Search PubMed⌕ Search

Biomedical subjects

S Siena

Publications and source records attributed to S Siena.

At least 55 records · Page 3Linked to original sources
PubMed1996

Long-term hematopoietic culture-initiating cells are more abundant in mobilized peripheral blood grafts than in bone marrow but have a more limited ex vivo expansion potential.

Mobilized peripheral blood hematopoietic progenitor cells obtained from cancer patients treated with high-dose cyclophosphamide (7g/m2) followed by G-CSF, GM-CSF, IL-3, PIXY321, or combinations of these cytokines have been successfully used for autologous stem cell transplantation. We investigated the ability of hematopoietic progenitor cells (HPC) derived from mobilized peripheral blood (PB) to undergo ex vivo expansion in short term cultures by enumerating numbers of de novo generated CD34+ cells, assayable progenitor cells, and the frequency of long-term hematopoietic culture-initiating cells (LTHC-IC). These parameters were examined in CD34+ cells generated in culture through the use of cell tracking with the membrane dye PKH2. Fresh isolated mobilized CD34+ cells contained 0.49 +/- 0.36% LTHC-IC. However, due to the high number of total CD34+ cells in mobilized PB, the absolute number of LTHC-IC was higher than that contained in a bone marrow (BM) harvest. Mobilized CD34+ cells were stained with PKH2 and incubated with SCF, IL-3, and IL-6. After 5 to 6 days, numbers of total CD34+ cells and clonogenic progenitors increased 1.4- and 2.2-fold, respectively. Numbers of total progenitors continued to increase such that 10 to 12 days after the initiation of cultures a 6.4-fold increase was demonstrable. However, between days 5 and 7 of culture, the frequency of LTHC-IC in CD34+PKH2bright cells (cells which did not divide) was less than 50% of that determined for fresh cells, while the frequency among CD34+PKH2dim cells (cells that had divided) was very low or undetectable. However, moderately higher frequencies of LTHC-IC were detected following expansion for 48 hours only. In similar assays, both BM and cord blood cells were capable of generating LTHC-IC in CD34+PKH2dim cells but not to expand the overall number of these progenitors. These observations suggest that although mobilized PB CD34+ cells contain large numbers of LTHC-IC, these cells might not be capable of further ex vivo expansion and generation of additional LTHC-IC in vitro. Furthermore, these data indicate that mobilized PB CD34+ cells may have undergone maximal "in vivo expansion" such that additional ex vivo expansion of primitive progenitor cells may not be possible.

Antigens, CD34↗
PubMed1996

Combined negative and positive selection of mobilized CD34 blood cells.

We tested four negative and two positive selection methods for separation of CD34+ cells from mobilized blood cells, and analysed fold-enrichment, purity and recovery of CD34+ cells after selection procedures. The elimination of mature CD34- cells was achieved by adhesion to nylon-wool fibre (5.9 +/- 1.0 mean fold-enrichment and 65.2 +/- 2.3 mean recovery of CD34+ cells). Standard or modified Ficoll-Hypaque and Percoll density gradients, as well as phagocytosis with magnetic beads, were less effective in eliminating CD34- cells, both purity and fold-enrichment of CD34+ cells being lower than those obtained with separation by nylon-wool. Both positive selection methods tested. Ceprate and MiniMacs System, generated highly purified CD34+ cell populations ranging from 80% to 90%. The recovery of CD34+ cells was optimal with MiniMacs (77.9 +/- 3.6) and low with Ceprate (28.8 +/- 2.8). Based on these results, in two large-scale experiments we combined nylon-wool fibre and MiniMacs System in a two-step separation procedure obtaining a 36.9 +/- 2.6 mean fold-enrichment and a 50.5 +/- 0.3 mean recovery of CD34+ cells. In this way we achieved optimal enrichment and recovery of CD34+ cells, with a substantial saving of cost compared to either selection method alone.

Antigens, CD34↗
PubMed1996

Comparative effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor after high-dose cyclophosphamide cancer therapy.

PURPOSE: We compared hematologic and clinical effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) after treatment with high-dose cyclophosphamide (HD-CTX, 7 g/m2), given as the first phase of a high-dose sequential chemotherapy program that includes a myeloablative therapy with mobilized progenitor cell autografting. PATIENTS AND METHODS: Forty-nine consecutive patients with non-Hodgkin's lymphoma, Hodgkin's disease, or poor-prognosis breast cancer received GM-CSF (n = 27) or G-CSF (n = 22) after HD-CTX in two consecutive, nonrandomized studies. Cytokines were administered in continuous intravenous (i.v.) infusion for 14 to 15 days at a median dose of 5.5 and 10 micrograms/kg/d, respectively, starting 24 hours after HD-CTX. RESULTS: Neutrophil recovery was faster with G-CSF administration (11.5 v 13.2 days; P = .01), whereas platelet counts recovered more rapidly with GM-CSF (13.7 v 16.6 days; P = .01). Prophylactic platelet transfusions were administered more frequently to patients treated with G-CSF than with GM-CSF (66% v 22% of the patients; P = .02). No clinically significant difference was observed between the two groups concerning days of absolute neutropenia or neutropenic fever. Both cytokines reduced the time to eligibility for subsequent chemotherapy administration compared with historical controls not given cytokine (14 to 16 v 20 days). Both cytokines increased circulation of hematopoietic progenitors. Most side effects were World Health Organization (WHO) median grade 1 to 2, were more frequent during GM-CSF than during G-CSF treatment, and were reversible by simple supportive measures and/or by dose reduction or suspension of the cytokine. Permanent suspension of cytokine administration was never required in either group. CONCLUSION: GM-CSF or G-CSF administration after HD-CTX reduces hematologic toxicity of high-dose chemotherapy and induces circulation of large amounts of hematopoietic progenitors suitable for autografting in cancer patients.

Adult↗
PubMed1996

Benefits of blood cell transplant cryopreservation with oxypolygelatine (Gelifundol) plasma substitute.

In two groups of 11 patients with poor prognosis malignancies undergoing high-dose sequential chemotherapy, we have evaluated the cryopreservation of blood cell transplants with oxypolygelatine-containing (55% oxypolygelatine, 6% hydroxyethylstarch, 5% dimethyl sulfoxide) vs standard human serum-containing (55% human serum, 6% hydroxyethylstarch, 5% dimethyl sulfoxide) cryoprotectant mixtures. Evidence is presented demonstrating that substitution of human serum proteins with oxypolygelatine has no detrimental effect either in vitro on the post-thawing recovery of hematopoietic progenitors or in vivo on the capacity of marrow reconstituting function in patients treated with myeloablative cancer therapy and autologous blood cell transplant. Oxypolygelatine is commercially available for clinical use as a plasma expander, is 30-fold less expensive than human serum albumin, is certified free of foreign serum proteins and antibodies as well as free of pyrogen, viral, mycoplasmal and bovine spongiform encephalopathy contaminants. Because of these characteristics, oxypolygelatine permits avoidance of: (1) the use of expensive serum albumin; (2) the fastidious preparation of autologous plasma or serum, and (3) the risk of infection associated with the infusion of allogeneic serum. Because of these practical advantages, we recommend the clinical use of oxypolygelatine as a substitute for human serum proteins for the routine cryopreservation of blood cell transplants.

Adult↗
PubMed1996

Elimination of bcl-2-IgH-positive follicular lymphoma cells from blood transplants with high recovery of hematopoietic progenitors by the miltenyi CD34+ cell sorting system.

Contamination of autologous blood cell transplants with cells of follicular non-Hodgkin's lymphoma (F-NHL) may contribute to relapse of the malignancy after potentially curative high doses of chemotherapy and radiotherapy. In an attempt to circumvent this limitation, we have evaluated various techniques of selection of CD34+ cells to eliminate malignant cells from blood cell transplants of five patients with F-NHL undergoing high-dose sequential therapy. The contamination of F-NHL cells was evaluated using a nested PCR assay for the detection of bcl-2-IgH rearrangement with a sensitivity of one F-NHL cell in 10(5) normal cells. In two experiments with blood cell transplant fractions of 0.5 x 10(9) nucleated cells, negative selection of CD34+ cells by removal of B cells and other mature cells that naturally adhere to nylon wool fibers decreased the number of CD19+ B cells detectable by flow cytometry but failed to eliminate bcl-2-IgH-positive F-NHL cells detectable by PCR. In contrast, positive selection of CD34+ cells by the Miltenyi MiniMACS high gradient magnetic cell sorting system in five separate experiments resulted in: (1) the elimination of F-NHL cells in four out of five cases as detected both flow cytometry and bclk-2-IgH PCR; (2) a highly purified population of hematopoietic progenitors comprising 90.8% +/- 2.3% CD34+ cells; and (3) the recovery of 77.9% +/- 3.2% CD34+ cells. These favorable results were confirmed on a large-scale with a blood cell transplant comprising 5.8 x 10(9) nucleated cells in which positive selection of CD34+ cells by the Miltenyi SuperMACS system resulted in: (1) the elimination of F-NHL cells as detected both by flow cytometry and bcl-2-IgH PCR; (2) a highly purified population of hematopoietic progenitors comprising 94.6% CD34+ cells; and (3) the recovery of 62.7% CD34+ cells. These results, attained with the newly available Super MACS system, compare favorable with previous techniques because they show the feasibility of eliminating F-NHL cells from blood cell transplants without relevant nonspecific loss of hematopoietic progenitors.

Adsorption↗
PubMed1995

Circulating progenitors following high-dose sequential (HDS) chemotherapy with G-CSF: short intervals between drug courses severely impair progenitor mobilization.

Sequential administration of high-dose chemotherapy courses possibly allows extensive in vivo purging before circulating progenitor collection for autograft. To evaluate whether progenitor cell mobilization was negatively affected by repeated high-dose chemotherapy courses, we studied 23 lymphoma patients undergoing the HDS regimen. The scheme includes the sequential administration of cyclophosphamide (CY) given at 7 g/m2 and etoposide (VP16) given at 2 g/m2, each followed by G-CSF (filgrastim) at 5 micrograms/kg/day. Eleven patients received the standard HDS sequence, with a short interval between first and second myelotoxic courses of less than 45 days (median: 30 days); the remaining 12 patients received a modified HDS where the interval between first and second high-dose course was protracted over 2 months (median: 70 days); in this latter group, 2 to 4 conventional debulking courses were delivered prior to HDS. In patients receiving the standard HDS, progenitor mobilization following the first course was consistently high (median circulating CFU-GM/ml peak value: 29,022); however, significantly lower values were observed at the second course (median CFU-GM/ml peak value 3757, P = 0.002). Circulating BFU-E and CD34+ cell values paralleled those of CFU-GM. No significant difference was observed in progenitor mobilization following either course in patients receiving HDS with extended interval (median circulating CFU-GM/ml peak value: 14,363 vs 9208, at first and second course respectively, P = 0.27). Eleven patients had their progenitor cells harvested following the second delayed course and 2-4 leucaphereses allowed very satisfactory harvests in all of them (CFU-GM/kg ranging from 39-340 x 10(4)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Massive ex vivo generation of functional dendritic cells from mobilized CD34+ blood progenitors for anticancer therapy.

We report that blood cell autografts, collected by single leukapheresis in cancer patients (n = 11) at the time of mobilization of hematopoietic progenitors into peripheral blood following anticancer therapy with high-dose cyclophosphamide (HD-CTX) plus interleukin-3 (IL-3) and granulocyte colony-stimulating factor (G-CSF/filgrastim), comprise 1.98 +/- 0.39 x 10(5)/kg (mean +/- SE) CD34+ progenitors of dendritic cells (DCs). This number corresponds to 140-fold more progenitors than in a control autograft collected in the steady state. DCs derived from mobilized CD34+ cells, morphologically and immunophenotypically undistinguishable from skin Langerhans cells and DCs from bone marrow and cord blood CD34+ cells, are shown to be powerful stimulators of allogeneic T cell proliferation in primary MLR and of autologous HLA-DR-restricted CD4+ T cell proliferation in response to presentation of xenogenic antigens. We show that the GM-CSF-plus-TNF-alpha-dependent ex vivo generation of DCs from mobilized CD34+ cells is 2.5-fold enhanced by flk-2/flt-3 ligand or c-kit ligand (stem cell factor) and five-fold enhanced by a combination of these growth factors. In addition, the optimal serum for the generation of DCs is autologous HD-CTX recovery-phase serum rather than fetal calf serum (FCS) or steady-state human serum, which are clinically inadequate and ineffective, respectively. In practice, the stimulation of CD34+ cells in a blood cell autograft (15.75 +/- 2.46 x 10(6)/kg) provided by the above four growth factors should permit ex vivo generation of approximately 40 x 10(9) DCs in an adult patient. These new findings provide advantageous tools for the large-scale generation of DCs that are potentially usable for clinical protocols of immunotherapy or vaccination in patients undergoing cancer treatment.

Adult↗
PubMed1994

Durability of hematopoiesis following autografting with peripheral blood hematopoietic progenitors.

BACKGROUND: It is still not known whether hematopoiesis reconstituted by autografting with the peripheral blood hematopoietic progenitors (CPCs) after myeloablative high dose radiotherapy and/or chemotherapy is durable and capable of coping with the increased demand imposed by boost radiotherapy, surgery, or infection. PATIENTS AND METHODS: The durability of hematopoiesis was evaluated in 34 consecutive cancer patients treated with myeloablative total body irradiation (n = 17, median follow-up 3 years, range 3-49 months) and/or alkylating-agent chemotherapy (n = 17, median follow-up 8 months, range 6-41 months) and autografted with CPCs because bone marrow autografting was contraindicated. CPCs (> or = 8 x 10(6) CD34 + cells/kg) had been collected during mobilization into the circulation in response to previous anticancer therapy and hematopoietic growth factor(s). RESULTS: Following brief temporary pancytopenia, all patients achieved normal and durable hematopoiesis. The newly reconstituted hematopoietic system was capable of reacting favorably to stressful and debilitating events such as surgery, radiotherapy, or varicella-zoster infection. No secondary irreversible failure of blood cell production occurred. CONCLUSIONS: The documentation of the durability of normal hematopoiesis following myeloablative cancer therapy and autografting with mobilized CPCs implies that the latter procedure, rather than being solely an alternative to bone marrow autografting, represents an advantageous tool of choice permitting substantial amelioration of the therapeutic index of high-dose cancer therapy.

Adult↗
PubMed1994

High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma.

PURPOSE: To assess the toxicity, efficacy, and applicability of high-dose therapy with bone marrow and/or peripheral-blood autotransplantation in high-risk, previously untreated patients with multiple myeloma. PATIENTS AND METHODS: Thirteen consecutive patients with high-labeling index (LI) multiple myeloma received a novel high-dose sequential (HDS) regimen consisting in the high-dose administration of cyclophosphamide (7 g/m2) followed by vincristine (1.4 mg/m2) plus methotrexate (8 g/m2 with leucovorin rescue), etoposide (2 g/m2) and, finally, total-body irradiation (TBI; 10 Gy) plus melphalan (120 mg/m2) with autografting of peripheral-blood hematopoietic progenitor cells. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 5 micrograms/kg/d) was continuously infused after cyclophosphamide and etoposide both to accelerate hematopoietic recovery and to expand/mobilize the hematopoietic progenitor-cell pool. RESULTS: Among 13 patients, 12 completed the program; 10 (or 77%) achieved a complete response and five are alive and disease-free after a median follow-up duration of 36 months (range, 24 to 52). The durations of both freedom from progression (FFP; median, 38 months) and overall survival (OS; median, 41 months) were significantly superior in the 13 HDS-treated patients as compared with 19 well-matched historical controls. CONCLUSION: HDS emerges as a highly effective, well-tolerated, and widely accessible regimen capable of imparting a survival benefit to patients with high-LI multiple myeloma. Larger studies using this or similar programs in standard-risk myeloma are clearly warranted.

Adult↗
PubMed1994

Large-scale enrichment of mobilized CD34+ peripheral blood hematopoietic progenitors by removal of nylon wool-adherent mature cells.

With the aim of facilitating the ex vivo manipulation of peripheral blood hematopoietic progenitors (CPCs = circulating progenitor cells) collected by leukapheresis, we removed polymorphonuclear cells and monocytes that naturally adhere to nylon wool fibers. Leukapheresed cells harvested at the time of hematopoietic recovery after cancer therapy with high-dose cyclophosphamide plus hematopoietic growth factors were incubated with nylon wool fibers for 1 h at 37 degrees C. Evaluation of the cells non-adherent to the nylon wool in all experiments (n = 14) showed that the median recovery of nucleated cells and CPCs detected as CD34+ cells, CFU-GM and BFU-E was 16.4% (range 4.8%-34.0%), 60.0% (range 30.8-80.8%), 60.9% (range 33.4-74.5%) and 65.5% (range 30.8-69.2%), respectively. Therefore exposure to the nylon wool determined a selective removal of mature cells and a complementary enrichment of CPCs. The wide range of results depended on the significantly different cell compositions of the unmanipulated leukaphereses. The latter from patients receiving rhG-CSF (n = 10) comprised a median of 88.5% (range 77.8-93.8%) and 11.5% (range 6.2-22.2%) polymorphonuclear and mononuclear cells, respectively. In contrast, leukaphereses from patients receiving rhGM-CSF or PIXY321 (n = 4) comprised a median of 71.1% (range 55.4-85.0%) and 28.9% (range 15.0-44.6%) polymorphonuclear and mononuclear cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1994

Primitive hematopoietic progenitor cells are present in peripheral blood autografts.

In this report we have used an in vitro assay for long-term culture-initiating cells (LTC-IC) to detect primitive hematopoietic progenitor cells (HPC) in the peripheral blood (PB) of cancer patients who received high-dose cyclophosphamide (HD-CTX) followed by a combination of recombinant hematopoietic growth factors (C-HGF) including either interleukin-3 (IL-3) + granulocyte colony-stimulating factor (G-CSF), IL-3 + granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3/GM-CSF fusion protein (PIXY-321). In addition, we have developed a quantitative assay for cells capable of generating additional colony-forming cells (pre-CFC) as a means of determining primitive HPC present in mobilized PB cells. CD34+ human leukocyte A (HLA)-DR- cells isolated from the mobilized PB were capable of initiating long-term hematopoiesis in vitro that persisted for 10 weeks, while CD34+ HLA-DR- cells obtained from the nonmobilized PB or BM were capable of sustaining long-term hematopoiesis in vitro for only 4 weeks and 8 weeks, respectively. As determined by a limiting dilution analysis of mobilized PB CD34+ HLA-DR- cells, the frequency of pre-CFC was 4.3% (range, 1.0-8.3%). Pre-CFC comprised 0.01% (range, 0.001-0.02%) of mobilized PB mononuclear cells, and 151 pre-CFC were calculated to be present in one milliliter of mobilized PB (range, 20-310/ml). These results suggest that PB mononuclear cells collected by leukapheresis following mobilization with HD-CTX + C-HGFs contain not only differentiated HPCs but also more primitive HPC.

Antigens, CD↗
PubMed1994

Characterization and quantitation of primitive hematopoietic progenitor cells present in peripheral blood autografts.

In this report, we assess the content of primitive hematopoietic progenitor cells (HPC) that circulate transiently in the peripheral blood (PB) of cancer patients (group A) who received a PB stem-cell-mobilizing regimen that included high-dose chemotherapy (HD-CTX) of 7 g/m2 cyclophosphamide followed by a combination of recombinant hematopoietic growth factors (C-HGF), including either interleukin-3 (IL-3) plus granulocyte-colony stimulating factor (G-CSF), IL-3 plus granulocyte-macrophage colony-stimulating factor (GM-CSF), or a recombinant GM-CSF/IL-3 fusion protein (PIXY-321). These data were compared to the HPC content of PB obtained from a similar group of cancer patients that had not received such a mobilization regimen (group B). Monoclonal antibody staining and fluorescence-activated cell sorting (FACS) were used to identify and isolate cell populations enriched for more differentiated HPC (CD34+HLA-DR+) and more primitive HPC (CD34+HLA-DR-). The content of CD34+HLA-DR+ and CD34+HLA-DR- cells in the PB of group A patients was significantly greater than that observed in the PB of group B patients. In addition, HD-CTX plus C-HGF mobilization resulted in the appearance of greater numbers of PB colony-forming units-granulocyte/macrophage, -granulocyte/erythroid/macrophage/megakaryocyte, and -megakaryocyte (CFU-GM, CFU-GEMM, and CFU-Mk), and burst-forming units-erythroid and -megakaryocyte (BFU-E and BFU-Mk) than those observed in the PB of group B patients (p < 0.01). CD34+HLA-DR- cells isolated from the PB of group A patients were capable of initiating long-term hematopoiesis in vitro, which persisted for 10 weeks, while CD34+HLA-DR- cells obtained from the PB of group B patients were capable of sustaining long-term hematopoiesis in vitro for only 4 weeks. As determined by a limiting dilution analysis of group A PB CD34+HLA-DR- cells, the frequency of cells capable of giving rise to hematopoietic progenitor cells (pre-CFC) after 2 weeks in liquid culture was 4.3% (range 1.0-8.3%). Pre-CFC constituted 0.01% (range 0.001-0.02%) of group A PB mononuclear cells, and 151 pre-CFC were calculated to be present in 1 mL mobilized PB (range 20-310/mL). These results suggest that peripheral blood mononuclear cells (PBMC) collected by leukapheresis following HD-CTX plus C-HGF mobilization contain not only differentiated HPC but also more primitive HPC.

Blood Transfusion, Autologous↗
PubMed1993

Clinical implications of the heterogeneity of hematopoietic progenitors elicited in peripheral blood by anticancer therapy with cyclophosphamide and cytokine(s).

Clinical investigators have found that the hematopoietic system irreversibly damaged by cancer therapy with myeloablative high doses of chemoradiotherapy can be reconstituted by transplantation of autologous hematopoietic progenitors retrieved from peripheral blood. In comparison with patients transplanted with bone marrow, those who receive peripheral blood progenitors undergo shorter periods of neutropenia and thrombocytopenia, require less platelet and erythrocyte transfusions and, most importantly, experience overall reduced treatment-related morbidity. In this article, we speculate that an explantation for this clinical achievement may be that committed hematopoietic progenitors as well as ancestral uncommitted pluripotent stem cells are retrieved from circulation and transplanted after myeloablative cancer therapy. As indicated by studies in rodents, transplantation of hematopoietic progenitors is followed by two phases of engraftment associated with progenitors at different stages of maturation. An initial phase corresponding to early hematopoietic recovery is produced by committed progenitors, and a second sustained engraftment phase is produced by the pluripotent stem cell. Should this multiphase engraftment model be true of humans also, the exceptionally prompt and sustained blood cell count recovery achieved by transplanting blood progenitor cells may reflect transplantation of heterogeneous progenitors such as committed progenitors and pluripotent stem cells producing an early engraftment phase and then sustained hematopoiesis, respectively.

Antineoplastic Agents↗
PubMed1993

High-dose sequential chemo-radiotherapy with peripheral blood progenitor cell support for relapsed or refractory Hodgkin's disease--a 6-year update.

BACKGROUND: Very few studies using high-dose therapy and autologous bone marrow transplantation have a long (i.e., > 3 years) follow-up. We report here the 6-year update of a study employing high-dose sequential chemo-radiotherapy in 25 patients with poor-risk Hodgkin's disease. PATIENTS AND METHODS: All patients were either refractory (7 patients) or partial responders (9 patients) or early relapses (9 patients) following induction chemotherapy consisting of MOPP/ABVD in 20 patients and MOPP/ABVD followed by salvage CEP for the remaining 5 patients. The high-dose chemo-radiotherapy regimen employed consisted in the rapid sequential administration of high-doses of cyclophosphamide, methotrexate, etoposide and total body irradiation plus melphalan. RESULTS: As compared to 4-year results, the 6-year probabilities of relapse-free survival, freedom from progression and overall survival were almost superimposable. In fact, during the two additional years elapsed since prior survey, only one event occurred (fatal cerebral hemorrhage) that was unrelated to Hodgkin's disease. In particular, the proportion of patients remaining event-free was 78% for those with short initial complete response and 31% for patients who had failed initial MOPP/ABVD. According to previous experience, both groups have a very low or no chance of long-term event-free survival when treated with standard-dose salvage chemotherapy. CONCLUSIONS: The very favorable long-term results of the high-dose sequential regimen together with its excellent tolerability and lack of early or late fatal toxicities, will assist clinicians in defining optimal timing for high-dose therapy in the management of Hodgkin's disease. According to a revised cost/benefit analysis, it would appear that, at present, the best timing of high-dose sequential therapy in patients failing MOPP/ABVD is at first early relapse.

Actuarial Analysis↗
PubMed1993

Recombinant human interleukin-3 hastens trilineage hematopoietic recovery following high-dose (7 g/m2) cyclophosphamide cancer therapy.

BACKGROUND: Interleukin-3, a recombinant cytokine with multilineage stimulatory effect on hematopoietic cells, was administered to 22 previously untreated breast cancer patients following high-dose therapy with cyclophosphamide (7 g/m2). PATIENTS AND METHODS: The growth factor, administered through continuous intravenous infusion at 1 (3 patients), 2.5 (3 patients), 5 (10 patients) and 10 micrograms/kg/day (6 patients), was well tolerated up to 5 micrograms/kg/day. RESULTS: Nausea, vomiting, fever and headache prevented administration of the intended dose to all 6 patients in the 10 micrograms/kg/day cohort. At the maximal tolerable dose (5 micrograms/kg/day) the growth factor significantly accelerated granulocyte, platelet and reticulocyte recovery as compared to matched historical controls who received high-dose cyclophosphamide without cytokine infusion. Moreover, no platelet transfusions and fewer erythrocyte transfusions were required in interleukin 3-treated patients. In contrast to GM-CSF and G-CSF, interleukin 3 showed no effect on the mobilization of hematopoietic progenitor cells in the peripheral blood. CONCLUSIONS: Interleukin-3 represents a well-tolerated cytokine, clinically useful for accelerating trilineage hematopoietic recovery following severely myelotoxic treatments such as high-dose cyclophosphamide.

Adolescent↗