Shifting to outpatient management of acute myeloid leukemia: a prospective experience
2006; Elsevier BV; Volume: 17; Issue: 5 Linguagem: Inglês
10.1093/annonc/mdl011
ISSN1569-8041
AutoresMary Lynn Savoie, T.J. Nevil, Kevin Song, Donna L. Forrest, Donna E. Hogge, S.H. Nantel, John D. Shepherd, Clay Smith, Heather J. Sutherland, Cynthia L. Toze, Julye C. Lavoie,
Tópico(s)Acute Myeloid Leukemia Research
ResumoBackground: We assessed the feasibility of outpatient chemotherapy and supportive care in patients with acute myeloid leukemia (AML).Patients and methods: All patients receiving curative intent chemotherapy between 09/01 and 10/02 and meeting our criteria received supportive care post induction chemotherapy as well as their entire consolidation chemotherapy cycles as outpatients. Patients received antimicrobial prophylaxis; those developing episodes of fever and not meeting the criteria for admission were treated with outpatient intravenous antibiotics.Results: Seventy-one cycles of induction chemotherapy were administered for newly diagnosed or relapsed AML. In 25 cycles the patient was discharged post chemotherapy prior to count recovery. Of these, 14 patients developed one or more febrile episodes as an outpatient and nine (36%) required readmission to hospital. Sixty-seven consolidation cycles were given on an outpatient basis. In 39 cycles there was one or more febrile episodes and in 14 (21%) admission was required. Infections were documented in four cases during induction and in 27 during consolidation. There were no treatment-related deaths.Conclusions: Outpatient management of AML is safe and feasible using the strategies outlined in this report. Background: We assessed the feasibility of outpatient chemotherapy and supportive care in patients with acute myeloid leukemia (AML). Patients and methods: All patients receiving curative intent chemotherapy between 09/01 and 10/02 and meeting our criteria received supportive care post induction chemotherapy as well as their entire consolidation chemotherapy cycles as outpatients. Patients received antimicrobial prophylaxis; those developing episodes of fever and not meeting the criteria for admission were treated with outpatient intravenous antibiotics. Results: Seventy-one cycles of induction chemotherapy were administered for newly diagnosed or relapsed AML. In 25 cycles the patient was discharged post chemotherapy prior to count recovery. Of these, 14 patients developed one or more febrile episodes as an outpatient and nine (36%) required readmission to hospital. Sixty-seven consolidation cycles were given on an outpatient basis. In 39 cycles there was one or more febrile episodes and in 14 (21%) admission was required. Infections were documented in four cases during induction and in 27 during consolidation. There were no treatment-related deaths. Conclusions: Outpatient management of AML is safe and feasible using the strategies outlined in this report. introductioAcute myeloid leukemia (AML) state of the art treatment includes induction chemotherapy, usually anthracycline and cytarabine based, followed by either high-dose cytarabine based consolidation chemotherapy or stem cell transplantation if indicated [1.Smith M. Barnett M. Bassan R. et al.Adult acute myeloid leukaemia.Crit Rev Oncol Hematol. 2004; 50: 197-222Crossref PubMed Scopus (146) Google Scholar]. Chemotherapy with curative intent is followed by a prolonged period of profound pancytopenia the complications of which require immediate intervention. Patients have traditionally been hospitalised for the duration of chemotherapy and until count recovery.Outpatient care of patients with malignancies has become increasingly common driven by health care costs, increased demand for existing inpatient resources, improved supportive care and patient wishes to spend the least amount of time in the inpatient setting. Outpatient therapy has regularly been described in solid tumours [2.Dollinger M. Guidelines for hospitalization for chemotherapy.Oncologist. 1996; 1: 107-111Crossref PubMed Google Scholar], high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), [3.Summers N. Dawe U. Stewart D.A. A comparison of inpatient and outpatient ASCT.Bone Marrow Transplant. 2000; 26: 389-395Crossref PubMed Scopus (41) Google Scholar, 4.Gluck S. des Rochers C. Cano C. et al.High-dose chemotherapy followed by autologous blood cell transplantation: a safe and effective outpatient approach.Bone Marrow Transplant. 1997; 20: 431-434Crossref PubMed Scopus (37) Google Scholar] and more recently in the allogeneic nonmyeloablative HSCT setting despite earlier studies of protective isolation suggesting an infection preventative benefit [5.Gómez-Almauger D. Ruiz-Argüelles A. González-Llano O. et al.Hematopoietic stem cell autografts using a non-myeloablative conditioning regimen can be safely performed on an outpatient basis: report of four cases.Bone Marrow Transplant. 2000; 25: 131-133Crossref PubMed Scopus (67) Google Scholar, 6.Ruiz-Argüelles G.J. Gómez-Almauger D. Ruiz-Argüelles A. et al.Results of an outpatient-based stem cell allotransplant program using nonmyeloablative conditioning regimens.Am J Hematol. 2001; 66: 241-244Crossref PubMed Scopus (70) Google Scholar, 7.van Tiel F.H. Harbers M.M. Kessels A.G. Schouten H.C. Home care versus hospital care of patients with hematological malignancies and chemotherapy-induced cytopenia.Ann Oncol. 2005; 16: 195-205Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar]. In selected patients with AML, successful early discharge post chemotherapy along with outpatient administration of consolidation cycles has also been reported [8.Ruiz-Argüelles G.J. Apreza-Molina M.A.G. Alemán-Hoey D.D. et al.Outpatient supportive therapy after induction to remission therapy in adult acute myelogenous leukaemia (AML) is feasible: a multicentre study.Eur J Haematol. 1995; 54: 18-20PubMed Google Scholar, 9.Gillis S. Dann E.J. Rund D. Selective discharge of patients with acute myeloid leukemia during chemotherapy-induced neutropenia.Am J Hematol. 1996; 51: 26-31Crossref PubMed Scopus (38) Google Scholar, 10.Girmenia C. Latagliata R. Tosti S. et al.Outpatient management of acute promyelocytic leukemia after consolidation chemotherapy.Leukemia. 1999; 13: 514-517Crossref PubMed Scopus (20) Google Scholar, 11.Girmenia C. Alimena G. Latagliata R. et al.Out-patient management of acute myeloid leukemia after consolidation chemotherapy.Role of Hematologic Emergency Unit. Haematologica. 1999; 84: 814-819PubMed Google Scholar, 12.Allan D.S. Buckstein R. Imrie K.R. Outpatient supportive care following chemotherapy for acute myeloblastic leukemia.Leuk Lymphoma. 2001; 42: 339-346Crossref PubMed Scopus (33) Google Scholar].In September 2001 our centre moved as much as possible of the management of patients with AML to the outpatient setting. This was driven by an increasing number of patients waiting to be admitted into a restricted number of inpatient beds creating the possibility of detrimental delays between chemotherapy cycles. No changes were made to the actual chemotherapy administered. Patients with AML have typically been considered high risk with febrile neutropenia; here outpatient antibacterial therapy was attempted. Surveillance was necessary to assure a constant level of care therefore data was gathered prospectively on all patients.patients and methoddesigBetween September 2001 and October 2002 a systematic prospective observation of all AML patients treated at the Vancouver General Hospital and British Columbia (BC) Cancer Agency through the Leukemia/Bone Marrow Transplant (L/BMT) Program of BC was performed. This centre is the only tertiary referral centre for acute leukemia in BC allowing for a population based assessment. All patients gave informed consent. Many of these patients were discharged soon after induction chemotherapy was completed or received consolidation chemotherapy entirely as an outpatient. The goal was to assess safety and feasibility of this approach and to determine if strategy modifications were required.eligibility criteriAll patients at our centre with AML receiving intensive induction or consolidation chemotherapy were eligible for outpatient management. This was regardless of age and included patients with both newly diagnosed and relapsed disease. Early discharge (ED) during induction was defined as any discharge after chemotherapy prior to absolute neutrophil count (ANC) recovery > 0.5 × 109/l. Inclusion criteria for ED and outpatient management included: absence of fever (T < 38.3°C), introduction of an appropriate prophylactic or therapeutic antimicrobial regimen, hemodynamic stability, and resolution of any coagulopathy, availability of an accommodation within 60 min of the centre, a willing and able caregiver and the absence of serious co-morbidities. Patients in complete remission received further treatment based on risk assessment. Patients with a good risk karyotype or patients with intermediate risk cytogenetics without an available matched sibling donor received two further cycles of consolidation chemotherapy. All other patients underwent HSCT in first remission. Patients in partial remission and patients aged greater than 55 years received further therapy according to the decision of their primary hematologist [1.Smith M. Barnett M. Bassan R. et al.Adult acute myeloid leukaemia.Crit Rev Oncol Hematol. 2004; 50: 197-222Crossref PubMed Scopus (146) Google Scholar]. Our intention was to treat patients with consolidation chemotherapy entirely as outpatients provided they met the above eligibility criteria.treatment descriptioA variety of chemotherapeutic regimens were utilised and are described in Table 1. Those with AML M3 according to FAB subtype received chemotherapy regimen AML-M3 regardless of age. The remainder of newly diagnosed patients received HIDAC/Dauno if they were less than 60 years of age or 7 + 3 if they were older than 60 years of age. Patients older than 65 years of age were only offered curative intent chemotherapy if they had no serious comorbidities leading to a relatively young cohort. VP-16/CY was given as a salvage regimen to those with primary refractory disease or those who relapsed within one year. Carbo/ara C was used for relapsed disease at greater than 1 year from the end of consolidation therapy. 5 + 2 was used in advanced age or to prevent toxicity.Table 1Chemotherapy regimensHIDAC/DaunoCytarabine 3.0 gm/m2/d days 1–6 and daunorubicin 45 mg/m2/d days 1–37 + 3Cytarabine 200 mg/m2/d days 1–7 and daunorubicin 45 mg/m2/d days 1–3AML-M3Cytarabine 200 mg/m2/d days 1–7, daunorubicin 60 mg/m2/d days 1–3 and ATRA 30 mg/m2/d days 1–60VP-16/CYEtoposide 2.4 gm/m2 day 1 and cyclophosphamide 50 mg/kg/d on days 3–5Carbo/ara CCytarabine 1.5 gm/m2/d bid days 1–4 and carboplatin 300 mg/m2/d CIVI days 5–85 + 2Cytarabine 200 mg/m2/d days 1–5 and daunorubicin 30 mg/m2/d days 1–2 Open table in a new tab Supportive care consisted of the use of 5-HT3 antagonists for nausea and vomiting as well as good oral hygiene. Starting on the day following the last dose of chemotherapy, all patients received antimicrobial prophylaxis with Ciprofloxacin 500 mg p.o. bid. Acyclovir 600 mg p.o. qid or Valacyclovir 500 mg p.o. od was used if the HSV IgG titre was positive; Fluconazole 200 to 400 mg p.o. od was used as antifungal prophylaxis or, in cases of previously documented or probable invasive fungal infection, Itraconazole 200 mg p.o. bid. The prophylactic antimicrobials were stopped when the ANC reached 0.5 × 109/l. Patients were not routinely treated with Granulocyte Colony Stimulating Factor. Patients were transfused two units of packed red cells if the hemoglobin fell below 90 gm/l and either five units of random donor platelets or one unit of single donor platelets if the platelet count was less than 15 × 109/l and the patient was afebrile, or if the platelet count was less than 20 × 109/l and the patient was bleeding or febrile. The transfusion of five platelet units was considered to be one platelet transfusion. All patients had indwelling Hickman type catheters.Patients were seen in the outpatient day-care clinic at least three times per week. The day-care clinic includes all patients treated by the L/BMT Program and averaged 32 patient visits per day during the observation period. An attending physician, a clinical fellow and four to seven nurses staff this clinic. Walk-in assessments, laboratory, blood bank and pharmacy support are available during clinic hours. At each visit patients have routine vital signs measured, complete a symptom checklist, and have bloodwork and a clinical assessment done. The care team discusses all patients on a daily basis. Further testing is ordered and therapy modified according to their current clinical situation. Outside clinic hours patients are instructed to contact the L/BMT physician on call if they develop a temperature greater than 38°C or if they have other concerns. As required the physician can then chose to evaluate the patient further by having them present to the hospital's emergency unit within the hour.For the purpose of this study a febrile episode was defined as an oral temperature of greater than 38.3°C, a temperature greater than 38.0°C for at least 48 h or if the patient developed rigors or appeared septic. Blood cultures were taken the first time the patient had a temperature of more than 38.3°C orally and cultures were taken from the urine, nasopharynx, and/or stool as clinically indicated. A chest X-ray and a skin swab from the Hickman catheter exit site were also performed as indicated. Subsequent blood cultures were obtained when patients had a new temperature elevation and/or chills, twice weekly in the event of a continuous fever and daily for 3 days if bacteremia was documented. A second febrile episode was assigned if a patient developed a new fever after being afebrile for at least 48 hours or if new infectious symptoms developed even if the patient had never completely defervesced. With each febrile neutropenic episode empiric antibiotic therapy was immediately initiated at the day-care clinic or emergency department with a once daily dosing regimen consisting of Tobramycin 5 mg/kg IV daily [13.Aiken S.K. Wetzstein G.E. Once-daily aminoglycosides in patients with neutropenic fever.Cancer Control. 2002; 9: 426-431Crossref PubMed Scopus (10) Google Scholar], Ceftriaxone 1–2 g IV daily and Vancomycin 20 mg/kg IV daily [14.Hughes W.T. Armstrong D. Bodey G.P. et al.Guidelines for the use of antimicrobial agents in neutropenic patients with cancer.Clin Infect Dis. 2002; 34: 730-751Crossref PubMed Scopus (1729) Google Scholar]. The choice of antibiotics in patients with documented penicillin and/or cephalosporin allergies was left to the discretion of the attending physician. Vancomycin was discontinued after 48 h if there was no documented microbiologic or clinical reason for it. Amphotericin B was commenced on day 5 of persistent fever. Antibiotics were modified as clinically and microbiologically indicated. Intravenous antibiotics were continued until microbiological and/or clinical evidence of infection had resolved or until the patient had been afebrile for five consecutive days. Once the patient satisfied these criteria antibiotics were changed from intravenous to oral therapy, until hematopoietic recovery i.e. ANC > 0.5 × 109/l [15.Horowitz H.W. Holmgren D. Seiter K. Stepdown single agent antibiotic therapy for the management of the high risk neutropenic adult with hematologic malignancies.Leuk Lymphoma. 1996; 23: 159-163Crossref PubMed Scopus (24) Google Scholar]. Central venous catheters were removed for Staphylococcus aureus bacteremia, persistent bacteremia, clinical tunnel infection, persistent fever with associated exit site infection, in the event of septic shock and in patients with fungemia [16.Mermel L.A. Farr B.M. Sheretz R.J. et al.Guidelines for the management of intravascular catheter-related infections.CID. 2001; 32: 1249-1272Crossref PubMed Scopus (128) Google Scholar].Criteria for admission to hospital included hemodynamic instability (hypotension unresponsive to fluid challenge or marked tachycardia), hypoxia (O2 saturation 0.5 × 109/l. Patients with febrile neutropenia not admitted to hospital were re-evaluated on a daily basis by medical staff in daycare.data collecteData gathered includes age, sex, chemotherapy given, white blood cell count and differential at discharge, number of visits to the outpatient treatment facility, duration of neutropenia as an outpatient, number of febrile episodes, day of chemotherapy cycle at time of each febrile episode, neutrophil count at each febrile episode, source of infection, organism(s) isolated during febrile episodes, need for admission, day of chemotherapy cycle at admission, length of hospital stay, need for vasopressor medication, need for ICU admission, mortality, need for removal of indwelling vascular device and clinically significant bleeding. Days of inpatient hospitalisation were calculated to include days for investigations and Hickman line insertion prior to onset of chemotherapy. The first day a patient received chemotherapy was defined as day 1 of that cycle, with the cycle considered as ending upon recovery of ANC to 0.5 × 109/l.resultinduction cycleDuring our prospective observation period 61 patients received induction chemotherapy for newly diagnosed AML at our institution, while eight received induction chemotherapy for refractory or relapsed disease (re-induction). One other patient received both induction and re-induction chemotherapy within the time frame of the study (total number of induction cycles: 71). All had their initial work-up and induction chemotherapy administered in hospital. According to our criteria 25 of 71 times (36%) the patients were discharged early with only 35% (nine patients) of those discharged requiring readmission. Their characteristics and outcomes are described in Table 2 and in Figure 1.Table 2Cycles of AML early discharge post induction or re-induction chemotherapy (n = 26)Age, years Median46 Range22–67Chemotherapy, number of patients HIDAC/Dauno15 7 + 34 AML-M34 VP-16 + CY2 Carbo/ara C1Disease stage, number of patients New diagnosis23 Relapse/refractory3Discharge Day of cycleMedian12Range8–28 ANC (×109/l)Median0.0Range0.0–0.16Days as inpatient Median17.5 Range10–30Total days neutropenic Median25 Range15–37Days neutropenic as outpatient Median13 Range1–26Number of day-care visits Median10 Range1–26Febrile episodes Number of episodes/number of patients21/14 Day of cycleMedian20Range11–40ANC (×109/l)Median:0.0Range0.0–28.0Re-Admissions Number of re-Admissions/number of patients10/9 Day of cycleMedian20Range11–40 ANC (×109/l)Median0.0Range0.0–5.2Duration (days) Median9.5 Range1–50Abbreviation: ANC, absolute neutrophil count. Open table in a new tab All re-admissions to hospital post-induction chemotherapy were associated with febrile neutropenic episodes or infections, but not all patients with fever or even clinically documented infections required admission. Out of the 21 febrile neutropenia episodes (14 patients) the etiology was clear in four instances. One patient had pneumonia with multiple positive sputum cultures. A second patient had a bacteremia with Streptococcus oralis. The final two patients had abnormal radiographic findings consistent with probable pulmonary aspergillosis and sinusitis respectively. Of note, none of these patients required vasopressor support or ICU admission and all survived. None of the patients had greater than grade 2 mucositis [17.Bearman S.I. Appelbaum F.R. Buckner C.D. et al.Regimen-related toxicity in patients undergoing bone marrow transplantation.J Clin Oncol. 1988; 6: 1562-1568Crossref PubMed Scopus (788) Google Scholar], cerebellar toxicity or non-infective Hickman line complications. Bleeding episodes were clinically insignificant, (WHO Grade 1 or 2) did not require hospitalisation and responded to outpatient transfusions alone. A median of two units of red blood cells per cycle (range 0–6) was transfused as outpatients. Patients received a median of three (range 0–7) platelet transfusions at the outpatient day-care clinic.consolidation cycleDuring the observation period 73 cycles of consolidation were given to 45 patients. Six of 73 cycles (8%) were planned as inpatient cycles as patients did not meet the criteria for outpatient management because of morbid obesity (two cycles), poor mobility (two cycles), poorly controlled diabetes mellitus (one cycle) and lack of an appropriate caregiver (one cycle). An attempt was made at early discharge in two of these cycles however both patients required readmission and therefore were excluded from this analysis.Admission occurred during 14/67 (21%) of consolidation cycles planned as an outpatient at a median of 17.5 (1–34) days after the start of chemotherapy. All admissions were associated with febrile neutropenic episodes or documented infections, but not all patients with fever or infection met the admission criteria. The characteristics and outcomes of these patients are described in Table 3 and in Figure 2. Sites of infection were determined in 27 instances. These are detailed in Table 4. In 19 of these a bacteria was isolated. There were 13 positive cultures for Gram-positive organisms. A Gram-negative organism was isolated in six cases. Two isolates, Klebsiella pneumonia and Escherichia coli, were resistant to Ciprofloxacin. Seven patients had their Hickman catheters removed. With respects to fungal findings, four patients had a proven [1.Smith M. Barnett M. Bassan R. et al.Adult acute myeloid leukaemia.Crit Rev Oncol Hematol. 2004; 50: 197-222Crossref PubMed Scopus (146) Google Scholar] or probable [3.Summers N. Dawe U. Stewart D.A. A comparison of inpatient and outpatient ASCT.Bone Marrow Transplant. 2000; 26: 389-395Crossref PubMed Scopus (41) Google Scholar] pulmonary aspergillosis. Three consolidation patients required vasopressor support and/or ICU admission although all survived. None of the patients had greater than grade 2 mucositis and there were no non-infective Hickman line complications. One instance of cytarabine induced cerebellar toxicity was suspected. Bleeding episodes were clinically insignificant (WHO grade 1or 2), did not necessitate admission and responded to platelet transfusions alone. A median of two (range 0–10) units of packed red cells were transfused per consolidation cycle in the outpatient setting. For platelets the median number of transfusions at the day-care clinic was also two (range 0–15).Table 3Cycles of AML consolidation chemotherapy given as outpatients (n = 67)Age, years Median51 Range22–74Chemotherapy, number of cycles HIDAC/Dauno23 7 + 316AML-M316 HIDAC10 5 + 22Days neutropenic as outpatient Median10 Range0–33Number of Clinic visits Median18 Range4–43Febrile episodes Number of episodes/number of cycles54/39 Days of cycleMedian6.5Range1–38 ANC (×109/l)Median0.0Range0.0–13.1Admissions Number of admissions/number of cycles16/14 Day of cycleMedian17.5Range1–34 ANC (×10/9/l)Median0.0Range0.0–13.0Duration (days) Median7 Range4–25Abbreviation: ANC, absolute neutrophil count. Open table in a new tab Figure 2Outcome of cycles of AML consolidation chemotherapy. Abbreviations; outpt, outpatient; inpt, inpatient; d/c, dischargeView Large Image Figure ViewerDownload (PPT)Table 4Consolidation: infectious complicationsSites of infection*Four patients had simultaneous infections at different sites.• bacteremia13• lung9• skin at catheter site3• abdomen2• peri-rectal2• sinus1• stool1* Four patients had simultaneous infections at different sites. Open table in a new tab discussioThere is limited data looking specifically at outpatient chemotherapy management with curative intent in AML. An attempt has been made to summarise the most important findings, as well as our comparable data, in Table 5. In the majority of previous reports high risk febrile neutropenic AML patients were initially admitted to hospital for antibiotic therapy. At some institutions patients were then kept in hospital until defervescence and count recovery [8.Ruiz-Argüelles G.J. Apreza-Molina M.A.G. Alemán-Hoey D.D. et al.Outpatient supportive therapy after induction to remission therapy in adult acute myelogenous leukaemia (AML) is feasible: a multicentre study.Eur J Haematol. 1995; 54: 18-20PubMed Google Scholar, 9.Gillis S. Dann E.J. Rund D. Selective discharge of patients with acute myeloid leukemia during chemotherapy-induced neutropenia.Am J Hematol. 1996; 51: 26-31Crossref PubMed Scopus (38) Google Scholar] while at others, if patients were clinically stable and afebrile, antibiotics were continued through an outpatient program. Both strategies appeared safe with only four reported treatment-related deaths (1%). This low incidence of fatal complication is in keeping with previously reported 3–7% treatment related mortality rate for chemotherapy for AML [18.Bishop J.F. The Treatment of adult acute myeloid leukemia.Semin Oncol. 1997; 24: 57-69PubMed Google Scholar, 19.Cassileth P.A. Harrington D.P. Appelbaum F.R. et al.Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission.N Engl J Med. 1998; 339: 1649-1700Crossref PubMed Scopus (533) Google Scholar]. Of these four deaths reported in the literature one was due to an intracerebral haemorrhage and one to multi-organ system failure secondary to E. coli bacteremia; the cause of death in the other two cases is uncertain. We did not experience any treatment related death during the study period perhaps not surprisingly given the relatively young age and strict selection of patients. Girmenia et al. [11.Girmenia C. Alimena G. Latagliata R. et al.Out-patient management of acute myeloid leukemia after consolidation chemotherapy.Role of Hematologic Emergency Unit. Haematologica. 1999; 84: 814-819PubMed Google Scholar] commented on the impact of age on the ability to treat AML patients in the outpatient setting and found no correlation between age and tolerability. We could not study the impact of age on our small outpatient population. However, older patients are more likely to have coexisting comorbidities or the lack of an appropriate caregiver.Table 5Review of literatureArticleProphylaxisInductionConsolidationNo. pts ED/% CohortReadmission %No. pts ED or outpt /% CohortReadmission %Deaths*Deaths: two from disease; four from treatment related mortality.Ruiz-Arguelles8Ciprofloxacin cotrimoxazole, itraconazole24/4029UnknownUnknown0Gillis9nil4/129446/87942Girmenia11Ciprofloxacin127/95541Allan12nil10/539030/97813SavoieCiprofloxacin valacyclovir, fluconazole25/363567/92210Abbreviations: pts, patients; ED, early discharge; outpt, outpatient.* Deaths: two from disease; four from treatment related mortality. Open table in a new tab Interestingly not all studies utilised antimicrobial prophylaxis, whereas we felt this to be an important part of our outpatient program. For inpatient neutropenia we typically use antiviral and antifungal prophylaxis only. Antimicrobial prophylaxis, generally quinolone-based, has been found to reduce the incidence and morbidity of documented gram negative infection, but it may lead to an increased gram-positive infection [20.Cruciani M. Rampazzo R. Malena M. et al.Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis.Clin Infect Dis. 1996; 23: 795-805Crossref PubMed Scopus (220) Google Scholar]. Although increased survival as a result of antibacterial prophylaxis has not been demonstrated, we believe that in the outpatient setting such prophylaxis should be undertaken in an attempt to minimise the risk of ambulatory sepsis. We monitored all organisms isolated for possible resistance to fluoroquinolones and only documented two such cases and both responded to other appropriate therapy. We observed a relative increase in Gram-positive organisms in neutropenic patients, [21.Madani T.A. Clinical infections and bloodstream isolates associated with fever in patients undergoing chemotherapy for acute myeloid leukemia.Infection. 2000; 28: 367-373Crossref PubMed Scopus (70) Google Scholar, 22.Jagarlamudi R. Kumar L. Kochupillai V. et al.Infection in acute leukemia: an analysis of 240 febrile episodes.Med Oncol. 2000; 17: 111-116Crossref PubMed Scopus (55) Google Scholar] justifying our front line use of Vancomycin in our empiric regimen for neutropenic fever despite the potential for emergence of multi-resistant organisms and associate toxicity. No cases of Vancomycin resistant Enterococcus were documented. A complete comparative analysis evaluating the impact of the introduction of the outpatient AML management on the infectious complications in our program is ongoing.The re-admission rate was greater in ED induction chemotherapy (36%) compared to admission in outpatient consolidation (21%) despite our highly selective criteria, reflecting the increased vulnerability of these patients. During 44% of induction and 42% of consolidation outpatient cycles only supportive care with oral prophylaxis and blood product transfusions according to our guideline were required (Figure 1). It is with these patients that the grea
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