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The present study evaluated the clinical efficacity and tolerability of the subcutaneous (SC) administration of lenograstim, a glycosylated form of rHuG-CSF identical to human G-CSF, in the treatment of congenital agranulocytosis. Assessment criteria included neutrophil response and response stability, incidence and severity of infection and gingivostomatitis and quality of life. Lenograstim, at induction dosages of 5 (n = 9), 10 (n = 2) or 20 (n = 1) microgram/kg/day SC, produced neutrophil recovery in all of 12 children with congenital agranulocytosis. There was a median delay of 7 days to recovery after establishment of the effective induction dose. Whereas this dosage maintained a stable neutrophil response in 7 patients, the remaining 5 required dosage increases and dose reduction during maintenance therapy was not possible in these 5 cases. Among 4 patients stabilised at a dosage of 5 micrograms/kg/day, in 2 cases a lower minimum effective dose of 2 micrograms/kg/day was attained over the maintenance phase. Administration of twice the daily dose of lenograstim on alternate days was feasible in 3 of 8 patients. Lenograstim therapy reduced the incidence of infection and hospitalisation for infection relative to the prestudy period, while in 6 of 9 cases there was complete recovery from gingivostomatitis. Only one patient discontinued treatment on account of adverse events. Finally, perceived health and disease related symptoms showed a significant (p < 0.001) amelioration in the course of the study. Thus, lenogastrim produced sustained neurotrophil recovery in patients with congenital agranulocytosis, decreased the incidence and severity of infection and improved the quality of life.

The authors treated a patient with methimazol (Metothyrin)-induced agranulocytosis with human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). On day seven, after combined antibiotics, corticosteroid and at a dose of 270 ug daily subcutaneous GM-CSF therapy the septic state of the patients rapidly cured and the leucocytes reached the peripheric blood. No side effects were found. The publication of this case history might help to determine the place of human GM-CSF-s therapy in the treatment of agranulocytosis of different origin.

A 20-year-old woman had for the preceding 11 weeks been receiving clozapine (225 mg/d) for an endogenous psychosis when she developed a urinary tract infection with fever. The blood count showed 2100 white cells/microliter without any neutrophils, the count having been normal 5 days previously. Physical examination was normal except for a fever of 39 degrees C and parodontitis. The red cell count was 3.9 mill/microliters, platelet count 443,000/microliters. Bone marrow biopsy revealed almost complete stop of proliferation and maturation in granulocytopoiesis so that granulocyte colony-stimulating factor (300 micrograms daily subcutaneously) had to be administered in addition to supportive measures. The granulocyte count at first fell to 1400 cells/microliter, but nine days after starting the drug myeloblasts, promyelocytes and myelocytes reappeared in peripheral blood for the first time. On the tenth day, administration of the growth factor was discontinued. An overshoot granulocytopoiesis occurred in bone marrow on the 13th day; on the 22nd day after treatment had been started the patient had a normal blood picture and was discharged.

A 35-year-old female hematology technician with Graves' disease developed agranulocytosis a few days after starting therapy with Tapazole (methimazole). Because of a recent report of use of recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with propylthiouracil-induced agranulocytosis, 5 micrograms/kg/day G-CSF was administered and her granulocyte count returned to normal after three doses, on the sixth day after the last dose of methimazole. We conclude that in patients with drug-induced agranulocytosis, the use of G-CSF, in addition to discontinuation of the offending drug, hastens recovery and reduces morbidity.

Background: Is clozapine-induced agranulocytosis amenable to treatment with recombinant granulocyte colony-stimulating factor (rG-CSF)? Will this treatment provide benefits in terms of morbidity, mortality, and costs compared with current treatment?, Method: Five patients with clozapine-induced agranulocytosis (granulocytes < 500/cu mm) were treated with the rG-CSF filgrastim, in addition to standard agranulocytosis therapy protocol., Results: Time from onset until resolution of agranulocytosis was 8.2 +/- 2.1 days compared with a historical study of seven cases where filgrastim was not used and 15.7 +/- 3.7 days were required for resolution., Conclusion: rG-CSF (filgrastim) may be an effective and cost-reducing way to provide improved treatment for clozapine-induced agranulocytosis. More research is required.

Background: Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal., Methods: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure., Results: Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed., Conclusion: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis.

Acute infection with the human immunodeficiency virus (HIV) is often characterised by a mononucleosis-like syndrome. We describe a patient who presented with the typical febrile syndrome associated with acute HIV infection, who also had significant granulocytopenia. Although granulocytopenia is relatively common in the later stages of HIV infection, it has only been described once before in the acute stage. The mechanism may be immune mediated, although data are limited. Clinicians should be aware of acute HIV infection as a possible cause of granulocytopenia.

143 aplastic episodes with fever in 91 haematological patients with granulocytopenia were treated empirically in a randomized prospective study using either imipenem (Imi) or a combination of tobramycin and cefuroxime (T/C). Response after 72 h was significantly better in patients receiving Imi (44/75 vs 27/68, p < 0.05). This was seen especially in patients with bacteriologically proven infections where the isolated staphylococci and streptococci were more susceptible to Imi. In both groups, patients who failed to respond to the initial antibiotic therapy were given vancomycin and aztreonam (V/A). The response rate after another 72 h, measured using the same criteria as after the first 72 h, did not differ statistically between the groups. One patient in each study group died from the bacterial infection, both from Gram-positive bacteraemia. Duration of fever was significantly shorter in the Imi group (4 days vs 7 days, p < 0.04). Serum peak and trough concentrations of the antibiotics were comparable. Both regimens were well tolerated. Our results show that monotherapy with imipenem is superior to the combination of tobramycin and cefuroxime during the first 72 h of therapy and can be safely administered to neutropenic patients with predominantly Gram-positive infections. A combination of vancomycin and aztreonam, given when initial imipenem treatment has failed, was effective in only a few patients. Adjuvant glycopeptide therapy from the outset in the treatment of febrile granulocytopenic patients did not seem worthwhile.

Kostmann's syndrome is a congenital disorder characterized by impairment of myeloid differentiation in bone marrow with severe absolute neutropenia. A 17-month-old girl was admitted to the hospital with complaints of recurrent skin infections since birth and severe pneumonia of the right lung which had been resistant to antibiotics since the patient was eight months old. Anemia, severe neutropenia and maturational arrest of granulocytes at the myelocyte stage in bone marrow were detected. At the age of 20 months, a right pneumonectomy was performed because of resistant cystic infection. Postoperatively, she was diagnosed with Kostmann's syndrome. Recombinant human granulocyte-colony-stimulating factor (rhG-CSF) was administered intravenously at a dose of 3 micrograms/kg/day, gradually increasing to 60 micrograms/kg/day in sequential seven-day courses to obtain a neutrophil count of more than 500 cells/mm3. Absolute neutrophil counts increased to greater than 1000 cells/mm3 at a dose of 60 micrograms/kg/day, and at that time bone marrow aspiration revealed an increase in neutrophilic granulocytic precursors beyond the myelocyte stage. In order to maintain the neutrophil response, a dose of 20 micrograms/kg/day rhG-CSF subcutaneously was continued successfully. The patient has tolerated rhG-CSF treatment without complications, and infectious attacks have significantly decreased.

A study was carried out to investigate the efficacy of therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 patients with granulocytopenia and sepsis who had failed to respond to antibiotics. The mean leukocyte count at the start of the study was 911 +/- 334/microliter. Patients were injected subcutaneously with 75 micrograms rhG-CSF once daily for a mean of 5.2 days. The plasma G-CSF concentration was measured by ELISA. The leukocyte count increased approximately 9-fold after 1 week in 19 patients and the percentage of granulocytes rose from 46.2% to 78.9%. These 19 patients survived, while the 5 patients with no leukocyte response to rhG-CSF died. High plasma G-CSF levels were found in patients with granulocytopenia. Plasma G-CSF levels decreased as levels of granulocyte increased in survivors. A high plasma G-CSF concentration persisted in the 5 non-responding patients resulting in a fatal outcome. This study suggests that rhG-CSF both increased the leukocyte count and was a useful therapeutic manoeuvre for sepsis.

Agranulocytosis is the most serious problem, potentially fatal, that can occur during antithyroid drug therapy. The use of hematopoietic growth factors is an attractive approach to reduce the period of this drug-induced neutropenia. We report two cases of severe antithyroid drug-related agranulocytosis (granulocyte count < 0.1 x 10(9)/L) treated with Granulocyte Colony-Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). The delay to observe a granulocyte count superior to 1 x 10(9)/L was respectively 1 and 5 days. Our results, with others, clearly show that hematopoietic growth factors are effective in severe antithyroid drug-induced agranulocytosis.

Conventional amphotericin B (Amph-B) is the drug of choice for treating systemic fungal infections. Recently, a new formulation has become available, encapsulated in liposomes (Amph-lip). This new form of administration was developed in order to lower the acute side effects and to offer the possibility of administering high doses of amphotericin B. Experience with Amph-lip is limited, especially in children. We treated four children with documented systemic fungal infections with Amph-lip and administered it empirically to 12 children. Fifteen of these 16 children were severely granulocytopenic oncologic patients. One 3-month-old baby suffered from systemic candidiasis. Amph-lip was preferred to conventional Amph-B in children with organ dysfunction developing as a consequence of conventional chemotherapy or bone marrow transplantation, after failure of conventional Amph-B to improve a fungal infection, and after adverse drug reactions had occurred. The daily doses of Amph-lip ranged from 1 to 6 mg/kg (median 3 mg/kg), the cumulative doses from 13 to 311 mg/kg (median 75 mg/kg). Acute adverse reactions or organ function abnormalities attributable to Amph-lip did not occur in 402 administrations. Amph-lip has proven to be well tolerated by children in terms of acute toxicity and in the long term. Although large cumulative doses were given, organ function abnormalities attributable to Amph-lip doses were not detected in any of ten long-term survivors over a median observation time of 36 months (range 30-44 months). Amph-lip appears to be a promising alternative antifungal treatment, especially for patients with impaired organ function, when high doses of amphotericin B are necessary.

Two premenopausal female patients with Graves' hyperthyroidism and propylthiouracil (PTU)-induced agranulocytosis are presented. The first patient, age 47, received 300 mg of PTU per day and developed agranulocytosis within 6 weeks of the commencement of therapy. There were no granulocytes in the peripheral smear and a bone marrow biopsy demonstrated an absence of the entire myeloid cell line as well as the presence of many granulomas. The second patient, age 39, received PTU 1600 mg per day for two and half weeks and then 2 days of methimazole, 200 mg per day. She developed complete agranulocytosis on peripheral smear within 3 weeks of the initiation of therapy. Her bone marrow biopsy demonstrated maturation arrest of the granulocytic cell line at the myelocyte stage. In addition to discontinuing their antithyroid drugs, both patients were treated with G-CSF subcutaneously. The first patient received 300 micrograms of G-CSF on days 2 and 4 after discontinuing PTU with the appearance of 4.7 x 10(9)/L granulocytes and granulocyte precursors on day 4. The second patient received 575 micrograms of G-CSF for 2 days and 300 micrograms for 1 additional day beginning on the third day after discontinuing antithyroid drugs. On the second treatment day there were 5.8 x 10(9)/L granulocytes and granulocyte precursors on the peripheral smear. A comparison to previously published cases on antithyroid drug induced agranulocytosis suggests that the use of G-CSF decreased the amount of time required for marrow recovery after the cessation of the offending drug.

Drug-induced agranulocytosis in the outpatient setting is a rare but potentially fatal adverse effect of many classes of medications. Five patients with this disorder presented to Yale-New Haven (Conn) Hospital during 1990 through 1992. Three patients treated with granulocyte-colony stimulating factor and two patients treated with routine care were studied for relevant clinical outcomes. Treatment with granulocyte-colony stimulating factor was associated with a shorter duration of neutropenia and a decreased length of hospital stay, consistent with recent case reports. Despite the high cost of the drug, treatment with granulocyte-colony stimulating factor was found to be cost-effective for patients with uncomplicated drug-induced agranulocytosis.

Agranulocytosis, although extremely infrequent, is a serious complication of antithyroidal drug therapy in patients with hyperthyroidism. Presently, there is no specific therapy for this life-threatening complication, and recovery time is highly variable. Recently, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was reported to be effective in shortening the recovery time of the neutropenia in patients undergoing chemotherapy. The present study was undertaken to determine the efficacy of rhG-CSF administration in patients with methimazole-induced (MMI) agranulocytosis. Thirty-four patients (7 males and 27 females, ages 16-68 yr) with MMI agranulocytosis were divided into 3 groups: group A (n = 11) was treated with antibiotics only; group B (n = 11) received antibiotics and dexamethasone, 8 mg/day; and group C (n = 12) was treated with antibiotics and im injections of rhG-CSF, 75 micrograms/day. Patients in groups A and B were studied retrospectively. When rhG-CSF became available, patients in group C were studied prospectively. Bone marrow sternal punctures were performed in all group C patients who were then divided into 2 subgroups according to the granulocyte to erythrocyte count ratio (G:E). Group C1 (n = 6) had a G:E ratio of less than 0.5, and group C2 (n = 6) had a ratio of more than or equal to 0.5. Recovery time in all groups was defined as the number of days required for the peripheral granulocyte count to be greater than 1.0 x 10(9)/L. There was no significant difference in recovery time between groups A and B: 10.1 +/- 2.2 and 12.3 +/- 1.9 days (mean +/- SE), respectively. P was not significant; the administration of dexamethasone proved to be ineffective in shortening the time for recovery from peripheral granulocytes. On the other hand, recovery time was significantly shorter in group C (6.8 +/- 1.2 days mean +/- SE) compared with groups A and B (P < 0.05). Group C2 recovered in 2.2 +/- 0.6 days whereas group C1 took much longer, 9.8 +/- 1.3 days (P < 0.001). There was a direct correlation between the G:E ratio and the peripheral leucocyte count, r = 0.806, P < 0.01. Furthermore, rhG-CSF significantly shortened recovery time when the peripheral granulocyte count was greater than 0.1 x 10(9)/L (group C2) compared with patients whose counts were less than 0.1 x 10(9)/L (group C1), 2.2 +/- 0.4 vs. 8.6 +/- 1.3 days, respectively (P < 0.001). These data indicate that administration of steroids is ineffective in shortening the duration of recovery in patients with MMI agranulocytosis.(ABSTRACT TRUNCATED AT 400 WORDS)

After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease the next day to < 0.050 x 10(9) l-1, and this complete agranulocytosis continued for 10 days. As no response was obtained after 1 week the dosage of filgrastim was increased to 10 micrograms kg-1 day-1 with immediate improvement. A rapid and pronounced leucocytosis developed with maximal value of neutrophil granulocytes (including immature forms) of 33.108 x 10(9) l-1 on day 12 after admission. The patient only had minor infectious complications during the neutropenic period. In conclusion, early treatment with filgrastim seems warranted in severe cases of clozapine-induced agranulocytosis. A dosage of 10 micrograms kg-1 day-1 can be recommended.

Chlorpromazine-induced agranulocytosis is an uncommon disorder associated with a high frequency of fatality. We describe two patients with chlorpromazine-induced granulocytosis in whom granulocyte colony stimulating factor (G-CSF) administration enhanced the speed of neutrophil recovery. No toxicity was noted with G-CSF and both patients made a successful recovery. We propose there is a role for such cytokine therapy in patients with life-threatening agranulocytosis in order to speed the recovery of neutrophils.

This article describes the use of granulocyte macrophage colony stimulating factor and granulocyte colony stimulating factor in two patients with drug induced granulocytopenia. A granulocyte count > 1 x 10(9)/l was obtained after 7 days' treatment. These results suggest that the haematopoietic growth factors shortened the period of agranulocytosis and subsequently may improve the survival of these patients.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was given to an intensive-care patient with polytrauma in a life-threatening situation with acquired agranulocytosis and sepsis. Mature granulocytes reappeared in the blood 2 days after initiation of rhGM-CSF therapy; granulocyte precursors peaked at 43% after 5 days. Bone marrow examination performed 7 days after the beginning of rhGM-CSF therapy revealed complete regeneration of granulopoiesis. The functional analysis of these blood leukocytes in vitro showed regular production of reactive oxygen radicals. Clinically, the patient recovered without any serious side effects due to the rhGM-CSF therapy. These results suggest that rhGM-CSF accelerates granulocyte recovery from acquired agranulocytosis with the presence of their functional activity.

Objective: To report a case of clozapine- and molindone-induced agranulocytosis and to discuss treatment using filgrastim, a granulocyte colony-stimulating factor., Case Summary: A 64-year-old woman who had been on long-term clozapine therapy for schizophrenia was hospitalized with presumed drug-induced agranulocytosis. She had also been on short-term molindone therapy. A bone marrow biopsy and the initial white blood cell (WBC) count were consistent with drug-induced agranulocytosis. Following seven days of treatment with subcutaneous filgrastim 300 micrograms/d, her absolute neutrophil count was above 500 x 10(6)/L., Discussion: Reports in the literature discussing antipsychotic drug-induced agranulocytosis are reviewed. A relationship between treatment with filgrastim and WBC response is postulated., Conclusions: Filgrastim may be useful in ameliorating the effects of clozapine- and molindone-induced agranulocytosis.

Objective: To report a case of sulfasalazine-induced agranulocytosis that was successfully treated with granulocyte-colony stimulating factor (G-CSF)., Case Summary: An 82-year-old woman developed agranulocytosis within two months of initiating sulfasalazine therapy. She was hospitalized, empiric antibiotic and antifungal agents were prescribed, and sulfasalazine therapy was stopped. The patient received G-CSF 600 micrograms/d subcutaneously for six consecutive days, starting on hospital day 5. Agranulocytosis resolved on day 5 and leukopenia on day 6 of G-CSF therapy. No adverse reactions were attributed to administration of this agent and the patient was discharged on hospital day 13., Discussion: Numerous agents, including sulfasalazine, have been associated with agranulocytosis. Agranulocytic patients frequently experience life-threatening bacterial and fungal infections. Administration of colony stimulating factors may reduce the duration of agranulocytosis and incidence of life-threatening infections., Conclusions: G-CSF administration appears to have decreased the duration of this elderly patient's agranulocytosis and hospitalization.

A 56 year old female patient treated with carbimazole for hyperthyroidism developed agranulocytosis complicated by pneumonia. She was treated by sc administration of 6 micrograms/kg rhGM-CSF for 10 days. The first neutrophils appeared in the peripheral blood on the 4th day and normal numbers are reached on the 7th day of treatment. This was accompanied by a rapid resolution of fever. The use of growth factors may be justified in cases of drug-induced agranulocytosis.

An unusual instance of severe and potentially lethal depression of the bone marrow is described as a result of the administration of phenytoin for seizure prophylaxis. The patient was treated successfully by prompt cessation of phenytoin and intravenous administration of human recombinant granulocyte-macrophage colony-stimulating factor.

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C +/- T), both agents being administered only if the initial granulocyte count was below 200/microliters, or ceftazidime plus piperacillin (C + P). The overall response rate was 71% (39 of 60 for C +/- T and 45 of 58 for C + P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C + P regimen (P = 0.06), there was no difference in response for patients with bacteremia and profound (< 100/microliters) sustained granulocytopenia. The double beta-lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced excellent serum bactericidal levels (C +/- T geometric mean peak 1:170; C + P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C + P and in 6 of 89 trials in the C +/- T group (P = 0.19). The incidence of secondary infections in patients with profound (< 100/microliters) sustained granulocytopenia was lower in the C +/- T group (P = 0.04). Alimentary canal anaerobic flora preservation with C +/- T, and suppression with C + P, was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of human macrophage-colony-stimulating factor (hM-CSF) on tumoricidal activity was examined in athymic mice bearing the human ovarian cancer cell line, HRA, injected intraperitoneally (i.p.). The survival period and survival rate in the groups treated daily with hM-CSF were significantly longer (P < 0.01) than in the untreated group. The peritoneal cell smears showed that ascitic tumor cells were markedly decreased in the hM-CSF-treated groups, and macrophages phagocytosed tumor cells, indicating a contact-mediated direct cytolysis. The combined therapeutic effects of cisplatin and hM-CSF on HRA-bearing athymic mice were also studied. The mean survival period was 25.4, 47.2, 42.4 and 67.4 days, respectively, in the untreated group, and in the groups treated with cisplatin alone, with hM-CSF alone, and with combined cisplatin and hM-CSF. The survival period and rate were significantly longer (P < 0.01) in the group treated with combined cisplatin and hM-CSF than in those treated with cisplatin or hM-CSF alone, indicating the therapeutic effectiveness of the combined use. Moreover, hM-CSF is effective against granulocytopenia due to bone marrow suppression caused by cisplatin. Our data demonstrate that hM-CSF administered i.p. has a tumoricidal activity in athymic mice bearing human ovarian cancer i.p., which is mediated by activated macrophages, and that the combined administration of cisplatin and hM-CSF has a significant therapeutic effect.

Clozapine-induced agranulocytosis is usually reversible after discontinuation of the drug. A patient who developed agranulocytosis after termination of clozapine therapy responded to treatment with granulocyte macrophage colony stimulating factor.

Five patients with drug-induced agranulocytosis received 300 micrograms recombinant human granulocyte colony-stimulating factor (rh G-CSF) subcutaneously twice daily for 2-5 days. G-CSF therapy resulted in a steep increase of the neutrophil count, which was faster than that in patients with spontaneous recovery reported in the literature. In all four patients with infectious complications fever rapidly declined with the increase of granulocytes. G-CSF may be useful in the management of drug-induced agranulocytosis.

A 65 year-old woman was admitted in May 1990, because of fever, generalized lymphadenopathy and eruption. Laboratory examination showed granulocytopenia, polyclonal hypergammaglobulinemia, positive Coombs' test, positive cold antibody and positive anti-E erythrocyte antibody. 7 days after admission autoimmune hemolytic anemia developed. The appearance of the anti neutrophil leukocyte antibody was suspected because of the absence of the segmented neutrophils in marrow specimen. Histological findings of the biopsied lymph node and the marker study of the tumor cell disclosed IBL-like T cell lymphoma. The patient was treated with G-CSF and VEPA chemotherapy. Granulocytes increased and she showed marked symptomatic improvement with complete remission. Our case showed various clinical pictures with hemolytic anemia and granulocytopenia, which could be based on the autoimmune mechanisms.

To investigate the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on cytotoxic chemotherapy-induced granulocytopenia, we performed an open nonrandomized clinical trial in 46 patients with malignancies receiving cytotoxic chemotherapy regimen. Twenty-six patients who received two cycles of the identical chemotherapy regimen and had granulocytopenia less than 1 x 10(9) cells/l after the first cycle of chemotherapy were eligible for this study. They received 60, 125 or 250 micrograms/m2/day of rhGM-CSF randomly. The nadirs of peripheral granulocytes demonstrated significantly much higher levels in all dosages studied than those of control cycles. The duration of granulocytopenia was shortened with rhGM-CSF support. Such granulocyte recovery appeared in parallel with increasing dosages of GM-CSF, thus, infections with febrile episodes were reduced. Toxicity of rhGM-CSF was generally well tolerated.

In Brazil, 226 children with cancer presenting 299 episodes of fever and neutropenia (< or = 500/mm3) were treated with two consecutive empirical regimens. Regimen I-Cefoxitin Amikacin-Carbenicillin; and Regimen II Ceftriaxone-Amikacin. 67.0% of the patients had leukemias or lymphomas, documented infections occurred in 47.2%, superinfections occurred in 18.7% (Reg. I) and 17.8% (Reg. II) of the episodes. The most common agents identified in Reg. I and Reg. II were, respectively, Gram negative rods (55.0%) and Gram positive cocci (52.6%). The overall rate of success with modifications (Amphotericin B, Vancomycin, Clindamycin, Metronidazole) was higher in Reg. II (93.0%) than in Reg. I (84.0%). This study shows that the appropriate formula to maximize the successful treatment of children with cancer, fever and neutropenia in developing nations includes adherence to established principles of supportive care, utilizing the optimal antibiotic agents available in the country. It is important to promote the necessary modifications along the treatment having in mind the high index of resistant agents.