Allogeneic Hematopoietic Cell Transplantation For Patients With Mycosis Fungoides and Sezary Syndrome: The Experience Of The EBMT Lymphoma Working Party With An Extended Five-Year Follow Up
Authors: Duarte Rafael F. , Boumendil Ariane , Onida Francesco , Gabriel Ian H , Arranz Reyes , Arcese William , Poire Xavier , Kobbe Guido , Narni Franco , Cortelezzi Agostino , Olavarría Eduardo , Schmitz Norbert , Sureda Anna , Dreger Peter 
Published: October 2019

Abstract

Purpose
In 2010 the EBMT Lymphoma Working Party reported our experience on allogeneic HCT in patients with mycosis fungoides and SŽzary syndrome (MF/SS) in what remains the largest series on this topic published to date [JCO 2010; 28: 4492-4499]. Despite the encouraging results, the main shortcoming of our initial report was a limited follow up of 36 months; in particular, for a series in which 73% of the cases received a reduced-intensity conditioning prior to HCT. The purpose of this study is to analyze our experience in this setting with an extended follow up, including standard outcomes of non-relapse mortality (NRM), incidence of relapse/progression (R/P), progression-free survival (PFS) and overall survival (OS), as well as to identify factors associated with patient outcome 5 years after allogeneic HCT.

Patients and Methods
Sixty patients with MF (n=36) and SS (n=24) who received a first allogeneic HCT from matched related (mRD, n=45) or unrelated (mUD, n=15) donors between 1997 and 2007, included in our original series were analyzed: 37 men and 23 women, median age 46.5 years (22-66). Forty-four patients (73%) had TNM stage IV, and 40 (67%) were at advanced disease phase at transplantation, defined as either those on third or later complete response (CR), partial response (PR) or relapse/progression, or those primary refractory to systemic therapy. Forty-four patients (73%) received reduced-intensity (RIC) and only 16 (27%) myeloablative (MAC) conditioning regimens, with 25 (42%) undergoing T-cell depletion (TCD). Extended follow up data was collected from the EBMT Registry and closed in July 2013.

Results
With an extended median follow up in survivors of 60 months (4–117), allogeneic HCT continues to offer patients with MF/SS an advantageous estimated OS of 66% at 1 year, 54% at 3 years and 48% at 5 years (95% CI: 36% - 64%), and a first PFS of 41% at 1 year, 35% at 3 years and 33% at 5 years (95% CI: 23% - 48%). Disease R/P remains the main complication, with a total of 26 cases (43%) at a median of 3.8 months (1-37) after HCT. While 16 of them died from disease R/P, it is worth noting that at present 10 of these patients (38%) remain alive at last follow up, suggesting that after R/P, patients can be successfully rescued with donor lymphocyte infusions and other lines of therapy. Indeed, at last follow up, a total of 31 patients remain alive, and of these only 2 have active disease, while 29 of them are also in sustained or re-attained CR from their MF/SS. NRM has remained stable at 22% (13 cases; median 52 days from HCT, 8-403) in this analysis. As described in Table 1, the outcome of MF/SS patients 5 years after allogeneic HCT is primarily driven by the type of donor, the intensity of conditioning, and the status of the disease at the time of transplant. In addition, patients with a poor performance status (Karnofsky <70) have a higher risk of NRM, and patients receiving TCD, a higher incidence of disease R/P, none of which translate into a significant impact on OS.

Conclusions
Our data with a prolonged patient follow up provides a clearer picture of the value of allogeneic HCT as a therapeutic strategy for high-risk patients with advanced-stage MF/SS. They further suggest the existence of a clinically relevant graft-versus-MF/SS effect that provides prolonged survival with no evidence of disease to patients with advance phase at the time of transplant and even to many of those who relapse/progress after allogeneic HCT. This study identifies as well factors that may influence the overall outcome of these patients at a longer 5-year term after transplant.

Disclosures:
Dreger: Riemser Pharma : Consultancy, Honoraria, Research Funding.