Use of granulocyte-macrophage colony stimulating factor in the treatment of prolonged haematopoietic dysfunction after chemotherapy alone or chemotherapy plus bone marrow transplantation.

This study evaluates the use of granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with prolonged haematopoietic dysfunction (> 21 days) after using chemotherapy to treat cancer. One hundred and seven patients were identified who had a leucocyte count below 1000 cells/mm3 more than 21 days after start of chemotherapy (81 patients) or after bone marrow transplantation (BMT)(26 patients). There were 66 males and 40 females ranging in age from 4.5 to 82 years. The duration of aplasia was 48 +/- 43 days in the chemotherapy alone group, and 79 +/- 57 days in the post BMT group. Over 80% of the patients had haematologic malignancies and 70% had an infection prior to the start of the cytokine. Patients received 5 micrograms GM-CSF/kg1 body weight daily i.v. or s.c. for 14 +/- 11 days in the chemotherapy group and 20 +/- 26 days in the BMT group. Sixty percent of chemotherapy patients and 58% of BMT patients had a haematological response to treatment (leucocyte count > 2000 cells/mm3. Median times to haematologic recovery were 7 days in the chemotherapy group and 10 days in the BMT group. There was a significant reduction in the number of infections (73% to 28% in the chemotherapy group). Clinical responses in the two groups were 55% and 50%, respectively. No severe, drug-related adverse events were reported and no evidence of stimulation of malignant clones was observed. It is concluded that GM-CSF is effective and well tolerated in patients with prolonged bone marrow dysfunction after chemotherapy or BMT. Although results from an open-label trial must be viewed with caution, this observation confirms the value and safety of GM-CSF therapy in patients with this severe, and often fatal, condition.

A Role for Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in the Treatment of Neutropenic Patients with Pneumonia.

Pneumonia is a serious, difficult to manage, and often fatal infection in neutropenic patients. The availability of hematopoietic growth factors has made it possible to evaluate the role of reversing the neutropenic state. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used in an investigator-initiated, open-label clinical trial in approximately 1200 patients. Data collected on each patient was reviewed to identify all patients who had the combination of neutropenia and pneumonia. Sixty-eight patients (5% of the patients for whom GM-CSF was requested) met the criteria for having neutropenic pneumonia. In this patient population there were 45 males and 20 females (gender was not indicated in 3). Ages ranged from 3 to 83 years (mean 39 +/- 18 years). The underlying diseases included: 7 patients who were receiving chemotherapy for solid malignant tumors, 14 for lymphoma, and 22 for leukemia; 15 post bone marrow transplantation primarily for hematologic malignancy; 3 idiosyncratic drug-induced neutropenia; and 7 with other causes of neutropenia. The type of pneumonia was predominantly fungal in 21 patients, bacterial in 23, viral in 2, protozoal in 1, and uncertain in 21 (presumed to be bacterial in 19 and viral in 2). Patients received a mean of 5µ/kg GM-CSF (range 1.3-12.5µg/kg) daily for a mean of 13 +/- 10 (range 2-57) days. The mean leukocyte count at start of treatment was 600 +/- 500 cells/mm(3), and at the end of treatment was 5600+/-9200 cells/mm(3) (P=0.001). The time between start of GM-CSF and a leukocyte level in excess of 1500/mm(3) was a median of 13 days. Hematopoietic recovery was shown in 46/62 (74%), 40/64 (63%) showed good clinical and/ or radiologic improvement, and 41/68 (60%) survived. Four illustrative case reports are provided. By comparing the hematologic responders to non-responders, it is clear that persistent neutropenia contributed significantly to poor clinical outcome and mortality. Only 3/22 (13%) of non-responders survived, whereas 38/46 (83%) of responders survived. There were 7 adverse events (rash 1, fever/chills 2, malaise 1, myalgia/bone pain 2, increased myeloblasts 1) which were considered to be related to use of the cytokine. Aggravation of the pulmonary inflammation or sepsis syndrome was not observed. Tolerability was good or very good in 89% of patients. Based on this open-label study, the use of GM-CSF in combination with appropriate antibiotics is effective and safe for the management of patients with pneumonia and severe hematopoietic dysfunction.

[Somatostatin analog (octreotide) in clinical use: current and potential indications]. / Somatostatin-Analog (Octreotid) im klinischen Einsatz: neuere und potentielle Indikationen.

The long-acting somatostatin analogue octreotide is a synthetic cyclic peptide consisting of 8 amino acids. Depending on the organ, it acts either as a hormone or as a neurotransmitter. The effect on various physiological functions in the brain and the gastrointestinal tract is mainly inhibitory. Due to its inhibitory actions, the possibility of intravenous and subcutaneous administration and the lack of serious side-effects, octreotide offers a broad spectrum of possible indications. Today octreotide is recommended in acromegaly patients and for the treatment of hormone dependent symptoms in patients with gastroenteropancreatic tumours. New indications are enterocutaneous and pancreatic fistulas and the prevention of complications in major pancreatic surgery. In patients with dumping and short-bowel syndrome, octreotide may be helpful until dietary regimens are established. In Aids patients with severe diarrhea, octreotide can be used to stabilize patients with severe dehydration and malnutrition. The clinical effectiveness on upper GI-bleeding due to gastric ulcer and oesophageal varices is still controversial. Future studies must prove whether octreotide may be helpful in treating diabetic retino- and nephropathy because of the possibility of suppressing growth hormone and IGF-I. The antiproliferative effect of octreotide also allows its use in patients with somatostatin-receptor-positive, non-endocrine solid tumors (e.g. brain, breast and small-cell lung cancer). A promising area is the scintigraphic visualization of somatostatin-receptor-positive tumors with a radio-labelled octreotide analogue and the possible target irradiation of these tumors by beta-particle emitting isotopes attached to such analogues.