essential thrombocythemia or polycythemia vera. MF is associated with a poor prognosis, with a risk of leukemic transformation and a median survival of approximately 6 years [1]. Although the advent of JAK inhibitors has significantly reduced the symptom burden, allogeneic hematopoietic cell transplantation (allo‐HCT) remains the only potentially curative treatment option for patients with MF.

However, the outcome of allo‐HCT in MF is influenced by multiple factors, with significant splenomegaly representing one of the major clinical barriers [2]. The enlarged spleen acts as a site of extramedullary hematopoiesis and clonal cell retention, and may sequester infused donor hematopoietic stem cells, thereby contributing to delayed engraftment or graft failure [3]. A recent multicenter study from China demonstrated that pretransplant massive splenomegaly is an independent risk factor for graft failure, increasing the risk more than threefold [4]. Furthermore, the EBMT collaborative group also recognizes marked splenomegaly as a risk factor for adverse transplant outcomes and recommends considering spleen‐directed therapy before transplantation in selected patients [5]. Accordingly, appropriate pretransplant management of marked splenomegaly represents an important component of transplant optimization, particularly for promoting hematopoietic engraftment and mitigating the risk of graft failure. Traditionally, although splenectomy alleviated the negative impact of splenomegaly on transplantation, it was associated with perioperative complications (27.7%) and mortality (6.7%) [6, 7]. In addition, although JAK inhibitors can reduce spleen size, their efficacy is time‐dependent and responses are achieved in only some patients [8]. Splenic irradiation (SI) has been demonstrated to be a safe and effective bridging strategy for allogeneic transplant MF patients who have failed or are intolerant to JAK inhibitors [9]. Furthermore, whether administered as a reduced‐intensity conditioning or myeloablative conditioning, fludarabine/busulfan (Flu/Bu)‐based therapy confers clinical benefit in patients with MF [10].

Current evidence largely supports the use of JAK inhibitors or SI as alternative options to reduce spleen size before transplantation. However, these modalities are generally used independently, and whether a sequential strategy combining systemic disease control with rapid local spleen reduction can further facilitate transplantation remains unclear. Here, we report our single‐center experience with sequential high‐dose ruxolitinib followed by low‐dose splenic irradiation (LDSI) for pretransplant management of significant splenomegaly before allo‐HCT with Flu/Bu‐based conditioning in patients with MF.

2. Methods

2.1. Patients

Nine consecutive patients with MF who underwent allo‐HCT with Flu/Bu‐based conditioning after sequential high‐dose ruxolitinib and LDSI between January 2020 and December 2025 at Shenzhen People's Hospital were enrolled. MF was diagnosed according to the 2016 World Health Organization (WHO) diagnostic criteria [11]. The Dynamic International Prognostic Scoring System (DIPSS), DIPSS‐plus, Mutation‐Enhanced International Prognostic Scoring System 70+ version 2.0 (MIPSS70+ v2.0) and Myelofibrosis Transplant Scoring System (MTSS) were calculated according to the original definition [12, 13, 14, 15]. This retrospective study was approved by the Ethics Committee of Shenzhen People's Hospital and was conducted in accordance with the Declaration of Helsinki. All patients and donors provided written informed consent for transplantation and data use.

2.2. Transplant Procedure

The transplant protocol consisted of pretransplant high‐dose ruxolitinib, LDSI on Day −6 for rapid spleen reduction, and a Flu/Bu‐based conditioning regimen incorporating decitabine (DAC) and total marrow irradiation (TMI), with antithymocyte globulin (ATG)‐based GVHD prophylaxis (Figure 1). It is noteworthy that high‐dose ruxolitinib was commenced only after the patient had provided consent for allo‐HCT and donor readiness had been confirmed. It was administered orally at an initial dose of 25 mg twice daily. Ruxolitinib dose tapering began on Day −8 before stem cell infusion, with a 50% reduction every 3 days, and the drug was discontinued on the day of infusion. DAC was administered intravenously at 15 mg/m²/day on Days −9 to −7, Flu at 30 mg/m²/day on Days −7 to −3, and Bu at 3.2 mg/kg/day on Days −6 to −4.

FIGURE 1.

Sequential peri‐transplant strategy integrating high‐dose ruxolitinib‐based systemic JAK inhibition, low‐dose splenic irradiation, and fludarabine/busulfan‐based conditioning in myelofibrosis.

TMI and LDSI were each delivered on Day −6 to a total prescribed dose of 4 Gy in two fractions (2 Gy per fraction). For LDSI planning, patients underwent noncontrast CT simulation and were immobilized using a vacuum cushion. The entire spleen was contoured as the gross tumor volume (GTV), and a 3‐mm isotropic margin was added to generate the planning target volume (PTV). Treatment was planned using volumetric modulated arc therapy (VMAT) and delivered with 6‐MV photon beams. The stomach, bowel, and both kidneys were delineated as organs at risk, and their doses were minimized during plan optimization. Setup verification and image guidance were performed using cone‐beam CT (CBCT) in conjunction with an optical surface monitoring system (OSMS). Similar CT‐based whole‐spleen planning and image‐guidance approaches have been reported for pretransplant SI [16].

GVHD prophylaxis for HLA‐mismatched related or unrelated donor transplantation consisted of cyclosporine A (CsA), short‐course methotrexate (MTX), mycophenolate mofetil (MMF), and rabbit antithymocyte globulin (r‐ATG). CsA was administered by continuous infusion at 3 mg/kg/day from Day −10, with a target trough concentration of 200–300 ng/mL. MTX was administered at 15 mg/m² on Day +1 and 10 mg/m² on Days +3 and +6. MMF was administered orally at 1.0 g twice daily from Day −10 until neutrophil engraftment and was then tapered until Day +30. r‐ATG was administered at 2.5 mg/kg/day on Days −3 to −1. Recipients of HLA‐matched donor grafts received CsA, short‐course MTX, and r‐ATG, with the r‐ATG dose reduced to a total dose of 4.5 mg/kg. Acute graft‐versus‐host disease (GVHD) was graded according to the modified criteria based on the schema of the Mount Sinai Acute GVHD International Consortium [17]. Chronic GVHD was graded according to the National Institutes of Health Chronic GVHD Consensus Criteria [18].

2.3. Chimerism Analysis

Donor chimerism was assessed by short tandem repeat polymerase chain reaction (STR‐PCR) in bone marrow nucleated cells on Days +30, +60, +100, and +180 after allo‐HCT and at 1 year, when available. Additional peripheral blood chimerism testing was performed when clinically indicated. Full donor chimerism was defined as a donor‐cell proportion of > 95% [19].

2.4. Definition

Neutrophil and platelet recovery were defined according to previous report [20]. Primary GF was defined as an ANC < 0.5 × 10⁹/L by Day +28 following stem cell infusion, hemoglobin level < 80 g/L, and platelet count < 20 × 10⁹/L. Poor graft function (PGF) was operationally defined as cytopenia meeting at least two of the following thresholds: An absolute neutrophil count of ≤ 1.5 × 10⁹/L, a platelet count of ≤ 30 × 10⁹/L, and a hemoglobin level of ≤ 85 g/L. Cytopenia was required to persist for more than two consecutive weeks following documented engraftment and to require transfusion, hematopoietic growth factor support, or both. The diagnosis also required full donor chimerism and exclusion of alternative causes, including disease relapse or progression, active infection, drug‐related myelosuppression, clinically significant GVHD, and transplant‐associated thrombotic microangiopathy (TMA) [21, 22]. In this study, secondary PGF was defined as PGF developing after initial neutrophil and platelet recovery.

Relapse was defined as the reappearance of host cells and the morphological criteria for MF after remission [21]. Overall survival (OS) was calculated from the date of transplant until last follow‐up or death. GVHD‐free and relapse‐free survival (GRFS) was calculated as described previously [23]. Cumulative incidence of relapse (CIR) and non‐relapse mortality (NRM) were calculated as previous description [24]. Spleen size, assessed by ultrasound, was categorized as enlarged (craniocaudal length > 170 mm), mildly enlarged (130–170 mm), or normal (< 130 mm). High‐dose ruxolitinib was defined in this study as ≥ 25 mg twice daily.

2.5. Statistical Analysis

Continuous variables were analyzed using nonparametric tests. The Kaplan–Meier method was used to estimate 2‐year OS and GRFS. Cumulative incidence functions were used to estimate relapse, NRM, and GVHD, with competing events defined as described above. GRFS was calculated according to the EBMT definition of “refined GRFS,” counting acute GVHD III–IV, severe chronic GVHD, relapse/progression, and death as events [25]. Competing events were defined as follows: For relapse, death from any cause without relapse; for NRM, relapse/progression; for GVHD, engraftment failure, relapse without GVHD, death from any other cause. Statistical analysis was performed by using R statistical software, version 4.2.0 (R Foundation for Statistical Computing, Vienna, Austria). A two‐sided p ˂ 0.05 was defined as statistically significant. The last follow‐up date was March 15, 2026, with a median follow‐up of 15 months (range, 5–49 months).

3. Results

3.1. Patient Characteristics

The clinical characteristics and treatment profiles of these nine patients are summarized in Table 1. The median age of the patients was 54 years (range, 44–63 years), and the median time from diagnosis to transplantation was 8 months (range, 4–46 months). All patients underwent bone marrow stem cells (BMSCs) and/or peripheral blood hematopoietic stem cells (PBSCs) transplantation, with infused median CD34+ cell and mononuclear cell counts of 5.43 × 10⁶/kg (2.88–8.93) and 5.15 × 10⁸/kg (range, 3.20–21.45), respectively. Seven patients (77.8%) received HCT from Haploidentical donors and other two patients (22.2%) received from matched sibling donors (MSDs).

TABLE 1.

Patient characteristics and transplant outcomes.

Patient ID	Gender	Age (years)	Diagnosis at HCT	DIPSS	DIPSS‐plus	MIPSS70+ v2.0	MTSS	Ruxolitinib exposure	Donor type	Graft source	Neutrophil engraftment (days)	Platelet engraftment (days)	aGVHD (grade)	cGVHD (grade)	EBV/CMV infection	Survival	OS time (months)	Cause of death
1	Male	63	Post‐ET MF	Int‐1 risk	Int‐2 risk	High risk	Intermediate risk	Yes	Haploidentical	BM+PB	11	27	None	None	CMV, EBV	Alive	48.63	NA
2	Male	61	Post‐PV MF	Int‐2 risk	High risk	High risk	High risk	Yes	Haploidentical	PB	16	19	Liver (II)	None	CMV	Deceased	5.26	Pulmonary infection
3	Male	48	PMF	High risk	Int‐2 risk	High risk	Intermediate risk	Yes	Haploidentical	PB	14	23	None	None	None	Alive	43.21	NA
4	Male	45	PMF	Int‐2 risk	High risk	High risk	Low risk	Yes	MSD	PB	18	26	None	None	None	Alive	14.88	NA
5	Male	54	PMF	Int‐2 risk	High risk	Very high risk	Intermediate risk	Yes	Haploidentical	PB	14	18	None	None	CMV	Alive	14.68	NA
6	Male	56	PMF	Int‐2 risk	High risk	High risk	Intermediate risk	Yes	Haploidentical	PB	15	17	Skin (I)	None	None	Alive	12.10	NA
7	Male	46	PMF	Int‐2 risk	Int‐2 risk	High risk	Intermediate risk	Yes	Haploidentical	PB	21	31	None	None	None	Alive	6.31	NA
8	Male	44	PMF	Int‐2 risk	High risk	Very high risk	Intermediate risk	Yes	MSD	PB	15	16	None	Moderate	None	Alive	11.18	NA
9	Female	59	PMF	Int‐2 risk	High risk	High risk	High risk	Yes	Haploidentical	PB	12	17	None	None	None	Alive	23.88	NA

Abbreviations: aGVHD, acute graft‐versus‐host disease; BM, bone marrow; cGVHD, chronic graft‐versus‐host disease; CMV, cytomegalovirus; DIPSS, Dynamic International Prognostic Scoring System; EBV, Epstein–Barr virus; HCT, hematopoietic cell transplantation; MIPSS70+ v2.0, mutation‐enhanced international prognostic scoring system 70+ version 2.0; MSD, matched sibling donor; MTSS, myelofibrosis transplant scoring system; NA, not applicable; OS, overall survival; PB, peripheral blood.

3.2. Efficacy of High‐Dose Ruxolitinib and LDSI

• The median cumulative administration time of high‐dose ruxolitinib (25 mg twice daily) was 59 days (range, 43–70 days), and the median pretreatment spleen size was 185 mm (range, 167–247 mm). Following high‐dose ruxolitinib treatment, median spleen size was 172 mm (range, 149–206 mm), representing a median reduction of 18 mm (95% CI: 3–30 mm) from pretreatment values (p = 0.0090). LDSI was administered on Day −6 prior to transplantation, resulting in rapid spleen size reduction in all patients. Compared with pre‐irradiation values, median spleen length decreased from 172 mm (range, 149–206 mm) to 137 mm (range, 132–162 mm) after LDSI (p = 0.0039), with an additional median reduction of 35 mm (95% CI, 24–44 mm) observed across all patients (Table 2). A reduction in splenic size was observed in all patients, suggesting a sequential and cumulative effect of high‐dose ruxolitinib followed by LDSI in the peri‐transplant setting.

TABLE 2.

Efficacy and hematologic toxicity of high‐dose ruxolitinib and splenic irradiation.

Characteristic	Ruxolitinib treatment			Splenic irradiation
	Pre‐ruxolitinib	Post‐ruxolitinib	p	Pre‐irradiation	Post‐irradiation	p
Spleen size (mm)	185 (167–247)	172 (149–206)	0.0090	172 (149–206)	137 (132–162)	0.0039
WBC (×109/L)	2.57 (1.36–32.04)	1.03 (0.16–18.57)	0.0039	0.43 (0.13–7.85)	0.38 (0.15–4.84)	0.2936
Hb (g/L)	77 (63–110)	73 (54–98)	0.0177	71 (55–99)	74 (49–93)	0.9054
PLT (×109/L)	81 (28–253)	55 (9–180)	0.0091	31 (14–146)	40 (22–105)	0.4258

Abbreviations: Hb, hemoglobin; PLT, platelet; WBC, white blood cell count.

3.3. Safety of High‐Dose Ruxolitinib and LDSI

High‐dose ruxolitinib was associated with a decrease in hematologic parameters during the pretransplant debulking phase. Platelet counts decreased from a median of 81 × 10⁹/L (range, 28–253) at baseline to 55 × 10⁹/L (range, 9–180) after treatment (p = 0.0091). A similar decline was observed in leukocyte counts and hemoglobin levels following ruxolitinib exposure. Following subsequent LDSI, hematologic parameters remained stable. No further reduction in platelet counts was observed after irradiation, and post‐irradiation values were comparable to those recorded immediately after ruxolitinib. Leukocyte and hemoglobin levels remained similarly stable prior to conditioning (Table 2). Only one patient experienced a non‐hematologic adverse event (abdominal pain) during irradiation, which was effectively managed with supportive care and analgesics. No hemorrhagic complications or treatment‐related mortality were observed.

3.4. Transplant Outcomes

All nine patients achieved neutrophil and platelet engraftment. The median time to neutrophil engraftment was 15 days (range, 11–21 days), whereas the median time to platelet engraftment was 19 days (range, 16–31 days). Notably, two patients developed secondary PGF on Days +59 and +76, respectively, after initial neutrophil and platelet recovery. Both patients ultimately achieved hematologic recovery, one after a CD34+ cell boost and the other after treatment with eltrombopag.

Serial bone marrow chimerism analysis demonstrated full donor chimerism in all nine patients at Days +30, +60, and +100. Full donor chimerism was maintained in all evaluable patients at Day +180 (n = 8) and at 1 year (n = 6). Both patients who developed secondary PGF retained full donor chimerism near PGF onset: 98.02% in bone marrow on Day +60 (PGF onset, Day +59) and 98.32% in peripheral blood on Day +76 (PGF onset, Day +76), respectively (Table S1).

The cumulative incidence of all grades of aGVHD within 100 days was 22.2% (95% CI: 0%–45.2%). During this period, two patients developed aGVHD, with one Grade I skin involvement and the other Grade II liver involvement. The 2‐year cumulative incidence of cGVHD was 11.1% (95% CI: 0.47%–40.6%), with only one patient developing moderate disease involving primarily the skin and lungs. Three patients developed cytomegalovirus (CMV) infection and one patient developed EBV reactivation. No CMV disease, EBV‐related posttransplant lymphoproliferative disorder (PTLD), TMA, or sinusoidal obstruction syndrome/venous occlusive disease (SOS/VOD) was observed.

At a median follow‐up of 15 months (range, 5–49 months), 8 of 9 patients (88.9%) were alive. The estimated 2‐year OS was 88.9% (95% CI, 70.6%–100%) (Figure 2A). Furthermore, the estimated 2‐year GRFS rate was 76.2% (95% CI, 52.1%–100%) (Figure 2B). The estimated 2‐year CIR was 12.7% (95% CI, 0.46%–45.3%), whereas the estimated NRM rate was 11.1% (95% CI, 0.0%–29.4%) (Figure 2C,D). At the last follow‐up, only one patient had died. This patient underwent transplantation with PBSCs derived from his 51‐year‐old brother (HLA 8/12 matched). The patient achieved successful engraftment on Day 16 posttransplantation, and no cardiac, hepatic, renal toxicity, or severe infection was observed during the peri‐transplant period. However, the patient subsequently developed severe pneumonia secondary to bacterial and Aspergillus co‐infection and ultimately died despite aggressive medical management.

FIGURE 2.

Posttransplant outcomes in patients with myelofibrosis. (A) Overall survival (OS), (B) graft‐versus‐host disease‐ and relapse‐free survival (GRFS), (C) cumulative incidence of relapse (CIR), (D) non‐relapse mortality (NRM).

4. Discussion

Splenomegaly represents an important clinical challenge in MF transplantation. Marked splenomegaly not only serves as a surrogate marker of advanced disease biology and active extramedullary hematopoiesis but may also directly impair engraftment by sequestering infused donor stem cells, amplifying the inflammatory milieu, and delaying hematopoietic recovery [4, 26]. The importance of pretransplant spleen management is underscored by a recent Chinese multicenter study, which found that massive splenomegaly was associated with a threefold higher risk of graft failure and inferior disease‐free survival [4].

Historically, the main strategies for pretransplant spleen reduction in MF have included splenectomy, JAK inhibitors, and SI. EBMT registry studies have demonstrated that although splenectomy can accelerate hematopoietic recovery and reduce NRM, it may increase the risk of relapse [26]. In addition, splenectomy itself is associated with substantial perioperative risks, with mortality and complication rates of 6.7% and 27.7%, respectively [6, 7]. Moreover, although splenectomy may facilitate subsequent allo‐HCT, its applicability is limited to a select patient population [27]. By contrast, ruxolitinib can reduce splenomegaly and alleviate constitutional symptoms. Its pretransplant use, particularly when a sustained spleen response is achieved, has also been associated with favorable outcomes after transplantation, supporting its use as bridging therapy [28, 29]. However, spleen response is often time‐dependent and limited by toxicities like thrombocytopenia, and complete response is not universal [8]. Consistent with our study, although all patients received high‐dose ruxolitinib, one‐third exhibited no significant spleen response while experiencing notable hematological toxicity. Thus, ruxolitinib monotherapy may have limited efficacy as a bridging strategy for spleen reduction prior to transplantation in MF patients. Notably, SI has emerged as an important strategy for spleen reduction and has gained increasing attention. A global collaborative study demonstrated that SI induced rapid spleen reduction in 97% of patients (median reduction of about 5 cm) and was associated with a 3‐year OS of 62%. Furthermore, the relapse rate was significantly lower with SI (12%) than with either no intervention (29%) or splenectomy (38%) [9]. These data provide a strong rationale for incorporating LDSI into our conditioning regimen.

A key feature of this approach is therefore the sequential combination of high‐dose ruxolitinib and LDSI, which was designed to achieve short‐term systemic cytokine and symptom control while enabling rapid local spleen reduction immediately before transplantation. Furthermore, following high‐dose ruxolitinib and LDSI, all patients proceeded to stem cell infusion according to the planned transplant schedule. In our cohort, all nine patients achieved successful engraftment. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively, within the range reported in previous studies, suggesting favorable early hematopoietic recovery in this high‐risk setting [9, 30]. The observed survival, relapse, and GVHD outcomes compare favorably with those reported in previous MF transplant cohorts and pooled analyses [9, 28, 31]. However, cross‐study comparisons are inherently limited by differences in patient selection and transplant practices. Despite these limitations, these findings support further evaluation of a sequential strategy combining systemic and local approaches to pretransplant spleen management, which may help address a key challenge in transplantation for MF.

In addition to pretransplant spleen management, the choice of conditioning regimen is also an important determinant of transplant outcomes in MF. A recent retrospective study conducted by CIBMTR demonstrated that Flu/Bu‐based conditioning was superior to other regimens in both RIC and MAC settings, due to its association with superior survival and lower rates of aGVHD [10]. This study employs a Flu/Bu backbone augmented with DAC and TMI, reflecting a disease‐specific conditioning approach wherein Flu/Bu provides an established framework for myeloablation and immunosuppression, DAC exerts anti‐clonal effects, and TMI is designed to enhance bone marrow‐targeted cytoreduction. At the same time, we incorporated ATG into our GVHD prophylaxis regimen based on its favorable profile, which included a significant reduction in the risk of Grades II–IV acute GVHD (HR = 0.54) and a trend toward improved OS (HR = 0.66), without increasing the risk of relapse [32].

This study has several limitations that should be acknowledged. First, the retrospective single‐center design and small sample size limit generalizability and preclude definitive causal inference. Second, the absence of a comparator group limits comparison of the effects of sequential ruxolitinib and SI with alternative pretransplant strategies such as splenectomy or JAK inhibitor monotherapy. Third, the use of ATG‐based GVHD prophylaxis for haploidentical HCT in this cohort may limit the generalizability of the observed posttransplant outcomes to posttransplant cyclophosphamide (PTCy)‐based haploidentical platforms. Fourth, spleen assessment was based on ultrasound measurements rather than volumetric imaging, which may introduce interobserver variability and reduce precision in assessing dynamic changes in splenic size. Finally, the relatively short follow‐up limits interpretation of long‐term relapse risk and survival outcomes after transplantation.

5. Conclusion

Despite these limitations, our findings provide clinically relevant evidence supporting the clinical feasibility of a sequential spleen‐directed strategy in MF patients undergoing allo‐HCT. The combination of systemic disease control with high‐dose ruxolitinib followed by rapid LDSI was associated with effective pretransplant splenic reduction, without a further significant decline in peripheral blood counts after LDSI, and may facilitate timely progression to transplantation within a Flu/Bu‐based conditioning platform. In line with previous reports highlighting splenomegaly as a major risk factor for graft failure and inferior transplant outcomes, our findings support the concept that effective pretransplant spleen management may represent a modifiable element of the transplant strategy in MF. However, these findings warrant validation in larger prospective multicenter studies with appropriate comparator groups to better define the safety and efficacy of this sequential strategy in reducing spleen size and to determine whether it improves engraftment and long‐term transplant outcomes compared with existing pretransplant spleen‐directed approaches.

Author Contributions

Peng Ke: writing – original draft, methodology, investigation, funding acquisition, data curation. Guoqiang Li: formal analysis, data curation. Chun Feng: formal analysis, data curation. Xiaoyong Chen: software, resources, methodology. Yixuan Cao: software, resources, methodology. Lina Hu: resources, project administration, formal analysis, data curation. Jiahe Zhang: resources, project administration, formal analysis, data curation. Linlin Wang: writing – review and editing, visualization, validation, supervision, data curation, conceptualization. Jihao Zhou: writing – review and editing, visualization, validation, supervision, data curation, conceptualization.

Funding

This study was supported by Shenzhen Science and Technology Program (Grant No. JCYJ20250604141706008) and the National Natural Science Foundation of China (Grant No. 82500213).

Ethics Statement

The study was approved by the Ethics Committee of Shenzhen People's Hospital, and written informed consent was obtained from the patients.

Conflicts of Interest

The authors declare no conflicts of interest. The authors have nothing to report.

Supporting information

Supporting File: jha270383‐sup‐0001‐TableS1.docx.

Data Availability Statement

The data of this study are not publicly available due to information that could compromise the privacy of the patient but are available from the corresponding author upon reasonable request.