Effects of recombinant granulocyte colony-stimulating factor treatment on hematopoietic cycles and cellular defects associated with canine cyclic hematopoiesis.

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by 14-day cycles of neutropenia, monocytosis, thrombocytosis, and reticulocytosis. Platelets from CH dogs have decreased dense-granule serotonin pools and decreased aggregation responses to collagen, platelet-activating factor (PAF), and thrombin. Recombinant granulocyte colony-stimulating factor (rG-CSF) was administered (5 micrograms/kg, b.i.d.) to four CH and six normal dogs to determine if G-CSF therapy corrected qualitative platelet defects in CH dogs. Neutrophil counts increase to greater than 25,000 cells/microliters within 24 h after starting treatment in all dogs. Treatment with G-CSF blocked neutropenic episodes in the CH dogs. Platelet aggregation, and serotonin content and secretion were significantly (p less than 0.05) decreased in the CH dogs both before and during recombinant human (rh) G-CSF treatment compared to normal dogs. Neutrophil myeloperoxidase, a primary granule enzyme, was significantly (p less than 0.05) decreased in CH dogs and was not corrected by rhG-CSF treatment. Administration of rG-CSF to CH dogs eliminated cell cycles but apparently did not correct cellular defects in CH dogs. Identification of primary biochemical defects in cells from CH dogs may be crucial to investigating the biochemical basis for cyclic hematopoiesis.     

Occurrence of periodic oscillations in the differential blood counts of congenital, idiopathic, and cyclical neutropenic patients before and during treatment with G-CSF

Using techniques developed in astrophysics to deal with unequally sampled data sets, we have analyzed serial differential cell counts from 45 congenital, idiopathic, and cyclic neutropenic patients before and during treatment with recombinant human G-CSF (rhG-CSF). Our results show that the occurrence of significant cycling in the absolute neutrophil count (ANC) of neutropenics not classified as cyclical is much more prevalent than had been previously thought, and that not all the patients classified as cyclic show significant ANC periodicity. In these patients, cycling in more than one cell line may be involved. The range of periods encountered in these patients is much broader (between 11 and 52 days) than is usually associated with classical cyclical neutropenia, and there is no obvious connection between the range of periods and the patient's diagnostic category. Administration of rhG-CSF is able to induce significant cycling in neutropenic patients that were not cycling prior to treatment. In patients who had significant cycling before treatment, rhG-CSF may either decrease the period to between 11 and 14 days, or may obliterate any statistical evidence of cycling.     

Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in nonhuman primates

We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 micrograms/kg/d) plus rhG- CSF (100 micrograms/kg/d) while a second group received rhG-CSF alone (100 micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopreserved autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that using a single 2-hour leukapheresis to collect cells, the blood cells mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more rapidly than do blood cells mobilized by rhG- CSF alone.     

Are white blood cell count, platelet count, erythrocyte sedimentation rate and C-reactive protein useful in the diagnosis of septicaemia and endocarditis?

In 851 predominantly adult patients with septicaemia or endocarditis data regarding white blood cell (WBC) count, platelet count, ESR and C-reactive protein (CRP) obtained within 3 days of admission were analyzed retrospectively. Among 232 patients with complete laboratory data none had the combination of normal ESR, negative CRP and lack of both leukocytosis and thrombocytopenia. CRP was positive (greater than 10 mg/l) in 93%, ESR was elevated (greater than 20 mm/h) in 90%, leukocytosis (WBC greater than 9 X 10(9)/l) was present in 60% and thrombocytopenia (platelets less than 150 X 10(9)/l) in 35% of the patients. Patients with pneumococcal infection had generally higher ESR and CRP values and WBC counts than patients with other infections.     

An application of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a case of hepatocellular carcinoma combined with liver cirrhosis in which leukopenia developed after chemoembolization.

A 63-year-old Japanese woman who was being treated for liver cirrhosis was diagnosed as having hepatocellular carcinoma in the caudate lobe of the liver. Transcatheter hepatic arterial chemoembolization was performed for this lesion, but severe neutropenia occurred. To restore white blood cell (WBC) counts, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (250 micrograms per day during 10 days, intravenously). Subsequently, WBC counts recovered immediately without side effects. This suggests that rhG-CSF could be useful for the treatment of neutropenia after chemoembolization, even in cirrhotic patients.     

Efficacy of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with AIDS.

The efficacy of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutropenia was evaluated in 14 patients with AIDS and AIDS-related complex (ARC). In all patients, including 11 neutropenic patients, 100 or 200 micrograms/m2 of rhG-CSF significantly increased the neutrophil counts. The response was greater in patients with higher neutrophil counts before the treatment, and was also dose-dependent. Although the effect seemed to be less potent, the agent also increased the neutrophil counts even when zidovudine (azidothymidine, AZT) and other myelosuppressive antiviral agents were administered simultaneously. These observations indicate that rhG-CSF may be beneficial in preventing and treating some secondary infections, and will make it easier to continue therapy with antiviral agents in patients with AIDS or ARC.     

Abnormal function and thromboxane release from platelets of dogs with cyclic hematopoiesis

Investigation of platelet function in dogs with cyclic hematopoiesis (CH) revealed a platelet aggregation disorder. Collagen-induced aggregation of CH dog platelets was significantly abnormal, although normal aggregation in response to ADP was observed. Aggregation was particularly defective on days 2-4 and 14 of the 14-day neutrophil cycle that is typical of CH dogs. The lack of response to collagen suggested a defect in the arachidonic acid pathway of platelet metabolism, since platelet-generated thromboxane-B2 levels were about 30% (p less than 0.0005) of control values. Platelets from dogs heterozygous for CH demonstrated moderately depressed responses to collagen that were intermediate between the values found for platelets from CH dogs and platelets from normal, mixed-breed dogs. Not only does this work indicate a platelet defect in CH dogs, but this phenomenon may be useful as a genetic marker for identification of dogs heterozygous for the CH gene.     

Effect of recombinant human granulocyte colony-stimulating factor on white blood cell count and neutrophil functions in patients with malignant lymphoma

We studied the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on white blood cell (WBC) count and neutrophil functions in nine patients with malignant lymphoma. The WBC count and absolute neutrophil count were rapidly increased without a nadir phase after chemotherapy. Neutrophil alkaline phosphatase (NAP) scores also markedly increased following chemotherapy in all patients. Phagocytosis of India ink and nitroblue tetrazolium (NBT) reduction were revealed tend to be increased, but not exceeded significantly to normal range. RhG-CSF repaired neutrophil function in patients with decreasing that. Thus, rhG-CSF may be useful for prevention and treatment of infection after chemotherapy.     

Cyclic hormonogenesis in gray collie dogs: interactions of hematopoietic and endocrine systems

Cortisol, ACTH, T4, and T3 concentrations were determined in six cyclic hematopoietic (CH) dogs to determine if hormonal cycles were a feature of this hematopoietic disorder. It was determined that there were 12- to 14-day cycles of these hormones in CH dogs. Plasma cortisol and ACTH concentrations peaked 4-8 days after the onset of neutropenia and were concurrent with peak neutrophil counts. The peak ACTH concentration occurred 1-2 days before or concurrent with the cortisol peak concentration. T4 and T3 peak concentrations were opposite the cortisol cycles, and maximal concentrations were seen when cortisol levels were lowest. ACTH, GH-releasing factor and TRH response tests were performed in the CH dogs. No frank deficiencies in hormone production were seen with the ACTH, GH-releasing factor, and TRH responses in CH dogs relative to those in normal dogs. It was concluded that cyclic hormonogenesis is a central feature of CH disease. These findings are the first demonstration of extrahematopoietic system cyclicity in this rare disease and suggest the presence of common regulatory factors in the hematopoietic and endocrine systems.     

Recombinant human granulocyte colony-stimulating factor accelerates hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.

We studied whether treatment of dogs with recombinant human granulocyte colony-stimulating factor (rhG-CSF), after 920 cGy total body irradiation (TBI) and transplantation of 3.3 +/- 1.0 x 10(8) bone marrow cells per kilogram from a DLA-identical littermate, accelerated hematopoietic recovery and influenced the incidence of subsequent marrow graft failure or graft-versus-host disease (GVHD). Ten animals were treated with 100 micrograms rhG-CSF/kg/d from days 1 through 10 after TBI. Results were compared with those of historical control of 14 dogs not administered rhG-CSF. Neither group of dogs received GVHD prophylaxis. The median time to recovery of 1,000 neutrophils/mm3 was 8 days for dogs administered rhG-CSF compared with 14 days in controls (logrank test: P less than .03). The median time to reach 100 monocytes/mm3 was 17 days in G-CSF-treated dogs compared with 49 days in controls (P less than .002). The median time to attain 500 lymphocytes/mm3 was 15 days versus 31 days, respectively (P less than .01). The median time to reach 20,000 platelets/mm3 was 26 versus 20 days (P = .68). Graft failure occurred in 1 of 10 G-CSF-treated dogs versus 2 of 14 controls (two-tailed Fisher's exact test: P = 1.00). GVHD was seen in 4 of 9 rhG-CSF-treated dogs compared with 1 of 12 controls (P = .12). Two G-CSF-treated dogs died of GVHD versus none of the controls (P = .17). No unusual toxicities were seen in dogs receiving rhG-CSF. In summary, rhG-CSF significantly accelerated recovery of neutrophils, monocytes, and lymphocytes after DLA-identical littermate marrow transplantation without altering platelet recovery. Graft failure was not seen more often than in controls, but there was a trend toward an increased incidence of GVHD.     

The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis [see comments]

The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG- CSF in normal granulocyte donors are warranted.     

Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis in normal cats.

The objective of this study was to determine how recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects hematopoiesis in normal cats. Recombinant human G-CSF was given at 3.0, 5.0, and 10.0 micrograms/kg to two cats each s.c. twice daily for 21 days. This resulted in significant (p less than 0.01) elevations of peripheral blood neutrophils from 3.0- to 9.2-fold above pretreatment levels and significantly (p less than 0.02) above levels of nontreated control cats (n = 4). A statistically significant dose-related response was not seen at these dosages in any parameter evaluated. The period of maximum neutrophilia occurred between days 10 and 14 of rhG-CSF treatment, with maximum neutrophil counts ranging from 20,370 cells/microliters to 61,400 cells/microliters (normal is less than 12,500). Lymphocytosis (greater than 7000 lymphocytes/microliters) and monocytosis (greater than 850 monocytes/microliters) were observed in 50% of the cats receiving rhG-CSF during the period of maximal neutrophil stimulation. Monocyte counts in treated cats were significantly (p less than 0.01) elevated over those of treatment controls on days 12-17. Lymphocyte numbers in rhG-CSF-treated cats were significantly elevated (p less than 0.05) over pretreatment controls on days 12 and 14 of rhG-CSF treatment. No significant changes were observed in reticulocyte counts, platelet counts, or hematocrit levels. By day 19, neutrophil levels had dropped significantly (p less than 0.01) from the maximum neutrophil levels, with one cat attaining a normal blood neutrophil count by day 21 of rhG-CSF treatment. Marrow aspirates revealed an overall increase in marrow cellularity through day 14 of treatment in rhG-CSF-treated cats, with increased myeloid:erythroid ratios (two- to ninefold) over those of nontreated controls. The erythroid and lymphoid component of the marrow decreased from day 0 to day 14, whereas the early myeloid progenitors (myeloblasts, progranulocytes, and myelocytes) increased significantly (p less than 0.05). No significant differences in the percentage of later myeloid forms in the marrow were observed over the treatment period. In vitro colony-forming assays of marrow obtained from treated cats revealed increases in granulocyte-macrophage colony-forming units (CFU-GM) through day 14, with subsequent decreases by day 21 of rhG-CSF treatment. Recombinant human G-CSF was also effective at in vitro stimulation of feline marrow cells from untreated cats in a dilution study, with maximal CFU-GM formation at 0.1 microgram rhG-CSF/ml assay.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mobilization of hematopoietic progenitor cells with paclitaxel (taxol) as a single chemotheraupetic agent, associated with rhG-CSF

We assessed the mobilization capacity of taxol with rhG-CSF, both as a single chemotherapeutic agent and in the presence of cyclophosphamide (CY), and compared the effect with yields achieved when mobilization was performed solely with rhG-CSF. Fifteen patients with breast cancer received taxol 170 mg/m2 (continuous infusion, day 1) and rhG-CSF (8 microg/kg/day, from day 2 until the end of apheresis) (T-G group), while seven breast cancer patients were additionally treated with CY (4 g/m2) on day 2, followed by rhG-CSF starting at similar doses on day 3 (T-CY-G group). The PBSC collections after taxol with/without CY were compared with those of 30 breast cancer patients who had received rhG-CSF (8 microg/kg/day) for mobilization. No differences were found in the characteristics of patients included in any of the three mobilization groups. The median yield of CD34+ cells from all patients included in taxol containing schedules was 9 x 106/kg (range 2-26) collected with a median of one apheresis procedure (range 1-4). Leukaphereses began earlier in the T-G group (median day 8, range 7-10) than in the T-CY-G group (median day 13, range 11-17). In most patients (20 out of 22) who received taxol containing regimens, more than 2.5 x 106 CD34+ cells/kg, a threshold considered to be sufficient for hematopoietic reconstitution, were collected with a single apheresis. Those patients in the T-G group experienced less neutropenic and thrombocytopenic days, with all neutropenic fever episodes developing in patients treated with the T-CY-G schedule (43%). When considering priming with rhG-CSF alone in our historical cohort of 30 breast cancer patients, a significant detrimental effect was observed in comparison with taxol mobilizing schedules, in the number of aphereses performed, in the total yield CD34+cells and in the number of patients who achieved the target dose of 2.5 x 106/kg CD34+ cells within the first collection procedure. We conclude that taxol containing schedules are effective in mobilizing PBSC and facilitate the collection of high yields of CD34+ cells (usually more than 5 x 106/kg recipient body weight) with a reduced number of apheresis procedures. Taxol, as a single agent with rhG-CSF, exhibits less hematological toxicity than the combination chemotherapy mobilization regimen including CY. Bone Marrow Transplantation (2000) 25, 231-235.     

Long-term treatment of canine cyclic hematopoiesis with recombinant canine stem cell factor

Grey collie dogs have cyclic fluctuations in their blood cell counts caused by a regulatory defect of hematopoietic stem cells. To examine the role of stem cell factor (SCF) or its receptor in this disorder, we investigated the stimulatory effects of recombinant canine SCF (rc-SCF) on in vitro marrow cultures, cloned and sequenced the grey collie SCF gene, and treated three grey collies with rc-SCF, either alone or in combination with recombinant canine granulocyte colony-stimulating factor (rcG-CSF). Colony-forming unit granulocyte-macrophage formation from grey collie or normal dog marrow showed similar dose-response curves for rc-SCF. Cloning and sequencing the SCF gene for two grey collies showed no evidence of mutations in the coding region of the SCF gene. Treatment with rc-SCF (10 to 100 micrograms/kg/d) did not induce neutrophilia except at the highest dose (100 micrograms/kg/d), but daily rc-SCF abrogated the neutropenic periods in doses of 20 micrograms/kg/d or greater. Combination of rc-G-CSF (0.5 to 1.0 microgram/kg/d) with rc-SCF treatment (20 to 50 micrograms/kg/d) suggested a synergistic effect, ie, the neutrophil levels on combined therapy were higher than the sum of the levels when these two cytokines were given separately. Long-term treatment of these dogs with rc-SCF in doses of 10 to 30 micrograms/kg/d was generally well tolerated, suggesting that SCF may be useful as a therapy for some chronic hypoproliferative disorders of hematopoiesis.     

Physiologic and biochemical abnormalities in self-induced drug overdosage.

The following abnormalities were observed during the first 24 hours of admission for 162 drug overdosage (OD) episodes in 152 patients: abnormal chest x-ray films; increased A-aO2 gradient; elevated white blood cell (WBC) counts; elevated serum enzyme levels; gross myoglobinuria; skin lesions suggestive of pressure necrosis; and abnormal electrocardiograms. Many sputum cultures were positive for single or multiple potentially pathogenic organisms. These correlations existed: all patients with OD duration of less than 12 hours were hyperthermic; as temperatures increased so did WBC counts; hyperthermic patients had higher creatine phosphokinase (CPK) values than those with hypothermia or normothermia; patients with skin lesions had higher temperatures and CPK values and longer OD duration; serum enzme levels increased with increasing OD duration; patients with CPK levels greater than 10,000 mU/ml had myoglobinuria; and patients with the most abnormal chest x-ray films had higher temperatures and larger A-aO2 gradients. Incidence of pneumonitis is low, even with abnormal chest radiograms, leukocytosis, hyperthermia, and positive sputum cultures. Abnormal temperatures and leukocytosis are probably secondary to stress, hypoxemia, acidosis, and specific drug ingestion rather than infection.     

Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.     

Kinetics of circulating hematopoietic stem cells following chemotherapy in patients with hematopoietic malignancies]

The number of circulating hematopoietic progenitor cells was determined during 47 courses of chemotherapy in 23 patients with hematopoietic malignancies. rhG-CSF was given subcutaneously to 14 patients to rescue chemotherapy-induced neutropenia following 22 courses of chemotherapy. The mean numbers of CFU-GM in patients with malignant lymphoma (ML), acute leukemia (AL) and myeloma (MM) were 56.0 +/- 58.8 (mean +/- SD), 46.7 +/- 66.0 and 11.0 +/- 11.1 CFU-GM/ml, respectively. The number of CFU-GM in MM was significantly less than in normal subjects (51.2 +/- 30.6 CFU-GM/ml). The number of CFU-GM in PB in all patients began to rise between 2 days before and 8 days after nadir of WBC count, and then reached the peak at the subsequent 5 days. The peak values of CFU-GM in ML, AL and MM were 711.3 +/- 974.7, 660.0 +/- 374.7 and 403.6 +/- 232.5 CFU-GM/ml, respectively, but there was no statistical difference among them. When ML patients were treated with rhG-CSF, the CFU-GM peak values increased as much as 5.5-folds compared with those following chemotherapy only. However, neither the period from nadir to start of increase in the CFU-GM count nor the time of the CFU-GM peak showed any significant change. These results indicate that the administration of rhG-CSF makes it possible to increase the number of circulating progenitor cells. It appears possible in most of the patients with hematopoietic malignancies to harvest the sufficient number of progenitor cells which are necessary for autologous blood stem cell transplantation.     

Abnormal GM-CSA generation by lymphocytes in patients with cyclic hematopoiesis

Human cyclic hematopoiesis (CH) is a disease characterized by regular 21-day cyclic fluctuations of blood cell counts due to fluctuations in bone marrow cell production. The regular periodicity of the fluctuations suggests a defect in a regulatory feedback control loop. We examined the production of monocyte-derived recruiting activity (MRA) by monocytes and the response to MRA of lymphocytes from three patients with CH. MRA production was normal or increased in patients' monocytes, but granulocyte-macrophage colony-stimulating activity (GM-CSA) production in response to MRA was decreased in lymphocytes from patients with CH (p = 0.005). These data suggest that the regulatory defect in CH may involve defective lymphocyte generation of GM-CSA, resulting in deficient production of mature neutrophils.     

Treatment of idiopathic neutropenia in the elderly with recombinant human granulocyte colony-stimulating factor.

We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) intravenously for 2 weeks to 2 elderly patients with severe neutropenia. The absolute neutrophil count (ANC) recovered promptly after the initiation of rhG-CSF therapy and reached a peak (greater than 10 x 10(9)/l) on the 13th day. The ANC fell rapidly after rhG-CSF was discontinued, but it remained within the normal range after therapy. There were no side effects during the entire course of treatment. Therefore, rhG-CSF seems to be a most beneficial treatment in elderly patients with severe neutropenia.     

A retrospective study of neutropenia in HIV disease

In aiming to define the characteristics of HIV-infected subjects developing neutropenia and describe the causes, features and effects of neutropenia we undertook a retrospective study in a dedicated HIV unit in London, UK. Two hundred and forty-four patients with documented neutropenia, defined as absolute neutrophil count (ANC) < 1,000/mm3, during a 12-month period were studied. First neutropenia occurred at a median CD4 count of 30 cells/mm3. Low CD4 count was associated with longer episodes of neutropenia with a more profound nadir. Two-thirds of episodes lasted less than 2 weeks. ANC nadir was < 500 cells/mm3 in 45% of episodes. Infections were most frequent in patients with profound but brief neutropenic episodes. Neutropenia was generally mild, short-lived and associated with late-stage disease. However, profound neutropenia did develop suddenly in some patients with no prior history of neutropenia (in 13% first neutropenic ANC recorded was < or =500 cells/mm3), and at CD4 count > 200 cells/mm3. Most patients were receiving multiple myelosuppressive therapies. Infection was associated with brief, profound neutropenia.