Treatment selection and survival outcomes in Early-Stage peripheral T-Cell lymphomas: does anaplastic lymphoma kinase mutation impact the benefit of consolidative radiotherapy?

2020 ◽  
pp. 1-11
Author(s):  
Joshua L. Rodríguez-López ◽  
Ankur K. Patel ◽  
Goundappa K. Balasubramani ◽  
Scott M. Glaser ◽  
Sushil Beriwal ◽  
...  
Keyword(s):  
T Cell ◽  
Anaplastic Lymphoma Kinase ◽  
Early Stage ◽  
Survival Outcomes ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Mutation Impact ◽  
Consolidative Radiotherapy ◽  
Kinase Mutation ◽  
Peripheral T Cell Lymphomas

scholarly journals Combining the mTOR Inhibitor Everolimus and Gemcitabine in Relapsed/Refractory Peripheral T-Cell Lymphomas

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Ling Huang ◽  
Xinmiao Jiang ◽  
Wenyu Li ◽  
Hanguo Guo ◽  
Xiaojuan Wei ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Anaplastic Lymphoma Kinase ◽  
Mtor Inhibitor ◽  
Response Rate ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Background: Relapsed/refractory Peripheral T-cell lymphomas (PTCL) is an aggressive and heterogeneous Non-Hodgkin's T cell lymphoma, which is resistant to conventional chemotherapy with poor prognosis. Therefore, there is an urgent need to exploit potential therapeutics and novel treatment for R/R PTCL. Targeting PI3K/AKT/mTOR pathway is an effective therapy for PTCL. However, recent research demonstrated that the mTOR inhibitor everolimus monotherapy has low response rate and short duration time in treating with R/R PTCL. Methods:We retrospectively reviewed 18 patients with pathologically diagnosed T cell lymphoma who received the mTOR inhibitor everolimus combined with gemcitabine for six cycles (everolimus 10mg qd, gemcitabine 1000mg/m2 d1, every 21 days a cycle) and sequential autologous stem cell transplantation, at Guangdong Provincial People's Hospital from November 2015 through October 2019. We evaluated the objective response rate (ORR), progressive free survival (PFS) and safety. Results:Of the 18 patients, 33.3% (n=6) had PTCL-not otherwise specified (PTCL-NOS), 27.8% (n=5) had angioimmunoblastic T-cell lymphoma(AITL), 27.8% (n=5) had anaplastic large cell lymphoma(ALCL) (anaplastic lymphoma kinase positive ALCL: 20.0%, n=1; anaplastic lymphoma kinase negative ALCL: 80.0%, n=4), and 11.1%(n=2) had other subtypes. The median age was 46.5 years (range 26-64) old and most patients were males (66.7%) with advanced stage disease (III/IV, 73.7%). The ORR was 55.6% (n=10), with complete response rate of 50% and partial response rate of 5.6%. One patient was stable disease (5.6%), and seven patients were progressive disease (33.8%). For subtypes, the ORR was 80% in ALCL, 66.7% in PTCL-NOS and 20% in AITL, respectively. With a median follow-up time of 18.9 months (range 3.1-99.6), the median PFS was 4.5 months and overall survival(OS) was 18.9 months, respectively. The most frequent hematological adverse events were thrombocytopenia (27.8%), anemia (22.2%), leukopenia (11.1%). The non-hematological adverse events were inappetence (22.2%), diarrhea (11.1%), rash(11.1%), fatigue (11.1%). Conclusions:Our pilot studies have shown that combined everolimus with gemcitabine have better efficacy than monotherapy reported previously for R/R PTCL patients, but the mechanism is still unclear. It suggests that further investigation for mechanisms and predictive biomarker is needed. Figure Disclosures No relevant conflicts of interest to declare.

Efficacy of a Dose-Intensified CHOP (Double-CHOP) Regimen for Peripheral T-Cell Lymphomas

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4855-4855
Author(s):  
Hiromichi Takahashi ◽  
Noriyoshi Iriyama ◽  
Yoshihiro Hatta ◽  
Katsuhiro Miura ◽  
Yujin Kobayashi ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
High Dose ◽  
Chop Regimen ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 4855 Background: Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of non-Hodgkin lymphomas, often resulting in poor prognoses. The CHOP chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone, had been used previously to treat other types of lymphomas. Here, we examined the efficacy and safety of a dose-intensified CHOP regimen (Double-CHOP), which was followed by autologous stem-cell transplantation (ASCT) or high-dose methotrexate (HDMTX), in PTCL patients. Patients and Methods: Twenty-eight PTCL patients, who received 3 courses of Double-CHOP at our institution, were retrospectively studied from 1996 to 2012. Patients with anaplastic lymphoma-kinase-positive anaplastic large-cell lymphoma (ALK+–ALCL) were excluded from this study. The Double-CHOP regimen consisted of 3 courses of intravenous (iv) administration of cyclophosphamide (750 mg/m2, days 1–2, over 2 h), doxorubicin (50 mg/m2, days 1–2, over 30 min), vincristine (1.4 mg/m2, day 1, max 2 mg/Kg body weight), and per os (p.o.) prednisone (50 mg/m2, days 1–5). For patients aged >60, cyclophosphamide and doxorubicin doses were modified. The third cycle of Double-CHOP regimen was used for stem cell mobilization. Consolidating high-dose therapy (HDT) regimen consisted of cyclophosphamide (60 mg/kg, day 6 and 7, iv, over 3 h), etoposide (500 mg/m2; day 4, 5, and 6; iv; over 6–8 h), and ranimustine (250 mg/m2, day 2 and 3, iv, over 1 h). ASCT was performed on day 0 and G-CSF administered from day 1 until neutrophil engraftment. As an alternative to HDT/ASCT, HDMTX (8 g/m2, day 1, iv, over 4 h) was indicated for patients who could not yield a sufficient number of stem cells or were ineligible for HDT/ASCT. Results: Patients' median age was 58 years (range: 17–69). They had low-intermediate (n = 11), high-intermediate (n = 10), or high (n = 7) risk according to the International Prognostic Index (IPI). The overall complete remission (CR) rate following Double-CHOP treatment was 68%. Of all the CR patients, 10 could successfully tolerate a consolidated HDT followed by ASCT, and 7 received HDMTX. Only a single case of treatment-related mortality was recorded during the study. On a median 31-month follow-up, the estimated 3-year overall survival (OS) rate and 3-year relapse-free survival (RFS) rate after CR were 68% and 60%, respectively. Conclusion: Although this study included elderly and excluded low-risk IPI and ALK+–ALCL patients, both RFS and OS results were superiorly favorable, indicating the efficacy of this Double-CHOP regimen and Double-CHOP followed by ASCT/HDMTX consolidations is safe and may achieve prolonged EFS, especially in patients with poor prognostic factors. However, an effective treatment strategy for refractory or relapsing patients needs to be validated and established. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Therapies for Peripheral T-Cell Lymphomas

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 515-524 ◽  
Author(s):  
Kerry J. Savage
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
Large Cell ◽  
Cure Rate ◽  
Limited Evidence ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Histologic Subtypes ◽  
Peripheral T Cell Lymphomas

AbstractPeripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders that, for the most part, are associated with a very poor prognosis. The standard therapy for PTCLs is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or a comparable CHOP-like regimen that incorporates anthracyclines. With the exception of anaplastic lymphoma kinase–positive anaplastic large cell lymphoma (ALK+ ALCL), the cure rate for PTCLs with CHOP is low, and limited evidence suggests that anthracyclines do not improve the prognosis. However, there is no compelling evidence that any other regimen or approach is superior. It remains challenging to compare alternative therapies or treatment strategies with CHOP because the majority of data are retrospective and include diverse patient populations. Recently, prospective studies have been initiated exclusively for PTCL, and in some, select histologic subtypes are evaluated in an effort to remove heterogeneity. Encouragingly, there have been several new therapies emerging with activity in PTCLs and exciting novel combinations under consideration that will hopefully move the field forward and improve outcome in this challenging group of diseases.

scholarly journals Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 505-511 ◽  
Author(s):  
B Schlegelberger ◽  
A Himmler ◽  
E Godde ◽  
W Grote ◽  
AC Feller ◽  
...  
Keyword(s):  
T Cell ◽  
The Other ◽  
Low Grade ◽  
High Grade ◽  
Angioimmunoblastic Lymphadenopathy ◽  
Prolymphocytic Leukemia ◽  
Anaplastic Lymphoma ◽  
Kiel Classification ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Cytogenetic studies on lymph node and skin biopsy specimens and peripheral blood in 104 patients with peripheral T-cell lymphomas (PTL) were compared with histopathologic diagnoses made according to the updated Kiel classification. Low-grade lymphomas presented normal metaphases more frequently than high-grade ones (P < .0001). This difference remained significant if cases with greater than 10% and greater than 50% normal metaphases in unstimulated cultures and in cultures stimulated by different mitogens were compared. On the other hand, high-grade lymphomas more often showed aberrant clones (P < .05), triploid to tetraploid clones (P < .0001), and complex clones with more than four chromosome changes (P < .01). Low-grade PTL showed consistent cytogenetic features. Clones with both inv(14)(q11q32.1) and trisomy 8q, mostly caused by i(8q)(q10), were found in all cases of T-cell chronic lymphocytic leukemia (T-CLL) and T-cell prolymphocytic leukemia (T-PLL). Trisomy 3 was observed only in angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-type PTL, T-zone lymphoma, and lymphoepithelioid lymphoma. Moreover, the proportion of normal metaphases in these PTL was higher than in the other low-grade PTL (P < .01). On the contrary, T-CLL, T-PLL, and cutaneous T-cell lymphomas (CTCL) showed complex clones (P < .0001), duplications in 6p (P <.01), deletions in 6q (P < .01), trisomy 8q (P < .00001), inv(14) (P < .00001), and monosomy 13 or changes of 13q14 (P < .001) more frequently than the other low-grade PTL. Trisomy 5 and + X predominated in AILD- type PTL. A cytogenetic feature characteristic of AILD-type PTL and CTCL was unrelated clones, which were found in 15% of AILD-type PTL and 17% of CTCL. The only chromosome aberration restricted to a certain high-grade PTL was t(2;5)(p23;q35) in large-cell anaplastic lymphoma. Deletions in 6q, total or partial trisomies of 7q, and monosomy 13 or changes of 13q14 turned out to be significantly more frequent in high- grade than in low-grade lymphomas (P < .01, P < .01, and P < .05, respectively). In summary, the cytogenetic findings in our series of 104 PTL enabled us to distinguish not only between low-grade and high- grade lymphomas but also between various entities of PTL. Thus, the cytogenetic findings paralleled the histopathologic diagnoses made according to the updated Kiel classification.

scholarly journals Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 505-511
Author(s):  
B Schlegelberger ◽  
A Himmler ◽  
E Godde ◽  
W Grote ◽  
AC Feller ◽  
...  
Keyword(s):  
T Cell ◽  
The Other ◽  
Low Grade ◽  
High Grade ◽  
Angioimmunoblastic Lymphadenopathy ◽  
Prolymphocytic Leukemia ◽  
Anaplastic Lymphoma ◽  
Kiel Classification ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Cytogenetic studies on lymph node and skin biopsy specimens and peripheral blood in 104 patients with peripheral T-cell lymphomas (PTL) were compared with histopathologic diagnoses made according to the updated Kiel classification. Low-grade lymphomas presented normal metaphases more frequently than high-grade ones (P < .0001). This difference remained significant if cases with greater than 10% and greater than 50% normal metaphases in unstimulated cultures and in cultures stimulated by different mitogens were compared. On the other hand, high-grade lymphomas more often showed aberrant clones (P < .05), triploid to tetraploid clones (P < .0001), and complex clones with more than four chromosome changes (P < .01). Low-grade PTL showed consistent cytogenetic features. Clones with both inv(14)(q11q32.1) and trisomy 8q, mostly caused by i(8q)(q10), were found in all cases of T-cell chronic lymphocytic leukemia (T-CLL) and T-cell prolymphocytic leukemia (T-PLL). Trisomy 3 was observed only in angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-type PTL, T-zone lymphoma, and lymphoepithelioid lymphoma. Moreover, the proportion of normal metaphases in these PTL was higher than in the other low-grade PTL (P < .01). On the contrary, T-CLL, T-PLL, and cutaneous T-cell lymphomas (CTCL) showed complex clones (P < .0001), duplications in 6p (P <.01), deletions in 6q (P < .01), trisomy 8q (P < .00001), inv(14) (P < .00001), and monosomy 13 or changes of 13q14 (P < .001) more frequently than the other low-grade PTL. Trisomy 5 and + X predominated in AILD- type PTL. A cytogenetic feature characteristic of AILD-type PTL and CTCL was unrelated clones, which were found in 15% of AILD-type PTL and 17% of CTCL. The only chromosome aberration restricted to a certain high-grade PTL was t(2;5)(p23;q35) in large-cell anaplastic lymphoma. Deletions in 6q, total or partial trisomies of 7q, and monosomy 13 or changes of 13q14 turned out to be significantly more frequent in high- grade than in low-grade lymphomas (P < .01, P < .01, and P < .05, respectively). In summary, the cytogenetic findings in our series of 104 PTL enabled us to distinguish not only between low-grade and high- grade lymphomas but also between various entities of PTL. Thus, the cytogenetic findings paralleled the histopathologic diagnoses made according to the updated Kiel classification.

scholarly journals How I treat the peripheral T-cell lymphomas

Blood ◽  
2014 ◽  
Vol 123 (17) ◽  
pp. 2636-2644 ◽  
Author(s):  
Alison J. Moskowitz ◽  
Matthew A. Lunning ◽  
Steven M. Horwitz
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
T Cell Lymphoma ◽  
Significant Shift ◽  
Cell Transplant ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Historical Series ◽  
Peripheral T Cell Lymphomas

Abstract The peripheral T-cell lymphomas (PTCLs) encompass a heterogeneous group of diseases that have generally been associated with poor prognosis. The most common PTCLs, peripheral T-cell lymphoma, not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALK-negative), despite their unique presentations and histologies, are currently treated similarly. Here we discuss our general approach to the treatment of the most common PTCLs. Based on the best data currently available, which include retrospective analyses and phase 2 prospective studies, our approach has involved cyclophosphamide, doxorubicin, vincristine, prednisone-based therapy followed by consolidation in first remission with autologous stem cell transplant. This treatment strategy likely improves the outcome for patients compared with historical series; however, progression-free survival rates remain disappointing, ranging from 40% to 50%. This is currently an exciting time in the treatment of PTCL due to the advent of recently approved drugs as well as new targeted agents currently under investigation. In addition, gene expression profiling is allowing for a better understanding of underlying disease biology, improved diagnostic accuracy, and prognostication in PTCL. As a result, over the next few years, we expect a significant shift in our management of these diseases with a move toward more individualized therapy leading to improved outcomes.

Outcomes Using Doxorubicin-Based Chemotherapy with or without Radiotherapy for Early-Stage Peripheral T-cell Lymphomas

2002 ◽  
Vol 43 (9) ◽  
pp. 1769-1775 ◽  
Author(s):  
Hoon K. Lee ◽  
Richard B. Wilder ◽  
Dan Jones ◽  
Chul S. Ha ◽  
Barbara Pro ◽  
...  
Keyword(s):  
T Cell ◽  
Early Stage ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas
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