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

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.¹ Therefore, 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 characteristics³

• 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-HCST³

• 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) vs complete 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 vs CR ≥ 2/PR ≥ 2 vs PD) 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) vs RIC, 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 the graft-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.