Effect of allo-HSCT and BM fibrosis regression on OS in patients with MF

Patients diagnosed with intermediate-2 and high-risk myelofibrosis (MF) are currently only able to achieve curative therapy through allogeneic hematopoietic stem cell transplantation (allo-HSCT).¹ Gandhi¹ presented a study investigating the impact of pre-allo-HSCT splenomegaly, splenic irradiation, and pre- and post-HSCT marrow fibrosis on overall survival (OS) at the 2023 Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR, and we are pleased to summarize the key findings from the study below.

The MPN Hub recently published a related article summarizing the association between changes in bone marrow fibrosis and clinical efficacy of MF treatments here.

Study design

A total of 34 patients diagnosed with either primary or secondary MF and who underwent allo-HSCT between 2005 and 2021 were enrolled in the study. Baseline patient characteristics are shown in Table 1.

Table 1. Baseline patient characteristics*

allo-HSCT, allogeneic hematopoietic stem cell transplant; DIPSS, Dynamic International Prognostic Scoring System; KPS, Karnofsky performance score; MAC, myeloablative conditioning; MF, myelofibrosis; NMA, non-myeloablative conditioning; RIC, reduced-intensity conditioning. *Adapted from Gandhi.1
Characteristic, % (unless otherwise stated)	N = 34
Age at allo-HSCT (range), years	62 (42–73)
KPS
90	32.4
80	58.8
70	8.8
Primary MF	61.8
Secondary MF	38.2
DIPSS score
Intermediate-1 risk	5.9
Intermediate-2 risk	58.9
High risk	29.4
N/A	5.9
JAK2 mutation
Yes	58.9
No	29.4
N/A	11.8
Pre-allo-HSCT spleen size
≤20 cm	58.8
>20 cm	41.2
Pre-allo-HSCT splenic irradiation
Yes	44.1
No	55.9
Pre-allo-HSCT marrow fibrosis
Grade 1	14.7
Grade 2	23.5
Grade 3	61.8
Conditioning regimen
MAC	23.5
RIC	64.7
NMA	11.8

Results

The median follow-up for patients was 47 months. Median OS was not reached; however, the 1-year overall OS rate was 58.8% (95% confidence interval [Cl], 44–78)² and both reduced intensity conditioning and myeloablative conditioning regimens yielded similar 1-year OS rates (Figure 1).

MAC, myeloablative conditioning; NMA, non-myeloablative conditioning; OS, overall survival; RIC, reduced-intensity conditioning.
*Adapted from Gandhi.¹

• Neutrophil and platelet engraftment took a median of 17 and 31 days, respectively.
• Patients with a spleen size >20 cm and those undergoing splenic irradiation experienced delayed neutrophil engraftment (hazard ratio [HR], 0.44; p = 0.033; and HR, 0.37; p = 0.012, respectively) and delayed platelet engraftment (HR, 0.55; p = 0.153; and HR, 0.38; p = 0.026, respectively).
• The median dose of CD34 cells administered to patients was 5.9 × 10⁶ cells/kg.²
• Higher CD34 cell doses were associated with faster neutrophil engraftment (HR, 1.42 per 10⁶ cells; p < 0.001) but had no effect on platelet engraftment or OS.
• 19 patients experienced Grade ≥2 acute graft-versus-host disease (GvHD),² with a median onset of 54 days after transplantation.
• 15 patients experienced chronic GvHD,² with a median onset of 8 months after transplantation (Table 2).

Table 2. Rates of post-HSCT GvHD*

GvHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplantation. *Adapted from Gandhi.1
Characteristic, %	N = 34
Acute GvHD
None	32.3
Grade 1	8.8
Grade 2	17.6
Grade 3–4	38.2
Engraftment syndrome	2.9
Chronic GvHD
None	55.9
Limited	14.7
Extensive	26.5
Unknown extent	2.9

Bone marrow fibrosis grade results were available in 24 patients. Over 1 year, 17 patients experienced bone marrow fibrosis regression, whereas 7 patients experienced none (Figure 2).^1,2 Patients with Grade ≥2 acute GvHD were less likely to have bone marrow regression after 1 year (p = 0.292).

*Adapted from Gandhi.^1,2

Predictors of any cause mortality were identified as:

• Bone marrow fibrosis regression (HR, 0.20; 95% CI, 0.04–1.08; p = 0.061)
• Grade ≥2 acute GvHD (HR, 4.42; 95% CI, 1.22–16.08; p = 0.024)
• Secondary MF (HR, 3.16; 95% CI, 1.16–8.61; p = 0.024)

Conclusion

The results from this study indicate a strong correlation between acute GvHD, lack of marrow fibrosis regression, and increased risk of patient mortality. Further investigation of the potential for novel treatment strategies such as T-cell depletion to rapidly remodel the bone marrow niche, thus improving OS in MF is warranted.