PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia

Abstract

Summary:We ؉ cells were collected with a median of two aphereses in 14 out of 17 patients; three failed to mobilize a number of CD34 ؉ cells adequate for subsequent manipulation. We found that in CR patients CD34؉ cell yield per apheresis was significantly higher than in PR patients (P Ͻ 0.05). Sixteen selection procedures were performed in 13 patients. CD34؉ cell recovery was 33.5% (10-85) with a median final yield of 1 × 10 6 /kg CD34 ؉ . Two patients underwent marrow collection due to the low number of CD34 ؉ cells recovered. Final purity was 59% (range 22-94) and CD5/20 ؉ cell depletion was 2.7 log (1.6-4.4). Our data showed a statistically higher CD34 ؉ cell recovery and purity with the Isolex device compared to Ceprate (P Ͻ 0.01 and 0.01, respectively). All the evaluable samples remained PCR positive after selection. The main issues to be addressed in the future are the identification of patients who fail mobilization and the improvement of purging methods. Keywords: CLL; PBSC mobilization; CD34 + selectionIn relatively young patients with CLL, autologous transplantation is a promising modality of treatment. High-dose therapy followed by infusion of autologous progenitor cells is able to induce complete remission in a fraction of cases, even with disappearance of the disease at the molecular level in some.

Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning?

“…In three of 17 patients studied by Scime et al, 60 the harvest was insufficient. The yield was greater in patients who had achieved a complete remission prior to transplant than in those in partial remission.…”

Clinical relevance of minimal residual disease monitoring in non-Hodgkin’s lymphomas: a critical reappraisal of molecular strategies

“…14,40 In contrast, CD34 + selection was largely unsuccessful in SLL/CLL patients. 17 Thus, both negative and positive selection methods proved to be successful in eradicating PCR-detectable disease in a significant proportion of FCL patients. Comparative studies are probably required to define which approach should be considered more appropriate and cost-effective.…”

“…22 The IgH gene rearrangement has been used in different subtypes of NHL, including SLL/CLL, FCL and MCL. 17,18,22,25,26,33 This method relies on the amplification and sequencing of the IgH rearranged variable region (VDJ). VDJ amplification is performed using consensus primers derived from the leader or framework regions of IgH genes.…”

“…1,2 Major advances in the field have been the introduction of high-dose chemotherapy regimens followed by autologous or allogeneic transplantation of hematopoietic cells, [3][4][5][6][7][8] the development of novel drugs such as purine analogues 9 and monoclonal antibodies, 10 and the use of innovative methods for ex vivo manipulation of autologous stem cells. [11][12][13][14][15][16][17][18][19] Treatment evolution has been particularly remarkable in low grade subtypes, where palliative approaches have been progressively substituted by treatments aimed at improving disease-free survival and possibly curing at least patients younger than 60-65 years.…”

“…In the NHL setting, several studies have been published on the prognostic significance of minimal residual disease (MRD) detection. Most of these studies focus on indolent lymphomas: small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), 17,18 follicular (FCL) [19][20][21] and mantle cell lymphomas (MCL). 20,22 This is mostly because these tumors, unlike more aggressive NHL histotypes, are disseminated disorders with frequent microscopic or submicroscopic bone marrow (BM) and peripheral blood (PB) involvement, and thus they represent ideal targets for MRD evaluation with PCR-based assays.…”