Infusion Of Peripheral Blood Stem Cells Research Articles

Optimization of peripheral blood stem cell mobilization.

Peripheral blood stem cells (PBSC) are increasingly utilized in lieu of marrow for hematopoietic support due to the ease of collection and the rapid kinetics of recovery relative to bone marrow (BM). Neutrophil and platelet recovery times after PBSC transplantation average less than 8-12 days after infusion in contrast to the usual two to four weeks experienced after BM transplantation. This has simplified autologous transplantation and made it safer because patients require fewer days of antibiotic and blood component support and are discharged earlier from the hospital. The administration of hematopoietic growth factors during recovery from high-dose chemotherapy increases the number of circulating hematopoietic progenitor cells to levels as much as 1,000-fold greater than levels normally found in blood and 10-50 times greater than with chemotherapy alone. More recently, it has been shown that adequate numbers of PBSC can be collected using growth factors alone without prior chemotherapy. Although not yet universally accepted, the CD34+ cells content of PBSC appears to be the single most powerful predictor of recovery kinetics in patients receiving myeloablative therapy and PBSC infusion. Infusion of > 5 x 10(6) CD34+ cells/kg is associated with a rapid engraftment of neutrophils and platelets, although successful engraftment has also been reported with the infusion of 2.5-5 x 10(6) CD34+ cells/kg. By measuring the CD34 or colony forming units-granulocyte-macrophage (CFU-GM) content of PBSC collections, mobilization chemotherapy and cytokine regimens, age, marrow disease, prior radiation and prior chemotherapy treatment have been found to be important factors influencing the numbers of stem cells collected. The current challenge for clinical investigators is to improve methods of identifying patients who will fail to mobilize sufficient numbers of PBSC prior to collection and to utilize new strategies for stem cell mobilization. The relative ease of collection and the rapid engraftment after myeloablative therapy suggest that PBSC will likely supplant marrow for both allogeneic and autologous transplantation in the next five years.

Factors that influence collection and engraftment of autologous peripheral-blood stem cells.

To analyze factors that affect the collection of peripheral-blood stem cells (PBSC) before transplant and the tempo of engraftment after transplant. A consecutive series of 243 patients with breast cancer (n = 87), malignant lymphoma (n = 90), multiple myeloma (n = 32), or other malignancies (n = 34) had PBSC collected following stimulation with colony-stimulating factors (CSFs) or after chemotherapy followed by CSF. Infusion of PBSC was performed following myeloablative chemotherapy with chemotherapy with or without total-body irradiation (TBI). Postinfusion CSFs were administered to 72 patients. An analysis of factors that influence CD34+ cell yield was performed by linear regression. Cox regression analysis was used to determine factors that affect the kinetics of granulocyte and platelet recovery following infusion of PBSC. Mobilization with chemotherapy followed by CSF, a diagnosis of breast cancer, absence of marrow disease, no prior history of radiation therapy, and fewer cycles of conventional-dose chemotherapy were associated with a higher average daily yield of CD34+ cells. In the multivariate analysis, the CD34 content of infused cells and the use of a posttransplant CSF influenced neutrophil recovery after infusion of PBSC. CD34 content was also important for predicting platelet recovery. The use of postinfusion CSF was associated with a significant delay in platelet recovery in patients who received less than 5.0 x 10(6) CD34+ cells/kg, but there was no discernable effect in patients who received greater than 5.0 x 10(6) CD34+ cells/kg. Disease status and prior treatment influence the ability to mobilize PBSC. CD34 cell dose is an important predictor of engraftment kinetics after PBSC transplant, regardless of disease or mobilization technique. The use of postinfusion CSF improves neutrophil recovery, but at low CD34 doses can delay platelet recovery.

High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants

One hundred and thirty-five patients with advanced and refractory myeloma received one of three high-dose therapy regimens: melphalan at doses of 90 to 100 mg/m2 (MEL 100; 47 patients) without autotransplant; total body irradiation (TBI; 850 cGy) with either melphalan 140 mg/m2 or thiotepa 750 mg/m2 and autologous bone marrow transplant (ABMT) (< or = 30% plasma cells; 21 patients); melphalan 200 mg/m2 (MEL 200) supported by both peripheral blood stem cells (PBSC) and ABMT plus GM- CSF intended as a double-transplant program (67 patients; 42 have completed and 3 are still awaiting a second autotransplant; 5 additional patients received an allograft for their second transplant). Mortality within 2 months of therapy was 20% to 25% with MEL 100 and TBI regimens, but less than 1% with MEL 200, mainly because severe neutropenia (< 500/microL) was shortened to less than 1 week due to infusion of PBSC and use of growth factor therapy. Low beta 2- microglobulin (beta 2M) levels < or = 2.5 mg/L and MEL 200 therapy were identified as the two most important independent favorable variables associated with prolonged event-free survival (EFS) and overall survival (OS). On the basis of these two parameters, three risk groups were defined: 29 good-risk patients with low beta 2M receiving MEL 200 had the best outcome, with median durations of EFS of 37 months and projected OS of > or = 43 months; 54 intermediate-risk patients displaying one of the two favorable parameters had EFS and OS durations of 16 and 36 months, respectively; and 52 poor-risk patients with high beta 2M not receiving MEL 200 had a dismal prognosis, with EFS of 3 months and OS of 5 months (all P > .0001). Further analysis that excluded treatment as a variable identified high beta 2M and resistant relapse as the two major adverse prognostic factors, one of which was present in 80% of the 135 patients. Among these 108 high-risk patients, prognosis was improved markedly with MEL 200 because of both better supportive care (PBSC and hematopoietic growth factors) and more intensive therapy using the double-transplant approach. This study supports the concept that safer and potentially more-effective therapies can be developed in the setting of advanced and resistant disease.

High-Dose Therapy for Refractory Multiple Myeloma: Improved Prognosis With Better Supportive Care and Double Transplants

One hundred and thirty-five patients with advanced and refractory myeloma received one of three high-dose therapy regimens: melphalan at doses of 90 to 100 mg/m2 (MEL 100; 47 patients) without autotransplant; total body irradiation (TBI; 850 cGy) with either melphalan 140 mg/m2 or thiotepa 750 mg/m2 and autologous bone marrow transplant (ABMT) (< or = 30% plasma cells; 21 patients); melphalan 200 mg/m2 (MEL 200) supported by both peripheral blood stem cells (PBSC) and ABMT plus GM-CSF intended as a double-transplant program (67 patients; 42 have completed and 3 are still awaiting a second autotransplant; 5 additional patients received an allograft for their second transplant). Mortality within 2 months of therapy was 20% to 25% with MEL 100 and TBI regimens, but less than 1% with MEL 200, mainly because severe neutropenia (< 500/microL) was shortened to less than 1 week due to infusion of PBSC and use of growth factor therapy. Low beta 2-microglobulin (beta 2M) levels < or = 2.5 mg/L and MEL 200 therapy were identified as the two most important independent favorable variables associated with prolonged event-free survival (EFS) and overall survival (OS). On the basis of these two parameters, three risk groups were defined: 29 good-risk patients with low beta 2M receiving MEL 200 had the best outcome, with median durations of EFS of 37 months and projected OS of > or = 43 months; 54 intermediate-risk patients displaying one of the two favorable parameters had EFS and OS durations of 16 and 36 months, respectively; and 52 poor-risk patients with high beta 2M not receiving MEL 200 had a dismal prognosis, with EFS of 3 months and OS of 5 months (all P < .0001). Further analysis that excluded treatment as a variable identified high beta 2M and resistant relapse as the two major adverse prognostic factors, one of which was present in 80% of the 135 patients. Among these 108 high-risk patients, prognosis was improved markedly with MEL 200 because of both better supportive care (PBSC and hematopoietic growth factors) and more intensive therapy using the double-transplant approach. This study supports the concept that safer and potentially more-effective therapies can be developed in the setting of advanced and resistant disease.

Dose intensive therapy with autologous blood stem cell transplantation in breast cancer

Breast cancer is the commonest form of cancer in Australian women. Although approximately 50% of women with breast cancer achieve long term survival by current management methods, recurrent or metastatic disease is generally incurable. In addition, women with Stage II disease with > 10 positive axillary lymph nodes and also women with locally advanced disease (Stage III) have a poor survival even with adjuvant therapy. To assess the toxicity and efficacy of high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation in women with both metastatic and poor prognosis primary breast cancer. Twenty-eight women with either metastatic (15) or poor prognosis (13) primary breast cancer were enrolled in the study between November 1988 to January 1993. PBSC were harvested using high-dose cyclophosphamide (Cy) with or without granulocyte-colony stimulating factor (G-CSF) and a myeloablative regimen of Cy, melphalan and carboplatin (CMCp) was used in the transplantation phase. Optimum numbers of stem cells were harvested in 85% of patients. The use of five G/m2 Cy plus G-CSF resulted in better PBSC yields and a significant reduction in haematologic morbidity when compared to mobilisation with Cy alone. Twenty-two women underwent 23 PBSC transplants (PBSCT). There have been two early deaths due to sepsis. The predominant morbidities observed following high dose chemotherapy and transplantation have been nausea, mucositis and diarrhoea. The median number of days to discharge following infusion of PBSC was 15 (range 11-21). At a median follow up time of 1.1 years (range 0 months-3.6 years), 8/22 (36%) evaluable patients remain alive and disease free while 14/22 (64%) have relapsed or progressed or died. High-dose chemotherapy and autologous PBSCT is a potentially highly effective treatment of women with metastatic and poor prognosis primary breast cancer. Randomised studies are required to compare this form of therapy to more standard forms of treatment in breast cancer.

Peripheral Blood Stem Cell (PBSC) Mobilization and Transplantation (PSCT) in Patients with Malignant Lymphomas and Solid Tumors

Peripheral blood stem cells can reconstitute bone marrow function after high-dose chemo-/radiotherapy. We describe 44 patients related with a three-day course of chemotherapy, for hematopoietic stem cell mobilization, consisting of cyclophosphamide or ifosfamide and etoposide (malignant lymphoma and germ cell tumor) or a one-day course of 5-fluorouracil, epirubicin and cyclophosphamide (breast cancer), followed by the administration of recombinant human granulocyte colony-stimulating factor (G-CSF). Maximum numbers peripheral blood stem cells (PBSC) were recruited on day 9-10 of the G-CSF administration. The total number of PBSC cells harvested with median 3.6 leukaphereses was 46 x 10(4)/kg (7.5-136) CFU-GM or 8 x 10(6)/kg (0.7-25.0)CD34+ cells for patients with solid tumors and 26 (4.5-258) CFU-GM's or 6.1 (1-0-39.2) CD34+ cells for patients with malignant lymphomas. Thirty-five patients with malignant lymphomas or solid tumors received high-dose chemotherapy followed by bone marrow and PBSC infusion (n = 8) or PBSC cell infusion alone (n = 27). The recovery of granulocytes, platelets and reticulocytes after peripheral stem cell transplantation (-PSCT) in addition to or instead of bone marrow, was markedly accelerated compared with the infusion of BM alone. The accelerated haemopoietic recovery was associated with a reduction in platelet and red blood cell transfusion, reduction in fever periods and earlier discharge from hospital. PSCT is an important alternative to autologous bone marrow transplantation (ABMT). This transplantation technique may also allows application of multiple-cycle intensive chemotherapy.