Biomedical subjects

R Pettengell

Publications and source records attributed to R Pettengell.

At least 37 records · Page 2Linked to original sources

PubMed1997

Interferons in oncology.

The interferons are natural glycoproteins secreted in response to various stimuli, including viral infection. They have antiviral, antiproliferative and immunomodulatory effects on different target cell populations. Since recombinant human interferons have become available, they have been tested in a wide range of malignancies. They are well established in the treatment of hairy cell leukaemia, chronic myelogenous leukaemia and multiple myeloma. Although they have documented activity against lymphoma, melanoma, renal cell cancer and carcinoid tumours, their role in the treatment of these tumours is less clear. In the common solid tumours, such as lung cancer and colorectal cancer, the use of interferons remains experimental. Here we will summarise their practice applications in oncology, using randomised studies where available to establish their place in multi-modality treatment. We will not discuss their use as antiviral or immunomodulating agents in viral and autoimmune diseases, multiple sclerosis or after organ transplantation.

Antineoplastic Agents↗

PubMed1996

A study of ovarian cancer patients treated with dose-intensive chemotherapy supported with peripheral blood progenitor cells mobilised by filgrastim and cyclophosphamide.

We have shown that large numbers of haemopoietic progenitor cells are mobilised into the blood after filgrastim [granulocyte colony-stimulating factor (G-CSF)] alone and filgrastim following cyclophosphamide chemotherapy in previously untreated patients with ovarian cancer. These cells may be used to provide safe and effective haemopoietic rescue following dose-intensive chemotherapy. Using filgrastim alone (10 micrograms kg-1), the apheresis harvest contained a median CFU-GM count of 45 x 10(4) kg-1 and 2 x 10(6) kg-1 CD34+ cells. Treatment with filgrastim (5 micrograms kg-1) following cyclophosphamide (3 g m-2) resulted in a harvest containing 66 x 10(4) kg-1 CFU-GM and 2.4 x 10(6) kg-1 CD34+ cells. There was no statistically significant difference between these two mobilising regimens. We have also demonstrated that dose-intensive carboplatin and cyclophosphamide chemotherapy can be delivered safely to patients with ovarian cancer when supported by peripheral blood progenitor cells and filgrastim. Carboplatin (AUC 7.5) and cyclophosphamide (900 mg m-2) given at 3 weekly intervals with progenitor cell and growth factor support was well tolerated in terms of haematological and systemic side-effects. Double the dose intensity of chemotherapy was delivered compared with our standard dose regimen when the treatment was given at 3 weekly intervals. Median dose intensity could be further escalated to 2.33 compared with our standard regimen by decreasing the interval between treatment cycles to 2 weeks. However, at this dose intensity less than a third of patients received their planned treatment on time. All the delays were due to thrombocytopenia.

Adult↗

PubMed1996

The effect of the GM-CSF/IL-3 fusion protein PIXY321 on bone marrow and circulating haemopoietic cells of previously untreated patients with cancer.

This is a phase I/II study of the GM-CSF/IL-3 fusion protein (PIXY321. Patients were treated with PIXY321 at a daily subcutaneous dose of 500, 750 and 1000 micrograms/m2 for 14 d. Side-effects were mild and consisted mainly of injection-site reactions and constitutional symptoms. A biphasic modest increase of white blood count (2-5-fold) and platelets (1-1.5 fold) was seen, accompanied by an increased bone marrow cellularity and an increase in circulating progenitors. Colony-forming cells in the blood rose to a median of 184 granulocyte/macrophage-colony forming cells (GM-CFC)/ml, eight Mix-CFC/ml, 250 burst forming units-erythroid (BFU-E)/ml and 140 CFU-mega-karyocytes/ml, corresponding to a 10-, 2.5, 8- and 30-fold increase respectively. When seeded for long-term culture on irradiated bone marrow stroma, the mobilized cells were not able to sustain haemopoiesis in vitro to the same degree as bone marrow. Taken together these results indicate that PIXY321 has a biological effect in humans more similar to that of IL-3 than to that of GM-CSF.

Adult↗

PubMed1996

Survival benefit from high-dose therapy with autologous blood progenitor-cell transplantation in poor-prognosis non-Hodgkin's lymphoma.

PURPOSE: To compare standard and intensive treatment strategies for patients with high-grade non-Hodgkin's lymphoma (NHL) of poor prognosis, defined by the international prognostic index. PATIENTS AND METHODS: Thirty-four patients received standard chemotherapy with 11 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone, and methotrexate (VAPEC-B), and 33 received intensive treatment with 7 weeks of VAPEC-B, three cycles of ifosfamide/cytarabine, then high-dose busulfan/cyclophosphamide followed by autologous blood progenitor-cell (BPC) transplantation. RESULTS: Twelve of 33 patients in the intensive group and 26 of 34 patients in the standard group have died. The median follow-up time for the surviving patients is 31 months and 68 months, respectively. At 2 years, the actuarial estimates of event-free survival (EFS) were 61% versus 35% (P = .01) and of overall survival, 64% versus 35% (P = .01). A significant reduction in the event rate (progression or death) was maintained after adjustment for age and the number of risk factors. The estimated risk of experiencing an event was 0.37 (95% confidence interval [CI], 0.16 to 0.84) in the intensive group compared with the standard group. CONCLUSION: Patients with poor prognostic features who received high-dose therapy and BPC rescue had a superior EFS. The survival differences observed in this study justify a formal comparison in a randomized study.

Adolescent↗

PubMed1995

Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors.

Endothelial cells are a major component of the bone marrow (BM) microenvironment that regulate the trafficking and homing of hematopoietic progenitor and stem cells. In this paper, we provide evidence that BM endothelial cells (BMECs) also support multilineage hematopoiesis by elaboration of soluble cytokines. Hematopoietic progenitor cells incubated in direct contact with BMEC monolayers, or physically separated by microporous membrane, expanded five-fold to sevenfold at 7 days, in the absence of exogenous cytokines. Flow cytometric analysis of proliferating progenitor cells grown in the presence of BMEC monolayers showed that by day 14 of coculture, 70% to 80% of hematopoietic cells were myeloid, expressing CD15 or CD14, and 14% to 19% were megakaryocytic, expressing GPIIb/IIIa or GPIb. CD34+ cells derived from umbilical cord blood, cultured in the upper chamber of transwell culture plates, as well as the cells grown in direct contact with BMEC monolayers, generated progenitors for up to 70 days. Unstimulated BMEC monolayers constitutively produce interleukin-6, Kit-ligand, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor. These data suggest that BMEC regulate proliferation of hematopoietic progenitor cells and long-term culture initiating cells by elaboration of lineage-specific cytokines.

Antigens, CD↗

PubMed1995

Biology of blood progenitor cells used in transplantation.

Blood progenitor cells (BPC) are increasingly used in a variety of clinical settings. These include autologous and allogeneic transplantation after myeloablative therapy, and gene therapy. The optimal blood products for each of these applications have not been defined. The use of different cytotoxic drugs and cytokines, alone and in combination, results in the mobilisation of different total numbers and relative proportions of primitive and committed BPC. Some cytotoxics and cytokines not only are poor at mobilising BPC, but also are myelotoxic. Here we review the biology of BPC mobilisation and its implications for their clinical use.

Antineoplastic Agents↗

PubMed1995

Practical applications for peripheral blood progenitor cells in the treatment of lymphomas and solid tumours.

Autologous blood progenitor cell (BPC) support is used in conjunction with high-dose chemotherapy regimens and also permits the use of increasing dose-intensity schedules of conventional cytotoxic chemotherapy. However, our understanding of the optimal BPC support to be used in these different conditions is incomplete. These difficulties result from the use of different BPC collection procedures in different centres, to different patient populations and considerable variability between patients. For such treatment to be cost effective, greater knowledge is required about the best way of achieving mobilisation, collection, storage and engraftment of BPC. The use of G-CSF in combination with chemotherapy can yield sufficient BPC at a single apheresis to achieve haematopoietic reconstitution after high-dose therapy. This was partly achieved by accurate prediction of the optimum timing of cell collection, which coincided with the early exponential increase in white blood cells (WBC) after the chemotherapy induced nadir. BPC in apheresis product or whole blood from patients primed with chemotherapy and filgrastim (G-CSF) were found to be viable for 48 hours when stored at 4 degrees C. Patients receiving multicyclic ifosfamide, carboplatin and etoposide (ICE) chemotherapy received BPC in apheresis product or whole blood, which had been stored at 4 degrees C, on day 3 of each treatment cycle. Such an approach allowed a 200% increase in dose intensity without any increase in toxicity or the need for supportive care. Optimal use of BPC support may increase the effectiveness of chemotherapy for the common solid tumours.

Cell Separation↗

PubMed1995

Expanding the role of blood progenitor cells.

Five years ago the haemopoietic growth factors were introduced to clinical practice with the aim of reducing the depth and duration of chemotherapy induced neutropenia. Now, they have a wider remit, with important roles in supporting dose intensive treatments and mobilising BPC. Similarly, BPC themselves have until now been predominantly used in autologous transplantation following myeloablative treatments. In the next five years we can expect to see BPC from novel sources manipulated to feature in many new roles, including allogeneic transplantation, multicyclic dose-intensive chemotherapy and gene therapy.

Animals↗

PubMed1995

Effects of interleukin-6 on mobilization of primitive haemopoietic cells into the circulation.

Twenty-seven patients with advanced adenocarcinoma were studied. Groups of three patients received interleukin-6 (IL-6) in doses ranging from 0.5 to 20 micrograms/kg by daily subcutaneous injection on days 1-7 and 22-49. Four patients received IL-6 2.5 micrograms/kg/d with GM-CSF 5 micrograms/kg/d and three patients received IL-6 2.5 micrograms/kg/d with IL-3 5 micrograms/kg/d. Circulating platelet numbers increased 1.65-fold during IL-6 treatment, in a dose-dependent fashion (P = 0.01). This increase is inferior to that expected from laboratory studies. No significant change in total WBC was seen after IL-6 alone. After treatment with IL-6, significant increases in numbers of circulating mononuclear cells (2.2-fold, P = 0.006) and GM-CFC numbers (3.2-fold, P = 0.01) were seen, but there were no changes in circulating megakaryocyte-CFC numbers. In contrast, after treatment with IL-6 and GM-CSF, larger increases in both circulating GM-CFC (20-fold, P = 0.04) and megakaryocyte-CFC numbers (18-fold, P = 0.03) were seen. Increases in blood progenitors after treatment with IL-6 and IL-3 did not achieve statistical significance. The ability of peripheral blood mononuclear cells to generate and sustain long-term haemopoiesis in vitro was similar in IL-6-treated patients to that in untreated control subjects. No significant changes in the incidence of bone marrow progenitors or their cycling status (assessed by thymidine suicide) were seen. These data suggest that IL-6 alone will not be clinically useful to mobilize blood progenitor cells in cancer patients.

Adenocarcinoma↗

PubMed1995

Multicyclic, dose-intensive chemotherapy supported by sequential reinfusion of hematopoietic progenitors in whole blood.

PURPOSE: To support multicyclic, dose-intensive chemotherapy, we assessed the effects of reinfusing hematopoietic progenitors collected at each cycle in leukapheresis product or whole blood. PATIENTS AND METHODS: Twenty-five patients with small-cell lung cancer (SCLC) were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE) with granulocyte colony-stimulating factor (G-CSF) 300 micrograms/d subcutaneously (SC) on days 4 to 15. Hematopoietic progenitors collected during each cycle were reinfused on day 3 of the next cycle. Cohort 1 (n = 6) was treated every 3 weeks, with leukapheresis after 2 weeks and cryopreservation of the leukapheresis product. Chemotherapy was given if the WBC count was > or = 3 x 10(9)/L and platelet count > or = 100 x 10(9)/L. Cohort 2 (n = 7) was treated every 2 weeks, with leukapheresis on day 1 of the next cycle and storage of the leukapheresis product at 4 degrees C. Cohort 3 (n = 12) was treated every 2 weeks, with 500 to 750 mL of blood drawn by venesection on day 1 of the next cycle and stored at 4 degrees C. In cohorts 2 and 3, chemotherapy was given if the WBC count was > or = 3 x 10(9)/L and platelet count > or = 30 x 10(9)/L. Blood and leukapheresis products were assayed for hematopoietic progenitors. RESULTS: ICE chemotherapy with G-CSF was effective in mobilizing blood progenitors (median, 120-fold). Long-term cultures showed no evidence of stem-cell depletion. The cytotoxic dose-intensity of standard every-4-weeks ICE is 100%. In the first three cycles, it was 134% (median) in cohort 1 and 200% in cohorts 2 and 3 (P < .0001). Toxicity and supportive care requirements were not increased. CONCLUSION: The dose-intensity of ICE chemotherapy can be doubled by reinfusing hematopoietic progenitors collected by leukapheresis or venesection and stored at 4 degrees C.

Adult↗

PubMed1995

Time-course of the recovery of cellular immune function after high-dose chemotherapy and peripheral blood progenitor cell transplantation for high-grade non-Hodgkin's lymphoma.

Chemotherapy induces high remission rates in high-grade lymphoma. However relapse remains a major problem. One approach to this is myeloablative chemotherapy with transplantation of autologous bone marrow or peripheral blood progenitor cells (PBPC). Immunological mechanisms have been suggested to play a role in the prevention of relapse after transplantation. We investigated the recovery of cellular immune functions after high-dose chemotherapy and PBPC transplantation in 5 patients with high grade non-Hodgkin's lymphoma. All patients showed rapid reconstitution of natural killer (NK) and inducible lymphokine-activated killer (LAK)-activity 10-14 days after transplantation. Four of 5 patients showed higher levels of LAK-generation in the post-transplant period compared with levels prior to myeloablative treatment. Absolute lymphocyte counts in peripheral blood reached 1.0 x 10(9)/l between days 10 and 13 with a predominance of CD8+ cells and an inversion of the CD4/CD8 ratio. Four of 5 patients had a transient increase in CD56+ and CD16+ cell counts post-transplant. No change in the proportion of CD25+ cells was noted. These results show that PBPC transplantation leads to a rapid recovery of cellular immune functions after myeloablative chemotherapy and provides evidence for an increased presence of LAK precursor cells early in the post-transplant period which can be activated by IL-2 to exert high levels of cytotoxicity.

Adolescent↗

PubMed1994

Direct comparison by limiting dilution analysis of long-term culture-initiating cells in human bone marrow, umbilical cord blood, and blood stem cells.

Limiting-dilution analysis of long-term culture-initiating cells (LTCIC) is a quantitative method of estimating hematopoietic stem cell activity in clinical samples. We compared the numbers of LTCIC in bone marrow (BM), umbilical cord blood, and blood progenitor cells (obtained from patients with solid tumors at leukapheresis after mobilization with induction chemotherapy and filgrastim administration), using a two-stage long-term culture system and a limiting-dilution technique, scoring cobblestone areas of greater than 15 hematopoietic cells weekly for up to 8 weeks. Samples were obtained from 30 normal BMs, 20 human umbilical cords, and 32 leukapheresis products. Direct comparison of LTCIC in the three sources showed that the median proportions of cells generating hematopoietic foci from unfractionated mononuclear cells at 5 and 8 weeks, respectively, were 1:13,314 and 1:33,949 for BM, 1:12,506 and 1:34,546 for umbilical cord blood, and 1:10,302 and 1:12,891 for leukapheresis product. The estimated proportions of LTCIC from unfractionated mononuclear cells and CD34+ cells were similar in experiments with leukapheresis product. Leukapheresis product was superior to umbilical cord blood and cord blood to BM at 5 and 8 weeks of culture (P = .01). In two-stage long-term cultures, more colonies per flask and CD34+ cells were found in assays of leukapheresis product than in BM or umbilical cord blood cultures (P = .0005). Results obtained by this simplified limiting-dilution analysis correlated well with standard long-term cultures and can be used as a measure of the stem cell population. These data suggest that the incidence of putative stem cells in leukapheresis product and umbilical cord blood are at least comparable with that of BM.

Antigens, CD↗

PubMed1994

A reliable approach for sequencing clone-specific CDRIII regions in B-cell lymphoma.

We report a reliable approach for sequencing lymphoma-specific CDRIII regions. CDRIII regions present in DNA prepared from routinely fixed and paraffin-embedded diagnostic lymph node material were amplified by the use of consensus VH and JH primers via PCR. PCR products were subcloned directly, without purification or modification of PCR fragments. Only small amounts of miniprep plasmid DNA of recombinant clones were required for cycle sequencing, resulting in autoradiograms of high quality. The easy and reproducible method which we describe has enabled us to determine the lymphoma-specific CDRIII region in 7/11 high-grade non-Hodgkin's lymphomas as well as in 3/3 cases of ALL and 1/1 case of a centroblastic/centrocytic lymphoma. The obtained sequence data can serve to generate lymphoma-specific oligonucleotides, which then can be used as PCR primers or hybridization probes for the detection of minimal residual disease in individual patients.

Base Sequence↗

PubMed1994

Haemopoietic growth factor and dose intensity in high-grade and intermediate-grade lymphoma.

Here we review the evidence that cytotoxic dose intensity is an important determinant of outcome in high- and intermediate-grade non-Hodgkin's lymphoma. The results of retrospective analyses and prospective studies support this proposition but confirmatory studies are required. We discuss the role of haemopoietic growth factors and mobilized peripheral blood progenitor cells to increase dose intensity. Studies using these modalities will enable the importance of dose intensity to be tested.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Viability of haemopoietic progenitors from whole blood, bone marrow and leukapheresis product: effects of storage media, temperature and time.

High-dose cytotoxic chemotherapy can be supported with autologous haemopoietic cells. Cryopreserved bone marrow has conventionally been used for this but blood stem cells are now in common use. We have examined different storage conditions for haemopoietic cells from bone marrow, leukapheresis product and whole blood primed with chemotherapy and filgrastim. The mean number of GM-CFC surviving cryopreservation was 80% in leukapheresis product (95% CI 66-96). At 4 degrees C, GM-CFC viability in all three sources of haemopoietic progenitors declined at the same rate, with mean recovery at 24 h of 90% (95% CI 82-98), at 48 h of 68% (95% CI 61-75) and at 72 h of 47% (95% CI 40-53). Progenitors remained viable for longer in autologous serum and citrate phosphate dextrose or Iscove's medium than in phosphate buffered saline. There was no significant difference in GM-CFC recovery from whole blood or whole blood buffy layer at 4 degrees C. The capacity to generate and sustain haemopoiesis in long-term culture is a feature of the more primitive progenitor cells. This capacity was similar in cryopreserved bone marrow and leukapheresis product, cryopreserved or stored for up to 5 days at 4 degrees C, suggesting that long-term culture-initiating cells are more resilient than colony-forming cells when cryopreserved or stored at 4 degrees C. These data indicate that primed whole blood, in addition to leukapheresis product and bone marrow, could be stored at 4 degrees C and used to support multicyclic high-dose chemotherapy.

Blood Cells↗

PubMed1994

Effects of erythropoietin on mobilisation of haemopoietic progenitor cells.

Peripheral blood progenitor cell (PBPC) mobilising regimens that do not include cytotoxic drugs are needed if PBPC are to be used for allogeneic transplantation. We have studied the effects of erythropoietin on bone marrow and circulating haemopoietic progenitors. Eleven patients with untreated lymphoma received epoetin-alpha 300 or 450 iu/kg subcutaneously (sc) thrice weekly for 2 weeks. Their bone marrows and peripheral bloods were normal at entry. There were no differences between dose levels. Peripheral blood colony-forming cell (CFC) numbers increased fivefold over baseline (p = 0.003) including a sevenfold increase in GM-CFC (p = 0.003). CD34-positive cell numbers increased 4.6-fold (P < 0.01). Maximal CFC release was seen at days 5-8. No consistent change in megakaryocyte numbers was seen. The increase in numbers of cells capable of long-term haemopoiesis was not significant. The ratio of myeloid:erythroid cells in bone marrow reduced from 2.7 to 0.86 after erythropoietin treatment (p = 0.047). In bone marrow the only significant rise in CFCs was in erythroid progenitors. Erythropoietin alone resulted in a modest increase in PBPC that is unlikely to be useful for transplantation. The effects of erythropoietin in combination with other cytokines or with cytotoxic drugs remain to be explored.

Adult↗

PubMed1993

Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis.

Myeloablative treatment and peripheral blood progenitor cell (PBPC) transplantation are increasingly used for lymphomas and leukemias. We have sought to optimize conditions for priming, collection, and engraftment of the leukapheresis product. Fifty-four consecutive adult patients were eligible, 31 with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic leukemia. Filgrastim was administered after routine chemotherapy with VAPEC-B or HiCCOM to mobilize PBPC. A rapidly increasing white blood cell count was used to predict the time of peak PBPC release and plan leukapheresis. Forty-five patients underwent leukapheresis. A median of 14 L of blood was processed at a single apheresis. A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+ cells were obtained. Slightly fewer MNCs were obtained from the heavily pretreated Hodgkin's disease group. There were no other significant differences in the size or composition of the leukapheresis harvest in the three patient groups. Forty patients underwent high-dose therapy and PBPC transplantation. Filgrastim was administered by daily subcutaneous injection until the absolute neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days. Rapid and sustained hematopoietic engraftment occurred in all patients. The median time to achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days); to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88 days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range, 10 to 100 days). Neutrophil recovery was faster than that of a historical control group treated with autologous bone marrow transplantation and filgrastim, but platelet recovery times were halved in the PBPC group. There was no secondary engraftment failure. Requirements for blood and platelet transfusions, antibiotic use, and parenteral nutrition were similar in the three patient groups. The median number of days in the hospital was 13 (range, 10 to 55) in the PBPC patients, compared with 19 (range, 14 to 51) in the historical controls. Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for predicting the times to engraftment. We have shown that sufficient PBPC for transplantation can be obtained at a single leukapheresis after mobilization with routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1993

Transplantation potential of hematopoietic cells released into the circulation during routine chemotherapy for non-Hodgkin's lymphoma.

Primitive hematopoietic cells released into the peripheral blood (PB) were studied in 50 patients with high-grade non-Hodgkin's lymphoma enrolled in a phase III trial of intensive weekly chemotherapy (VAPEC-B) alone or with granulocyte colony-stimulating factor (G-CSF). Mononuclear cells numbers were monitored and their in vitro growth potential assessed in clonogenic progenitor cell assays and in long-term culture. Total colony-forming cells (granulocyte-macrophage [GM], burst-forming unit, erythroid [BFU-E], Mix-CFC) were increased 40-fold (median) over baseline with chemotherapy alone and 106-fold with chemotherapy and G-CSF after the final dose. CD34+ cells were increased to a median of 4%, equivalent to that in normal bone marrow (BM) controls. Circulating colony-forming cell levels were maximal when the recovering total white blood cell (WBC) count reached 5 to 10 x 10(9)/L. The timing of the maximum was reproducible in individual patients. Therefore the WBC count can be used as a guide to the timing of leukapheresis. PB cells from normal controls' and patients' prechemotherapy were unable to sustain hemopoiesis in two-stage long-term cultures. In contrast, PB cells collected from patients primed with chemotherapy alone or chemotherapy with G-CSF at the time of predicted maximal colony-forming cell release were able to generate and sustain hematopoiesis in long-term cultures at a level comparable or superior to normal BM. These findings indicate that the use of G-CSF after routine outpatient chemotherapy stimulates maximal release of primitive hemopoietic cells into the circulation, including colony-forming cells and long-term culture-initiating cells. Their numbers are comparable with those in normal BM and are such that a single leukapheresis will usually yield enough cells for hemopoietic reconstitution after myeloablative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗