Outcomes after Allogeneic Stem-Cell Transplant in Patients with High-Risk Large-Cell Transformation of Mycosis Fungoides (MF-LCT)

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Background: Large cell transformation (LCT) occurs in about 20-50% of mycosis fungoides (MF) cases. LCT is associated with a poor prognosis with a median survival of 3.6 years. Most patients experience a relapsed, refractory disease course without an established standard of care. Allogeneic stem cell transplant (SCT) has demonstrated potential as a curative option for advanced mycosis fungoides in recent studies, but the clinical benefit in patients with LCT has not yet been well studied. Our study aimed to characterize outcomes of SCT in patients with MF and LCT. Method: We retrospectively analyzed data from single tertiary, MD Anderson Cancer Center registry spanning 1982 to 2023. The study included patients who underwent allogeneic SCT after a biopsy-proven diagnosis of LCT from MF. Patient clinical characteristics and treatment were obtained by chart review. A global response score was used to define the lymphoma response to SCT(Olsen et al., 2011). Survival data was updated as of July 2024. Results: A total of 43 patients were identified and included in the study. Study patients underwent SCT between 1998 to 2024, and 74% underwent SCT in 2010 or after. The median age at diagnosis of LCT and at SCT were 47 years (range 17-68) and 49 years (range 19-69), respectively. Forty percent of patients were female; 51% and 26% were Caucasian/white and African-American, respectively. Forty-six percent of patients had LCT at diagnosis. The median time from MF diagnosis to LCT was 40 [IQR 9-65] months. Fifty-nine percent (n=26) of patients were stage 4 at LCT diagnosis, with 15 and 11 patients with stage IVA2 and IVB disease, respectively. The median number of LCT-directed treatments before SCT was 3 (range 0-8). Stem cells from matched-unrelated donors (47%) and matched-related donors (40%) were frequently used, followed by 14% use of haploidentical-donor stem cells. Most donor stem cells were obtained from peripheral blood (71%). Fifty-two percent of patients had achieved a CR, and 45% were in partial remission at staging before SCT. After SCT, 48% of patients achieved the best response with CR after SCT, but the rest, 40%, and 13%, had relapsed or progressive disease. At the last follow-up, 41% of patients remained in CR, and 53% had active disease. 16 out of 36 patients received post-SCT systemic therapy, and the median number of lines of therapy was 1 (range 1-4). Majority of patients received reduced intensity conditioning; 86% of patients received Fludarabine/Melphalan (FM), followed by 10% of patients who received Fludarabine/Busulfan. All patients who underwent SCT received total skin electron beam therapy prior to transplant. Thirty-one percent of patients received cyclophosphamide, mycophenolate mofetil, and tacrolimus as graft-versus-host-disease (GVHD) prophylaxis, and 68% received methotrexate and tacrolimus. The median progression-free survival and overall survival from SCT were 12.2 months (95% CI 4.5-26.9 months) and 29.0 months (95% CI at 10.1-42.5 months), respectively. The 2-year PFS and OS was 40% and 54%, respectively. The 1-, 3-, and 5-year non-relapse mortality were 3.4%, 3.4% and 25%, respectively. Of 22 patients with identifiable cause of death, the common causes of death were progression of disease (n=9, 41%) and infection (n=8, 36%); the rest were attributed to other post-SCT-related complications (n=6, 27%). The matched-related donors (MRD) had a better survival (hazard ratio 0.42, p=.042) with median OS at 44.4 months compared to non-MRD donors (including matched-unrelated or haplo donors) with median OS at 12.4 months. The response to SCT was also associated with better survival in those who achieved a CR (median OS not reached), compared to relapsed (HR 4.6, p=.023) or progressive (HR 7.8, p<.001) disease. Conclusion: Patients with MF with LCT who underwent SCT, at our center were heavily pre-treated with and had advanced disease. Our study demonstrates that high-risk LCT patients who achieved remission after SCT experienced long-term survival. However, half of patients progress with inferior survival outcomes, and there is an unmet need for further therapeutic advances.