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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 3  |  Page : 1189-1197

Long-term outcomes of peripheral blood stem cell transplantation for 38 patients with peripheral T-cell lymphoma


Department of Hematology, Chinese People's Liberation Army General Hospital, Beijing 100853, China

Date of Web Publication4-Jan-2017

Correspondence Address:
Honghua Li
Department of Hematology, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853
China
Li Yu
Department of Hematology, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.189235

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 > Abstract 

Objective: In this study, to investigate clinical characteristics, response, outcome, and prognosis of peripheral blood stem cell transplantation (PBSCT) for patients with peripheral T-cell lymphoma (PTCL).
Methods: This study retrospectively analyzed the efficacy of PBSCT in 38 patients with PTCL. Kaplan–Meier methods were used in survival analysis, and the Cox regression model was applied in multivariate analysis. There were ten clinical parameters were analyzed.
Results: The 2-year overall survival (OS) was 46%, and the 5-year OS was 34% after a median follow-up of 40 months. The patients who received allogeneic PBSCT (allo-PBSCT) had a higher nonrelapse mortality than autologous PBSCT (auto-PBSCT), but they could achieve a longer-term disease-free survival in the former, which OS could achieve 40%. Survival analysis with Kaplan–Meier method showed the pretransplant disease status, B symptoms, serum lactate dehydrogenase (LDH) in early (>275 U/L), Eastern Cooperative Oncology Group (ECOG) score (>1), prognostic index for PTCL score (>2) were all prognostic factors for posttransplant OS. Pretransplant disease status is the only prognostic factor for allo-PBSCT.
Conclusion: The key was to reducing transplant-related mortality of allo-PBSCT by reduced-intensity conditioning. Factors such as level of early serum LDH, extranodal involvement, B symptoms, ECOG score, Ann Arbor stage, and pretransplant disease status were all related to the prognosis of patients treated with PBSCT. Allo-PBSCT maybe suggested as the first line therapy for late-stage PTCL patients who could reach treatment remission before transplantation.

Keywords: Peripheral blood stem cell transplantation, peripheral T-cell lymphoma, reduced-intensity conditioning


How to cite this article:
Bo J, Zhao Y, Zhang S, Hua W, Wang S, Gao C, Wang Q, Li H, Yu L. Long-term outcomes of peripheral blood stem cell transplantation for 38 patients with peripheral T-cell lymphoma. J Can Res Ther 2016;12:1189-97

How to cite this URL:
Bo J, Zhao Y, Zhang S, Hua W, Wang S, Gao C, Wang Q, Li H, Yu L. Long-term outcomes of peripheral blood stem cell transplantation for 38 patients with peripheral T-cell lymphoma. J Can Res Ther [serial online] 2016 [cited 2017 May 23];12:1189-97. Available from: http://www.cancerjournal.net/text.asp?2016/12/3/1189/189235


 > Introduction Top


Peripheral T-cell lymphoma (PTCL), a subtype of heterogeneity malignancies, originates from mature T-cells, thymocytes, or natural killer cells (NK cells). Common subtypes include PTCL not otherwise specified (PTCL-NOS), systemic anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), and some aggressive types, such as hepatosplenic T-cell lymphoma, intestinal disease-associated T-cell lymphoma, and extranodal NK/T-cell lymphoma (ENKTCL).[1] PTCL accounts for 15% to 30% of non-Hodgkin lymphoma (NHL), with distinctive regional and racial difference. Extranodal lymphomas are common, such as ENKTCL, nasal type associated with African Epstein–Barr virus.[1]

A number of novel therapies are under investigation in relapsed or refractory PTCL; however, their relative impact on disease outcome in patients was unknown. We examined the survival of patients with PTCL after relapse or progression in the absence of hematopoietic stem-cell transplantation and explored factors influencing survival. PTCL is an aggressive lymphoma, with low sensitivity to conventional chemotherapy and poor prognosis. Disease manifestations are diverse.[2] Even within the same cases, PTCL still shows significant morphological diversity and histological variability. In terms of treatments, conventional anthracycline antibiotics are proved to be not efficient. Therefore, high-dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT) has been widely clinically used. In this study, we conducted follow-up engagement on 38 patients who were diagnosed with PTCL and had received PBSCT in our hospital. Discussed in this study are the clinic features of PTCL, different types of PBSCT, and their respective prognoses.


 > Design and Methods Top


Patients

The current study includes 38 patients diagnosed PTCL based on histopathologically and immunohistochemically and having received PBSCT in our hospital from October 1994 to October 2010. It included seven cases (18%) of ALCL, two of which were anaplastic lymphoma kinase (ALK) negative and the other five positive. There are two cases (5%) of subcutaneous panniculitic T-cell lymphoma, three cases (8%) of AITL, 14 cases (37%) of PTCL-NOS, 12 cases (32%) of ENKTCL in the study subjects, respectively. Twenty-three patients (60%) underwent autologous PBSCT (auto-PBSCT); the other 15 patients (40%), allogeneic PBSCT (allo-PBSCT) [Table 1]. Biopsy pathology diagnoses were according to the 2008 WHO classification of lymphomas.[3] All studies were approved by the Ethics Committee of Chinese Institution, and each patient has given informed consent.
Table 1: Clinical characteristics of patients and prognosis analysis with the Cox proportional hazards model

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The use of case data, in this research, was approved by the Ethics Committee of our hospital according to the Declaration of Helsinki. We clearly confirm that we had all the necessary consent from any patient involved in the study, including consent to participate in the study and consent to publish.

Treatment

All patients were given chemotherapy in preoperational phase, 33 (86.8%) of which were based on anthracycline chemotherapy (cyclophosphamide-doxorubicin-vincristine-prednisone [CHOP-like]), the other five (13.2%) non CHOP-like. Twenty-seven patients (71.1%) received more than four courses of chemotherapy; 11 patients (28.9%) less than five courses. The median number of chemotherapy cycles was 6.

Autologous-peripheral blood stem cell transplantation and allogeneic-peripheral blood stem cell transplantation

Patients, who are sensitive to chemotherapy and reached complete or partial remission, were suggested to performed auto-PBSCT; those who were the presence of drug-tolerant and with high-performance status or adjusted international prognostic index (a-IPI) score, or with high-risk prognostic factors were suggested to performed allo-PBSCT. Peripheral hematopoietic stem cells for transplantation all were collected from the blood. In terms of conditional regimen, we mainly used CsA, FK506, and MMF as graft-versus-host disease prophylaxis. A total of 14 cases were myeloablative allogeneic transplantation; one of them used reduced-intensity conditioning (RIC)-allo-PBSCT. In addition, after 2008, due to the development of allo-PBSCT, we conducted first-line therapy to some low-risk patients who were sensitive to chemotherapy and had reached complete or partial remission before transplantation. Seven patients received first-line therapy, accounting for 46.7% of the overall 15 allo-PBSCT patients.

Conditional regimens

Total-body irradiation/cyclophosphamide regimen

For patients with high tumor load or malignancy and aggressive tumor: usage: Total-body irradiation (TBI) 5.0 Gy/day × 2 days (lung dose controlled under 7.0 Gy); cyclophosphamide (CY) 60 mg/kg/day × 2 days. A total of 21 patients (55%) received this conditioning regimen, 14 of which were for auto-PBSCT, seven for allo-PBSCT.

Busulfan/cyclophosphamide regimen

For patients with potentially treatable risk factors such as high age, poor control of disease before transplantation, without complete remission. Usage: Busulfan (BU) 4 mg/kg/day × 4 days; CY 60 mg/kg/day × 2 days. Eight patients (24%) received this conditioning regimen, of which two were for auto-BSCT, six for allo-PBSCT.

Carmustine, etoposide, cytarabine, and melphalan regimen

For patients suffering from central nervous system disorders or who requested to preserve their fertility: Usage: Carmustine 300 mg/m 2 × 1 day; teniposide 150 mg/m 2 × 4 days; cytarabine 200 mg/m 2 × 4 days; melphalan 140 mg/m 2 × 1 days. Two patients (5%) received this carmustine, etoposide, cytarabine, and melphalan regimen without TBI, one of which was for auto-BSCT, the other one for allo-PBSCT.

Cyclophosphamide, etoposid, and BcNu regimen

For patients with effective chemotherapy, in complete remission (CR) or partial remission (PR) and promising indicators of a better prognosis, such as ALK positive. Usage: Carmustine 250 mg/m 2 on 6 days; CY 1300 mg/m 2 on 4 or 5 days; etoposide 600 mg/m 2 on 3 days; excessive giving the liquid supply, urine alkalinization to and enforce diuresis. All six patients (16%) receiving, this conditioning regimen was for auto-PBSCT.

Fludarabine-busulfan regimen

Fludarabine is a new chemotherapy drug targeting lymphocytic leukemia and lymphoma in recent years, with high efficiency on malignant lymphomas and low adverse effect. Usage: FU 50 mg × 6 days; BU 45 mg (0.8 mg/m 2) × 3 days. One female patient with high tumor load received this regimen, considering her poor progressive disease (PD) in Phase III biopsy (BX) involved in bone marrow. The transplantation conducted on her with RIC-allo-PBSCT, using HLA-identical sibling allogeneic stem cells.

Response assessment and follow-up

Responses were evaluated according to NHLs, Version 1.2013.[4] Response assessment after treatment results in a description with terms such as complete remission (CR), partial remission (PR), stable disease (SD), and PD. Follow-ups were conducted to all patients when they were in hospitals, clinic service, or by telephone before March 30, 2012. The median duration of follow-up was 40 months.

Statistical analysis

Overall, survival (OS) and relapse-free survival were measured between the time of transplantation and the last follow-up. All statistical analysis was performed using SPSS Version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Analysis of OS was performed using Kaplan–Meier survival curves with log-rank significance test. Risk factors for nonrelapse mortality (NRM) were estimated using a multivariate Cox regression model. P ≤ 0.05 was considered statistically significant.


 > Results Top


Patients' characteristics

The clinical features of all 38 patients were listed in [Table 1], including tumor staging and grading during diagnosis and prognosis after chemotherapy. The median age was 32.5 years old (range, 8–57 years). Thirty-five cases (92.7%) were at Stages III–IV Ann Arbor at diagnosis; high serum level of lactate dehydrogenase (LDH), 19 cases (50%); B symptoms positive, 23 cases (60.5%); 22 cases (57.9%) with a-IPI score ≥2; with more than one extranodal involvement, 25 patients (65.8%); 22 cases (57.9%) with prognostic index for PTCL (PIT) score ≤2 and 16 patients (42.1%) with PIT score >2; remission status in 21 cases (55.3%) before PBSCT, among which, 12 cases (31.6%) were in CR and nine cases (23.7%) in PR; nonremission status in 17 cases (44.7%) before PBSCT, including 11 cases (28.9%) in SD and six cases (15.8%) in PD. Among all 12 cases in CR, 11 were performed with allo-PBSCT. According to [Table 2], the total number of death was 24 (63.2%), until the last follow-up in March 30, 2012. Fifteen of them received auto-PBSCT, and the other nine death cases received allo-PBSCT. The specific causes of death were showed in [Table 2].
Table 2: Cause of death

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The reduced-intensity conditioning-allogeneic-peripheral blood stem cell transplantation case

The patient was female and 55-year-old diagnosed with PTCL-NOS, with tumor staging in Phase III BX, a-IPI score of 3, and PIT score of 3. She had eight courses of conventional chemotherapy before transplantation with unsatisfactory prognosis. She was in PD with bone marrow involvement (Stage IV BX). After conditioning regimen RIC-fludarabine-busulfan (RIC-FB), she received HLA-identical sibling allogeneic stem cell transplantation in October 11, 2010.

Effect of transplantation

The median time of survival after transplantation was 24 months. OS at 2 years was 46%; at 5 years, 34% [Figure 1]. For auto-PBSCT, OS at 2 years and 5 years were 52% and 34%; for allo-PBSCT, both were 40%. There is no significant progressive-free survival plateau in the survival curve for auto-PBSCT while all the nine death cases of allo-PBSCT were within 8 months, accounting for 60% of all allo-PBSCT cases. The other 40% survived for a long-term with an obvious survival-plateau [Figure 2]. We can also see that the early mortality is rather high for allo-PBSCT but average for auto-PBSCT. NRM is also compared in [Figure 3] where the result for allo-PBSCT is higher than for auto-BSCT. Even though the P = 0.08, which indicates no statistical significance, but the difference was shown. With more samples, the results are to be more clear and convincing. According to [Figure 3], both the PIT (P = 0.032) and prestatus (P = 0.044) for auto-PBSCT and allo-PBSCT showed significant statistical difference. Here follows the separate analysis of the two types of PBSCT.
Figure 1: Survival rate of patients treated with peripheral blood stem cell transplantation. The median time of survival after transplantation was 24 months. Overall survival at 2 years was 46%; at 5 years, 34%

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Figure 2: Survival rates of patients treated with autologous-peripheral blood stem cell transplantation and allogeneic-peripheral blood stem cell transplantation. For autologous-peripheral blood stem cell transplantation, overall survival at 2 years and 5 years were 52% and 34%; for allogeneic-peripheral blood stem cell transplantation both were 40%. There is no significant progressive-free survival plateau in the survival curve for autologous-peripheral blood stem cell transplantation while all the nine death cases of allogeneic-peripheral blood stem cell transplantation were within 8 months, accounting for 60% of all allogeneic-peripheral blood stem cell transplantation cases. The other 40% survived for a long-term with an obvious survival-plateau

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Figure 3: Nonrelapse mortality of patients treated with autologous-peripheral blood stem cell transplantation or allogeneic-peripheral blood stem cell transplantation. Nonrelapse mortality is also compared in Figure 3, where the result for allogeneic-peripheral blood stem cell transplantation is higher than for autologous-blood stem cell transplantation. Even though the P level was 0.08, which indicates no statistical significance, but the difference was shown. According to Figure 3, both the prognostic index for T-cell lymphoma (P = 0.032) and prestatus (P = 0.044) for autologous-peripheral blood stem cell transplantation and allogeneic-peripheral blood stem cell transplantation showed significant statistical difference

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Allogeneic-peripheral blood stem cell transplantation

Among the nine death cases treated with allo-PBSCT, two had been in remission before transplantation, and the other seven in nonremission status, which showed that mortality rate of patients in nonremission status (77.8%) before transplantation was much higher than those in remission status (33.3%). [Figure 4] was the OS curve according to disease status in the time of allo-PBSCT from which the difference of survival rate was significant with P = 0.046. With larger sample size, the difference would be much more distinct. We also used log-rank significance test [Figure 5],[Figure 6],[Figure 7],[Figure 8],[Figure 9],[Figure 10] to analyze these factors: PIT score (≤2 or >2), Eastern Cooperative Oncology Group (ECOG) (=0 or = 1 or >1), Ann Arbor stage (I, II, III, or IV), a-IPI score (≤1 or >1), LDH (≤275 or >275), and B symptoms (positive or negative). According to those results, disease status (P = 0.046) and Ann Arbor stage were influential factors, while a-IPI score in the time of transplantation, PIT score, B symptoms, and serum level of LDH did not impact long-term survival rate of allo-PBSCT. The remission status of the disease indicates tumor burden. Therefore, we believed high tumor load before allo-PBSCT maybe predict poor prognosis and early mortality after transplantation.
Figure 4: Survival rate related to disease status at time of allogeneic-peripheral blood stem cell transplantation. The figure showed that the overall survival curve according to disease status in time of transplantation in allogeneic-peripheral blood stem cell transplantation, from which the difference of survival rate was significant with P = 0.046

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Figure 5: Survival rate associated with prognostic index for T-cell lymphoma score in patients treated with allogeneic-peripheral blood stem cell transplantation. Survival rate associated with prognostic index for T-cell lymphoma score (≤2 or >2) was analyzed by log-rank significance test

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Figure 6: Survival rate associated with Eastern Cooperative Oncology Group score in patients treated with allogeneic-peripheral blood stem cell transplantation. Survival rate associated with Eastern Cooperative Oncology Group (=0 or = 1 or >1) was analyzed by log-rank significance test

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Figure 7: Survival rate related to Ann Arbor stage in patients treated with allogeneic-peripheral blood stem cell transplantation. Survival rate associated with Ann Arbor stage (I, II, III or IV) was analyzed by log-rank significance test

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Figure 8: Survival rate related to a-international prognostic index scores in patients treated with allogeneic-peripheral blood stem cell transplantation. Survival rate associated with a-international prognostic index score (≤1 or >1) was analyzed by log-rank significance test

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Figure 9: Survival rate related to the serum level of lactate dehydrogenase in patients treated with allogeneic-peripheral blood stem cell transplantation. Survival rate associated with lactate dehydrogenase (≤275 or >275) was analyzed by log-rank significance test

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Figure 10: Survival rate related to B symptom in patients treated with allogeneic- peripheral blood stem cell transplantation. Survival rate associated with B symptoms (positive or negative) was analyzed by log-rank significance test

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Autologous-peripheral blood stem cell transplantation

The analysis of disease status was also performed using log-rank significance test in patients treated with auto-PBSCT [Figure 11]. The P = 0.000. The CR/PR was then divided into two groups: CR1 (n = 7) and CR/PR (n = 8). According to [Figure 12], OS in CR1 is greatly higher than in patients with CR/PR treated with auto-PBSCT. [Figure 13],[Figure 14],[Figure 15],[Figure 16],[Figure 17],[Figure 18] showed the influence of other factors on OS, such as Ann Arbor stage, a-IPI score, PIT score, B symptoms, serum level of LDH, and ECOG. Moreover, the serum level of LDH, PIT score, ECOG, and B symptoms were significantly difference between the two groups. The a-IPI were not the statistically significant predictor (P = 0.079), which may be the result of the small sample size.
Figure 11: Survival rate related to disease status at the time of autologous-peripheral blood stem cell transplantation. The analysis of disease status was also performed using log-rank significance test in patients treated with autologous-peripheral blood stem cell transplantation

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Figure 12: Survival rate associated with disease status (complete remission 1 vs. complete remission/partial remission and stable disease/progressive disease) at the time of autologous-peripheral blood stem cell transplantation. Overall survival in complete remission 1 was greatly higher than in patients with complete remission/partial remission treated with autologous-peripheral blood stem cell transplantation

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Figure 13: Survival rate related to prognostic index for T-cell lymphoma score in autologous-peripheral blood stem cell transplantation. Figure showed the influence of prognostic index for T-cell lymphoma score on overall survival

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Figure 14: Survival rate related to Eastern Cooperative Oncology Group score in autologous-peripheral blood stem cell transplantation. Figure showed the influence of Eastern Cooperative Oncology Group score on overall survival

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Figure 15: Survival rate related to Ann Arbor stage in autologous-peripheral blood stem cell transplantation. Figure showed the influence of Ann Arbor stage on overall survival

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Figure 16: Survival rate related to a-international prognostic index scores in autologous-peripheral blood stem cell transplantation. Figure showed the influence of a-prognostic index for T-cell lymphoma score on overall survival

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Figure 17: Survival rate related to the serum level of lactate dehydrogenase in autologous-peripheral blood stem cell transplantation. Figure showed the influence of serum of lactate dehydrogenase on overall survival

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Figure 18: Survival rate related to B symptom in autologous-peripheral blood stem cell transplantation. Figure showed the influence of B symptom on overall survival

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Prognosis

We used log-rank significance test to analyze the influencing factors on OS after transplantation, including Ann Arbor stage, a-IPI score, PIT score, B symptoms, serum level of LDH, ECOG, the number of extranodal involvement, and disease status [Figure 4],[Figure 5],[Figure 6],[Figure 7],[Figure 8],[Figure 9],[Figure 10],[Figure 11]. The results demonstrated the statistical difference of OS between patients in remission (CR or PR) and those in nonremission (P = 0.04). In allo-PBSCT group, the P = 0.04, indicating a significant difference. However, there was no statistical difference in auto-PBSCT group (P = 0.473) [Figure 14] and [Figure 15]. Other influencings included serum level of LDH, Ann Arbor stage, extranodal involvement, ECOG, and B symptoms. The P value between PIT ≤2 group and PIT >2 group was 0.011, with significantly difference. While the P level between a-IPI ≤1 group and a-IPI >1 group was no difference (P = 0.126), which may be the result of the small sample size. The analyses using multivariate Cox regression model was showed in [Table 1], which indicated that the negative influencings on prognosis were serum LDH > 275 U/L, ECOG >1, and SD/PD status before transplantation [Table 1].


 > Discussion Top


PTCL is a subtype of malignant lymphoma, which is more aggressive than B-cell lymphoma. Its incidence differs greatly between different regions and is much more common in Asia than in the Western World. A recent retrospective worldwide analysis of OS at 5 years, concerning up to 1500 cases in 22 medical centers has been reported. For PTCL-NOS and AILT, the OS is 32%; ALCL with positive ALK, 70%; ALCL with negative ALK, 49%; ENKTCL and hepatosplenic T-cell lymphoma, 7% to 10%.[1] It was real that the effect of conventional treatment is quite limited due to the high recurrence rate and mortality rates of PTCL.

Auto-PBSCT combined with high-dose chemotherapy was proved to be much more efficient than conventional chemotherapy. Rodríguez et al. conducted first-line high-dose chemotherapy and auto-PBSCT to 26 high-risk patients with PTCL.[5] After three courses of high-dose CHOP, 50% of them reached CR. Followed with auto-PBSCT, the OS at 3 years was 73%, the progression-free survival (PFS) 53%. Similarly, Chen et al. conducted auto-PBSCT to 53 patients with PTCL and the OS at 5 years for patients with low a-IPI was 48%, the PFS 25%.[6] It also found that remission status (CR/PR) are positive factors for prognosis after transplantation. In our study, we performed auto-PBSCT on patients with high sensitivity to chemotherapy and remission status (65%). The OS and PFS at 2 years were 43% and 34% and at 5 years were 18% and 15%. Another finding of this work was that the long-term OS rate was not in accordance with short-term ones. Among all the 23 cases treated with auto-PBSCT, 18 patients did not survive, 13 (72%) in them died of recurrence. Therefore, it indicated the high recurrence risk of auto-PBSCT. Concerning prognosis, the study suggests that a-IPI was not the influencing factor of PTCL [Figure 10] so is identified by the study of Rodríguez. In a study conducted by Reimer et al., PIT was discussed as a factor affecting prognosis after the treatment of auto-PBSCT. The results of their prospective study suggested a substantial impact on outcome for upfront auto-SCT in PTCL and should be further evaluated in randomized trials. Pretransplantation treatment needs to be improved to increase the transplantation rate.[5],[7] We also investigated it in our study and found that OS for patients with low PIT score was distinctively higher than those with high PIT [Figure 11]. Therefore, our study indicated that PIT score may be an index for promoting prognostic assessment in PTCL patients treated with auto-PBSCT.

Because of the high relapse rate of PTCL, allogeneic transplantation has been more and more widely used in clinical, due to its unique graft-versus-leukemia (GVL). Recently, a retrospective analysis with a relatively large sample size was reported. 77 PTCL patients treated with myeloablative allo-PBSCT and median follow-up was 4 months. The OS and PFS at 5 years were 57% and 53%. The transplant-related mortality (TRM) was 33%. Kim et al. conducted myeloablative allo-PBSCT to 233 NHL patients, 111 of whom were with aggressive NHL.[8] The OS at 2 years was 42% and nearly 42% of the dead from TRM. Both the two reports suggested that the advantage of GVL in allo-PBSCT offset by the high TRM. It also indicated that the emphasis for increasing OS of PTCL patients treated with allo-PBSCT should be control the TRM. According to our study, the OS at 2 years and at 5 years were both 39%. The OS reached the survival plateau in 8 months after transplantation. Therefore, allo-PBSCT could improve long-term survival rate. Among all the 15 cases treated with allo-PBSCT in our study, nine patients had salvage transplantation, and eight of them were dead until the last follow-up. The other six patients had transplantation after remission after first-line treatment, and two of them were dead until the last follow-up, four of them have reached long-term survival. In conclusion, for PTCL patients with high sensitivity to chemotherapy, low PIT score and in remission, allo-PBSCT not only reduces mortality in early stage but also significantly improves long-term survival rate compared with auto-PBSCT.

In the 2006, Annual Meeting of the American Society of Hematology, RIC was defined as: (1) Total irradiation dose <500 cGy; (2) BU dose <9 mg/kg; (3) melphalan dose <140 mg/m 2; (4) thiotepa dose <10 mg/kg; (5) comprising a purine analogs-fludarabine, cladribine, or pentostatin. To determine the effect of RIC on allo-PBSCT, Sureda et al. compared the different OS of 168 lymphoma patients who received RIC to myeloablative allo-PBSCT.[9] The study found that RIC significantly reduced NRM and achieved high OS compared with myeloablative allo-PBSCT. There was still lack of studies focusing specifically on the effect of RIC for PTCL. Dodero et al. studied retrospective analysis on 52 patients with PTCL receiving allo-HSCT and found that the NRM, OS, and PFS at 5 years were 12%, 50%, and 40%. Preoperational disease status and age were both influencing factors on prognosis.[10] They considered RIC allo-HSCT was an adoptable salvage regimen for patients with aggressive PTCL and who were under 45 years old. In our study, only one patient received RIC/FB regimen before allo-HSCT and she still survives at the last follow-up (PFS = 12 months). She had been diagnosed with PTCL-NOS and was in PD with bone marrow involvement (Stage IV BX). Although the treatment is proved to be effective, it still requires further statistical support with larger sample size.


 > Conclusion Top


PTCL is a subtype of lymphoma with complex pathology and poor prognosis. Auto-PBSCT had low TRM but high risk of relapse; allo-PBSCT had high long-term survival rate but low early OS due to high TRM. The key to reducing TRM of allo-PBSCT was RIC. Influencing factors such as serum level of LDH, extranodal involvement, B symptoms, ECOG, Ann Arbor stage, and disease status before transplantation could affect the prognosis of PBSCT. First-line allo-PBSCT should be selective preferred to late-stage PTCL patients who reach remission before transplantation.

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 30600524, No. 81071990, and No. 81201758).

Financial support and sponsorship

The study sponsors had no involvement in the study.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: Pathology findings and clinical outcomes. J Clin Oncol 2008;26:4124-30.  Back to cited text no. 1
    
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Shipp MA, Neuberg D, Janicek M, Canellos GP, Shulman LN. High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non-Hodgkin's lymphoma: A dose-finding pilot study. J Clin Oncol 1995;13:2916-23.  Back to cited text no. 2
    
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Jaffe ES. The 2008 WHO classification of lymphomas: Implications for clinical practice and translational research. Hematology 2009;1:523-31.  Back to cited text no. 3
    
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Zelenetz AD, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, et al. Non-Hodgkin's lymphomas, version 1.2013. J Natl Compr Canc Netw 2013;11:257-72.  Back to cited text no. 4
    
5.
Rodríguez J, Conde E, Gutiérrez A, Arranz R, León A, Marín J, et al. Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: A prospective study from The Gel-Tamo Study Group. Eur J Haematol 2007;79:32-8.  Back to cited text no. 5
    
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Chen AI, McMillan A, Negrin RS, Horning SJ, Laport GG. Long-term results of autologous hematopoietic cell transplantation for peripheral T-cell lymphoma: The Stanford experience. Biol Blood Marrow Transplant 2008;14:741-7.  Back to cited text no. 6
    
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Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: Results of a prospective multicenter study. J Clin Oncol 2009;27:106-13.  Back to cited text no. 7
    
8.
Kim SW, Tanimoto TE, Hirabayashi N, Goto S, Kami M, Yoshioka S, et al. Myeloablative allogeneic hematopoietic stem cell transplantation for non-Hodgkin lymphoma: A nationwide survey in Japan. Blood 2006;108:382-9.  Back to cited text no. 8
    
9.
Sureda A, Robinson S, Canals C, Carella AM, Boogaerts MA, Caballero D, et al. Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: An analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2008;26:455-62.  Back to cited text no. 9
    
10.
Dodero A, Spina F, Narni F, Patriarca F, Cavattoni I, Benedetti F, et al. Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: Long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect. Leukemia 2011;9:1038.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18]
 
 
    Tables

  [Table 1], [Table 2]



 

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