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Patients with peripheral T-cell lymphoma (PTCL) that is either refractory or relapsed (R/R), have poor clinical outcomes. This includes PTCL subsets such as PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). For these patients, intensive salvage chemotherapy prior to either autologous hematopoietic cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) remains one of the limited treatment options. However, it remains uncertain which of these is the optimal treatment choice for those who are fit enough to undergo HSCT.
Here, we consider data from two studies exploring this challenging clinical question. Jun Du and colleagues published in JAMA Network Open, a systematic review of allo-HSCT vs auto-HSCT for patients with R/R PTCL.1 In addition, exploring the question of whether allo-HSCT or auto-HSCT represents the best treatment choice in patients with PTCL-NOS and AITL, Kazuaki Kameda and colleagues2 undertook a retrospective analysis of patients with T-cell lymphoma to examine how this treatment choice affected outcomes for these patients, results of which were presented at the 26th Congress of the European Hematology Association (EHA2021).
Du and colleagues1 conducted a systematic search on PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and the China National Knowledge Infrastructure database using the following terms:
Clinical trials and retrospective studies with more than 10 samples that were published between January 12, 2001, and October 1, 2020, were included. Patients in these studies had R/R PTCL with no age or sex restrictions and were treated with auto- or allo-HSCT. Studies that were included provided outcome measures such as complete response (CR), partial response (PR), overall survival (OS), progression-free survival (PFS), and transplantation-related mortality (TRM). Articles without OS, PFS, and TRM were excluded.
The prespecified outcome measures were OS, PFS, and TRM.
Of 6,548 records identified, 30 underwent data extraction. These selected studies included 880 patients who underwent allo-HSCT, and 885 who underwent auto-HSCT. Pooled results are reported in Table 1.
Table 1. OS, PFS, and TRM in patients receiving HSCT*
Results |
Allo-HSCT patients |
Auto-HSCT patients |
---|---|---|
3-year OS |
50 (41−60) |
55 (48−64) |
3-year PFS |
42 (35−51) |
41 (33−51) |
5-year OS |
54 (47−62) |
53 (44−64) |
5-year PFS |
48 (40−56) |
40 (24−58) |
3-year TRM |
32 (27−37) |
7 (2−23) |
Allo-HSCT, allogeneic hematopoietic cell transplantation; auto-HSCT, autologous hematopoietic cell transplantation; OS, overall survival; PFS, progression-free survival; TRM, transplantation-related mortality. |
The meta-analysis1 supports that OS and PFS are similar in patients treated with either allo-HSCT or auto-HSCT, and that HSCT is an effective treatment for R/R PTCL. The results of the pooled analysis also suggest a higher TRM associated with allo-HSCT compared with auto-HSCT. While the study had strict enrollment criteria, it should be noted that most of the eligible studies were single-arm trials, and the data for some outcome measures were insufficient to perform a subgroup analysis.
The study by Kameda and colleagues2 was a retrospective cohort analysis that identified patients from the Japan Society for Hematopoietic Cell Transplantation national database.
The study collected demographic, diagnostic, treatment, and clinical outcome data, including OS and PFS data.
Inclusion criteria stated that all patients must have
762 patients were identified:
Chemosensitivity and remission status among the overall population were variable:
Key differences between allo-HSCT and auto-HSCT patients, including demographic, clinical, and treatment considerations, can be seen in Table 2. Allo-HSCT were more likely to have a worse HSCT comorbidity index and worse performance status (both p < 0.001) than auto-HSCT patients.
Table 2. Demographics, treatment, and outcomes*
Parameter |
Allo-HSCT patients |
Auto-HSCT patients |
p value |
---|---|---|---|
Median age, years |
53 |
58 |
< 0.001 |
Received >2 lines of prior therapy, % |
63 |
33 |
< 0.001 |
Median months to HSCT from diagnosis (range) |
11 (2−214) |
11 (2−154) |
0.64 |
Median follow-up in months (range) |
36 (1−150) |
54 (3−160) |
— |
Allo-HSCT, allogeneic hematopoietic cell transplantation; auto-HSCT, autologous hematopoietic cell transplantation. |
OS and PFS data were considered at 4 years survival and were calculated for each treatment response group, alongside 2-year nonrelapse mortality; these are represented in Table 3.
Table 3. OFS, PFS, and nonrelapse mortality data for patients treated with allo- or auto-HSCT*
Outcome |
Auto-HSCT |
Allo-HSCT |
---|---|---|
4-year survival data, % (95%CI) |
||
Chemo-sensitive OS |
56 (49.9−61.1) |
59.8 (50.8−67.9) |
Chemo-sensitive PFS |
43 (37.1−48.6) |
54.2 (45.2−62.2) |
Chemo-refractory OS |
34.1 (23.5−44.9) |
41.1 (33.4−48.7) |
Chemo-refractory PFS |
23.4 (14.9−33) |
37.9 (30.2−45.2) |
2-year nonrelapse mortality, % (95%CI) |
||
Chemo-sensitive disease |
9.7 (6.7−13.3) |
23.3 (16.6−30.7) |
Chemo-refractory disease |
9.7 (4.7−16.8) |
36.3 (29−43.7) |
Allo-HSCT, allogeneic hematopoietic cell transplantation; auto-HSCT, autologous hematopoietic cell transplantation; OS, overall survival; PFS, progression-free survival. |
Multivariate analysis confirmed that treatment with allo-HSCT was a significantly better prognostic factor for PFS in chemo-sensitive patients (hazard ratio [HR], 0.68; 95% CI, 0.5−0.92; p = 0.01), but only marginally better for PFS in chemo-refractory patients (HR, 0.73; 95% CI, 0.52−1.01; p = 0.06). Further statistical analysis suggested a trend, without statistical significance, that allo-HSCT conferred better OS for relapsed-sensitive disease among chemo-sensitive patients (HR 0.61; 95% CI, 0.36−1.04; p = 0.07), and primary-refractory disease among chemotherapy refractory patients (HR 0.51; 95% CI, 0.29−0.89; p = 0.02).
The results of the study2 suggest that in patients with relapsed-sensitive or primary refractory PTCL-NOS or AITL, allo-HSCT may result in better outcomes for patients, including PFS and OFS. Given the higher morbidities associated with allo-HSCT compared to auto-HSCT, further work is needed to confirm these findings to inform future decisions about standard of care in this patient group.
Together, these studies suggest that for patients with R/R PTCL, both allo-HSCT and auto-HSCT are effective treatment choices. However, for certain subsets of R/R PTCL, allo-HSCT may result in increased survival, but with increased morbidities. Further work is needed to inform future clinical decision making for patients with R/R PTCL.
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