Efficacy of a dose-intensified CHOP (Double-CHOP) regimen for peripheral T-cell lymphomas

Abstract

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, has 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. 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 median age of patients 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 the CR patients, 10 successfully tolerated a consolidated high-dose chemotherapy followed by ASCT and 7 received HDMTX. A single case of treatment-related mortality was recorded during the study. On a median 31-month follow-up, the estimated 3- or 5-year overall survival (OS) rates were 68 or 63%, respectively, while 3- or 5-year relapse-free survival (RFS) rates after CR were 60 or 43%, respectively. Although this study included elderly and excluded low-risk IPI and ALK+-ALCL patients, OS results were superiorly favourable, indicating the efficacy of this Double-CHOP regimen. However, an effective treatment strategy for refractory or relapsing patients needs to be validated and established.

Evaluation of clinical trial eligibility and prognostic indices in a population‐based cohort of systemic peripheral T‐cell lymphomas from the Danish Lymphoma Registry

“…A number of retrospective [11][12][13][14][15][16][17][18]29] and prospective [8][9][10]22,30,31] studies have reported an apparent outcome advantage from the use of upfront HDT/ASCT in PTCL patients with chemosensitive disease. In the present study, less than half of PTCL patients were considered eligible for inclusion in CTs with multiagent chemotherapy followed by SCT.…”

“…Recently, large phase II trials testing upfront high-dose chemotherapy (HDT) and autologous SCT (ASCT) have shown good feasibility and a possible beneficial effect on clinical outcome [8][9][10]. With the obvious caveat of patient selection, retrospective studies also seem to support this impression, particularly in patients exhibiting chemosensitive disease [11][12][13][14][15][16][17][18]. National guidelines, such as those from the National Comprehensive Cancer Network, include HDT/ASCT as a recommended option for consolidation after first remission in patients with histologies other than anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) [19].…”

Pirarubicin‐based intensive chemotherapy followed by consolidative high‐dose chemotherapies for peripheral T‐cell lymphomas: A noncomparative phase 2 study

“…1 In our previous study, we developed dose-intensified CHOP therapy, followed by high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) or high-dose methotrexate (HD-MTX) for patients with high-risk PTCLs (double-CHOP protocol). 2 We treated 28 patients with PTCLs using double-CHOP from 1996 to 2012, excluding those with anaplastic large cell lymphoma kinase-positive anaplastic large cell lymphoma (ALK + ALCL). 2 In the study, the complete remission (CR) rate with double-CHOP, 3-year OS rate, and 3-year relapse-free survival rates…”

“…were 68%, 68%, and 60%, respectively. 2 However, comparative studies have not proven any dose-intensified chemotherapies against PTCLs to be superior to conventional CHOP with or without etoposide. 3,4 Pirarubicin, or tetrahydropyranyladriamycin (THP), is a unique anthracycline synthesized from derivatives of daunorubicin and adriamycin.…”

“…Based on THP's peculiar hematologic toxicities, we determined the THP dosage as 80% of the doxorubicin dosage originally used in the double-CHOP regimen. 2 For patients aged >60 years, the cyclophosphamide dose was modified as previously described. 2 The treatment interval was set at 3 weeks using primary prophylaxis with granulocyte colony-stimulating factors.…”