In this prospective trial, a total of 74 children who were scheduled to undergo high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) were prospectively randomized at diagnosis to evaluate the effectiveness of exogenous granulocyte colony-stimulating factor (G-CSF) treatment in accelerating hematopoietic recovery after PBSCT. The diagnosis included acute lymphoblastic leukemia (ALL) (n = 27), neuroblastoma (n = 29), and miscellaneous solid tumors (n = 18). Eligibility criteria included (1) primary PBSCT, (2) chemotherapy-responsive disease, and (3) collected cell number >1 x 10(5) colony-forming unit-granulocyte-macrophage (CFU-GM)/kg and >1 x 10(6) CD34(+) cells/kg patient's body weight. After applying the above criteria, 11 patients were excluded due to disease progression before PBSCT (n = 6) or a low number of harvested cells (n = 5), leaving 63 patients for analysis; 32 patients in the treatment group (300 microg/m2 of G-CSF intravenously over 1 hour from day 1 of PBSCT) and 31 in the control group without treatment. Two distinct disease-oriented high-dose regimens without total body irradiation consisted of the MCVAC regimen using ranimustine (MCNU, 450 mg/m2), cytosine arabinoside (16 g/m2), etoposide (1.6 g/m2), and cyclophosphamide (100 mg/kg) for patients with ALL, and the Hi-MEC regimen using melphalan (180 mg/m2), etoposide (1.6 g/m2), and carboplatinum (1.6 g/m2) for those with solid tumors. Five patients (two in the treatment group and three in the control group) were subsequently removed due to protocol violations. All patients survived PBSCT. The median numbers of transfused mononuclear cells (MNC), CD34(+) cells, and CFU-GM were, respectively, 4.5 (range, 1 to 19) x 10(8)/kg, 8.0 (1.1 to 25) x 10(6)/kg, and 3.7 (1.2 to 23) x 10(5)/kg in the treatment group (n = 30) and 2.9 (0.8 to 21) x 10(8)/kg, 6.3 (1.1 to 34) x 10(6)/kg, and 5.5 (1.3 to 37) x 10(5)/kg, respectively, in the control group (n = 28), with no significant difference. After PBSCT, the time to achieve an absolute neutrophil count (ANC) of >0.5 x 10(9)/L in the treatment group was less than that in the control group (median, 11 v 12 days; the log-rank test, P =.046), although the last day of red blood cell (RBC) transfusion (day 11 v day 10) and the duration of febrile days (>38 degrees C) after PBSCT (4 v 4 days) were identical in both groups. However, platelet recovery to >20 x 10(9)/L was significantly longer in treatment group than control group (26 v 16 days; P =.009) and >50 x 10(9)/L tended to take longer in the treatment group (29 v 26 days; P =.126), with significantly more platelet transfusion-dependent days (27 v 13 days; t-test, P =.037). When patients were divided into two different disease cohorts, ALL patients showed no difference in engraftment kinetics between the G-CSF treatment and control groups, while differences were seen in those with solid tumors. We concluded that the marginal clinical benefit of 1 day earlier recovery of granulocytes could be offset by the delayed recovery of platelets. We recommend that the routine application of costly G-CSF therapy in children undergoing PBSCT should be seriously reconsidered.

The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m2 day 3, BCNU 60 mg/m2 day 3, etoposide 75 mg/m2 days 4-7, Ara-C 100 mg/m2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34+ cells: 32.5 x 10(4)/kg vs 31.3 x 10(4)/kg CFU-GM, and 7.6 x 10(6)/kg vs 5.6 x 10(6)/kg CD34+ cells, for G-CSF and GM-CSF, respectively (U test, P= 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4, BCNU 150 mg/m2 days 1-4, etoposide 400 mg/m2 days 1-4. All patients transplanted with more than 5 x 10(6) CD34+ cells/kg had a rapid platelet recovery (20 x 10(9)/l) between 6 and 11 days and neutrophil recovery (0.5 x 10(9)/1) between 9 and 16 days, while patients transplanted with less than 5 x 10(6)/kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.

To assess the feasibility of repeated fluorescence in situ hybridization (FISH) procedures in the same nucleus of a human blastomere.

Mast cells are known to accumulate in tissue during allergic inflammation. However, the chemotaxins responsible are undefined. Using a modified Boyden chamber and the human mast-cell line HMC-1, we first identified mast-cell chemotactic activity in nasal lavage fluid collected before the pollen season after allergen provocation of allergic patients (n=29) (mean migratory response compared to medium control was 121%, range 85-198%). Mast-cell chemotactic activity was also detected in lavage fluid collected after allergen provocation at the end of a Swedish birch-pollen season from three different treatment groups: topical steroid treatment with budesonide; the topical antihistamine, levocabastine; and placebo. There was no significant difference in mast-cell chemotactic activity between nasal lavage fluid collected from the placebo group (mean=102%), the budesonide-treated group (mean=114%), or the levocabastine group (mean=125%). Stem cell factor (SCF), a known mast-cell chemotaxin, was present in the nasal lavage fluids from all three groups, and correlated with the mast-cell chemotactic activity (r=0.67, P<0.01). The mast-cell chemotactic activity was inhibited (range 5-100%) in some, but not all, nasal lavage fluids by a polyclonal antibody directed against SCF. This report describes the presence of mast-cell chemotactic activity in nasal lavage fluid during an allergic reaction. These findings show that SCF may play a pivotal role in the recruitment of mast cells in allergic rhinitis.

Seventy-one patients with poor-prognosis breast cancer were enrolled after informed consent in a multicentre randomized study to evaluate the use of selected peripheral blood CD34+ cells to support haematopoietic recovery following high-dose chemotherapy. Patients who responded to conventional chemotherapy were mobilized with chemotherapy (mainly high-dose cyclophosphamide) and/or recombinant human granulocyte colony-stimulating factor (rhG-CSF). Patients who reached the threshold of 20 CD34+ cells per microl of peripheral blood underwent apheresis and were randomized at that time to receive either unmanipulated mobilized blood cells or selected CD34+ cells. For patients in the study arm, CD34+ cells were selected from aphereses using the Isolex300 device. Fifteen patients failed to mobilize peripheral blood progenitors and nine other patients were excluded for various reasons. Forty-seven eligible patients were randomized into two comparable groups. CD34+ cells were selected from aphereses in the study group. Haematopoietic recovery occurred at similar times in both groups. No side-effect related to the infusion of selected cells was observed. The frequency of epithelial tumour cells in aphereses was low (8 out of 42 evaluated patients), as determined by immunocytochemistry. We conclude that selected CD34+ cells safely support haematopoietic recovery following high-dose chemotherapy in patients with poor-prognosis breast cancer.

High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a novel investigational approach to treating chronic myelogenous leukemia (CML) patients not responsive to conventional therapy with interferon-alpha (IFN-alpha) and not eligible for allogeneic transplantation. PBSC mobilization using either '5+2/7+3'-type chemotherapy or 'mini-ICE/ ICE' chemotherapy was investigated in 43 patients with advanced phases of Philadelphia (Ph)-positive CML. Thirty patients were in late chronic phase (>12 months post diagnosis) and 13 patients in accelerated phase (AP) or blast crisis (BC). Contamination with Ph-positive cells was evaluated in harvests from 37/43 patients. The outcome of PBSC mobilization was dependent on the type of chemotherapy administered: a complete or major cytogenetic response (<35% Ph-positive metaphases) in leukapheresis collections was obtained in ten of 15 patients treated with 'mini-ICE/ICE' but in only three of 28 patients treated with '5 + 2/7 + 3' chemotherapy. One patient (1/43) in blast crisis died during mobilization therapy (2%). Twenty-five patients underwent PBSC transplantation and all of them engrafted successfully. Transplantation-related mortality was 0%. The data show that in advanced phases of CML the chance of harvesting Ph-negative peripheral blood stem cells depends on the type of chemotherapy used for mobilization.

We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.

BB-10010 is a variant of the human form of macrophage inflammatory protein-1alpha (MIP-1alpha), which has been shown in mice to block the entry of hematopoietic stem cells into S-phase and to increase their self-renewal capacity during recovery from cytotoxic damage. Its use may constitute a novel approach for protecting the quality of the stem cell population and its capacity to regenerate after periods of cytotoxic treatment. Thirty patients with locally advanced or metastatic breast cancer were entered into the first randomized, parallel group controlled phase II study. This was designed to evaluate the potential myeloprotective effects of a 7-day regimen of BB-10010 administered to patients receiving six cycles of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) chemotherapy. Patients were randomized, 10 receiving 100 microgram/kg BB-10010, 11 receiving 30 microgram/kg BB-10010, and nine control patients receiving no BB-10010. BB-10010 was well-tolerated in all patients with no severe adverse events related to the drug. Episodes of febrile neutropenia complicated only 4% of the treatment cycles and there was no difference in incidence between the treated and nontreated groups. Studies to assess the generation of progenitor cells in long-term bone marrow cultures were performed immediately preceding chemotherapy and at the end of six dosing cycles in 18 patients. Circulating neutrophils, platelets, CD 34(+) cells, and granulocyte/macrophage colony-forming cell (GM-CFC) levels were determined at serial time points in cycles 1, 3, and 6. The results showed similar hemoglobin and platelet kinetics in all three groups. On completion of the six treatment cycles, the average pretreatment neutrophil levels were reduced from 5.3 to 1.7 x 10(9)/L in the control patients and from 4.3 to 1.9 and 4.5 to 2.5 x 10(9)/L in the 30/100 microgram/kg BB-10010 groups, respectively. Relative to their pretreatment values, 50% of the patients receiving BB-10010 completed the treatment with neutrophil values significantly higher than any of the controls (P = .02). Mobilization of GM-CFC was enhanced by BB-10010 with an additional fivefold increase over that generated by chemotherapy alone, giving a maximal 25-fold increase over pretreatment values. Bone marrow progenitor assays before and after this standard regimen of chemotherapy indicated little long-term cumulative impairment to recovery from chemotherapy. Despite the limited cumulative damage to the bone marrow, which may have minimized the protective value of BB-10010 during this regimen of chemotherapy, better recovery of neutrophils in the later treatment cycles with BB-10010 was indicated in a number of patients.

Twenty-seven patients undergoing matched sibling BMT were randomly assigned to be infused with bone marrow alone or bone marrow supplemented with allogeneic peripheral blood cells collected by apheresis after stimulation with filgrastim. Other transplant conditions were standard and identical for the two groups. There was no difference between the groups in survival or acute or chronic GVHD, however, the patients receiving blood cells had significantly more rapid neutrophil engraftment by a median of 2 days. We conclude that filgrastim-mobilised HLA-identical sibling allogeneic blood cells are biologically active and safe.

The purpose of this study was to evaluate the addition of cisplatin to cyclophosphamide, etoposide, and granulocyte colony-stimulating factor (G-CSF) for the mobilization of peripheral blood stem cells (PBSC). Eighty-one patients with malignant lymphoma were randomized to receive either cyclophosphamide 4 g/m2 and etoposide 600 mg/m2 (CE), and G-CSF 6 microg/kg/day (n = 41), or the same drugs with cisplatin 105 mg/m2 (CEP; n = 40) followed by collection of PBSC. Seventy-eight of 81 patients (96%) had apheresis performed and 70 (86%) received high-dose chemotherapy (HDC) with PBSC support. The median number of CD34+ cells collected after CE was 19.77 compared with 9.39 x 10(6)/kg after CEP (p = 0.09). More patients receiving CEP had grade 3-4 gastrointestinal (p = 0.03) and neurologic toxicities (p = 0.05), had significant delays in recovery of neutrophils (p = 0.0001) and platelets (p = 0.009), and received more red blood cell (p = 0.03) and platelet (p = 0.08) transfusions than patients receiving CE. There were no significant differences in treatment-related deaths, relapse, survival, or event-free survival between patients receiving CE or CEP when all 81 patients or the 70 patients receiving HDC were evaluated. It was concluded that the addition of cisplatin to CE did not improve CD34+ cell yields, was associated with more morbidity and resource utilization, and was not associated with improvement in outcomes.

This trial was designed to compare foscarnet with ganciclovir as pre-emptive therapy for CMV infection in patients undergoing allogeneic hemopoietic stem cell transplant (HSCT). Thirty-nine patients were randomized to receive foscarnet 90 mg/kg every 12 h (n = 20) or ganciclovir 5 mg/kg every 12 h (n = 19) for 15 days at the time of development of CMVAg-emia. Primary-end points of the study were (1) outcome of CMVAg-emia; (2) progression to CMV disease; and (3) side-effects of treatment. The secondary end-point was transplant-related mortality (TRM). The two groups were comparable for diagnosis, status of disease, donor type, acute graft-versus-host (aGVHD) prophylaxis, interval between HSCT and CMVAg-emia and number of CMVAg positive cells; the donor and recipient age were borderline older in the foscarnet group. Increments of serum creatinine in the foscarnet group, and cytopenia in the ganciclovir group were controlled by reducing the administered dose: in the first 15 days of therapy 9/20 foscarnet and 10/19 ganciclovir patients had a dose reduction greater than 20% (P = 0.43). Clearance of CMVAg-emia was faster in the foscarnet group although with borderline statistical significance. Failures of treatment occurred in 3/20 patients in foscarnet group vs 8/19 patients in ganciclovir group (P= 0.06): causes of failure were the need for combination therapy to control antigenemia (1/20 vs 5/19), and reactivation during treatment for 2 vs 3 patients, respectively. CMV disease was diagnosed in 1 vs 2 patients (P = 0.5) who subsequently died. The actuarial 1-year TRM was 25 vs 12%, respectively (P = 0.3). This study suggests that foscarnet and ganciclovir are both effective for pre-emptive therapy of CMVAg-emia, although the number of failures would seem to be slightly higher in the ganciclovir patients. Side-effects are seen in both groups and can be managed with appropriate dose reduction.

This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy.

By participating in a randomized safety and efficacy study of pegylated-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) post induction and consolidation chemotherapy for de novo acute myeloid leukaemia, serial determinations of circulating haemopoietic progenitor cells were performed during 18 chemotherapy courses in eight patients (three receiving placebo; one, 2.5; and four, 5.0 microg/kg/d MGDF, respectively). Whereas failure to achieve complete remission (CR) was generally associated with poor progenitor cell increments following chemotherapy, substantial progenitor cell mobilization consistently occurred during haemopoietic recovery in patients entering, or in CR, with significantly higher peak values in patients receiving 5 microg/kg/d of MGDF as compared to controls. The median increases of progenitor cell numbers by chemotherapy alone and chemotherapy plus 5.0 microg/kg/d MGDF over that in normal individuals with steady-state haemopoiesis were 10- and 45-fold for CFU-GM, 3- and 17-fold for BFU-E, and 2- and 18-fold for CFU-mix. CFU-Mk levels were not increased above normal by chemotherapy alone but were 15-fold enhanced by chemotherapy plus MGDF. Recruitment of CD34+ cells post chemotherapy was also potentiated by MGDF. Our results suggest MGDF as a potent agent to augment progenitor cell mobilization after successful induction or consolidation chemotherapy in patients with AML.

This study evaluated whether relapse of acute promyelocytic leukemia (APL) patients from clinical remissions achieved and/or maintained with all-trans retinoic acid (RA) in combination with intensive chemotherapy is associated with leukemic cellular resistance to RA and with alterations in the PML-RARalpha fusion gene. We studied matched pretreatment and relapse specimens from 12 patients who received variable amounts of RA, primarily in nonconcurrent combination with daunorubicin and cytarabine (DA) on Eastern Cooperative Oncology Group (ECOG) protocol E2491, and from 8 patients who received DA only on protocol E2491. Of 10 RA-treated patients evaluable for a change in APL cell sensitivity to RA-induced differentiation in vitro, 8 showed diminished sensitivity at relapse, whereas, of 6 evaluable patients treated with DA alone, only 1 had marginally reduced sensitivity. From analysis of sequences encoding the principal functional domains of the PML and RARalpha portions of PML-RARalpha, we found missense mutations in relapse specimens from 3 of 12 RA-treated patients and 0 of 8 DA-treated patients. All 3 mutations were located in the ligand binding domain (LBD) of the RARalpha region of PML-RARalpha. Relative to normal RARalpha1, the mutations were Leu290Val, Arg394Trp, and Met413Thr. All pretreatment analyses were normal except for a C to T base change in the 3'-untranslated (UT) region of 1 patient that was also present after relapse from DA therapy. No mutations were detected in the corresponding sequences of the normal RARalpha or PML (partial) alleles. Minor additional PML-RARalpha isoforms encoding truncated PML proteins were detected in 2 cases. We conclude that APL cellular resistance occurs with high incidence after relapse from RA + DA therapy administered in a nonconcurrent manner and that mutations in the RARalpha region of the PML-RARalpha gene are present in and likely mechanistically involved in RA resistance in a subset of these cases.

We investigated the feasibility of mobilizing peripheral blood stem cells (PBSC) with G-CSF alone in 24 patients with multiple myeloma. The median age was 53 years (range 33-62). All patients had stage II/III disease and responded to standard first-line (n = 6) or salvage chemotherapy (n = 18). The median number of previous chemotherapy cycles was 7 (4-18) and the median number of prior melphalan-cycles was 6 (0-14). Nine (35%) patients had experienced prior radiation therapy. The patients received either 10 microg/kg G-CSF (n = 18) or 24 microg/kg G-CSF (n = 7, including one patient with previous 10 microg/kg G-CSF stimulation) daily s.c. for 5 or more consecutive days until completion of harvesting, starting apheresis on the fifth day. G-CSF treatment was well tolerated, with only slight bone pain in half of the patients (51%). After a median of three (range 1-7) apheresis procedures, medians of 3.8 (0.3-17) x 10(6) CD34+ cells/kg, 8.5 (4.5-24) x 10(8) MNC/kg, 2.9 (0.6-39.4) x 10(4) CFU-GM/kg, and 5.6 (0.9-49) x 10(4) BFU-E/kg were harvested. Three patients (12%) with extensive melphalan pretreatment failed the target collection of at least 2.0 x 10(6) CD34+ cell/kg. Pretreatment with six or more cycles of melphalan yielded a smaller number of CD34+ cells than pretreatment with fewer than six cycles (2.5 vs 5.3 x 10(6)/kg; p = 0.001). Nineteen patients underwent high-dose chemotherapy consisting of either total marrow irradiation (9 Gy)/busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) (n = 10), or busulfan (14 mg/kg)/cyclophosphamide (120 mg/kg) (n = 5), or tandem melphalan (200 mg/m2). The median time for granulocyte (> 1.0/nl) and platelet (> 50/nl) recovery was 10 and 14 days (ranges 7-12 and 8-40), respectively. G-CSF alone is a safe, alternative approach to mobilizing sufficient PBSC in patients with multiple myeloma and allows an exact prediction of harvest time. G-CSF-mobilized PBSCs ensure rapid engraftment after myeloablative therapy. Melphalan treatment should be avoided in patients who are candidates for high-dose chemotherapy.

This study was designed to identify and quantify concentrations of growth factors/cytokines released by Vero cells during the co-culture interval. The factors screened for in this preliminary investigation, namely platelet-derived growth factor (PDGF), transforming growth factor beta (TGFbeta), interleukin-6 (IL-6), leukaemia inhibitory factor (LIF) and epidermal growth factor (EGF) have each been identified to impact on early embryo development or are secreted by embryos themselves, suggesting an autocrine regulatory role. Vero cell culture supernatants were collected at 2, 3, 4, 5 and 6 days after seeding. Samples were assessed by enzyme-linked immunoassay for growth factor/cytokine secretion at each designated time interval. Conditioned medium from all days contained IL-6, PDGF and LIF. The concentration of IL-6 increased from 294 pg/well on day 2 to almost 1600 pg/well on day 6. PDGF also accumulated rapidly in co-culture wells, rising from 19-40 pg/well early in the culture period to around 500 pg/ well by day 6. In the second half of this study, medium supernatants from patients enrolled in our co-culture programme were analysed. Retrospective evaluation of medium supernatants collected at the time of transfer from co-cultures from 11 randomly selected patients showed considerable patient-to-patient variation in concentrations of secreted growth factors and cytokines. These findings indicate that during the co-culture interval embryos are exposed to a dynamic environment, with increasing concentrations of growth factors and cytokines. The positive effects of co-culture on embryo quality and in-vitro blastulation need to be balanced against the variation that this technique can potentially introduce into the embryo culture system.

Circulating myeloid (CFU-GM) and erythroid (BFU-E) progenitor levels were evaluated weekly throughout 3 courses of treatment with vinorelbine (VNB) ifosfamide (IFO) and filgrastim (G-CSF) with or without addition of cisplatin (DDP) in 20 stage IIIB or IV non small-cell lung cancer patients. In IFO, VNB, DDP-treated patients, BFU-E mobilization in peripheral blood following chemotherapy and G-CSF was completely lacking, in contrast with the patients treated with IFO, VNB plus G-CSF. CFU-GM release, however, was of the same order in the 2 groups of patients. Further investigations are needed to explain why presence of DDP in this chemotherapeutic protocol hinders erythroid progenitor release in peripheral blood.

The addition of stem cell factor (SCF) to G-CSF and chemotherapy results in a dose-dependent, significantly increased mobilisation of peripheral blood progenitor cells compared with the use of chemotherapy and G-CSF alone. The enhanced mobilisation may benefit patients in several ways. Firstly, in clinical settings where currently multiple aphereses are having to be performed to obtain a specified target number of cells, the addition of SCF may lead to a reduction in this number. Alternatively, when only a single apheresis is currently being performed to obtain sufficient cells then the addition of SCF to the mobilisation regimen would allow between 5- and 8-fold reduction in the volume of blood required to be processed during the apheresis procedure to obtain a specified target of GM-CFC, CD34+ cells and LTC-IC for those receiving the highest dose of SCF (20 microg/kg) plus G-CSF following chemotherapy compared with those patients receiving G-CSF alone following chemotherapy. The increased mobilisation resulting from the addition of SCF to the regimen makes feasible the use of whole blood aliquots to support dose-intensive therapy. We have calculated that in patients mobilised using cyclophosphamide 3 g/m2, SCF 20 microg/kg and G-CSF 5 microg/kg a median 512 ml aliquot of whole blood would contain 2 x 10(6)/kg CD34+ cells and over 3.7 x 10(5)/kg GM-CFC. This aliquot would be sufficient to rescue the patient following a myeloablative therapy. Significantly, because less individual variation was seen after the administration of SCF the patient who showed the worst mobilisation in that group would have the usually required content of 2 x 10(6) CD34+ cells/kg and 1 x 10(5) GM-CFC/kg in only 731 ml of blood.

In order to find out the effect of peripheral blood (PB) hematopoietic progenitor cells on immune reconstitution the present study compares, through a randomized trial, some lymphoid subsets after peripheral blood (PBT) or bone marrow (BMT) autologous transplantation.