Annals of Oncology Advance Access originally published online on February 23, 2006
Annals of Oncology 2006 17(5):763-768; doi:10.1093/annonc/mdl011
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 European Society for Medical Oncology
Shifting to outpatient management of acute myeloid leukemia: a prospective experience
The Leukemia/Bone Marrow Transplant Program of British Columbia, Division of Hematology, Vancouver Hospital Health Sciences Centre, BC Cancer Agency and the University of British Columbia, Vancouver, Canada
* Correspondence to: Dr M. L. Savoie, Room 681, 1403 29th Street NW, Calgary AB, T2N 2T9, Canada. Tel: +011 403 944 1564; Fax: +011 403 944 2102; E-mail: lynn.savoie{at}calgaryhealthregion.ca
 |
Abstract |
|---|
 Top Abstract introductionpatients and methodsresultsdiscussionReferences |
|---|
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.
Key words: acute myeloid leukaemia, ambulatory, chemotherapy, febrile neutropenia, outpatient, supportive care
|
introduction |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
Acute 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
]. 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], high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), [3, 4] and more recently in the allogeneic nonmyeloablative HSCT setting despite earlier studies of protective isolation suggesting an infection preventative benefit [5–7]. In selected patients with AML, successful early discharge post chemotherapy along with outpatient administration of consolidation cycles has also been reported [8–12].
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 methods |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
design
Between 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 criteria
All 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 x 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]. Our intention was to treat patients with consolidation chemotherapy entirely as outpatients provided they met the above eligibility criteria.
treatment description
A 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.
|
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 x 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 x 109/l and the patient was afebrile, or if the platelet count was less than 20 x 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], Ceftriaxone 1–2 g IV daily and Vancomycin 20 mg/kg IV daily [14]. 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 x 109/l [15]. 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].
Criteria for admission to hospital included hemodynamic instability (hypotension unresponsive to fluid challenge or marked tachycardia), hypoxia (O2 saturation <92% on room air), a temperature greater than 39.5°C, fever unresponsive to therapy with antibiotics for 3 days, rigors, WHO Grade 3 bleeding, requirement of intravenous antibiotics more than once a day, failure to thrive as an outpatient or if the caregiver was unable to adequately care for the patient.. Hospitalized patients becoming afebrile for at least 3 days and without other issues requiring continued hospitalisation were discharged regardless of their ANC or platelet count. Antibiotic therapy was continued as an outpatient, either orally or with the once daily intravenous regimen until count recovery, i.e. ANC > 0.5 x 109/l. Patients with febrile neutropenia not admitted to hospital were re-evaluated on a daily basis by medical staff in daycare.
data collected
Data 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 x 109/l.
|
results |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
induction cycles
During 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.
|
|
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
], 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 cycles
During 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] or probable [3] 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).
|
|
|
|
discussion |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
There 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
, 9] 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, 19]. 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] 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.
|
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
]. 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, 22] 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 greatest benefits financially and socially are to be observed with a program such as ours.
There are obvious limitations to our data. This was an observational report conducted at a highly specialised centre with a small number of patients. A number of cytotoxic therapies were used and the sample size precludes our ability to perform subgroup analyses such as outcome according to regimen or age. Also, we have currently no reliable method to estimate the financial impact of this treatment modification. Our results would not be reproducible in every centre as a specialised and dedicated day-care is essential. We have had to show flexibility during this transition time with an increase in day-care operating hours along with an increase in nurses and physicians to adequately staff the unit. 1.5 medical clinical associate positions were created along with three new nursing positions.
The syndrome of fever and neutropenia is an iatrogenic complication of cytotoxic therapy for leukemia. Although ambulatory antimicrobial therapy for high-risk hematologic malignancies is not standard of care it has become a growing field of interest. [23–26]. In our hands this has proven safe and feasible. We also believe that patients have experienced fewer delays between cycles of chemotherapy compared to historical controls at our centre although we have not formally analysed this data. We intend to continue monitoring this group of patients to ensure that our regimen is safe, continues to facilitate timely access to care and does not compromise optimal patient therapy.
|
Acknowledgements |
|---|
The authors wish to acknowledge the contribution of the medical and nursing staff of Leukemia/BMT Ward T15A, BMT Daycare at the Vancouver General Hospital and 6 West Ward at the British Columbia Cancer Agency. We would also like to thank Janet Nitta for data assistance and Shawna Moore for help with manuscript preparation.
Received for publication August 29, 2005. Revision received January 11, 2006. Accepted for publication January 12, 2006.
|
References |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
1. Smith M, Barnett M, Bassan R et al. Adult acute myeloid leukaemia. Crit Rev Oncol Hematol 2004; 50: 197–222.[Web of Science][Medline]
2. Dollinger, M. Guidelines for hospitalization for chemotherapy. Oncologist 1996; 1: 107–111.
3. Summers N, Dawe U, Stewart DA. A comparison of inpatient and outpatient ASCT. Bone Marrow Transplant 2000; 26: 389–395.[CrossRef][Web of Science][Medline]
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: 431–434.[CrossRef][Web of Science][Medline]
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: 131–133.[CrossRef][Web of Science][Medline]
6. Ruiz-Argüelles GJ, 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: 241–244.[CrossRef][Web of Science][Medline]
7. van Tiel FH, Harbers MM, Kessels AG, Schouten HC. Home care versus hospital care of patients with hematological malignancies and chemotherapy-induced cytopenia. Ann Oncol 2005; 16: 195–205.
8. Ruiz-Argüelles GJ, Apreza-Molina MAG, Alemán-Hoey DD 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: 18–20.[Web of Science][Medline]
9. Gillis S, Dann EJ, Rund D. Selective discharge of patients with acute myeloid leukemia during chemotherapy-induced neutropenia. Am J Hematol 1996; 51: 26–31.[CrossRef][Web of Science][Medline]
10. Girmenia C, Latagliata R, Tosti S et al. Outpatient management of acute promyelocytic leukemia after consolidation chemotherapy. Leukemia 1999; 13: 514–517.[CrossRef][Web of Science][Medline]
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: 814–819.
12. Allan DS, Buckstein R, Imrie KR. Outpatient supportive care following chemotherapy for acute myeloblastic leukemia. Leuk Lymphoma 2001; 42: 339–346.[Web of Science][Medline]
13. Aiken SK, Wetzstein GE. Once-daily aminoglycosides in patients with neutropenic fever. Cancer Control 2002; 9: 426–431.[Medline]
14. Hughes WT, Armstrong D, Bodey GP et al. Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002; 34: 730–751.[CrossRef][Web of Science][Medline]
15. Horowitz HW, 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: 159–163.[Web of Science][Medline]
16. Mermel LA, Farr BM, Sheretz RJ et al. Guidelines for the management of intravascular catheter-related infections. CID 2001; 32: 1249–1272.
17. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1988; 6: 1562–1568.
18. Bishop JF. The Treatment of adult acute myeloid leukemia. Semin Oncol 1997; 24: 57–69.[Web of Science][Medline]
19. Cassileth PA, Harrington DP, Appelbaum FR 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: 1649–700.
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: 795–805.[Web of Science][Medline]
21. Madani TA. Clinical infections and bloodstream isolates associated with fever in patients undergoing chemotherapy for acute myeloid leukemia. Infection 2000; 28: 367–373.[CrossRef][Web of Science][Medline]
22. Jagarlamudi R, Kumar L, Kochupillai V et al. Infection in acute leukemia: an analysis of 240 febrile episodes. Med Oncol 2000; 17: 111–116.[Web of Science][Medline]
23. Karthaus M, Carratala J, Jürgens H, Ganser A. New strategies in the treatment of infectious complications in haematology and oncology: is there a role for out-patient antibiotic treatment for febrile neutropenia? Chemotherapy 1998; 44: 427–435.[CrossRef][Web of Science][Medline]
24. Herrmann RP, Trent M, Cooney J, Cannell PK. Infections in patients managed at home during autologous stem cell transplantation for lymphoma and multiple myeloma. Bone Marrow Transplant 1999; 24: 1213–1217.[CrossRef][Web of Science][Medline]
25. Johansson E, Björkholm M, Wredling R et al. Outpatient parenteral antibiotic therapy in patients with haematological malignancies. Support Care Cancer 2001; 9: 619–624.[CrossRef][Web of Science][Medline]
26. Rolston KVI. Ambulatory antimicrobial therapy for hematologic malignancies. Oncology 2000; 14: 17–22.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Naithani, R. Kumar, M. Mahapatra, N. Agrawal, and P. Mishra Early discharge from hospital after consolidation chemotherapy in acute myeloid leukemia in remission: febrile neutropenic episodes and their outcome in a resource poor setting Haematologica, September 1, 2008; 93(9): 1416 - 1418. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Halim, K. Song, M. Barnett, D. Forrest, D. Hogge, S. Nantel, T. Nevill, J. Shepherd, C. Smith, H. Sutherland, et al. Positive impact of selective outpatient management of high-risk acute myelogenous leukemia on the incidence of septicemia Ann. Onc., July 1, 2007; 18(7): 1246 - 1252. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||