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Biomedical subjects

G Egerer

Publications and source records attributed to G Egerer.

At least 55 records · Page 3Linked to original sources

Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m(-2)) and epirubicin (120 mg m(-2)) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12,000 mg m(-2)), carboplatin (900 mg m(-2)) and epirubicin (180 mg m(-2)). Patients were autografted with a median number of 3.7 x 10(6) CD34+ cells kg(-1) (range, 1.9-26.5 x 10(6)) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

Adult↗

Ceftriaxone in the outpatient treatment of cancer patients with fever and neutropenia.

A study was performed in low-risk cancer patients with chemotherapy-induced febrile neutropenia to determine the safety and efficacy of ceftriaxone given in an outpatient setting. A total of 126 episodes of febrile neutropenia in 120 clinically stable outpatients were treated with intravenous ceftriaxone alone (n=100) or in combination with other antibiotics (n=26). The mean neutrophil count was 460/mm3; severe neutropenia (< 100/mm3) was observed in 18 episodes. The initial treatment with ceftriaxone (alone or in combination) was successful in 99 episodes (78%). Ninety-five episodes (76%) were successfully treated in an outpatient setting only; admission to hospital was necessary in 31 episodes (24%), but no infection-related death was observed. Ceftriaxone seems to be safe and effective for outpatient therapy of patients with low-risk febrile neutropenia.

Adolescent↗

A case of mu heavy-chain disease associated with hyperglobulinemia, anemia, and a positive Coombs test.

We report here for the first time a patient with mu heavy-chain disease (HCD), hyperimmunoglobulinemia, and a positive direct antiglobulin test (DAT, Coombs test). The heavy-chain diseases involve the proliferation of lymphoplasma cells of B cell origin and are characterized by the production of incomplete heavy chains devoid of light chains. The association of mu heavy-chain disease with either hyperglobulinemia or a positive DAT has not been reported in the literature to date. In this patient, immunofixation of serum proteins with monospecific antisera to alpha-, gamma-, mu,- or delta-chains and to kappa- and lambda-chains revealed a precipitation band with antibody to IgM, but not with kappa and lambda light-chain antibodies, indicating mu heavy-chain disease. Hyperglobulinemia was present, which is very uncommon for HCD. A DAT of the patient's red blood cells (RBC) was found to be strongly positive for anti-IgG but negative for anti-IgM, -IgA, -C3c, and -C3d. However, when the eluate from the patient's red blood cells was investigated with nephelometry, it was found to contain antigens reactive with anti-y as well with anti-mu-antiserum. When a DAT was performed with a randomly chosen test cell incubated with the eluate, the antibody-containing eluate was shown to react with anti-IgG as well as with anti-IgM-antiserum. In summary, the eluate from the patient's RBCs contained IgG and an immunoglobulin structure reactive with anti-IgM in an RBC agglutination assay as well as with anti-mu antiserum in a nephelometric investigation. Whether this IgM on the patient's erythrocytes is penta- or oligomeric, complete IgM, or the heavy chain cannot be concluded from these observations.

Aged↗

Increased risk of catheter colonization and catheter-related infections in severe immunocompromized patients with multiple myeloma undergoing high-dose glucocorticoid treatment.

Catheter-related infections (CRI) are an important problem in medicine because of major consequences for treatment, prolongation of hospitalization and increasing therapy costs. Malignancies, immunodeficiency, severe burns and malnutrition compromise host defense. Studies to quantify the increased risk of CRI in immunocompromised patients are required. We analyzed the influence of immunoglobulin deficiency and high-dose glucocorticoid treatment in patients with multiple myeloma with regard to catheter colonization and CRI. In patients with multiple myeloma, central venous catheters (CVC) were significantly more frequently colonized (> 15 CFU) as compared to patients with other malignancies undergoing chemotherapy. We found a tendency towards a higher CRI rate in the myeloma patient group. Interestingly, despite of the significantly higher incidence of catheter colonization and a tendency towards higher CRI rates in severely immunocompromised patients, the incidence of signs of local (redness of the entry site) and systemic (fever) host reactions is reduced in myeloma patients. To decrease the CRI rate in myeloma patients during chemotherapy which includes high-dose glucocorticoids, we use antibacterial (silver-coated) catheters.

Adolescent↗

Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells.

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.

Adult↗

[Therapy of febrile neutropenia episodes in systemic hematologic illnesses with new once daily ceftriaxone administration].

In this open label prospective multicenter trial, 420 patients with neutropenia < 1000/microliter, fever > 38.5 degrees C and hematological malignancies were treated with ceftriaxone. Acute leukemia (n = 238) and high-grade lymphoma patients (n = 182) from 35 centers were enrolled. Between February 1992 and January 1996, patients were treated with 2 g ceftriaxone i.v. per day either as monotherapy (n = 135), or in combination with aminoglycosides (n = 235), glycopeptides (n = 37), or other antimicrobial agents (n = 13). Patients' median age was 54 years (range 15 to 97) with a median Karnofsky-performance-score of 6.0. The median neutrophil counts were 400/microliter. Fever was of unknown origin (FUO) in 268 (63.8%) of patients. Clinically defined infections (CDI) were diagnosed in 152 (36.2%) cases, including 74 (17.8%) episodes with pneumonia. Response to the initial approach with ceftriaxone was observed in 56.2% of febrile episodes, including 93 (68.8%) treatment courses with ceftriaxone alone. Concerning defervescence of fever ceftriaxone monotherapy was successful as compared to ceftriaxone in combination. Analysis revealed a low risk characterized by higher neutrophil counts (> or = 500/microliter; p < 0.0001), better Karnofsky-performance-score (> or = 7; p = 0.01), duration of neutropenia (< or = 5 days; p = 0.008) from start of antimicrobial treatment and duration of neutropenia per cycle (< or = 10 days; p = 0.0016). At the end of the observation, an overall response was obtained in 88.3% of the patients (n = 371) without statistical difference between patients treated with ceftriaxone alone or in combination. Once daily ceftriaxone either alone or in combination was effective in patients with hematological malignancies. Monotherapy was effective in a low risk group characterized by neutrophil counts (> or = 500/microliter), a Karnofsky-performance-score (> or = 7) and a duration of neutropenia (< or = 5 days) at the commencement of treatment.

Acute Disease↗

[Ambulatory therapy of multiple myeloma with vincristine, adriamycin and dexamethasone].

BACKGROUND AND OBJECTIVE: If multiple myeloma (MM) progresses in patients after chemotherapy with alkylating agents, the combination of vincristine, adriamycin and dexamethasone (VAD) can achieve a response in 40-70% of cases. Because of its low toxicity for haematopoetic stem-cells this form of chemotherapy is often undertaken before high-dose blood stem-cell transplantation. It was the objective of this study to examine effectiveness and complications of ambulant VAD treatment. PATIENTS AND METHODS: Within four years VAD chemotherapy was given to 62 ambulant MM patients, administered by microprocessor-regulated pumps via intravenously polyurethane catheters with a safety valve. Response to treatment, treatment-associated complications and infections were documented prospectively and analysed. RESULTS: VAD treatment achieved tumour reduction of more than 25% in 50 of 62 patients. This treatment had to be discontinued in two of 192 pump-infusions because of irreversible catheter occlusion. Eight patients were hospitalised because of infections and two for noninfectious complications. Severe infectious complications (> or = WHO grade III) occurred in 4% of treatment cycles. CONCLUSION: VAD chemotherapy can be performed with a low rate of infection in ambulant patients despite the need for prolonged intravenously infusion of the drugs. But to avoid complications by intravenously catheters, random prospective tests should first be done with oral alkylating agents.

Adult↗

Comparison of oral itasetron with oral ondansetron: results of a double-blind, active-controlled phase II study in chemotherapy-naive patients receiving moderately emetogenic chemotherapy.

Itasetron hydrochloride is a new 5-hydroxytryptamine3 (5-HT3) antagonist. Experimental investigations show that orally it is rapidly absorbed (about 90 min), is highly bioavailable (greater than 90%), has a long half-life (about 12 h) and is more potent (about 10 times) in animal models than ondansetron, currently standard therapy for the prophylactic control of chemotherapy induced nausea and vomiting. This paper describes the results of a study designed to assess the efficacy and tolerability of five (0.5, 1, 2, 4 and 8 mg) twice-daily doses of itasetron hydrochloride, in comparison with 8 mg b.i.d. ondansetron. Assessments were made in patients (n = 104) with histologically confirmed cancer (excluding head and neck tumors) and about to receive their first course of moderately emetogenic chemotherapy. Itasetron hydrochloride demonstrated comparable efficacy to ondansetron; no statistically significant between-group differences were observed in the primary (complete response rate) or secondary (nausea and delayed emesis) efficacy criteria. Adverse events were similar in type and incidence across all treatment groups, and were those expected for this therapeutic class. The tolerability of itasetron hydrochloride was assessed as 'very good' or 'rather good' by 81% of patients and 89% of physicians. In conclusion, itasetron hydrochloride is effective and well tolerated in patients receiving moderately emetogenic chemotherapy. Oral doses of 1 mg b.i.d. or above will be used in further clinical studies.

Adult↗

[Rehabilitation of patients with alcoholic liver cirrhosis after orthotopic liver transplantation: a 7-year follow-up].

Alcoholic liver cirrhosis is the main indication for orthotopic liver transplantation. Since 1988, 52 patients with alcoholic liver cirrhosis have been transplanted at the Department of Surgery of the University of Heidelberg. The survival rates are as follows: 73% of the patients survived for 1 year, 68% for 2 and 3 years, 64% for 4 years, and 57% survived for 5 years. After transplantation, recidivism occurred in 6 patients. Remarkable in this case was the fact that all 6 patients had a relatively short period of abstention prior to surgery (2 to 5 months). In 12 patients, a small carcinoma was found in the cirrhotic liver. This had neither been seen previously by ultrasound nor by computer tomography. In summary, orthotopic liver transplantation is an excellent mode of treatment in end-stage alcoholic liver cirrhosis. However, the patients have to be carefully selected in order to avoid recidivism following transplantation.

Adult↗

Alcohol dehydrogenase in the human colon and rectum.

Alcohol dehydrogenase (ADH) activities were measured in rectal biopsies from 55 patients (28 males, 27 females aged 22-81 years), in colonic biopsies from 19 patients (10 males, 9 females aged 21-81 years) and in three surgical specimens. All patients had normal mucosa as determined by light microscopy. The activity of rectal ADH was comparable to gastric ADH activity and did not exhibit any significant gender effect (5.5 +/- 1.1 vs. 6.7 +/- 1.0 nmol/mg protein x min; nonsignificant). No significant correlation was found between age and rectal ADH activity. Compared to ADH activities in other colonic segments, rectal ADH activity was found to be significantly increased (ascending colon: 3.9 +/- 0.7 nmol/mg protein x min; p < 0.05; transversal colon: 3.4 +/- 1.1 nmol/mg protein x min; p < 0.05; descending colon 2.3 +/- 0.4 nmol/mg protein x min; p < 0.001; rectum 6.1 +/- 0.8 nmol/mg protein x min). This higher activity of ADH in the rectum could result in increased acetaldehyde levels after alcohol administration and could therefore play a role, at least in part, in the ethanol-associated rectal cocarcinogenesis.

Adult↗

Gastric emptying and first-pass metabolism of ethanol in elderly subjects with and without atrophic gastritis.

BACKGROUND: Oral ethanol intake results in lower blood ethanol concentrations than intravenous administration of the same dose of ethanol. This first-pass metabolism is thought to be due to gastric metabolism of ethanol via alcohol dehydrogenase and also to hepatic first-pass metabolism. METHODS: Since a loss of gastric mucosa may decrease first-pass metabolism of ethanol, this metabolism was studied in 10 elderly subjects (6 women and 4 men) with atrophic gastritis and bacterial overgrowth and in 17 control subjects with normal gastric secretory function. Atrophic gastritis was verified by means of the serum pepsinogen I to pepsinogen II ratio and the hypochlorhydria occurring after pentagastrin stimulation. Bacterial overgrowth was assessed by bacteria. In addition, gastric emptying rates of ethanol solution with technetium-99m sulfur colloid were calculated from scintigraphic images. Furthermore, gastric biopsy specimens were taken from 12 female patients with atrophic gastritis and from 12 controls for determination of alcohol dehydrogenase activity. RESULTS: Neither gender (female versus male, 28 +/- 5% versus 42 +/- 5%), atrophic gastritis (normal versus atrophic gastritis, 35 +/- 4% versus 32 +/- 6%), nor tetracycline treatment in atrophic gastritis subjects (before versus after, 32 +/- 6% versus 41 +/- 5%) had a statistically significant effect on the first-pass metabolism of ethanol in the elderly. Gastric alcohol dehydrogenase activity was significantly lower in atrophic gastritis subjects than in controls (p < 0.01). A significant correlation was found between the first-pass metabolism of ethanol in healthy controls and gastric half-emptying time (p = 0.032). CONCLUSIONS: We conclude from these data that the rate of gastric emptying modulates first-pass metabolism of ethanol in elderly individuals.

Aged↗

Ethanol metabolism in the gastrointestinal tract and its possible consequences.

Ethanol is oxidised not only in the liver, but also in the gastrointestinal tract. Although this ethanol metabolism is less than that of the liver, it has some important relevance with respect to the first pass metabolism of alcohol and to ethanol induced tissue toxicity. In the gastrointestinal tract, ethanol can be metabolised not only in the mucosal cell via alcohol dehydrogenase (ADH) and microsomal ethanol oxidising system (MEOS), but also in a great variety of bacteria. Depending on the gastrointestinal location, one or the other metabolic pathway of alcohol may be predominant. The metabolism of ethanol by gastric ADH, the so called first pass metabolism, influences ethanol blood concentrations not only in the portal vein and thus in the liver, but also in the systemic circulation. As gastric ADH activity is decreased in younger women, in the elderly, in the alcoholic, during fasting and after treatment with certain H-2-receptor antagonists, increased blood ethanol concentrations may occur in these situations after oral intake of ethanol. However, this first pass metabolism of alcohol is influenced not only by ADH activity but also by the speed of gastric emptying (e.g. slow gastric emptying leads to increased first pass metabolism). Finally, gastric morphology also determines first pass metabolism. Chronic atrophic gastritis and Helicobacter pylori associated gastric injury lead to a decrease of gastric ADH activity, and thus possibly to a decreased first pass metabolism of alcohol. In addition, the local production of acetaldehyde from ethanol in the oesophagus, where significantly more sigma-ADH is present, may contribute to tissue injury and this may lead to the well known ethanol associated oesophageal cancer development. Various isoenzymes of ADH exist in the colorectum and they are also capable of producing acetaldehyde in amounts sufficient to injure the mucosa. Besides ADH, the MEOS, a mixed function oxidase, also metabolises ethanol. This system is inducible by chronic alcohol consumption and is involved in the metabolism of various xenobiotics including drugs and procarcinogens. Thus, an increased activation of dietary procarcinogens by this enzyme system may also contribute to carcinogenesis in the alcoholic. Finally, a great variety of gastrointestinal bacteria are capable of metabolising ethanol to acetaldehyde. This is possibly of major importance in the colorectum where faecal bacteria, especially anaerobes in the rectum, can produce high amounts of acetaldehyde, and this correlates with mucosal hyperregeneration suggesting an acetaldehyde mediated mucosal damage.

Adult↗

Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p < 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p < 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people.

Adolescent↗

[Liver transplantation in alcoholic liver cirrhosis: social psychological aspects and occupational rehabilitation].

Social-psychological aspects and rehabilitation after liver transplantation were examined in 21 patients. One-year survival was not different in patients with alcoholic liver disease compared with patients with other end-stage liver disease (65% vs 71%). After liver transplantation a temporary return to alcohol drinking was observed in 3 patients (14%). 52% of patients transplanted for alcoholic liver disease are occupationally rehabilitated. Social-psychological conflicts were reported by 46%. Patients with alcoholic liver disease are potential candidates for hepatic transplantation.

Adult↗

Human gastric alcohol dehydrogenase: in vitro characteristics and effect of cimetidine.

The presence of at least two types of alcohol dehydrogenase has been demonstrated in surgical specimens from the human stomach. One isoenzyme has a Km of approximately 1-2 mM for ethanol comparable to that of class I alcohol dehydrogenase isoenzyme as defined for the liver. This isoenzyme can also be detected by immunohistology using a polyclonal rabbit antibody against human liver class I alcohol dehydrogenase. The other isoenzyme of alcohol dehydrogenase has a much lower affinity to ethanol (greater than 300 mM), but with activities that become significant at ethanol concentrations of more than 100 mM commonly present in the human stomach. Cimetidine was found to be a noncompetitive inhibitor of gastric alcohol dehydrogenase at concentrations as low as 1 mM in vitro. Since the human gastric alcohol dehydrogenase is responsible for the first-pass metabolism of ethanol, its inhibition by cimetidine may explain the reduced first-pass metabolism of alcohol which is associated with elevated ethanol blood concentrations seen after cimetidine therapy.

Aged↗

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) subsequent to chemotherapy improves collection of blood stem cells for autografting in patients not eligible for bone marrow harvest.

Fourteen patients with relapsed Hodgkin's disease responded to a salvage therapy with Dexa-BEAM (dexamethasone, BCNU, etoposide, Ara-C and melphalan). In seven patients a continuous i.v. infusion with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was started subsequent to Dexa-BEAM (+rhGM-CSF) while the other seven patients received no hemopoietic growth factor (-rhGM-CSF). It was our objective to study the impact of rhGM-CSF on the collection of blood-derived hemopoietic stem cells in patients with extensive prior chemo- and radiotherapy not eligible for marrow harvest. Compared to baseline, we observed a significant increase of colony-forming units granulocyte-macrophage (CFU-GM) in the peripheral blood of patients receiving rhGM-CSF (p less than 0.05). On average, the yield of total nucleated cells and CFU-GM collected per single leukapheresis was 2.2 and 2.4-fold higher in the rhGM-CSF-treated patients respectively (p less than 0.05). With rhGM-CSF the interval from the start of chemotherapy to the end of blood stem cell collection could be reduced by 6 days (p less than 0.05). Following the CBV pretransplant regimen (cyclophosphamide, BCNU, etoposide), the reinfusion of rhGM-CSF-exposed stem cells resulted in a shorter time of leukocyte recovery (p less than 0.05). The number of CFU-GM/kg body weight transplanted was found to be predictive for the time of neutrophil recovery (p less than 0.05). In patients with bone marrow hypoplasia or fibrosis, rhGM-CSF as part of an effective salvage therapy improves the collection of blood stem cells that are capable of restoring hemopoiesis after high-dose pretransplant therapy.

Adult↗

Successful autologous transplantation of blood stem cells mobilized with recombinant human granulocyte-macrophage colony-stimulating factor.

We investigated the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) on the pool of circulating hemopoietic progenitor cells in 11 patients with hematological malignancies of nonmyeloid origin and 1 patient with sarcoma. These patients were eligible for autologous blood stem cell transplantation rather than autologous bone marrow transplantation because sufficient marrow aspirates could not be performed due to damage at the usual sites of bone marrow harvest by previous chemo- and/or radiotherapy. Recombinant human GM-CSF was given as continuous i.v. infusion via central venous line for a median time of 11.5 days (range 5-22 days), during which a median number of six aphereses were performed. In comparison to the pretreatment level the median increase in the number of granulocyte-macrophage colony-forming units (CFU-GM)/ml of peripheral blood was 8.5-fold. In all 12 patients a median decrease of the platelet count of 21% (range 7%-67%) was observed during rhuGM-CSF treatment prior to the start of the apheresis procedures. Six patients were treated with a myeloablative conditioning therapy consisting of total body irradiation and/or high-dose polychemotherapy followed by autografting with blood stem cells. Five of them achieved a sustained engraftment. Recombinant human GM-CSF proved to be highly efficient in increasing the number of circulating progenitor cells in these patients with severely compromised hemopoiesis. Blood stem cells harvested under a rhuGM-CSF treatment are capable of restoring hemopoiesis in man after a myeloablative pretransplant therapy.

Adolescent↗