Blood Progenitor Cell Harvest Research Articles

175 - The Addition of Paclitaxel Allows for the Successful Harvest of Blood Progenitor Cells (BPC) in Patients Who Had Failed to Mobilize Bpc with Tbo-GCSF and Plerixafor

175 - The Addition of Paclitaxel Allows for the Successful Harvest of Blood Progenitor Cells (BPC) in Patients Who Had Failed to Mobilize Bpc with Tbo-GCSF and Plerixafor

The Era of High-Dose Chemotherapy for Breast Cancer: Revisiting a Troubled Quest

The Era of High-Dose Chemotherapy for Breast Cancer: Revisiting a Troubled Quest

Large volume peripheral blood progenitor cell (PBPC) harvest in 27 pediatric solid tumor patients weighing less than 20 Kg

9061 While PBPC collection has become a safe and common procedure in adults, fewer reports exist about its efficacy and safety in low weight pediatric patients. PBPC harvest might be difficult in this patient population and extracorporeal separator line priming with red blood cells is usually required to improve hemodynamic stability and effectiveness of the collection. We present our experience in 27 children (11 females, 16 males) weighing less than 20 kg and autografted between May 2001 and December 2005. Median age and weight at the time of apheresis were 2.7 years (0.7 to 8) and 14.3 kg (9.7 to 20), respectively. Diagnosis were neuroblastoma in 15, brain tumor in 10, and others in 2. Harvest of PBPC started after mobilization with G-CSF 10 ug/kg/day SC for 4 days. A double lumen (Arrow 7Fr) central venous catheter was surgically placed under sedation in the OR. Collections were performed using a COBE Spectra separator primed with irradiated, white cell-depleted and CMV-negative packed red cells. A median of 2 (1 to 7) procedures were performed, resulting in the harvest of 12.9 (3.6–33.1) × 108/kg mononuclear cells and 4.98 (2.33–12.69) × 106/kg CD34 (+) cells. The apheresis were performed in the presence of the parents and did not require sedation. Only 1 patient had as side-effect perioral paresthesias with normal serum calcium. No patient had vasovagal reactions. A median platelet count reduction of 66% was observed, comparing pre and post apheresis values. All patients completed the procedure with a median of 71.800 platelets (25.000 to 152.000) and a median hemoglobin of 10.8 g/dl (8.2 to13.6). All children were successfully transplanted with myeloid engraftment (ANC >500 × 109/L) at a median of 11 days (9 to 14) and independence from platelet transfusions (> 20,000x × 109/L) at a median of 17 days (8 to 39) after PBPC infusion. Median of hospitalization days was 23 (18 to 42). We conclude that PBPC harvesting using large volume continuous flow cell separation was safe, even in this low-weight pediatric population. This procedure shortens the total number of apheresis, providing an adequate number of CD34 + cells, resulting in satisfactory hematological recovery and duration of hospitalization. No significant financial relationships to disclose.

Midpoint CD34 measurement as a predictor of PBPC product yield in pediatric patients undergoing high-dose chemotherapy

High-dose chemo/radiotherapy of sensitive tumors requires PBPC rescue doses of >3 x 10(6) CD34/kg (range: 3-20 x 10(6) CD34/kg). Because of the diversity of stem cell treatment protocols and clinical presentation of patients at the time of peripheral blood progenitor cell (PBPC) harvest, the use of the mid-point CD34 positive cell measurement was initiated to predict the final CD34-positive cell product yield/stem cell harvest. The measurement of CD34-positive cells at the mid-point of the initial setting of 5 total blood volumes (TBV) allows for the extension, shortening, or no change in the TBV processing to achieve a maximum goal of CD34-positive cells/kg body weight required for stem cell transplantation. The estimation of mid-point CD34-positive cells guided our center to extend 22 procedures, shorten 26 procedures, and leave 20 procedures unchanged. This investigation addresses three aspects of PBPC collection in pediatric patients: (1) the processing of large blood volumes (more than the defined 3 TBV and maximum up to 13 TBV in one session) to achieve good efficiency of the procedure; (2) the use of the mid-point CD34 measurement at 2.5 of 5 TBV initially set to predict the maximum goal of CD34 cells /kg needed on the same day of PBPC collection; and (3) PBPC collection in pediatric patients <10 kg body weight (as low as 5.8 kg body weight).

Circulating CD34+ cells to predict the adequate harvest of peripheral blood progenitor cells in platinum-based chemotherapy.

The aim of this study was to clarify the appropriate timing for peripheral blood progenitor cells (PBPC) harvesting after platinum-based mobilization chemotherapy by measurement of the circulating CD34+ cell concentrations. PBPC were collected for autotransplantation via a total of 68 leukaphereses in 16 patients with gynecological cancer. Circulating CD34+ cell concentrations were measured by CD34-side scatter parameter analysis. Data could be fitted into a linear regression line described by the equation y = 0.33 + 4.14 x (x) (R2 = 0.256), where y = the number of harvested colony-forming unit granulocyte macrophage (CFU-GM (x10(5)/kg) and x = the percentage of circulating CD34+ cells and y = 1.747 + 44.53 x (x) (R2= 0.475), where y = the number of harvested CD34+ cells (x10(6)/kg) and x = the percentage of circulating CD34+ cells. Failure to mobilize sufficient CFU-GM numbers (>1 x 10(5)/kg) occurred in 29 of 31 leukaphereses when the percentage of circulating CD34+ cells was less than 0.10%. Harvesting procedure may be avoided when circulating CD34+ cells showed less than 0.10% after platinum-based mobilization chemotherapy.

Tumour Kinetics in Multiple Myeloma Before, During, and After Treatment

Tumour progression was monitored in seven multiple myeloma (MM) patients undergoing a novel oral chemotherapy regimen (cyclophosphamide, idarubicin and dexamethasone; CID) followed by early autologous stem cell transplantation (ASCT). Allele-specific oligonucleotide PCR (ASO-PCR) was used to semi-quantitate the number of tumour cells within the peripheral blood (PB) and PB progenitor cell (PBPC) harvests and compared with paraprotein levels and morphological bone marrow (BM) assessments. Tumour cells were detected in the PB of all patients at diagnosis, but decreased in response to CID therapy. All but two of the 22 PBPC collections contained MM cells, the levels of which were statistically correlated with overall clinical response to therapy, but not with individual BM or PB tumour loads prior to mobilisation. We also found no correlation between the day of leucapheresis collection and the number of contaminating MM cells, CD34+ cells or MM cells per CD34+ cell. Regardless of tumour contamination levels in the PBPC collections, the majority of patients demonstrated post-ASCT clearing of circulating MM cells. This study suggests that levels of circulating MM cells may be the best indication of patient response to treatment and argues against the theory of differential mobilisation of tumour cells and CD34+cells in response to cytokine treatment.

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

Blast counts in blood progenitor cell (BPC) correlate with CD34+ cells and CFU-GM and are useful predictor of haemopoietic recovery after autologous BPC transplantation collections.

Assessment of the quality of blood progenitor cell (BPC) collections is based mainly on CD34+ cell enumeration by flow cytometry, or scoring of granulocyte-macrophage colony-forming cells (CFU-GM). A minimum cell dose for haemopoietic recovery can be defined by both assays; however, the CFU-GM assay can not be used for 'real-time' decisions, whereas CD34+ cell scoring requires facilities and expertise which are not universally available. We have investigated the possibility of using morphologically defined blast cells within BPC harvests as a surrogate marker of harvest haemopoietic stem/progenitor cell content, as well as their correlation with CD34+ cells and CFU-GM within the harvests. We have found that blast counts correlate strongly with both CD34+ cell counts and CFU-GM within BPC harvests, as well as with time to granulocyte and platelet recovery after autologous BPC transplantation (ABPCT). Furthermore, we have defined a threshold value of 1.3 x 10(6)/kg blasts, above which there is a high probability of rapid haemopoietic recovery after ABPCT. We conclude that blast count is a simple, rapid and reliable method of assessing BPC harvest quality.

Platelet Depletion During Pediatric Peripheral Blood Progenitor Cell (PBPC) Harvesting

Platelet Depletion During Pediatric Peripheral Blood Progenitor Cell (PBPC) Harvesting

Fas Antigen (CD95) Expression in Peripheral Blood Progenitor Cells from Patients with Leukaemia and Lymphoma

Fas antigen (CD95) is a cell surface receptor belonging to the tumour necrosis factor/nerve growth factor superfamily and is able to induce apoptosis when triggered by it's natural ligand or an anti-Fas antibody. Fas expression is low on CD34+ bone marrow (BM) progenitor cells, but is increased by various cytokines in vitro. We investigated Fas expression on CD34+ cells from 39 peripheral blood progenitor cell (PBPC) harvests and from 5 normal BM harvests by dual colour flow cytometry to determine if Fas expression was altered during mobilisation. By including calibrated microbeads during flow cytometry, we quantified the number of Fas antigen molecules per cell. A low percentage of PBPC (22%) and normal BM (23%) CD34+ cells expressed Fas antigen. Fas expression varied on CD34+ cells from different diseases and the highest expression was found in ALL (52%). There was a significant three fold increase in the number of Fas molecules/cell expressed on CD34+ cells (PBPC 6,230 molecules/cell, BM 2,236; p0.0003). This level of expression was considerably less than that for CD3/CD19 lymphocytes (33,095 molecules/cell) and CD 14 monocytes (47,467 molecules/cell) in the PBPC harvest. In conclusion, mobilisation including the use of growth of factors, has minimal effect on CD34 progenitor cell Fas expression.

Hematopoietic stem cell transplantation for cancer therapy

Bone marrow transplantation has become well established in the treatment of malignant disorders. High-dose chemotherapy with hematopoietic stem cell support is widely used for most hematological malignancies, as well as for some solid tumors. In the light of recent developments in blood progenitor cell harvest, these have been clinical trials with autologous and allogeneic transplants. In particular, the availability of large numbers of blood stem cells, mobilized by granulocyte colony-stimulating factor and collected by leukapheresis, has made it possible to overcome histocompatibility barriers in HLA-mismatched leukemia patients. Other recent developments include new methods for blood progenitor cells mobilization and ex vivo expansion, the use of umbilical cord blood as an alternative source of stem cells, and molecular techniques that may, in the future, provide other modalities of purging tumor cells from autologous grafts.

Colony-stimulating factors. Present status and future potential.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used successfully to enhance neutrophil recovery in patients with various malignancies undergoing standard or high dose chemotherapy, with or without autologous or allogeneic bone marrow transplantation support, and offer potential advantages in these settings in terms of reducing the total costs of healthcare and/or improving therapeutic outcomes. Clinical trials are now aimed at identifying which patients and which nonhaematological malignancies will respond best to colony-stimulating factor (CSF) support, and which of the 2 factors is the most appropriate in each setting. Two areas of considerable interest at present are the potential for chemotherapy dose optimisation and intensification with CSF therapy, and the use of CSFs to permit the harvest and reinfusion of peripheral blood progenitor cells as an alternative to autologous or allogeneic bone marrow transplantation. In the case of dose-intensified chemotherapy, costs of treatment increase but the gain may be an increase in survival rates or disease-free intervals. The potential of G-CSF and GM-CSF therapy in other conditions, notably haematological malignancies such as myelodysplasia and myeloid leukaemias, and AIDS, means that these agents are likely to make a significant impact on the treatment of a wide range of debilitating conditions in the future.