Search

Experimental and clinical data suggest that Ph-negative myeloid progenitor cells are present, albeit suppressed, in the bone marrow of chronic myeloid leukemia (CML) patients. These residual Ph-negative cells might, in certain circumstances, regain their proliferative advantage over the leukemic Ph-positive clone. Treating CML patients with intensive chemotherapy might allow the harvest, in the early phase of recovery, of Ph-negative stem cells to be used as graft after myeloablative regimen. In our study, 6 CML patients were admitted to a program of autograft with circulating stem cells (CSC) collected after high-dose (5 or 7 g/m2) cyclophosphamide (HD-CY) mobilization. All were autografted, using busulphan 16 mg/kg and melphalan 60 mg/m2. As graft, 4 patients received CSC only, while 2 patients were also given bone marrow, as their peripheral blood CFU-GM yield was unsatisfactory. Two previously alpha-IFN-responding patients showed a slow hematologic recovery, but achieved a marked and further reduction of their Ph-positive metaphases post-graft. Moreover, in one of them, cytogenetic analyses performed on apheresis product showed a more pronounced reduction of his Ph-positive metaphases, as compared to bone marrow samples, suggesting a potential purging effect of the mobilization procedure.

Eighteen patients with malignant lymphoma, 10 non-Hodgkin's and 8 Hodgkin's, were treated with high-dose CVB (cyclophosphamide 4 x 1.5 g/m2, etoposide 4 x 250-400 mg/m2, carmustine 4 x 150-200 mg/m2), followed by autologous peripheral blood stem cells (PBSC, 13 patients) or bone marrow (BM, 5 patients) transplantation. At the time of autograft 6 patients were in complete remission (CR), 3 in partial remission (PR) and 5 in relapse (4 sensitive, 1 resistant), whereas 4 had progressive disease. All CR patients had poor prognostic features at presentation. PBSC were collected at the time of rapid hematologic recovery after intense chemotherapy by means of a cell separator. All patients engrafted. Median time to achieve > or = 0.5 x 10(9)/l polymorphonuclear cells (PMN) and > or = 50 x 10(9)/l platelets was 13 days for both cell types in PBSC autografted patients, versus 20 and 28 days respectively in BM autografted patients. A significant advantage of PBSC over BM was found in terms of time needed to recover either PMN > or = 0.5 and PMN > or = 1 x 10(9)/l (p = 0.01). Autograft-related toxicity consisted mainly of moderate severity interstitial pneumopathy (3 patients), and veno-occlusive disease (1 patient) that resolved completely. Of the 12 patients autografted with detectable disease, 6 (50%) obtained a CR. Seven out of 18 autografted patients (39%) had disease progression within 1 to 5 months of autograft. The projected progression-free survival is over 50% at 4 years and it was significantly longer in patients with sensitive disease than in those with resistant disease (p = 0.01). The efficacy and the low toxicity of CVB suggest that autograft with PBSC may be proposed for the primary treatment of poor prognosis malignant lymphomas.

Procurement of a high number of progenitor cells is of primary interest in allogeneic PBSC transplantation. We have retrospectively compared toxicity, mobilization effect and progenitor cell yields of two different rhG-CSF schedules in 11 consecutive healthy individuals donating their PBSC. Five of them received rhG-CSF 16 micrograms/kg/d for 4 subsequent d in 2 divided subcutaneous injections (group A); similarly, 6 donors received rhG-CSF 10 micrograms/kg/d for 5 d (group B). The aphereses were started the last day of rhG-CSF treatment; 9 donors underwent 2 aphereses, one underwent 1 and another 3 procedures, always on subsequent days. Toxicity was mild, but moderate thrombocytopenia developed following apheretic collections, irrespective of rhG-CSF schedule. In all the donors WBC, as well as circulating CD34+ cells, CFU-GM, CFU-GEMM and BFU-E dramatically increased over the baseline values, peaking on d 5 or 6, with no statistical difference between the 2 groups for the height of the cell peaks. Also the peripheral lymphoid cell populations (CD3+, CD19+ and CD56+/CD3-) increased following the rhG-CSF administration. The number of MNC, CFU-GM, BFU-E, CFU-GEMM, as well as CD34+, CD3+, CD19+ and CD56+/CD3- cells collected by apheresis showed no statistical difference in the 2 groups. Overall, 8 of the 11 donors collected the target number of CD34+ cells > 4 x 10(6)/kg ideal recipient body weight with the first apheresis, with no difference between the 2 groups. Mobilization with rhG-CSF in healthy donors enables the collection of large number of progenitor cells with modest side effects. A schedule of 10 micrograms/kg for 5 d is as effective as 16 micrograms/kg for 4 d. A single apheresis would be enough in 80% of cases.