Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome



We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the International Blood and Marrow Transplant from 2000–2009. Median time from diagnosis to transplant was 30 (4–206) months and most subjects were with multiply relapsed/ refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (CI) 12–27%) and 22% (95% CI 15–31%), respectively. Risk of disease progression was 50% (95% CI 41–60%) at 1 year and 61% (95% CI 50–71%) at 5 years. PFS at 1 and 5 years was 31% (95% CI 22–40%) and 17% (95% CI 9–26%), respectively. OS at 1 and 5 years was 54% (95% CI 45–63%) and 32% (95% CI 22–44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in approximately one-third of patients and of those, half remain disease-free.


Cutaneous T-cell lymphoma (CTCL) constitutes approximately 2% of all lymphomas. Mycosis fungoides (MF) represents the most common subtype. Many patients with MF experience a prolonged clinical course. Patients with stage IVA and IVB disease have a median OS between 1.4–3.8 years from the time of diagnosis.1, 2 Newer treatment modalities have arisen over the last decade, with relapse still being common.

Historically, hematopoietic cell transplantation (HCT) was rarely used to treat MF/Sezary syndrome (SS) because of concern regarding the lack of skin integrity and possible increased risk of infection. However, there is renewed interest in consideration of HCT because MF/SS is incurable with conventional therapy. Autologous HCT has not resulted in long-term remissions in CTCL patients3, 4, 5 and is rarely used now. Relatively small retrospective studies of allogeneic HCT with both myeloablative (MAC) and non-myeloablative conditioning (NST)/reduced intensity conditioning (RIC) regimens have been described.5, 6, 7 Definitive conclusions are lacking because of small sample size and considerable heterogeneity in subject, disease and transplant variables. We analyzed outcomes of allogeneic HCT for MF/SS in 129 subjects reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).8

Patients and methods

The CIBMTR is a voluntary working group of more than 450 transplantation centers worldwide that contribute detailed data on consecutive allogeneic and autologous hematopoietic cell transplants to a Statistical Center at the Medical College of Wisconsin in Milwaukee and the NMDP Coordinating Center in Minneapolis. Participating centers are required to report all transplants consecutively; compliance is monitored by on-site audits. Patients are followed longitudinally, with yearly follow-up. Computerized checks for discrepancies, physicians’ review of submitted data and on-site audits of participating centers ensure data quality. Observational studies conducted by the CIBMTR are performed in compliance with the Privacy Rule (HIPAA) as a Public Health Authority, and in compliance with all applicable federal regulations pertaining to the protection of human research participants as determined by continuous review of the Institutional Review Boards of the National Marrow Donor Program and the Medical College of Wisconsin since 1985.

The CIBMTR collects data at two levels: Transplant Essential Data (TED) and Comprehensive Report Form (CRF) data. TED data include disease type, age, gender, pre-transplant disease stage and chemotherapy responsiveness, date of diagnosis, graft type (BM- and/or blood-derived progenitor cells), conditioning regimen, post-transplant disease progression and survival, development of a new malignancy and cause of death. All CIBMTR teams contribute TED data. More detailed disease and pre- and post-transplant clinical information is collected on a subset of registered patients selected for CRF data by a weighted randomization scheme. TED and CRF level data are collected pre-transplant, 100 days and six months post transplant and annually thereafter or until death.

Subject selection

We analyzed the outcomes 129 adult (18 years) recipients of an allogeneic HLA-matched related or unrelated HCT for MF/SS reported to the CIBMTR between 2000 and 2009. A subset of these patients (N=52) was reported at a higher level with comprehensive disease data and complete case report forms (CRF). Median follow-up for these 52 patients was 40 months with a range of 3–91 months. The overall cohort of 129 subjects and the comprehensive subset had similar OS outcomes.

Study endpoints and definitions

Outcomes analyzed included treatment-related mortality (non-relapse mortality (NRM)), relapse/progression, PFS and OS. Patient staging was done by Ann Arbor staging criteria at the time of treatment. Data for ISCL/EORTC for MF/SS were not captured in this data set. The intensity of conditioning was categorized based on consensus criteria.9 Neutrophil recovery was defined as the first of three subsequent days with absolute neutrophil counts 0.5 × 10e9/L without growth factor support. Platelet recovery was defined as the first of seven subsequent days with platelet counts 20 × 10e9/L without platelet transfusions. NRM was defined as death from any cause in the first 28 days after HCT or death without evidence of MF/SS progression/relapse. Progression was defined as an increase of ≥25% in the sites of lymphoma or development of new sites. Relapse was defined as recurrence of lymphoma after a CR. For PFS, patients were considered treatment failures at the time of relapse/progression or death from any cause. Patients alive without evidence of disease relapse or progression were censored at last follow-up and the PFS event was summarized by a survival curve. The OS interval variable was defined as the time from date of transplant to date of death or last contact and summarized by a survival curve.

Other outcomes analyzed included the incidence of acute (aGvHD) and chronic cGvHD graded by established criteria and cause of death.

Statistical analysis

Subject-, disease- and transplant-related variables are described for the entire cohort along with an additional subset with higher level CRF data. Univariate probabilities of NRM, relapse/progression, aGVHD, cGVHD, PFS and survival were described and compared. Causes of death are described.


Patients and transplant characteristics

In total, 129 MF/SS patients received an allogeneic transplant with characteristics described in Table 1. The majority received NST/RIC (n=83), 64% vs 36% receiving MAC. The NST/RIC cohort was older with a median age at transplant of 51 (27–72) years vs 44 (22–63) years in the MAC cohort (P=0.005). Eighty nine percent (n=74) of patients were transplanted 12 months or longer from diagnosis, with 49% (n=41) transplanted more than 36 months after diagnosis. Only one patient received allogeneic HCT in first CR, while 37% never achieved CR before transplant. No patient had a prior autologous HCT.

Table 1 Characteristics of patients who underwent allogeneic transplantation for mycosis fungoides and Sezary syndrome, registered to the Center for the International Blood and Marrow Transplant, between 2000 and 2009

The majority of patients (64%) were transplanted after 2006. A greater utilization of NST/RIC regimens was noted for this patient population. BM grafts were used in 13%, peripheral blood grafts in 86% and cord blood in one (1%) patient. Fludarabine-based combination conditioning regimens were used in 66 of the 83 (80%) patients receiving NST/RIC. Specific NST/RIC regimens are detailed in Table 1. CY with TBI was the most common MAC regimen used 16 of 45 or (35%) of patients.

A subset of 52 patients had higher level reporting with more disease-related information available for analysis (CRF cohort, Table 2). In this subset, 25 of 52 patients or 48% had four or more lines of chemotherapy before transplant. The use of alemtuzumab before transplant was limited to (13% of patients) and total skin electron beam (TSEB) radiation was used in only one patient recorded. Radiation therapy was used before transplant in 19% of 52 patients.

Table 2 Characteristics of patients who underwent allogeneic BM or peripheral blood transplantation for mycosis fungoides and Sezary syndrome, reported to the Center for International Blood and Marrow Transplant Research, between 2001 and 2009


Neutrophil engraftment was achieved in 95% (95% confidence interval (CI) 88–98) of patients at day 28. Platelet engraftment was achieved in 89% (95% CI 76–95%) of patients at day 100 (Table 3).

Table 3 Univariate outcomes of patients who underwent allogeneic BM or peripheral blood transplantation for mycosis fungoides and Sezary syndrome, registered with the Center for International Blood and Marrow Transplant Research, between 2000–2009


The incidence of grade II–IV aGVHD was 41% (95% CI 32–51%). The incidence of cGVHD was 33% (95% CI 23–43%), 42% (95% CI 31–52%) and 43% (95% CI 33–54%) at 180 days, 1 and 2 years, respectively (Table 3).

Treatment and disease outcomes

Irrespective of conditioning regimen intensity, OS was similar at 56% (95% CI 45–67%) and 41% (95% CI 29–53%) at 1 and 3 years, respectively for NST/RIC and 51% (95% CI 35–66%) and 31% (95% CI 16–49%), respectively, for MAC (log rank P-value=0.277) shown in Figure 1a. NRM for registered patients at 1 year and 5 years was 19% (95% CI 12–27%) and 22% (95% CI 15–31%) (Table 3). NRM did not differ significantly between the NST/RIC and MAC cohorts (Table 4). Progression/relapse was 50% (95% CI 41–60%) at 1 year and 61% (95% CI 50–71%) at 5 years. PFS at 1 year was 31% (95% CI 22–40%) and at 5 years was 17% (95% CI 9–26%). There was no significant difference in PFS between the NST/RIC and MAC cohorts (P-value=0.149; Figure 1b). There was no significant difference in the incidence of NRM with MAC vs NST/RIC (Figure 1c). There was no significant difference in PFS based on interval of diagnosis to transplant (Figure 1d). Progressive disease was the primary cause of death and treatment failure in this cohort of patients with advanced disease. Other causes of death are summarized in Table 5.

Figure 1

(a) Probability of OS in NST/RIC and MAC groups patients in the registered patients. (b) Probability of PFS in NST/RIC and MAC groups in the registered patients. (c) Cumulative incidence of NRM in NST/RIC and MAC groups in the registered patients. (d) Probability of PFS by time between diagnosis and transplant. (e) Probability of OS difference by year of transplant in the registered patients.

Table 4 Comparison of univariate outcomes between ablative and NST/RIC conditioning among patients who underwent allogeneic BM or peripheral blood transplantation for mycosis fungoides and Sezary syndrome, reported to the Center for International Blood and Marrow Transplant Research, between 2000–2009a
Table 5 Reported primary causes of death


To the best of our knowledge, this analysis represents the largest reported descriptive cohort of patients receiving allogeneic HCT for MF/SS. While we reviewed the data from 2000 until 2009, the majority of patients were transplanted in the latter 5 years. This may be due to increased availability of NST/RIC regimens, recognition of the safety of HCT in this population, and the more integrated multidisciplinary care these patients are receiving. Also surprisingly, our cohort demonstrated only 39% of the patients having stage IV MF/SS. Presumably, this cohort represents a minority of the patients with MF/SS, who may have had very aggressive disease.

Molina et al.6 in an early report described eight patients undergoing HCT with both MAC and NST/RIC. All patients achieved complete clinical remission and resolution of molecular and cytogenetic markers of disease within 30–60 days after HCT. Two patients died from transplantation-related complications. A comparison of NST/RIC vs MAC was not done due to small patient numbers.6 The European Group for Blood and Marrow Transplantation reviewed 60 recipients of HCT for MF and SS.7 This study confirmed the feasibility of HCT with NST/RIC or T-cell depletion in MF/SS with a 10% NRM at 2 years. Our data demonstrate a NRM of 22% at 3 years. Duarte et al.7 also reported the adverse impact of advanced disease phase at transplant. Although follow-up is longer in our series, we did not have enough patients with limited disease to compare with late-stage disease patients for survival differences. We did not find statistically significant differences in survival based on duration from diagnosis to transplant (Figure 1d). Our data also showed that conditioning intensity did not have an impact on NRM or OS. However, a prior European Group for Blood and Marrow Transplantation study did show survival advantage for NST/RIC.7

In addition, our data did not show any difference in PFS with conditioning regimens. In our study, relapse was noted in 50% of patients at 1 year and 61% at 5 years. This may indicate relapses are most common in the first year post transplant and that there is much less of a chance of progression after 1 year. Others have described evidence for a graft-versus-lymphoma effect in CTCL patients.10 Graft-versus-lymphoma in two CTCL patients after CR was achieved after post-allogeneic HCT relapse with either withdrawal of immunosuppression or DLI.11,12 In our series, 4 of 55 patients received DLI; however, no additional data on graft-versus-lymphoma effect were available. Further prospective study will be needed to address treatment of post-transplant relapse.

One of the limitations to this analysis is the capturing of staging in this population. In 2007, the International Society for Cutaneous Lymphomas (ISCL)13 published their consensus recommendations for the staging of MF and SS and later validated independently.2 Our data did not capture all of the components of the ISCL/EORTC staging for each patient in order to be able to assign this staging approach to our patient population. Our data set relies on the diagnosis and staging at individual sites. Their data were not captured for the updated staging criteria and therefore is not consistent with this manuscript.

Duvic et al.14 described a prospective series of 19 patients with advanced CTCL (median age, 50 years; four prior therapies) who underwent TSEB radiation followed by HCT with fludarabine and melphalan-based conditioning. Of these patients, 18 engrafted with 15 achieving full donor chimerism. At a median follow-up of 1.7 years, 13 of the 19 patients were still alive. Causes of death included bacterial sepsis, chronic GVHD, fungal infection and secondary malignancy. While eight patients had relapse in their skin alone, two patients died of progressive disease. Two-year OS and PFS were 79% and 53%, respectively.14 Progressive disease was the primary cause of treatment failure in this cohort of patients with advanced phase disease. In the recent retrospective French cohort of 37 cases of advanced and transformed MF treated with allogeneic transplantation,15 six of the 19 patients with post-transplant relapse achieved a CR with salvage therapy. While our data have a median follow-up for NST/RIC patients of 39 months (3–122) and PFS at 3 years of 24%, we do not have sufficient data to be able to confirm this observation.

Duvic et al.14 postulate the use of TSEB may have improved allogeneic HCT outcomes by reducing APCs in the skin. Only one of our patients, by report, had TSEB therapy before transplant. It is of interest whether TSEB conditioning is superior in inducing a remission before HCT or if there will be a prolongation of the disease-free interval with longer follow-up from Duvic’s study. Newer approaches to MF/SS such as TSEB, new anti-neoplastic and immunosuppressive agents may improve these patients’ outcomes.

In conclusion, this large series of allogeneic HCT in MF/SS confirms feasibility, acceptable NRM (19–28%) and evidence of benefit in an advanced cohort of MF/SS patients. Allogeneic HCT in MF/SS appears to be superior to autologous transplantation based on previous reports but relapse remains the major cause of mortality.3–5 Prospective studies will be necessary to determine the role of new modalities of therapy as well as the optimal timing of allogeneic HCT.


  1. 1

    Sausville EA, Eddy JL, Makuch RW, Fischmann AB, Schechter GP, Matthews M et al. Histopathological staging at initial diagnosis of mycosis fungoides and the Sezary syndrome. Definition of three distinctive prognostic groups. Ann Intern Med 1988; 109: 372–382.

    CAS  Article  Google Scholar 

  2. 2

    Agar NS, Wedgeworth E, Crichton S, Mitchell TJ, Cox M, Ferreira S et al. Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol 2010; 28: 4730–4739.

    Article  Google Scholar 

  3. 3

    Bigler RD, Crilley P, Micaily B, Brady LW, Topolsky D, Bulova S et al. Autologous bone marrow transplantation for advanced stage mycosis fungoides. Bone Marrow Transplant 1991; 7: 133–137.

    CAS  PubMed  Google Scholar 

  4. 4

    Olavarria E, Child F, Woolford A, Whittaker SJ, Davis JG, McDonald C et al. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement. Br J Haematol 2001; 114: 624–631.

    CAS  Article  Google Scholar 

  5. 5

    Duarte RF, Schmitz N, Servitje O, Sureda A . Haematopoietic stem cell transplantation for patients with primary cutaneous T-cell lymphoma. Bone Marrow Transplant 2008; 41: 597–604.

    CAS  Article  Google Scholar 

  6. 6

    Molina A, Zain J, Arber DA, Angelopolou M, O’Donnell M, Murata-Collins J et al. Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 2005; 23: 6163–6171.

    Article  Google Scholar 

  7. 7

    Duarte RF, Canals C, Onida F, Gabriel IH, Arranz R, Arcese W et al. Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and sezary syndrome: a retrospective analysis of the lymphoma working party of the european group for blood and marrow transplantation. J Clin Oncol 2010; 28: 4492–4499.

    Article  Google Scholar 

  8. 8

    Lechowicz M, Agovi M, Carreras J, Lazarus HM, Laport GG, Montoto S et al. Allogeneic Hematopoietic Cell Transplantation (AHCT) for Primary Cutaneous T Cell Lymphoma (CTCL): a Center for International Blood and Marrow Transplant Research (CIBMTR) Review. Blood 2010; 116: 2246 (Abstract 364).

    Google Scholar 

  9. 9

    Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 2009; 15: 1628–1633.

    Article  Google Scholar 

  10. 10

    Herbert KE, Spencer A, Grigg A, Ryan G, McCormack C, Prince HM . Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation. Bone Marrow Transplant 2004; 34: 521–525.

    CAS  Article  Google Scholar 

  11. 11

    Jacobsen ED, Kim HT, Ho VT, Cutler CS, Koreth J, Fisher DC et al. A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome. Ann Oncol 2011; 22: 1608–1613.

    CAS  Article  Google Scholar 

  12. 12

    Wu PA, Kim YH, Lavori PW, Hoppe RT, Stockerl-Goldstein KE . A meta-analysis of patients receiving allogeneic or autologous hematopoietic stem cell transplant in mycosis fungoides and Sézary syndrome. Biol Blood Marrow Transplant 2009; 15: 982–990.

    Article  Google Scholar 

  13. 13

    Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007; 110: 1713–1722.

    CAS  Article  Google Scholar 

  14. 14

    Duvic M, Donato M, Dabaja B, Richmond H, Singh L, Wei W et al. Total Skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sézary Syndrome. J Clin Oncol 2010; 28: 2365–2372.

    Article  Google Scholar 

  15. 15

    De Masson A, Beylot-Barry M, Bouaziz J-D, Peffault de Latour R, Aubin F, Garciaz S et al. Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas. Haematologica 2014; 99: 527–534.

    Article  Google Scholar 

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The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24 CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement U10 HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Allos Therapeutics, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;Gentium SpA; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government.

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Correspondence to P N Hari.

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Lechowicz, M., Lazarus, H., Carreras, J. et al. Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome. Bone Marrow Transplant 49, 1360–1365 (2014).

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