High Dose Chemotherapy with Thiotepa, Mitoxantrone and Carboplatin (TMJ) Followed by Autologous Stem Cell Support in 100 Consecutive Lymphoma Patients in a Single Centre: Analysis of Efficacy, Toxicity and Prognostic Factors

Abstract

High dose chemotherapy with autologous stem cell transplant is often used in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either do not respond to, or relapse after conventional chemotherapy. There is no consensus on the "ideal" pretransplant conditioning regimen. In this study, we analyzed the results of 100 consecutive patients with HD and NHL who met our eligibility criteria and underwent autologous stem cell transplant at New York Medical College and Zalmen A. Arlin Cancer Institute. All patients received high dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients had first complete remission. The source of stem cells was bone marrow (18 patients), peripheral blood (50 patients) and both bone marrow and peripheral blood (32 patients). With a median follow up of 91 months (range 23-147 months), the median survival of patients with HD and NHL who underwent autologous stem cell transplant is 107 months and the 5 years disease free survival is 43%. Median survival of patients with HD and NHL is 87 and 107 months respectively. There were 4 transplant related deaths. Median survival of patients who had sensitive relapse at the time of transplant is 87 months while median survival has not been reached for patients who had first complete remission at the time of transplant. Multivariate analysis identified age>35 years (P=0.02) as a predictor for poor survival for the whole group as well as for patients with NHL (P=0.04). TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL.

Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT

“…In keeping with published experience, [10][11][12][13][14][15][16][17][18][19][20] the main combination partners of TT were carmustine, melphalan, busulfan and cyclophosphamide. No significant differences for any safety or efficacy end point could be demonstrated between BEAM-and TT-based regimens for the whole population as well as for relatively large groups of the DLBCL, HL and FL subentities, except a significantly higher relapse risk with TT in the DLBCL CR/PR1 subset (which is not a standard indication for auto-SCT).…”

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre

“…Several studies in patients with relapsed Hodgkin's lymphoma have reported cumulative probability rates for 5-year OS and PFS after HDC and ASCT of 51-75 and 42-52%, respectively. [3][4][5][6][7][8][9][10][11][12] Other studies which have focussed on patients with chemorefractory relapse 13 or primary resistant disease 14 have demonstrated lower corresponding figures for outcome.…”

“…Examples include cyclophosphamide, etoposide, melphalan, thiotepa, platinum agents and BCNU (carmustine) which have been used widely in schedules such as BEAM (BCNU, etoposide, cytarabine and melphalan), 15 CBV (cyclophosphamide, BCNU and etoposide (VP16-213)), 3,4 CBVP (CBV plus cisplatin), 6 melphalan with etoposide, 7 and thiotepa with mitoxantrone and carboplatin. 8 Regimens combining total body irradiation with cyclophosphamide or etoposide have not demonstrated improved outcomes. 9 The reported 100-day treatmentrelated mortality after ASCT has been 3-5%.…”

“…18,19 Additionally bulky disease, extranodal site of the disease, B symptoms, elevated lactate dehydrogenase (LDH), greater number of chemotherapy regimens before ASCT and less than partial remission (PR) at the time of ASCT were shown to have a negative impact on outcome in other smaller studies. [5][6][7][8][9][10][11] Late treatment complications of HDC and ASCT, including loss of fertility, premature menopause, cardiopulmonary toxicity and increased risk of secondary malignancy, are an important issue for patients with relapsed Hodgkin's lymphoma considering the median age at initial diagnosis of approximately 35 years. Studies have suggested that the incidence of secondary malignancy following HDC and ASCT is higher in patients with Hodgkin's lymphoma than with non-Hodgkin's lymphoma (6-8 versus 3%) and that the number of relapses before ASCT and previous radiotherapy are associated with an increased risk.…”

“…9 The reported 100-day treatmentrelated mortality after ASCT has been 3-5%. [3][4][5][6][7][8] The International Prognostic Factor Project score including age, gender and disease features at diagnosis (disease stage, anaemia, albumin level, lymphocytopenia and leucocytosis) was developed for patients with newly diagnosed Hodgkin's lymphoma to predict event-free survival (EFS) and OS after initial chemotherapy. 16 This score was subsequently re-evaluated for patients who underwent ASCT for relapsed Hodgkin's lymphoma.…”