Mobilization of peripheral blood stem cells with high-dose cyclophosphamide or the DHAP regimen plus G-CSF in non-Hodgkin's lymphoma

Abstract

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/...

ESHAP plus G-CSF as an effective peripheral blood progenitor cell mobilization regimen in pretreated non-Hodgkin's lymphoma: comparison with high-dose cyclophosphamide plus G-CSF

“…6 Furthermore, DHAP was not superior to HDCY in mobilization potential. 16 Mobilization of stem cells following ESHAP should decrease the time to transplant by making separate MC unnecessary while controlling the patient's lymphoma. To date, however, ESHAP plus G-CSF has been utilized only to a limited extent for mobilization chemotherapy in NHL, [7][8][9] and there have been no comparisons between ESHAP and HDCY in terms of mobilization efficacy.…”

“…There were no between-group differences in apheresis initiation criteria and days of G-CSF use. Aphereses were started on day 16 (median) in the ESHAP (range [13][14][15][16][17][18][19][20][21][22] and on day 14 (median) in the HDCY group (range 12-22) (P ¼ 0.002). The number of total MNCs collected was significantly greater in the HDCY group (P ¼ 0.002), but the number of total CD34 þ cells was significantly higher in the ESHAP group (P ¼ 0.003).…”

Improving stem cell mobilization strategies: future directions

“…Some of the most frequently used chemotherapeutic regimens in lymphoma patients include IEV (ifosfamide, epirubicin and etoposide), DHAP and ESHAP (etoposide, Ara-C, methylprednisolone and cisplatin). 85,119 Patients with other hematologic malignancies are frequently treated with ICE (ifosfamide, carboplatin and etoposide) plus G-CSF for mobilization. 120 Mobilization that follows an induction or a salvage regimen can eliminate separate mobilization chemotherapy.…”

“…120 Mobilization that follows an induction or a salvage regimen can eliminate separate mobilization chemotherapy. 119 Pavone et al 85 compared mobilization with CY or the DHAP regimen followed by G-CSF in patients with relapsed NHL. As similar cell yields were collected after each regimen, DHAP, an excellent salvage chemotherapy for NHL, could be scheduled into the treatment for patients proceeding to transplantation.…”

ESHAP+fixed dose G-CSF as autologous peripheral blood stem cell mobilization regimen in patients with relapsed or refractory diffuse large cell and Hodgkin's lymphoma: a single institution result of 127 patients

“…[6][7][8][9] Many mobilization regimens have been reported in the literature but cyclophosphamide (1-7 g/m 2 ) followed by G-CSF is one of the most commonly reported in patients with lymphoma. [10][11][12][13][14][15][16][17] Lately, other combinations with superior antitumor efficacy have been tried with success. 13,15,[18][19][20][21][22] ESHAP 23 (Etoposide 40 mg/m 2 i.v.…”