High Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T-Cell Lymphoma (PTCL): Analysis of Prognostic Factors

SUMMARY

Patients with PTCL have a poor prognosis with current treatment approaches. We examined the outcomes of high-dose therapy (HDT) and autologous hematopoietic cell transplant (AHCT) on the treatment of PTCL and the impact of patient/disease features on long-term outcome. Sixty-seven patients with PTCL-not otherwise specified (n=30), anaplastic large cell lymphoma (n=30) and angioimmunoblastic T-cell lymphoma (n=7) underwent HDT/AHCT at City of Hope. The median age was 48 years (range: 5-78). Twelve were transplanted in 1CR/PR and 55 with relapsed or induction failure disease (RL/IF). With a median follow-up for surviving patients of 65.8 months (range: 24.5-216.0) the 5-year overall survival (OS) and progression-free survival (PFS) were 54% and 40% respectively. The 5-year PFS was 75% for 1CR/PR compared to 32% for RL/IF patients (p=0.01). When the Prognostic Index for PTCL unspecified (PIT) was applied at the time of transplant, patients in the PIT 3-4 group had 5-year PFS of only 8%. These results show that HDT/AHCT can improve long-term disease control in relapsed/refractory PTCL and that HDT/AHCT should ideally be applied either during 1CR/PR, or as part of upfront treatment. More effective and novel therapies are needed for patients with high-risk disease (PIT 3-4 factors) and allogeneic HCT should be explored in these patients.

INTRODUCTION

Peripheral T-cell lymphoma (PTCL) is an entity that was introduced relatively recently through the REAL (1) and WHO classification (2) systems. The most common aggressive forms of PTCL are usually nodal in origin and include PTCL-not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL). When compared to diffuse large B-Cell lymphoma (DLBCL), PTCL patients have more aggressive disease features at presentation, e.g., advanced clinical stage, B-symptoms, extranodal disease, elevated LDH and high International Prognostic Index score (IPI) (3,4). Several retrospective studies have shown that PTCL patients have poorer outcomes when treated with anthracycline-containing regimens; the 5-year overall survival (OS) and failure-free survival rates are 26% and 20% respectively (5). The recent International PTCL and National Killer/T cell Lymphoma Study showed that, unlike DLBCL, the majority of patients with PTCL (excluding ALCL anaplastic lymphoma kinase (ALK) positive patients) did not benefit from the use of an anthracycline-containing regimen (6) –making the standard combination chemotherapy regimen for PTCL undefined.

PTCL remains a heterogeneous group of neoplasms with variable prognosis; for example, ALK-positive ALCL has a more favorable prognosis than other PTCL (7). And although, historically, the International Prognostic Index (IPI) has been useful in predicting long-term survival and prognosis for both B and T-cell NHL, the value of the index is not well established in certain PTCL subtypes. More recently a new risk classification system was developed in PTCL-NOS from a retrospective multi-centered study (8). This Prognostic Index for PTCL (PIT) is based on four clinical variables recorded at the time of diagnosis: age (>60 years), performance status (ECOG ≥2), LDH (>1x normal value) and bone marrow involvement (yes). The results of this analysis defined four risk groups based on the number of adverse factors present and was strongly supported by clear differences in outcome. Through the application of the PIT classification, the results showed that nearly half of the patients with PTCL-NOS experienced dismal survival rates; a 5-year survival probability of only 26.8%. The results of this analysis support the assertion that innovative therapeutic strategies are desperately needed for these patients.

HDT and AHCT, which is considered the standard treatment for relapsed DLBCL, has also been shown to be an effective salvage therapy for PTCL in several retrospective studies (9-11). Given the general poor prognosis of patients with PTCL, HDT/AHCT has also been used as part of upfront treatment or as consolidation therapy during first remission in several prospective studies (12-15). A disappointing aspect of all these studies was the proportion of patients unable to proceed to AHCT, approximately one-third, due primarily to disease progression, which resulted in a progression-free survival (PFS) rate of only 30-53%. To explore the impact of HDT/AHCT on PTCL and prognostic significance of patient/disease characteristics recorded at the time of transplant, we analyzed a single institution case-series of 67 poor-risk, relapsed or primary refractory PTCL treated with HDT/AHCT.

PATIENTS AND METHODS

From February 1991 to July 2007, a consecutive case-series of 67 PTCL patients underwent HDT/AHCT at City of Hope National Medical Center (COH). Patients were identified and selected for analysis from a prospective observational research transplant database. The COH Institutional Review Board approved the analysis of these data. All pathology specimens were reviewed by the COH Hematopathology Department to confirm diagnosis prior to transplant. The histologic diagnoses were based on WHO classification. The categories of PTCL-NOS, AITL, and ALCL were included in this report. NK/T cell nasal/nasal type lymphomas were not included, since they belong to the extranodal lymphomas according to the WHO classification. The other rare subtypes of PTCL were also excluded. Disease status was confirmed by clinical assessment including physical examination, laboratory evaluation, imaging by CT scans and nuclear imaging, bone marrow biopsies and photo documentation per COH patient care standard operating procedures.

Eligibility Criteria

Patients were eligible for AHCT if they failed to achieve remission after initial induction chemotherapy or relapsed post induction chemotherapy. Patients with PTCL-NOS, ALK-negative ALCL and AITL who had advanced stage, or high-intermediate/high-risk IPI were eligible for AHCT during first CR/PR. Patients with ALK-positive ALCL were transplanted at the time of relapse or disease progression. All relapsed patients must have a biopsy to confirm recurrent disease. Patients were required to have: no bone marrow involvement and normal cytogenetic studies before stem cell mobilization or bone marrow harvest; adequate cardiac, pulmonary, renal and hepatic functions. Patients with positive human immunodeficiency virus antibodies were excluded.

High-Dose Regimens

Three high-dose regimens were used. Patients <60 years received total body irradiation (TBI) 1200cGy (days -8 to -5) followed by etoposide (VP16) 60 mg/kg on day -4 and cyclophosphamide (CY) 100mg/kg on day -2. For patients ≥60 years or those with prior radiotherapy, carmustine 450 mg/m² was given over 3 days on day -7 to day -5 instead of TBI or high-dose BEAM regimen (carmustine, etoposide, cytarabine and melphalan). No positive selection or in-vitro purging of bone marrow/peripheral blood stem cells was performed.

Response Criteria

Complete response (CR) was defined as the complete resolution of all measurable disease, sustained for at least 4 weeks. Partial remission (PR) was defined as a 50% or more reduction in the sum of the products of the diameters of all measurable lesions. Induction failure (IF) was defined as failure to achieve at least a PR with anthracycline-containing first-line therapy, or progression from a CR or PR within 4 weeks of first-line treatment. Relapse was defined as a clinical or radiological progression at least 4 weeks after an initial CR or PR to first-line therapy. Salvage chemotherapy was given to debulk disease and to determine chemosensitivity before AHCT. Chemosensitivity was defined as at least a PR to salvage treatment and resolution of all disease related symptoms, maintained for at least 4 weeks.

Staging was performed at: relapse, after salvage chemotherapy before AHCT, 100 days, 6-months, 12-months, every 6 months until 2 years post-transplant, and then every year thereafter or as clinically indicated. Staging included physical examination, complete blood counts, biochemical profiles, LDH, chest X-ray, computed topographies of the chest, abdomen and pelvis and unilateral or bilateral bone marrow biopsy if indicated. The IPI was calculated according to standard variables (16). The PIT was calculated for each patient at the time of AHCT based on age, LDH level, performance status and bone marrow involvement.

Statistical Analysis

Survival estimates were calculated based on the Kaplan-Meier product-limit method, 95% confidence intervals were calculated using the logit transformation and the Greenwood variance estimate (16a). Differences between Kaplan-Meier curves were assessed by the log-rank test. Patients who were alive at the time of analysis were censored at the last contact date. Overall survival (OS) was measured from transplant to death from any cause. Progression-free survival (PFS) was defined as time from transplant to recurrence, progression or death. Event-free survival (EFS) was defined as time from transplant to progression, secondary malignancy or death. The relapse/progression rate (RPR) was defined as time from transplant to recurrence or progression. The cumulative incidence for RPR was computed treating a non-relapse death event as a competing risk. Non-relapse mortality (NRM) was measured from transplant to death from any cause other than disease relapse or disease progression. Non-relapse-related mortality and relapse-related mortality were considered competing risks for mortality. The cumulative incidence of NRM and relapse-related mortality was calculated using the method described by Gooley et al (16b). Differences between cumulative incidence curves in the presence of a competing risk were tested using the Gray method (16c). The significance of demographic and treatment features was assessed using survival analysis and univariate Cox proportional hazards regression analysis (16d).

Univariate Cox proportional hazard models were used to model time to event endpoints (e.g., OS, PFS, EFS, RPR, and NRM), as a function of the prognostic variables. The list of prognostic variables was determined from a literature review that identified factors associated with survival and/or disease relapse/recurrence in patients treated with AHCT. These variables were: histopathological subtype, patient age at AHCT (<60 years, ≥60 years), disease status at the time of AHCT (1CR/PR; 2CR/RL; IF), disease stage at AHCT, KPS at AHCT (≥90, <90), LDH (normal, high), bone marrow involvement at AHCT (yes, no), prior radiation treatment (yes, no), number of prior regimens (>1, ≤1) and chemosensitive disease (yes, no). All calculations were performed using SAS 9.2 (SAS Institute, Cary, NC). Statistical significance was set at the P <0.05 level; all P values were two-sided. The data were locked for analysis on May 22, 2009 (analytic date).

RESULTS

Patient Characteristics

Between February 1991 and July 2007, 67 consecutively treated patients with PTCL underwent HDT/AHCT (Table 1). The median age was 48 years (range: 5-78) and 42 (63%) were male. The median time from diagnosis to transplant was 11.6 months (range: 3.7-123.0). The histology subtypes included ALCL, n=30; PTCL-NOS, n= 30; and AITL n=7. Among the 30 patients with ALCL, 13 were ALK-negative, 11 were ALK-positive and six were not tested. Fifty-three (79%) had advanced stage (III or IV) at diagnosis. Twelve (18%) were transplanted in 1^st CR or 1^st PR, 21 were in second CR, 14 were in relapse and 20 failed induction chemotherapy. All patients received CHOP (cyclophosphamide, adriamycin, oncovin, and prednisone (57 patients) or CHOP-like regimen (10 patients) as induction chemotherapy. Intensive regimens were not used in first remission patients. The salvage regimens commonly used were ICE (ifosamide, carboplation, etoposide), ESHAP (etoposide, steroid, cytarabine, cisplatin) or gemcitabine-based regimens. Eighteen patients received > 2 salvage regimens.

Table 1.

Patient, Disease, and Transplant Characteristics

	N (%) or Median (Range)
Patient Gender
Female	25 (37)
Male	42 (63)
Age at Transplant (Years)	48 (5 – 78)
Time from Diagnosis to Transplant (Months)	11.6 (3.7 – 123.4)
Histology
AILT	7 (10)
ALCL	30 (45)
PTCL-NOS	30 (45)
ALCL
ALK Positive	11 (37)
ALK Negative	13 (43)
Not tested	6 (20)
Disease Status at Transplant
1st Complete Remission	11 (16)
1st Partial Remission	1 (2)
2nd Complete Remission	21 (31)
1st Relapse	12 (18)
2nd Relapse	2 (3)
Induction Failure	20 (30)
Stem Cell Source
Bone Marrow	4 (6)
Peripheral Blood	63 (94)
Conditioning Regimen
TBI/VP16/CY	41 (61)
BCNU/VP16/CY	19 (29)
BEAM	7 (10)
ChemoSensitivity
Sensitive	56 (84)
Resistant	11 (16)
Stage at Diagnosis
I	6 (9)
II	8 (12)
III	21 (31)
IV	32 (48)
KPS at Diagnosis	90 (40 – 100)
Stage at Transplant
I	6 (9)
II	2 (3)
III	11 (17)
IV	13 (19)
Not Applicable	35 (52)
KPS at Transplant	90 (60 – 100)
Number of Prior Regimens	2 (1 – 5)
PIT Group
1-2	55 (82)
3-4	12 (18)

AITL: angioimmunoblastic T-cell lymphoma, ALCL: anaplastic large cell lymphoma, PTCL-NOS: peripheral T-cell lymphoma-not otherwise specified; ALK: anaplastic lymphoma kinase; TBI: fractioned total body irradiation, VP16: etoposide, CY: cyclophosphamide, BCNU: Carmustine, BEAM: carmustine, etroposide, cytarabine and melphalan; KPS: Karnofsky performance status; PIT: Prognostic Index for PTCL unspecified.

At transplant, 24 patients (36%) had stage III or IV disease and 55 (82%) were PIT group 1-2 while 12 were PIT group 3-4. The median number of prior regimens was 2 (range: 1-5). Most patients received peripheral blood stem cells, and 41 (61%) received a TBI-based conditioning regimen.

Treatment Outcome

At a median follow-up of 33.6 months (range: 0.5-216) for all patients and 65.8 months (range: 24.5-216) for surviving patients, 37 patients (55%) were alive and 30 (45%) expired (Table 2). The 5-year OS and PFS was 54% (95%CI: 47-60%) and 40% (95%CI: 35-44%), respectively (Figure 1a). The 5-year EFS estimate was similar to PFS although slightly lower: 35% (95%CI: 31-39) (Figure 1b). The 5-year PFS was significantly better for patients who were transplanted during 1CR/PR compared to those transplanted beyond 1CR/PR (75% vs. 32%, p= 0.0138) (Figure 2). The same advantage was seen among 1CR/PR patients for OS at 5-years: 92% vs. 45%, p= 0.0115) and EFS at 5 years: 75% vs. 26%, p=0.0062). The RPR was also significantly higher for those transplanted beyond 1CR/PR; the 2-year RPR was 60% vs. 25%, p=0.038. The 5-year PFS probability was significantly worse for PIT group 3-4 when compared to PIT group 1-2 (8% vs. 47%, p=0.0004) (Figure 3), the same was true for EFS at 5-years (8% vs. 40%, p=0.0007). There were no statistically significant differences in outcome across the three histologic subtypes. For the subset of ALCL, there was a trend for better survival in ALK-positive ALCL compared to ALK-negative ALCL (5-year OS: 82% vs. 54%; 5-year PFS: 73% vs. 46%; 5-year EFS: 73% vs. 46%), however, the result did not show significance due to small number of patients in each group.

Table 2.

Summary of Transplant Outcomes

	N (%) or Median (Range)
Engraftment: ANC ≥ 500 cells/μl (Days from Transplant to ANC recovery)	10 (8 – 22)
Engraftment: Platelets ≥ 20K cells//μl (Days from Transplant to Platelet recovery)	15 (9 – 778)
Relapse/Disease Progression post Transplant
Yes	34 (51)
No	33 (49)
Vital Status
Alive	37 (55)
Expired	30 (45)
Cause of Death
Disease Progression / Relapse	22
Cardiac / Myocardial Infarction	3
Interstitial Pneumonitis, Persistent Disease	1
Diffuse Pulmonary Failure	1
Acute Respiratory Distress Syndrome	1
Information not available	2
Non-Relapse Mortality
Yes	8 (12)
No	59 (88)
Mortality at Day 100
Expired	3 (5)
Disease Progression / Relapse	3
Other	0
Alive	64 (95)
Follow-Up (Months)
All patients	33.6 (0.5 – 216.1)
Alive	65.8 (24.5 – 216.1)
Expired	7.7 (0.5 – 40.5)
Time from Transplant to Relapse (Months)	3.6 (0.7 – 24.0)
Alive patients, current disease status
CR	27 (73)
Not in CR	10 (27)

ANC: absolute neutrophil count; CR: complete remission

Figure 1.

a. Probabilities of overall and progression-free survival

b. Probabilities of overall and event-free survival

Figure 2.

Progression-free survival stratified by disease status at transplant

Figure 3.

Progression-free survival stratified by PIT group

Relapse

Thirty-four patients (51%) relapsed at a median of 3.6 months (range: 0.7-24) post AHCT. The 2-year cumulative incidence of relapse/progression was 53% (95%CI: 47.8-59.3). There were no relapse/progression events seen beyond the two-year mark, with a plateau achieved and sustained two years post transplant; a similar finding was also noted for the survival endpoints. Additionally, there were no statistical differences seen in relapse/progression risk among the various histologic subtypes.

Transplant-Related Mortality

Transplant-related mortality at day 100 was 0.0% and non-relapse mortality was 6.3% at one year. There were eight deaths during the first year post transplant: due to cardiac causes (n=3), pulmonary complication/acute respiratory distress syndrome (n=3) and unknown causes (n=2). One patient developed therapy-induced myelodysplasia at 4 years post AHCT and was successfully treated with allogeneic stem cell transplant. Another patient developed therapy-induced acute myelogenous leukemia at 18 months post AHCT and died from cardiac causes.

Univariate and Multivariate Analysis: Prognostic Factors

The univariate analysis results for PFS and RPR are summarized in Table 3. The factors studied included: histology subtype, disease status at AHCT, age, stage at transplant, bone marrow involvement, at AHCT, extranodal involvement at AHCT, chemosensitivity, conditioning, PIT at AHCT, KPS at AHCT, and number of prior chemotherapy regimens. Disease status at AHCT, stage, age, KPS, LDH and PIT group were found to be significant predictors univariately for PFS. The same was true for EFS. Similar factors, with the exception of age were found to be significant predictors for RPR. An increase in hazard was seen among high-risk groups across all significant factors. The multivariate model, which included variables found to be significant univariately at the p≤0.10 level, showed that after adjusting for all other factors the single most significant factor was the AHCT PIT group. This was true for both endpoints: PFS and RPR. The modeling results for EFS were very similar to PFS.

Table 3.

Univariate/Multivariate Cox regression analysis

			Progression-Free Survival					Relapse/Progression Rate
				Univariate		Multivariate			Univariate		Multivariate
Variable	Value	N	# of events	Hazard Rate Ratio (95% CI)	p value	Hazard Rate Ratio (95% CI)	p value	# of events	Hazard Rate Ratio (95% CI)	p value	Hazard Rate Ratio (95% CI)	p value
Histology at Transplant	0: AILD/ALCL	37	19	Baseline		Baseline		16	Baseline		Baseline
	1: PTCL	30	21	1.56 (0.83, 2.91)	0.166	N/A	***	18	1.57 (0.8, 3.09)	0.193	N/A	***
Disease Status at Transplant	0: 1CR/PR	12	3	Baseline		Baseline		3	Baseline		Baseline
	1: 2CR/RL/IF	55	37	3.94 (1.21, 12.82)	0.023	3.92 (1.14, 13.48)	0.030	31	3.28 (1.00 10.75)	0.050	2.72 (0.76, 9.69)	0.123
Stage at Transplant	0: N/A	35	17	Baseline		Baseline		12	Baseline		Baseline
	1: I - IV	32	23	2.07 (1.1, 3.88)	0.024	1.21 (0.61, 2.40)	0.587	22	2.81 (1.38, 5.69)	0.004	0.77 (0.81, 3.85)	0.153
Age at Transplant	0: ≤ 60	51	27	Baseline		Baseline		24	Baseline		Baseline
	1: > 60	16	13	2.05 (1.05, 4)	0.036	N/A	***	10	1.72 (0.82, 3.61)	0.151	N/A	***
KPS at Transplant	0: 90 - 100	56	31	Baseline		Baseline		26	Baseline		Baseline
	1: <= 80	11	9	2.28 (1.07, 4.82)	0.032	N/A	***	8	2.43 (1.09, 5.41)	0.030	N/A	***
LDH at Transplant	0: Normal	40	17	Baseline		Baseline		14	Baseline		Baseline
	1: Elevated	26	22	2.72 (1.43, 5.16)	0.002	N/A	***	19	2.84 (1.41, 5.71)	0.003	N/A	***
Number of Prior Regimens	0: ≤ 2	12	27	Baseline		Baseline		23	Baseline		Baseline
	1: > 2	55	13	1.34 (0.69, 2.60)	0.387	2.51 (0.7, 9.04)	***	11	1.32 (0.65, 2.72)	0.444	N/A	***
Chemo Sensitivity	0: SR	56	33	Baseline		Baseline		28	Baseline		Baseline
	1: RR	11	7	1.24 (0.55, 2.82)	0.600	N/A	***	6	1.28 (0.53, 3.1)	0.582	N/A	***
PIT Group	0: Level 1/2	55	29	Baseline		Baseline		24	Baseline		Baseline
	1: Level 3/4	12	11	3.38 (1.66, 6.89)	0.001	3.49 (1.65, 7.39)	0.001	10	3.78 (1.78, 8.05)	0.001	3.52 (1.59, 7.79)	0.002

KPS: Karnofsky Performance Status; PIT: Prognostic Index for PTCL unspecified.

^***Not entered into multivariate model

DISCUSSION

Our results represent the largest single center experience of HDT/AHCT for PTCL and confirms that HDT/AHCT is an effective salvage therapy for patients with relapsed or refractory PTCL and about a third of patients can achieve long-term disease control with this treatment. Since we observed a plateau in survival and there were no relapses/progression events two years post transplant, these data suggest that HDT/AHCT may be a curative treatment for this aggressive disease.

In contrast to other reports, there were no differences in survival seen between ALCL and other PTCL subtypes in our study; we believe this may be due to small numbers. The impact of histologic subtype on HDT/AHCT outcomes have been evaluated in several studies and showed a superior outcome for ALCL patients compared to other PTCL subtypes. Jagasia et al reports a 3-year OS of 86% for ALCL compared to 47% for non-ALCL histology (p=0.0122). However, analysis based on ALK status showed that ALK-positive ALCL patients had a superior EFS compared to ALK-negative ALCL (100 % vs. 0%; p=0.0228)(17). Different results were reported from a retrospective study of T-cell lymphoma patients treated with HDT/AHCT from the GEL-TAMO Group. In this study, ALCL histology did not prove to have a positive impact on outcome [28]. Because patient selection and ALK status might account for these differences in outcome, ALK status should be included in future studies. In our study, we found a trend toward improved survival in ALK-positive ALCL. While the analysis of prognostic factors post HDT/AHCT are often hampered by the small number of patients and heterogeneity of the patient population, most studies have shown that chemosensitivity and response to salvage chemotherapy are predictive of better survival. The MD Anderson (18) and the Spanish Group for Lymphoma and AHCT (GEL/TAMO)(19), both identified pre-transplant LDH and IPI as the most important predictors for survival. More recently, PIT has been used to predict outcome of HDT/AHCT in PTCL. Yang et al analyzed factors post HDT/AHCT in 64 Korean patients with PTCL-NOS (21). They found that failure to achieve CR at transplant and PIT 2-3 were associated with decreased survival post-transplant. The 3-year OS was only 7.5% for PIT 2-3 groups. In another study reported by the Spanish Lymphoma and Autologous Transplantation Group, PIT was also found to predict outcome in 74 patients with PTCL who were transplanted in first CR (22). Patients with PIT 3-4 had 5-year OS and PFS of 31% and 27% respectively, compared to 74% and 69% for those with PIT 0-2. Our study also confirms the prognostic value of PIT using patient values recorded pre-transplant. Furthermore, our data suggest that PIT may be used to identify patients who likely will not benefit from AHCT, making alternative treatment approaches such as clinical trials or allogeneic HCT a more plausible option.

While our results do support the role of HDT/AHCT during 1^st CR/PR in PTCL, the role of AHCT for aggressive lymphoma patients in first CR is still an unresolved issue. There is evidence that HDT/ASCT may improve the outcome of selected 1^st CR patients, mainly those with a high IPI score (23). There are five prospective studies of HDT and AHCT during 1^st CR/PR in PTCL (12, 13, 15, 25, 26). Reimer et al reported results of a multicenter study of upfront AHCT in PTCL. Eighty-three patients were treated with 4-6 cycles of CHOP followed by AHCT. Sixty-six percent were able to proceed to AHCT. The estimated 3-year OS, DFS and PFS were 48%, 53% and 36%, respectively. More intensive induction chemotherapy such as CHOEP-14 (CHOP plus etoposide)(25) or MegaCHOP/IFE (ifosfamide and etoposide)(26) were used in other studies, however, about 23-59% of the patients were still unable to undergo AHCT mainly due to disease progression and about 25% of those who did undergo AHCT during 1^st CR experienced relapse post-transplant. Nevertheless, HDT/AHCT as consolidation therapy during 1^st CR is probably the most effective approach to improve prognosis of PTCL patients and should be further investigated in prospective randomized trials.

To explore whether the graft versus lymphoma effect exists in PTCL, allo-HCT has been performed in patients with refractory PTCL. Encouraging results were reported by Corradini et al in 17 patients with relapsed/refractory PTCL following reduced-intensity allo-HCT (27). The estimated 3-year OS and PFS were 81% and 64%, respectively, with a 2-year NRM of only 6%. Recently, Le Gouill et al reported their retrospective experiences of allo-HCT in 77 patients with several subtypes of T-cell NHL from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) (28). The median age was 36 years and 74% received a myeloablative regimen. The 5-year OS and EFS were 57% and 53%, respectively, however, the 5-year TRM was high at 34% probably related to the use of a myeloablative regimen. Even though allo-HCT may be an effective therapy for PTCL, further studies to define the optimal conditioning regimens and the group of patients who would benefit most from allo-HCT are necessary. Similarly the role of reduced-intensity allo-HCT in PTCL needs further investigation.

We conclude from our analysis, that one third of patients with relapsed or refractory PTCL may achieve long-term disease control with HDT/AHCT, a treatment that is associated with low acute transplant related toxicity. Unfortunately this approach does not seem to overcome the disease in patients with the poorest prognosis since relapse/progression events continue to occur. New innovative therapies are needed to induce remission in patients with PTCL so more patients with relapsed or refractory disease can be eligible for HDT/AHCT. Encouraging results have been reported with newer agents such as antimetabolite pralatrexate or histone deacetylase inhibitors in PTCL and incorporation of these agents into the treatment plan are being investigated. Our results based on small number of patients show that patients with high PIT scores do poorly with HDT/AHCT and perhaps, should be offered clinical trials or evaluated for allo-HCT. Given the poor outcome with conventional chemotherapy and AHCT at relapse in PTCL patients, HDT/AHCT during first remission should be recommended and further investigated in prospective randomized clinical trials. Additional studies are needed to evaluate the role of reduced intensity allo-HCT in PTCL patients.