We designed a phase 1-2 study to evaluate the safety and the efficacy of increasing doses of bendamustine (160 mg/m 2 , 180 mg/m 2 , and 200 mg/m 2 given on days ؊7 and ؊6) coupled with fixed doses of etoposide, cytarabine, and melphalan (BeEAM regimen) as the conditioning regimen to autologous stem cell transplantation for resistant/relapsed lymphoma patients. Forty-three patients (median age, 47 years) with non-Hodgkin (n ‫؍‬ 28) or Hodgkin (n ‫؍‬ 15) lymphoma were consecutively treated. Nine patients entered the phase 1 study; no patients experienced a dose-limiting toxicity. Thirty-four additional patients were then treated in the phase 2. A median number of 6 ؋ 10 6 CD34 ؉ cells/kg (range, 2.4-15.5) were reinfused. All patients engrafted, with a median time to absolute neutrophil count > 0.5 ؋ 10 9 /L of 10 days. The 100-day transplantation-related mortality was 0%.

Haemopoietic stem cell therapy is an increasingly adopted procedure in the treatment of patients with malignant lymphoma. In this retrospective analysis, we evaluated 262 patients, 57 (22%) with Hodgkin's and 205 (78%) with non-Hodgkin's lymphomas (NHL), and 665 harvesting procedures in order to assess the impact of poor mobilization on survival and to determine the factors that may be predictive of CD34 þ poor mobilization. The mobilization chemotherapy regimens consisted of highdose cyclophosphamide in 92 patients (35.1%) and a highdose cytarabine-containing regimen (DHAP in 87 patients -(33.2%), MAD in 83 (31.7%)). The incidence of poor mobilizers (o2 Â 10 6 CD34 þ cells/kg) was 17.9% overall, with a 10% of very poor mobilizers (p1 Â 10 6 / kg). Refractory disease status and chemotherapeutic load (43 regimens) before mobilization played a negative role and were associated with poor mobilization. Survival analysis of all harvested patients showed an overall survival at 3 years of 71% in good mobilizers vs 33% in poor mobilizers (P ¼ 0.002). The event-free survival at 3 years was 23% in poor mobilizers and 58% in good mobilizers (P ¼ 0.04). We conclude that in NHL patients, poor mobilization status is predictive of survival.

Summary:Our study analyzes the mobilization of hematopoietic stem cells after two chemotherapeutic regimens in nonHodgkin's lymphoma (NHL) patients. The study included 72 patients with NHL (42 follicular and 30 large cells). The mean age was 37 years (range 17-60). Sixty-four patients (88.9%) had stage III-IV disease. Forty-eight patients (66.7%) had bone marrow involvement. Systemic B symptoms were present in 42 patients (58.3%). Mobilization chemotherapy regimens were randomly assigned as DHAP in 38 patients (52.7%) or cyclophosphamide (CPM) (5 g/m 2 ) in 34 (47.2%) and the results of 132 procedures were analyzed. At the time of PBSC mobilization, 46 patients (63.9%) were considered to be responsive (complete remission, partial remission or sensitive relapse) and 26 (36.1%) not responsive (refractory relapse or refractory to therapy). Pre-apheresis CD34 + blood cell count and number of previous chemotherapy treatments were used to predict the total number of CD34 + cells in the apheresis product. The mobilizing regimens (CPM or DHAP) were similar in achieving the threshold CD34 + cell yield, for optimal engraftment. Since DHAP was very effective as salvage treatment, we suggest using DHAP as a mobilizing regimen in patients with active residual lymphoma at the time of stem cell collection. ( toxicity. [5][6][7][8] In the literature, high-dose cyclophosphamide (CPM) seems to be the gold standard for mobilizing hematopoietic progenitor cells in lymphoproliferative disorders. 9,10 Single high doses of alkylating agents (high-dose CPM or melphalan) have been used as mobilizing chemotherapy in NHL and other malignancies. [9][10][11][12] Combination chemotherapy regimens such as DHAP or MAD or ESHAP have also been used for stem cell harvesting. [13][14][15] In a previous study the DHAP protocol has already shown real efficacy in debulking and in vivo purging in refractory or in partial remission NHL. 16,17 The DHAP regimen was thus integrated into various treatment plans tailored for NHL patients as a second-line therapy and salvage chemotherapy for PR patients, or as an intensification and mobilizing regimen in CR high risk patients. 16,17 In our previous experience, we used the DHAP protocol as salvage treatment in patients in PR or with refractory NHL. Few randomised studies report a comparison of mobilizing capacity of two different chemotherapeutic regimens such as ESHAP or ifosfamide vs CPM in lymphoproliferative disorders. [18][19][20] In our study 72 NHL patients undergoing PBSC transplantation were prospectively randomized to mobilize PBSC with the DHAP regimen or with high-dose CPM in order to evaluate whether there were any differences in the number of mononuclear cells harvested (× 10 8 /kg), CD34 + cells (×10 6 /kg), colony-forming units granulocyte-macrophage (CFU-GM) (×10 4 /kg) obtained or engraftment speed. Bone Marrow Transplantation Patients and methodsThe following parameters were examined in the two different mobilized groups: (1) Clinical: (i) type of mobilizing regimen (DHAP (cisplatin 100 mg/...

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The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.