Feasibility Of High-dose Chemotherapy Research Articles

Efficacy and feasibility of autologous stem cell transplantation in patients with diffuse large B-cell lymphoma with secondary central nervous system involvement

Secondary central nervous system (CNS) involvement is a fatal complication of diffuse large B-cell lymphoma (DLBCL). We evaluated the efficacy and feasibility of high-dose chemotherapy containing busulfan and thiotepa followed by autologous stem cell transplantation (HDC-ASCT) in DLBCL with secondary CNS involvement. Thirty-one patients with secondary CNS involvement including CNS involvement at diagnosis (n = 9), isolated CNS relapse (n = 14), and CNS involvement with systemic disease progression or relapse (n = 8) were selected and analyzed from our prospective cohorts. Of these, 12 patients, including seven with isolated CNS relapse, successfully completed HDC-ASCT without engraftment failure or transplantation-related mortality. After ASCT, six patients were alive; however, three patients experienced post-transplantation relapse. With a median follow-up of 29 months after secondary CNS involvement, the median overall survival of 31 patients was 9 months (95% CI 5–12 months). The survival outcomes of patients who had undergone HDC-ASCT were significantly better than those of patients who did not (p < 0.01). Accordingly, patients with isolated CNS relapse tended to have a longer survival outcome than other cases. Our results suggest that HDC-ASCT may provide survival benefits in DLBCL patients with secondary CNS involvement, especially in case of isolated CNS relapse.

Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study.

Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×10⁹/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate.

Hodgkin's Disease in Patients with HIV Infection

Hodgkin lymphoma (HL) represents one of the most common non-AIDS-defining cancers with an increasing incidence overtime. Clinically, patients present advanced stages of disease with extranodal involvement in the majority of cases. In the last years, significant improvements in the treatment of patients with HL and HIV infection have been achieved. In the lack of randomized trials, several phase II studies have showed that in the era of highly active antiretroviral therapy (HAART) the same regimens employed in HIV-negative patients with HL can be used in HIV setting with similar results. Moreover, in the last years the feasibility of high dose chemotherapy and peripheral stem cell rescue has allowed to save those patients who failed the upfront treatment. Finally, in the near future, a better integration of diagnostic tools (including PET scan), chemotherapy (including new drugs), radiotherapy, HAART, and supportive care will significantly improve the outcome of these patients.

Feasibility of high-dose chemotherapy (HDCT) with doble autologous stem cell transplantation (ASCT) for Ewing and soft tissue sarcomas

21501 Background: To improve long-term outcome of metastatic sarcoma patients (pts), we started a tandem ASCT program in compassionate use. Its feasibility is analyzed. Methods: From January/2004 to April/2007, 11 pts (8 males, age 29 [19 - 51] years) were included: 7 Ewing, 2 rabdomyosarcoma, 1 sinovial and 1 leiomyosarcoma. Patients included in the program were those with CR or PR after conventional chemotherapy (CT). Median treatment lines before transplant was 1 (1–3). Conditioning regimen for both ASCTs was ICE protocol (HDCT) (ifosfamide 2,500 mg/m2 iv × 4 d, carboplatin 360 mg/m2 iv × 4 d., etoposide 310 mg/m2 iv × 4 d.). A minimum number of 4 × 106 CD34+/kg cels were collected. Results: 5 pts were in CR, 5 in PR just before ASCT. 1 pt that achieved a PR after CT, presented with an early progression just before the first ASCT. All pts underwent the first procedure. Post-transplant toxicity: grade (G) 4 neutropenia: (11d [7d-14d]), G4 thrombocytopenia: (7.7d [4–12]), G 3–4 gastrointestinal (GI) toxicity in 6 (54%) and severe venooclusive disease in 2 (18%) pts. All pts developed neutropenic fever. Two pts (18%) died from transplant related mortality (TRM). 3 other pts (27%) didn't proceed to 2nd intensive course due to early progression after first ASCT. Time interval between procedures was 3.6 (2–7) months. Second ASCT toxicity was: neutropenia G IV 11.5 (9–14) d and thrombocytopenia G4 5.8 (2–14) d. One pt (16%) developed G3 GI toxicity. TRM was 0%. With a median follow-up for all pts of 14.5 (1–35) months after the first transplant, 4 are alive (36%), 1 in CR, 3 in PR and 7 are death (63%). Conclusions: This tandem procedure is feasible but rather toxic: G 3–4 GI toxicity are higher than expected as well as TRM. Progression rate after the first ASCT procedure is not negligible. Other options should be sought for this bad-prognosis pts. No significant financial relationships to disclose.

Feasibility of High-Dose Chemotherapy without Stem Cell Support as a First-Line Treatment for Non-Hodgkin's Aggressive Lymphoma: A Pilot Study

A regimen which incorporates cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) is the standard treatment for patients with non-Hodgkin's lymphoma (NHL), but it has not been effective in patients with aggressive NHL who are at high risk. The aim of the present trial was to investigate the feasibility of high-dose chemotherapy (HDC) without stem cell support as a first-line treatment. The primary endpoint was a complete remission rate. The second endpoint was survival. Fourteen patients with aggressive NHL entered the study and were treated according to the K93 protocol (3 cycles of CHOP, high-dose etoposide and ifosfamide, and high-dose methotrexate) Eleven patients (79%) achieved complete remission (CR) and two (14%) achieved partial remission (PR). Overall survival (OS) after five years was 79%. The actuarial five year disease free survival (DFS) for the eleven cases of CR was 75%. During chemotherapy, grade IV hematologic toxicity was observed in all patients and grade IV non-hematologic toxicity in only one patient, who experienced oral ulcers. Peripheral blood stem cell (PBSC) apheresis was performed in eight cases. One harvesting was enough to provide an adequate number of CD34+ cells for the subsequent PBSC transplantation (PBSCT).In conclusion our study confirmed the efficacy of the K93 protocol in obtaining a good response (CR + PR) rate and a very good DFS rate in most cases of aggressive NHL, with acceptable toxicity. This regimen may improve the outcome in cases of aggressive NHL without stem cell support. It seems worthwhile to conduct a randomized controlled study comparing the K93 protocol with the standard CHOP regimen.