Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification

Savage, Kerry J.; Chhanabhai, Mukesh; Gascoyne, Randy D.; Connors, Joseph M.

doi:10.1093/annonc/mdh392

Cited by 330 publications

(308 citation statements)

References 42 publications

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“…However, in our study, the 12-year DFS of patients in CR before ASCT was projected at 60% and seems superior to the 5-year survival projection of less than 20-25% of patients treated with CHOP-like regimens only. 1,24,25 Therefore, our findings suggested that consolidation of CR with autografting seems crucial and offers a greater chance of long-term survival. These results were also supported by the multivariate analysis, which showed that CR achievement before autograft was the only parameter significantly associated with a favourable outcome, both for OS and EFS.…”

Section: Discussionmentioning

confidence: 69%

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

et al. 2006

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We report the results of two prospective phase II studies investigating the role of high-dose sequential chemotherapy, followed by autologous stem cell transplantation (ASCT) in 62 patients with advanced stage peripheral T-cell lymphomas (PTCLs) at diagnosis. Conditioning regimen consisted of mitoxantrone (60 mg/m 2 ) and melphalan (180 mg/m 2 ) or carmustine, etoposide, Ara-C and melphalan followed by peripheral blood stem cell autografting. In an intent-to-treat analysis, 46 out of 62 patients (74%) completed the whole programme, whereas 16 patients did not undergo ASCT, mainly because of disease progression. At a median follow-up of 76 months, the estimated 12-year overall (OS), disease-free and event-free survival (EFS) were 34, 55 and 30%, respectively. OS and EFS were significantly better in patients with anaplastic lymphomakinase (ALK)-positive anaplastic large-cell lymphoma (ALCL), as compared with the remaining PTCL. Multivariate analysis showed that patients attaining complete remission (CR) before ASCT had a statistically significant benefit in terms of OS and EFS (Po0.0001). Overall treatment-related mortality rate was 4.8%. In conclusion, our findings indicate (1) up-front high-dose therapy and ASCT are feasible, but could induce a high rate of long-term CR only in patients with ALK-positive ALCL and (2) the achievement of CR before autografting is a strong predictor of better survival.

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Section: Discussionmentioning

confidence: 69%

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

et al. 2006

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“…Peripheral T-cell lymphomas (PTCL) are a group of rare and heterogeneous non-Hodgkin lymphoma (NHL), which have a poor prognosis and low survival rate [1] . The 5-year overall survival (OS) for common subtypes of PTCL, such as PTCL not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma, is 32% compared with only 14% for adult T-cell leukemia lymphoma [2] , and there is no standard treatment regimen at present.…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic and pharmacokinetic study of pegylated liposomal doxorubicin combination (CCOP) chemotherapy in patients with peripheral T-cell lymphomas

et al. 2011

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Aim: To investigate the pharmacodynamic and pharmacokinetic parameters of pegylated liposomal doxorubicin (PLD) combined with cyclophosphamide, vincristine, and prednisolone in patients with peripheral T-cell lymphomas (PTCL). Methods: Seven chemonaive patients and four patients with relapsed peripheral T-cell lymphomas were treated with a CCOP regimen consisting of an intravenous administration of cyclophosphamide (750 mg/m 2 ), vincristine (1.4 mg/m 2 ), and PLD (30 mg/m 2 ) on d 1, as well as an oral administration of prednisolone (60 mg/m 2 ) on d 1-5. This regimen was repeated every 3 weeks for six cycles, and the clinical response and toxicity of the regimen were monitored. In addition, the plasma concentration of PLD at different time points was determined before and after treatment. The pharmacokinetics (PKs) software was used to estimate the pharmacokinetic parameters of PLD. Results: The 11 PTCL patients received 35 treatment cycles. Three of them achieved complete response (CR), two partial response (PR), four stable disease (SD), and two progressive disease (PD). The overall response rate (ORR) was 45.5%, and the CR rate was 27.3%. In the 7 chemonaive patients, three achieved CR, two PR, one SD, and one PD. The ORR was 71.4%, and CR rate was 42.9%. The median follow-up time was 15 months, but 6 out of 11 patients were dead at the time of data analysis. The 1-year overall survival rate was 45.5%, and the median progression-free survival (PFS) rate was 6.5 [95% confidence interval (95% CI) 3.17-19.02] with a survival rate of 11.5 months (95% CI 6.65-16.36). The main toxicity was myelosuppression. Oral mucositis and hand-foot syndrome seldom occurred. The PLD plasma concentration from nine patients ranged from 1.7036 to 9.2207 mg·L -1 after administration of the CCOP regimen (0-168 h). The pharmacokinetic parameters AUC 0-∞ , CL, t 1/2 , and V d were 910.76 mg/L·h, 0.043 L·h -1 ·m -2 , 68.40 h, and 3.56 L/m 2 , respectively. Conclusion: The CCOP regimen was effective and well tolerated in patients with peripheral T-cell lymphomas. The results of the pharmacokinetic parameters showed that PLD had long retention time in blood circulation.

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“…1 Novel therapeutic strategies, such as inhibiting protein tyrosine kinases (PTKs), might improve the outlook toward the treatment of patients with PTCL. Recently, a t(5;9)(q33;q22) translocation 2 was reported in a subgroup of PTCL with follicular involvement, 3 resulting in overexpression of the SYK gene under the control of the ITK promoter.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

Feldman,

Sun,

Law

et al. 2008

Leukemia

129

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Peripheral T-cell lymphomas (PTCLs) are fatal in the majority of patients and novel treatments, such as protein tyrosine kinase (PTK) inhibition, are needed. The recent finding of SYK/ITK translocations in rare PTCLs led us to examine the expression of Syk PTK in 141 PTCLs. Syk was positive by immunohistochemistry (IHC) in 133 PTCLs (94%), whereas normal T cells were negative. Western blot on frozen tissue (n ¼ 6) and flow cytometry on cell suspensions (n ¼ 4) correlated with IHC results in paraffin. Additionally, western blot demonstrated that Syk-positive PTCLs show tyrosine (525/526) phosphorylation, known to be required for Syk activation. Fluorescence in situ hybridization showed no SYK/ITK translocation in 86 cases. Overexpression of Syk, phosphorylation of its Y525/526 residues and the availability of orally available Syk inhibitors suggest that Syk merits further evaluation as a candidate target for pharmacologic PTK inhibition in patients with PTCL.

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Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification

Cited by 330 publications

References 42 publications

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

Pharmacodynamic and pharmacokinetic study of pegylated liposomal doxorubicin combination (CCOP) chemotherapy in patients with peripheral T-cell lymphomas

Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas

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