Evaluation of haematopoietic stem cell transplantation in patients diagnosed with cutaneous T cell lymphoma at a tertiary care centre
Poster
Patients with advanced cutaneous lymphoma have a poor prognosis with a median survival of 1-5 years (1). Current guidelines recommend tailoring treatment based on disease staging (2). Allogeneic haematopoietic stem cell transplant (HSCT) may be used to treat eligible patients with late stage disease, aggressive disease or those with poor prognostic factors who achieve a durable remission (2).
At our centre, the pre-transplant conditioning regimen adopted in 2013 consists of Total Skin Electron Beam Therapy/Total Nodal Irradiation and anti-thymocyte globulin (TSE/TNI/ATG), with Sezary Syndrome (SS) patients receiving additional extracorporeal photopheresis (ECP) (3). 19 patients including 9 males and 10 females, with a median age of 49 at the time of HSCT (range 35 to 67 years old) have since been transplanted. We present longer term follow up of these patients (3). 17 patients with MF (n=14) and SS (n=3) were staged IIB to IVB at the time of transplant with stage IVA2 being the most common. There were a further 2 patients with large cell anaplastic lymphoma at stage IV. The average time from diagnosis of cutaneous lymphoma to HSCT was 61 months with a range of 9 months to 21 years, including 2 patients treated within a year of diagnosis.
All 19 patients had received prior systemic therapies with the median number of 4 (range 1 to 9) systemic therapies, most frequently including interferon-alpha, bexarotene and gemcitabine. The treatments bridging to transplant included intravenous chemotherapy (n=10), brentuximab (n=5), ECP (n=2) and others.
Those who have complete remission at the time of HSCT tend to have better outcomes (2). In the study period, 7 patients had achieved complete response (CR) prior to HSCT, 11 had achieved a partial response (PR) and one patient had stable disease. All 19 patients had a favourable response following transplantation, 16 achieved CR and 3 achieved PR. However, 9 patients (47%) subsequently had a relapse of CTCL. Relapse was terminal in 3 patients, while in the other 6 it was mainly low grade and treated with donor lymphocyte infusion, tailoring of immunosuppression, local radiotherapy or ECP.
At present, 9 (47%) patients are currently in complete remission, 4 (21%) are currently in partial remission and 6 (32%) have died. Cause of death included relapsed disease (n=3), GVHD (n=1 out of the 10 patients who developed GVHD) and unrelated causes (n=2).
The overall survival rate was 89% at one year (16 out of 18 patients), 76% at 2 years (13 out of 17 patients) and 69% at 3 years (9 out of 13 patients) with a median follow up of 2.78 years (range 0.27 – 8.33 years).
One patient with graft failure received a second allogenic transplant after 1 year. A clinical trial has shown that 50% of patients achieve long term disease control following second transplantation (4) which is the overall aim of HSCT in MF/SS(2).
Though relapse is common, this is mostly early stage relapse and may be successfully managed with skin directed therapy or donor lymphocyte infusions. Our updated data further demonstrates that TSE/TNI/ATG HSCT is a safe treatment option for selected patients with low transplant related mortality in advanced MF/SS.
References:
At our centre, the pre-transplant conditioning regimen adopted in 2013 consists of Total Skin Electron Beam Therapy/Total Nodal Irradiation and anti-thymocyte globulin (TSE/TNI/ATG), with Sezary Syndrome (SS) patients receiving additional extracorporeal photopheresis (ECP) (3). 19 patients including 9 males and 10 females, with a median age of 49 at the time of HSCT (range 35 to 67 years old) have since been transplanted. We present longer term follow up of these patients (3). 17 patients with MF (n=14) and SS (n=3) were staged IIB to IVB at the time of transplant with stage IVA2 being the most common. There were a further 2 patients with large cell anaplastic lymphoma at stage IV. The average time from diagnosis of cutaneous lymphoma to HSCT was 61 months with a range of 9 months to 21 years, including 2 patients treated within a year of diagnosis.
All 19 patients had received prior systemic therapies with the median number of 4 (range 1 to 9) systemic therapies, most frequently including interferon-alpha, bexarotene and gemcitabine. The treatments bridging to transplant included intravenous chemotherapy (n=10), brentuximab (n=5), ECP (n=2) and others.
Those who have complete remission at the time of HSCT tend to have better outcomes (2). In the study period, 7 patients had achieved complete response (CR) prior to HSCT, 11 had achieved a partial response (PR) and one patient had stable disease. All 19 patients had a favourable response following transplantation, 16 achieved CR and 3 achieved PR. However, 9 patients (47%) subsequently had a relapse of CTCL. Relapse was terminal in 3 patients, while in the other 6 it was mainly low grade and treated with donor lymphocyte infusion, tailoring of immunosuppression, local radiotherapy or ECP.
At present, 9 (47%) patients are currently in complete remission, 4 (21%) are currently in partial remission and 6 (32%) have died. Cause of death included relapsed disease (n=3), GVHD (n=1 out of the 10 patients who developed GVHD) and unrelated causes (n=2).
The overall survival rate was 89% at one year (16 out of 18 patients), 76% at 2 years (13 out of 17 patients) and 69% at 3 years (9 out of 13 patients) with a median follow up of 2.78 years (range 0.27 – 8.33 years).
One patient with graft failure received a second allogenic transplant after 1 year. A clinical trial has shown that 50% of patients achieve long term disease control following second transplantation (4) which is the overall aim of HSCT in MF/SS(2).
Though relapse is common, this is mostly early stage relapse and may be successfully managed with skin directed therapy or donor lymphocyte infusions. Our updated data further demonstrates that TSE/TNI/ATG HSCT is a safe treatment option for selected patients with low transplant related mortality in advanced MF/SS.
References:
- Scarisbrick J, Prince H, Vermeer M et al. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. Journal of Clinical Oncology 2015; 33:3766-3773.
- Gilson D, Whittaker S, Child F et al. British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous lymphomas 2018. British Journal of Dermatology 2018; 180:496-526.
- Ritchie S, Qureshi I, Molloy K et al. Evaluation of haematopoietic stem cell transplantation in patients diagnosed with cutaneous T-cell lymphoma at a tertiary care centre: should we avoid chemotherapy in conditioning regimes? British Journal of Dermatology 2020; 182(3):807-809.
- Weng W, Arai S, Rezvani A et al. Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma. Blood Adv 2020 4 (18): 4474–4482.