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A retrospective analysis of allogeneic stem cell transplantation for peripheral T-cell lymphoma

Jul 10, 2020

Patients with peripheral T-cell lymphomas (PTCL) have poor prognosis and responses to currently recommended treatments which are often not durable. Novel targeted treatments, such as pralatrexate, romidepsin, crizotinib for ALK+ anaplastic large cell lymphoma (ALCL), and brentuximab vedotin for CD30+ PTCL, demonstrate improved responses, but their long-term efficacy is still unknown. The recommended first-line therapy, high dose chemotherapy followed by autologous hematopoietic stem cell transplant (auto-HSCT), has a high incidence of relapse. The use of allogeneic (allo)-HSCT in PTCL is debatable. Although it has been associated with graft- versus-lymphoma effects, the transplant-related mortality (TRM) is high. 1Therefore, at present, allo-HSCT is recommended only in the relapsed or refractory PTCL setting. 2

In a retrospective analysis, Anne-Claire Mamez and colleagues examined the outcomes of allo-HSCT in patients with non-primary cutaneous PTCL. The results of the study were published in the Journal of Hematology & Oncology. 3

Study design and patient characteristics

The study investigated data from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry of patients with non-primary cutaneous PTCL who underwent allo-HSCT between October 2006 and January 2014. Patients aged < 15 years were excluded.

The overall survival (OS), event-free survival (EFS), relapse, TRM, and associated variables were analyzed.

  • The median age at transplant was 49.5 years. The majority of patients were male and received reduced-intensity conditioning regimen (RIC) ( Table 1)
  • The most common subtype was PTCL not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma
  • The median number of treatment lines before the transplant was 2
  • The most frequent graft- versus-host disease (GvHD) prophylaxis was based on cyclosporin +/− mycophenolate mofetil or methotrexate

Table 1 . Selected patient, disease, and transplant characteristics 3

AITL, angioimmunoblastic T-cell lymphoma; ALCL, anaplastic large cell lymphoma; ALK+/−, with/without anaplastic lymphoma kinase mutation; allo, allogeneic; ATLL, adult T-cell leukemia/lymphoma; auto, autologous; CR, complete response; EATL, enteropathy-associated T-cell lymphoma; HLA, human leukocyte antigen; HSCT, hematopoietic stem cell transplant; HSTL, hepatosplenic T-cell lymphoma; MAC, myeloablative conditioning regimen; NK, natural killer; NOS, not otherwise specified; PBSC, peripheral blood stem cell; PD, progressive disease; PR, partial response; RIC, reduced-intensity conditioning regimen

*Missing data for 83 patients

Characteristic

Patients (N = 285)

Age

Median age (range), years

> 60, %

49.5 (16–69)

14

 

Gender, %

Male

67

 

Histological subtype, %

NOS

AITL

ALCL ALK+

ALCL ALK−

ATLL

NK/T

HSTL

EATL

Other

39

29

7

7

6

6

4

1

1

 

Stage at diagnosis*

I–II

III–IV

 

15

85

 

Allo-HSCT timing, %

Front-line consolidation

CR1

PR1

Second-line consolidation

CR2

CR > 2

PR2

PR > 2

Progressive disease

48

33

15

41

25

5

9

2

11

 

Previous auto-HSCT, %

No

Yes (relapse after auto-HSCT)

Yes (tandem auto/allo-HSCT)

67

23

9

 

Disease status at transplant, %

CR

PR

PD

62

27

11

 

Conditioning regimen, %

RIC

MAC

62

38

 

Graft source, %

PBSC

Bone marrow

Cord blood

71

17

12

 

HLA matching, %

Sibling identical

Matched unrelated

Mismatched unrelated

Cord blood

Haploidentical

45

36

5

12

2

 

T-cell depletion, %

In vivo

Ex vivo

50

1

 

 

  • Overall, 65 patients relapsed after allo-HSCT
  • 118/285 (41%) patients died during the follow-up, mainly due to
    • lymphoma relapse (14%)
    • infections (10%)
    • GvHD (8%) 
  • The GvHD occurrence rates were as follows:
    • Acute (a)GvHD – Grade ≥ II in 30% of patients, including Grade III–IV in 14.7%
    • Chronic (c)GvHD – in 37% of patients, including 14.8% with extensive involvement

Results

  • The median follow-up was 72.4 months
  • The main results of the analysis are presented in Table 2

Table 2. Efficacy after allo-HCST 3

CIR, cumulative incidence of response; EFS, event-free survival; GRFS, graft- versus-host disease-free relapse-free survival; OS, overall survival; TRM, transplant-related mortality

Outcome

Patients (N = 285)

OS rate, % (95% CI)

1-year

2-year

4-year

 

68 (0.63–0.74)

65 (0.59–0.70)

59 (0.53–0.65)

EFS, % (95% CI)

1-year

2-year

4-year

 

64 (0.58–0.70)

60 (0.54–0.66)

54 (0.48–0.61)

CIR, % (95% CI)

1-year

2-year

 

18 (0.13–0.23)

19 (0.14–0.24)

The median time from transplant to relapse, days

97

TRM, % (95% CI)

1-year

2-year

4-year

 

21 (0.17–0.27)

24 (0.30–0.19)

28 (0.34–0.23)

GRFS, % (95% CI)

1-year

2-year

4-year

 

49 (0.43–0.55)

46 (0.40–0.52)

43 (0.37–0.49)

 

  • Factors significantly associated with reduced 5-years OS included:
    • Grade III–IV aGvHD (HR = 2.57; 95% CI, 1.53–4.31; p = 0.00036)
    • Low Karnofsky score < 80% (HR = 5.14; 95% CI, 2.02–13.06; p = 0.00058)
    • Progressive disease (PD) vscomplete response (CR) prior to transplant (HR = 2.21; 95% CI, 1.25–3.89; p = 0.0062)
  • The main factors associated with TRM were:
    • Number of lines of treatment ≤ 2 (HR = 0.59; 95% CI, 0.35–0.99; p = 0.047)
    • Low Karnofsky score < 80% (HR = 3.43; 95% CI, 1.09–10.7; p = 0.034)
  • Analysis by histological subtype revealed that
    • the 1- and 2-year OS and EFS were the highest among patients with ALT+ ALCL, followed by PTCL-NOS and angioimmunoblastic T-cell lymphoma; while patients with ALK− ALCL and NK/T lymphoma had the lowest OS; the EFS was the lowest for adult T-cell leukemia/lymphoma and NK/T lymphoma
    • the highest TRM rates were recorded for hepatosplenic T-cell lymphoma (42%) and the lowest for enteropathy-associated T-cell lymphoma (0%) and ALT+ ALCL (5%)
  • Patients who underwent allo-HSCT during progressive disease had lower 4-year OS (37%) and the highest cumulative incidence of relapse (32%) compared with patients who had received it as a front or second-line (63% and 61%; 19 and 17%, respectively)
  • The disease status (CR1/PR1 vsCR ≥ 2/PR ≥ 2 vsPD) before transplant had a significant impact on OS (p < 0.01) and EFS (p = 0.02), but not on GRFS (p = 0.08)
  • The type of conditioning, myeloablative conditioning regimen (MAC) vsRIC, did not significantly influence OS (p = 0.5), EFS (p =0.55), TRM (p = 0.09), or relapse risk (p = 0.32)
  • Development of cGvHD did not had a significant impact on cumulative incidence of response

Conclusion

Results of this retrospective study, which analyzed a relatively large number of patients who underwent allo-HSCT for the treatment of non-cutaneous PTCL, show promising clinical activity. The study demonstrated low relapse rates with allo-HSCT following MAC and RIC, which authors attribute to thegraft- versus-lymphoma effect. However, high rates of GvHD and mortality rates suggest caution.

The authors believe that due to the current lack of targeted immune-based therapy for PTCL, allo-SCT could be considered the main treatment for aggressive lymphomas.


  1. Mamez A-C, Souchet L, Roos-Weil D, et al. Graft-versus-T-cell lymphoma effect: A sustained CR after tapering immunosuppressive drugs in a patient with angioimmunoblastic T-cell lymphoma in relapse after allogeneic transplantation. Bone Marrow Transplant.2015;50(2):304-306. DOI: 10.1038/bmt.2014.243
  2. Kharfan-Dabaja MA, Kumar A, Ayala E, et al. Clinical practice recommendations on indication and timing of hematopoietic cell transplantation in mature T cell and NK/T cell lymphomas: An international collaborative effort on behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant.2017;23(11):1826-1838. DOI: 10.1016/j.bbmt.2017.07.027
  3. Mamez A-C, Dupont A, Blaise D, et al. Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). J Hematol Oncol.2020;13(1). DOI: 10.1186/s13045-020-00892-4